The Role of p21 in Apoptosis, Proliferation, Cell Cycle Arrest, and Antioxidant Activity in UVB-Irradiated Human HaCaT Keratinocytes

PubMed Central

Chen, Aijun; Huang, Xin; Xue, Zhenan; Cao, Di; Huang, Kun; Chen, Jin; Pan, Yun; Gao, Yongliang

2015-01-01

Background Skin cancer is the most common cancer in the United States, and ultraviolet B (UVB) radiation-induced DNA damage is the major environmental factor underlying skin cancer development. p21, a p53-inducible protein, plays a key role in the cellular response to UVB-induced DNA damage. Material/Methods Through p21 silencing and overexpression, we investigated the role of p21 in apoptosis, proliferation, cell cycle arrest, and oxidative stress in UVB-irradiated HaCaT keratinocytes. Results We found that UVB exposure induced significant p21 downregulation (p<0.05) and was associated with significantly increased apoptosis, significantly decreased proliferation, and significantly increased G2 phase arrest (p<0.05) in UVB-irradiated HaCaT keratinocytes. p21 silencing significantly promoted apoptosis, significantly inhibited G2 phase arrest, and significantly inhibited proliferation (p<0.05), but after UVB irradiation, p21 silencing demonstrated a less significant pro-apoptotic effect and a more significant inhibition of G2 phase arrest (p<0.05), which was reflected in significantly higher proliferative activity (p<0.05). p21 overexpression acted in an anti-apoptotic manner in the absence of UVB-induced DNA damage but acted in a pro-apoptotic manner in the presence of UVB-induced DNA damage, displaying an “antagonistic duality” similar to other growth-promoting oncoproteins. p53 expression mirrored p21 expression, suggesting a regulatory feedback mechanism between p21 and p53 expression. p21 overexpression significantly downregulated glutathione peroxidase and superoxide dismutase antioxidant activity (p<0.05) while significantly upregulating hydrogen peroxide and malondialdehyde content (p<0.05), suggesting a role in decreasing antioxidant defense capabilities in UVB-irradiated HaCaT keratinocytes. Conclusions These findings reveal that p21 may play a key role in HaCaT keratinocytes’ response to UVB exposure. PMID:25925725

7-Hydroxycoumarin prevents UVB-induced activation of NF-κB and subsequent overexpression of matrix metalloproteinases and inflammatory markers in human dermal fibroblast cells.

PubMed

Karthikeyan, Ramasamy; Kanimozhi, Govindasamy; Prasad, Nagarajan Rajendra; Agilan, Balupillai; Ganesan, Muthusamy; Mohana, Shanmugham; Srithar, Gunaseelan

2016-08-01

Ultraviolet B (UVB) irradiation alters multiple molecular pathways in the skin, thereby inducing skin damage. Human dermal fibroblasts (HDFa) were subjected to single UVB-irradiation (18mJ/cm(2)) resulting in reactive oxygen species (ROS) generation, oxidative DNA damage and upregulation of nuclear factor kappa B (NF-κB) expression. Further, it has been observed that there was a significant cytokine production (TNF-α and IL-6) in UVB irradiated HDFa cells. Our results show that 7-hydroxycoumarin (7-OHC) prevents UVB-induced activation of NF-κB thereby subsequently preventing the overexpression of TNF-α and IL-6 in HDFa cells. Further, 7-OHC prevents UVB-induced activation of cyclooxygenase-2 (COX-2) expression, an inflammatory mediator in skin cells. Moreover, 7-OHC inhibited mRNA expression pattern of matrix metalloproteinases (MMP-1 and MMP-9) in UVB irradiated skin cells. Furthermore, 7-OHC restored antioxidant status, thereby scavenging the excessively generated ROS; consequently preventing the oxidative DNA damage. It has also been noticed that 7-OHC prevents UVB mediated DNA damage through activation of DNA repair enzymes such as XRCC1 and HOGG1. In this study, we treated HDFa cells with 7-OHC before and after UVB irradiation and we found that pretreatment showed better results when compared to posttreatment. Further, 7-OHC showed 9.8416 sun protection factor (SPF) value and it absorbs photons in the UVB wavelength rage. Thus, it has been concluded that sunscreen property, free radical scavenging potential and prevention of NF-κB activation play a role for photoprotective property of 7-OHC. Copyright © 2016 Elsevier B.V. All rights reserved.

Heat-mediated reduction of apoptosis in UVB-damaged keratinocytes in vitro and in human skin ex vivo.

PubMed

Calapre, Leslie; Gray, Elin S; Kurdykowski, Sandrine; David, Anthony; Hart, Prue; Descargues, Pascal; Ziman, Mel

2016-05-26

UV radiation induces significant DNA damage in keratinocytes and is a known risk factor for skin carcinogenesis. However, it has been reported previously that repeated and simultaneous exposure to UV and heat stress increases the rate of cutaneous tumour formation in mice. Since constant exposure to high temperatures and UV are often experienced in the environment, the effects of exposure to UV and heat needs to be clearly addressed in human epidermal cells. In this study, we determined the effects of repeated UVB exposure 1 kJ/m(2) followed by heat (39 °C) to human keratinocytes. Normal human ex vivo skin models and primary keratinocytes (NHEK) were exposed once a day to UVB and/or heat stress for four consecutive days. Cells were then assessed for changes in proliferation, apoptosis and gene expression at 2 days post-exposure, to determine the cumulative and persistent effects of UV and/or heat in skin keratinocytes. Using ex vivo skin models and primary keratinocytes in vitro, we showed that UVB plus heat treated keratinocytes exhibit persistent DNA damage, as observed with UVB alone. However, we found that apoptosis was significantly reduced in UVB plus heat treated samples. Immunohistochemical and whole genome transcription analysis showed that multiple UVB plus heat exposures induced inactivation of the p53-mediated stress response. Furthermore, we demonstrated that repeated exposure to UV plus heat induced SIRT1 expression and a decrease in acetylated p53 in keratinocytes, which is consistent with the significant downregulation of p53-regulated pro-apoptotic and DNA damage repair genes in these cells. Our results suggest that UVB-induced p53-mediated cell cycle arrest and apoptosis are reduced in the presence of heat stress, leading to increased survival of DNA damaged cells. Thus, exposure to UVB and heat stress may act synergistically to allow survival of damaged cells, which could have implications for initiation skin carcinogenesis.

Fisetin inhibits UVB-induced cutaneous inflammation and activation of PI3K/AKT/NFκB signaling pathways in SKH-1 hairless mice†

PubMed Central

Pal, Harish Chandra; Athar, Mohammad; Elmets, Craig A.; Afaq, Farrukh

2014-01-01

Solar ultraviolet B (UVB) radiation has been shown to induce inflammation, DNA damage, p53 mutations, and alterations in signaling pathways eventually leading to skin cancer. In the present study, we investigated whether fisetin reduces inflammatory responses and modulates PI3K/AKT/NFκB cell survival signaling pathways in UVB exposed SKH-1 hairless mouse skin. Mice were exposed to 180 mJ/cm2 of UVB radiation on alternate days for a total of seven exposures, and fisetin (250 and 500 nmol) was applied topically after 15 min of each UVB exposure. Fisetin treatment to UVB exposed mice resulted in decreased hyperplasia and reduced infiltration of inflammatory cells. Fisetin treatment also reduced inflammatory mediators such as COX-2, PGE2 as well as its receptors (EP1- EP4), and MPO activity. Furthermore, fisetin reduced the level of inflammatory cytokines TNFα, IL-1β and IL-6 in UVB exposed skin. Fisetin treatment also reduced cell proliferation markers as well as DNA damage as evidenced by increased expression of p53 and p21 proteins. Further studies revealed that fisetin inhibited UVB-induced expression of PI3K, phosphorylation of AKT, and activation of the NFκB signaling pathway in mouse skin. Overall, these data suggest that fisetin may be useful against UVB-induced cutaneous inflammation and DNA damage. PMID:25169110

Prevention of UVB Radiation-induced Epidermal Damage by Expression of Heat Shock Protein 70*

PubMed Central

Matsuda, Minoru; Hoshino, Tatsuya; Yamashita, Yasuhiro; Tanaka, Ken-ichiro; Maji, Daisuke; Sato, Keizo; Adachi, Hiroaki; Sobue, Gen; Ihn, Hironobu; Funasaka, Yoko; Mizushima, Tohru

2010-01-01

Irradiation with UV light, especially UVB, causes epidermal damage via the induction of apoptosis, inflammatory responses, and DNA damage. Various stressors, including UV light, induce heat shock proteins (HSPs) and the induction, particularly that of HSP70, provides cellular resistance to such stressors. The anti-inflammatory activity of HSP70, such as its inhibition of nuclear factor kappa B (NF-κB), was recently revealed. These in vitro results suggest that HSP70 protects against UVB-induced epidermal damage. Here we tested this idea by using transgenic mice expressing HSP70 and cultured keratinocytes. Irradiation of wild-type mice with UVB caused epidermal damage such as induction of apoptosis, which was suppressed in transgenic mice expressing HSP70. UVB-induced apoptosis in cultured keratinocytes was suppressed by overexpression of HSP70. Irradiation of wild-type mice with UVB decreased the cutaneous level of IκB-α (an inhibitor of NF-κB) and increased the infiltration of leukocytes and levels of pro-inflammatory cytokines and chemokines in the epidermis. These inflammatory responses were suppressed in transgenic mice expressing HSP70. In vitro, the overexpression of HSP70 suppressed the expression of pro-inflammatory cytokines and chemokines and increased the level of IκB-α in keratinocytes irradiated with UVB. UVB induced an increase in cutaneous levels of cyclobutane pyrimidine dimers and 8-hydroxy-2′-deoxyguanosine, both of which were suppressed in transgenic mice expressing HSP70. This study provides genetic evidence that HSP70 protects the epidermis from UVB-induced radiation damage. The findings here also suggest that the protective action of HSP70 is mediated by anti-apoptotic, anti-inflammatory, and anti-DNA damage effects. PMID:20018843

The Polyphenol Chlorogenic Acid Attenuates UVB-mediated Oxidative Stress in Human HaCaT Keratinocytes

PubMed Central

Cha, Ji Won; Piao, Mei Jing; Kim, Ki Cheon; Yao, Cheng Wen; Zheng, Jian; Kim, Seong Min; Hyun, Chang Lim; Ahn, Yong Seok; Hyun, Jin Won

2014-01-01

We investigated the protective effects of chlorogenic acid (CGA), a polyphenol compound, on oxidative damage induced by UVB exposure on human HaCaT cells. In a cell-free system, CGA scavenged 1,1-diphenyl-2-picrylhydrazyl radicals, superoxide anions, hydroxyl radicals, and intracellular reactive oxygen species (ROS) generated by hydrogen peroxide and ultraviolet B (UVB). Furthermore, CGA absorbed electromagnetic radiation in the UVB range (280–320 nm). UVB exposure resulted in damage to cellular DNA, as demonstrated in a comet assay; pre-treatment of cells with CGA prior to UVB irradiation prevented DNA damage and increased cell viability. Furthermore, CGA pre-treatment prevented or ameliorated apoptosis-related changes in UVB-exposed cells, including the formation of apoptotic bodies, disruption of mitochondrial membrane potential, and alterations in the levels of the apoptosis-related proteins Bcl-2, Bax, and caspase-3. Our findings suggest that CGA protects cells from oxidative stress induced by UVB radiation. PMID:24753819

Protective effect of pomegranate derived products on UVB-mediated damage in human reconstituted skin

PubMed Central

Afaq, Farrukh; Zaid, Mohammad Abu; Khan, Naghma; Dreher, Mark; Mukhtar, Hasan

2010-01-01

Solar ultraviolet (UV) radiation, particularly its UVB (290-320 nm) component, is the primary cause of many adverse biological effects including photoaging and skin cancer. UVB radiation causes DNA damage, protein oxidation and induces matrix metalloproteinases (MMPs). Photochemoprevention via the use of botanical antioxidants in affording protection to human skin against UVB damage is receiving increasing attention. Pomegranate, from the tree Punica granatum contains anthocyanins and hydrolyzable tannins and possesses strong anti-oxidant and anti-tumor promoting properties. In this study, we determined the effect of pomegranate derived products POMx juice, POMx extract and pomegranate oil (POMo) against UVB-mediated damage using reconstituted human skin (EpiDerm™ FT-200). EpiDerm was treated with POMx juice (1-2 μl/0.1 ml/well), POMx extract (5-10 μg/0.1 ml/well), and POMo (1-2 μl/0.1 ml/well) for 1 h prior to UVB (60 mJ/cm2) irradiation and was harvested 12 h post-UVB to assess protein oxidation, markers of DNA damage and photoaging by western blot analysis and immunohistochemistry. Pretreatment of Epiderm with pomegranate derived products resulted in inhibition of UVB-induced (i) cyclobutane pyrimidine dimers, (ii) 8-dihydro-2′-deoxyguanosine, (iii) protein oxidation, and (iv) PCNA protein expression. We also found that pretreatment of Epiderm with pomegranate derived products resulted in inhibition of UVB-induced (i) collagenase (MMP-1), (ii) gelatinase (MMP-2, MMP-9), (iii) stromelysin (MMP-3), (iv) marilysin (MMP-7), (v) elastase (MMP-12), and (vi) tropoelastin. Gelatin zymography revealed that pomegranate derived products inhibited UVB-induced MMP-2 and MMP-9 activities. Pomegranate derived products also caused a decrease in UVB-induced protein expression of c-Fos and phosphorylation of c-Jun. Collectively, these results suggest that all three pomegranate derived products may be useful against UVB-induced damage to human skin. PMID:19320737

Quercitrin Protects Skin from UVB-induced Oxidative Damage

PubMed Central

Yin, Yuanqin; Li, Wenqi; Son, Yong-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

2013-01-01

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. PMID:23545178

Quercitrin protects skin from UVB-induced oxidative damage.

PubMed

Yin, Yuanqin; Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

2013-06-01

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. Copyright © 2013 Elsevier Inc. All rights reserved.

Molecular and sensory mechanisms to mitigate sunlight-induced DNA damage in treefrog tadpoles.

PubMed

Schuch, André P; Lipinski, Victor M; Santos, Mauricio B; Santos, Caroline P; Jardim, Sinara S; Cechin, Sonia Z; Loreto, Elgion L S

2015-10-01

The increased incidence of solar ultraviolet B (UVB) radiation has been proposed as an environmental stressor, which may help to explain the enigmatic decline of amphibian populations worldwide. Despite growing knowledge regarding the UV-induced biological effects in several amphibian models, little is known about the efficacy of DNA repair pathways. In addition, little attention has been given to the interplay between these molecular mechanisms with other physiological strategies that avoid the damage induced by sunlight. Here, DNA lesions induced by environmental doses of solar UVB and UVA radiation were detected in genomic DNA samples of treefrog tadpoles (Hypsiboas pulchellus) and their DNA repair activity was evaluated. These data were complemented by monitoring the induction of apoptosis in blood cells and tadpole survival. Furthermore, the tadpoles' ability to perceive and escape from UV wavelengths was evaluated as an additional strategy of photoprotection. The results show that tadpoles are very sensitive to UVB light, which could be explained by the slow DNA repair rates for both cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6,4) pyrimidone photoproducts (6,4PPs). However, they were resistant to UVA, probably as a result of the activation of photolyases during UVA irradiation. Surprisingly, a sensory mechanism that triggers their escape from UVB and UVA light avoids the generation of DNA damage and helps to maintain the genomic integrity. This work demonstrates the genotoxic impact of both UVB and UVA radiation on tadpoles and emphasizes the importance of the interplay between molecular and sensory mechanisms to minimize the damage caused by sunlight. © 2015. Published by The Company of Biologists Ltd.

Fisetin inhibits UVB-induced cutaneous inflammation and activation of PI3K/AKT/NFκB signaling pathways in SKH-1 hairless mice.

PubMed

Pal, Harish Chandra; Athar, Mohammad; Elmets, Craig A; Afaq, Farrukh

2015-01-01

Solar ultraviolet B (UVB) radiation has been shown to induce inflammation, DNA damage, p53 mutations and alterations in signaling pathways eventually leading to skin cancer. In this study, we investigated whether fisetin reduces inflammatory responses and modulates PI3K/AKT/NFκB cell survival signaling pathways in UVB-exposed SKH-1 hairless mouse skin. Mice were exposed to 180 mJ cm(-2) of UVB radiation on alternate days for a total of seven exposures, and fisetin (250 and 500 nmol) was applied topically after 15 min of each UVB exposure. Fisetin treatment to UVB-exposed mice resulted in decreased hyperplasia and reduced infiltration of inflammatory cells. Fisetin treatment also reduced inflammatory mediators such as COX-2, PGE2 as well as its receptors (EP1-EP4) and MPO activity. Furthermore, fisetin reduced the level of inflammatory cytokines TNFα, IL-1β and IL-6 in UVB-exposed skin. Fisetin treatment also reduced cell proliferation markers as well as DNA damage as evidenced by increased expression of p53 and p21 proteins. Further studies revealed that fisetin inhibited UVB-induced expression of PI3K, phosphorylation of AKT and activation of the NFκB signaling pathway in mouse skin. Overall, these data suggest that fisetin may be useful against UVB-induced cutaneous inflammation and DNA damage. © 2014 The American Society of Photobiology.

Photobiological implications of melanin photoprotection after UVB-induced tanning of human skin but not UVA-induced tanning.

PubMed

Coelho, Sergio G; Yin, Lanlan; Smuda, Christoph; Mahns, Andre; Kolbe, Ludger; Hearing, Vincent J

2015-03-01

Repetitive suberythemal UVA and/or UVB exposures were used to generate comparable UV-induced tans in human skin over the course of 2 weeks. To evaluate the potential photoprotective values of those UVA- and/or UVB- induced tans and to avoid the confounding issue of residual UV-induced DNA damage, we waited 1 week before challenging those areas with a 1.5 MED of UVA+UVB after which we measure DNA damage. The results show that the type of UV used to induce skin pigmentation affects the redistribution of melanin in the skin and/or de novo melanin synthesis. The UVA-induced tans failed to even provide a minimal SPF of 1.5, which suggests that producing a tan with UVA-rich sunlamps prior to a holiday or vacation is completely counterproductive. Published 2014. This article is a US Government work and is in the public domain in the USA.

Tualang honey protects keratinocytes from ultraviolet radiation-induced inflammation and DNA damage.

PubMed

Ahmad, Israr; Jimenez, Hugo; Yaacob, Nik Soriani; Yusuf, Nabiha

2012-01-01

Malaysian tualang honey possesses strong antioxidant and anti-inflammatory properties. Here, we evaluated the effect of tualang honey on early biomarkers of photocarcinogenesis employing PAM212 mouse keratinocyte cell line. Keratinocytes were treated with tualang honey (1.0%, v/v) before a single UVB (150 mJ cm(-2) ) irradiation. We found that the treatment of tualang honey inhibited UVB-induced DNA damage, and enhanced repair of UVB-mediated formation of cyclobutane pyrimidine dimers and 8-oxo-7,8-dihydro-2'-deoxyguanosine. Treatment of tualang honey inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in murine keratinocyte cell line. The treatment of tualang honey also inhibited UVB-induced inflammatory cytokines and inducible nitric oxide synthase protein expression. Furthermore, the treatment of tualang honey inhibited UVB-induced COX-2 expression and PGE2 production. Taken together, we provide evidence that the treatment of tualang honey to keratinocytes affords substantial protection from the adverse effects of UVB radiation via modulation in early biomarkers of photocarcinogenesis and provide suggestion for its photochemopreventive potential. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

Cell damage caused by ultraviolet B radiation in the desert cyanobacterium Phormidium tenue and its recovery process.

PubMed

Wang, Gaohong; Deng, Songqiang; Liu, Jiafeng; Ye, Chaoran; Zhou, Xiangjun; Chen, Lanzhou

2017-10-01

Phormidium tenue, a cyanobacterium that grows in the topsoil of biological soil crusts (BSCs), has the highest recovery rate among desert crust cyanobacteria after exposure to ultraviolet B (UV-B) radiation. However, the mechanism underlying its recovery process is unclear. To address this issue, we measured chlorophyll a fluorescence, generation of reactive oxygen species (ROS), lipid peroxidation, and repair of DNA breakage in P. tenue following exposure to UV-B. We found that UV-B radiation at all doses tested reduced photosynthesis and induced cell damage in P. tenue. However, P. tenue responded to UV-B radiation by rapidly reducing photosynthetic activity, which protects the cell by leaking less ROS. Antioxidant enzymes, DNA damage repair systems, and UV absorbing pigments were then induced to mitigate the damage caused by UV-B radiation. The addition of exogenous antioxidant chemicals ascorbate and N-acetylcysteine also mitigated the harmful effects caused by UV-B radiation and enhanced the recovery process. These chemicals could aid in the resistance of P. tenue to the exposure of intense UV-B radiation in desertified areas when inoculated onto the sand surface to form artificial algal crusts. Copyright © 2017. Published by Elsevier Inc.

Silver nanoparticles protect human keratinocytes against UVB radiation-induced DNA damage and apoptosis: potential for prevention of skin carcinogenesis

PubMed Central

Arora, Sumit; Tyagi, Nikhil; Bhardwaj, Arun; Rusu, Lilia; Palanki, Rohan; Vig, Komal; Singh, Shree R.; Singh, Ajay P.; Palanki, Srinivas; Miller, Michael E.; Carter, James E.; Singh, Seema

2015-01-01

Ultraviolet (UV)-B radiation from the sun is an established etiological cause of skin cancer, which afflicts more than a million lives each year in the United States alone. Here, we tested the chemopreventive efficacy of silver-nanoparticles (AgNPs) against UVB-irradiation-induced DNA damage and apoptosis in human immortalized keratinocytes (HaCaT). AgNPs were synthesized by reduction-chemistry and characterized for their physicochemical properties. AgNPs were well tolerated by HaCaT cells and their pretreatment protected them from UVB-irradiation-induced apoptosis along with significant reduction in cyclobutane-pyrimidine-dimer formation. Moreover, AgNPs pre-treatment led to G1-phase cell-cycle arrest in UVB-irradiated HaCaT cells. AgNPs were efficiently internalized in UVB-irradiated cells and localized into cytoplasmic and nuclear compartments. Furthermore, we observed an altered expression of various genes involved in cell-cycle, apoptosis and nucleotide-excision repair in HaCaT cells treated with AgNPs prior to UVB-irradiation. Together, these findings provide support for potential utility of AgNPs as novel chemopreventive agents against UVB-irradiation-induced skin carcinogenesis. PMID:25804413

HAC1 and HAF1 Histone Acetyltransferases Have Different Roles in UV-B Responses in Arabidopsis.

PubMed

Fina, Julieta P; Masotti, Fiorella; Rius, Sebastián P; Crevacuore, Franco; Casati, Paula

2017-01-01

Arabidopsis has 12 histone acetyltransferases grouped in four families: the GNAT/HAG, the MYST/HAM, the p300/CBP/HAC and the TAFII250/HAF families. We previously showed that ham1 and ham2 mutants accumulated higher damaged DNA after UV-B exposure than WT plants. In contrast, hag3 RNA interference transgenic plants showed less DNA damage and lower inhibition of plant growth by UV-B, and increased levels of UV-B-absorbing compounds. These results demonstrated that HAM1, HAM2, and HAG3 participate in UV-B-induced DNA damage repair and signaling. In this work, to further explore the role of histone acetylation in UV-B responses, a putative function of other acetyltransferases of the HAC and the HAF families was analyzed. Neither HAC nor HAF acetyltrasferases participate in DNA damage and repair after UV-B radiation in Arabidopsis. Despite this, haf1 mutants presented lower inhibition of leaf and root growth by UV-B, with altered expression of E2F transcription factors. On the other hand, hac1 plants showed a delay in flowering time after UV-B exposure and changes in FLC and SOC1 expression patterns. Our data indicate that HAC1 and HAF1 have crucial roles for in UV-B signaling, confirming that, directly or indirectly, both enzymes also have a role in UV-B responses.

HAC1 and HAF1 Histone Acetyltransferases Have Different Roles in UV-B Responses in Arabidopsis

PubMed Central

Fina, Julieta P.; Masotti, Fiorella; Rius, Sebastián P.; Crevacuore, Franco; Casati, Paula

2017-01-01

Arabidopsis has 12 histone acetyltransferases grouped in four families: the GNAT/HAG, the MYST/HAM, the p300/CBP/HAC and the TAFII250/HAF families. We previously showed that ham1 and ham2 mutants accumulated higher damaged DNA after UV-B exposure than WT plants. In contrast, hag3 RNA interference transgenic plants showed less DNA damage and lower inhibition of plant growth by UV-B, and increased levels of UV-B-absorbing compounds. These results demonstrated that HAM1, HAM2, and HAG3 participate in UV-B-induced DNA damage repair and signaling. In this work, to further explore the role of histone acetylation in UV-B responses, a putative function of other acetyltransferases of the HAC and the HAF families was analyzed. Neither HAC nor HAF acetyltrasferases participate in DNA damage and repair after UV-B radiation in Arabidopsis. Despite this, haf1 mutants presented lower inhibition of leaf and root growth by UV-B, with altered expression of E2F transcription factors. On the other hand, hac1 plants showed a delay in flowering time after UV-B exposure and changes in FLC and SOC1 expression patterns. Our data indicate that HAC1 and HAF1 have crucial roles for in UV-B signaling, confirming that, directly or indirectly, both enzymes also have a role in UV-B responses. PMID:28740501

Solar UVB-induced DNA damage and photoenzymatic DNA repair in antarctic zooplankton

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malloy, K.D.; Holman, M.A.; Mitchell, D.

The detrimental effects of elevated intensities of mid-UV radiation (UVB), a result of stratospheric ozone depletion during the austral spring, on the primary producers of the Antarctic marine ecosystem have been well documented. Here we report that natural populations of Antarctic zooplankton also sustain significant DNA damage [measured as cyclobutane pyrimidine dimers (CPDs)] during periods of increased UVB flux. This is the first direct evidence that increased solar UVB may result in damage to marine organisms other than primary producers in Antarctica. The extent of DNA damage in pelagic icefish eggs correlated with daily incident UVB irradiance, reflecting the differencemore » between acquisition and repair of CPDs. Patterns of DNA damage in fish larvae did not correlated with daily UVB flux, possibly due to different depth distributions and/or different capacities for DNA repair. Clearance of CPDs by Antarctic fish and krill was mediated primarily by the photoenzymatic repair system. Although repair rates were large for all species evaluated, they were apparently inadequate to prevent the transient accumulation of substantial CPD burdens. The capacity for DNA repair in Antarctic organisms was highest in those species whose early life history stages occupy the water column during periods of ozone depletion (austral spring) and lowest in fish species whose eggs and larvae are abundant during winter. Although the potential reduction in fitness of Antarctic zooplankton resulting from DNA damage is unknown, we suggest that increased solar UV may reduce recruitment and adversely affect trophic transfer of productivity by affecting heterotrophic species as well as primary producers. 54 refs., 4 figs., 2 tabs.« less

DNA damage and repair in plants under ultraviolet and ionizing radiations.

PubMed

Gill, Sarvajeet S; Anjum, Naser A; Gill, Ritu; Jha, Manoranjan; Tuteja, Narendra

2015-01-01

Being sessile, plants are continuously exposed to DNA-damaging agents present in the environment such as ultraviolet (UV) and ionizing radiations (IR). Sunlight acts as an energy source for photosynthetic plants; hence, avoidance of UV radiations (namely, UV-A, 315-400 nm; UV-B, 280-315 nm; and UV-C, <280 nm) is unpreventable. DNA in particular strongly absorbs UV-B; therefore, it is the most important target for UV-B induced damage. On the other hand, IR causes water radiolysis, which generates highly reactive hydroxyl radicals (OH(•)) and causes radiogenic damage to important cellular components. However, to maintain genomic integrity under UV/IR exposure, plants make use of several DNA repair mechanisms. In the light of recent breakthrough, the current minireview (a) introduces UV/IR and overviews UV/IR-mediated DNA damage products and (b) critically discusses the biochemistry and genetics of major pathways responsible for the repair of UV/IR-accrued DNA damage. The outcome of the discussion may be helpful in devising future research in the current context.

Nrf1 CNC-bZIP protein promotes cell survival and nucleotide excision repair through maintaining glutathione homeostasis.

PubMed

Han, Weinong; Ming, Mei; Zhao, Rui; Pi, Jingbo; Wu, Chunli; He, Yu-Ying

2012-05-25

Skin cancer is the most common cancer in the United States. Its major environmental risk factor is UVB radiation in sunlight. In response to UVB damage, epidermal keratinocytes activate a specific repair pathway, i.e. nucleotide excision repair, to remove UVB-induced DNA lesions. However, the regulation of UVB response is not fully understood. Here we show that the long isoform of the nuclear factor erythroid 2-related factor 1 (Nrf1, also called NFE2L1), a cytoprotective transcription factor critical for the expression of multiple antioxidant response element-dependent genes, plays an important role in the response of keratinocytes to UVB. Nrf1 loss sensitized keratinocytes to UVB-induced apoptosis by up-regulating the expression of the proapoptotic Bcl-2 family member Bik through reducing glutathione levels. Knocking down Bik reduced UVB-induced apoptosis in Nrf1-inhibited cells. In UVB-irradiated surviving cells, however, disruption of Nrf1 impaired nucleotide excision repair through suppressing the transcription of xeroderma pigmentosum C (XPC), a factor essential for initiating the global genome nucleotide excision repair by recognizing the DNA lesion and recruiting downstream factors. Nrf1 enhanced XPC expression by increasing glutathione availability but was independent of the transcription repressor of XPC. Adding XPC or glutathione restored the DNA repair capacity in Nrf1-inhibited cells. Finally, we demonstrate that Nrf1 levels are significantly reduced by UVB radiation in mouse skin and are lower in human skin tumors than in normal skin. These results indicate a novel role of Nrf1 in UVB-induced DNA damage repair and suggest Nrf1 as a tumor suppressor in the skin.

Damage to DNA caused by UV-B radiation in the desert cyanobacterium Scytonema javanicum and the effects of exogenous chemicals on the process.

PubMed

Wang, Gaohong; Deng, Songqiang; Li, Cheng; Liu, Yongding; Chen, Lanzhou; Hu, Chaozhen

2012-07-01

Radiation with UV-B increased the damage to DNA in Scytonema javanicum, a desert-dwelling soil microorganism, and the level of damage varied with the intensity of UV-B radiation and duration of exposure. Production of reactive oxygen species (ROS) also increased because of the radiation. Different exogenous chemicals (ascorbate acid, ASC; N-acetylcysteine, NAC; glyphosate, GPS; and 2-methyl-4-chlorophenoxyacetic acid, MCPA-Na) differed in their effect on the extent of DNA damage and ROS production: whereas NAC and ASC protected the DNA from damage and resulted in reduced ROS production, the herbicides (GPS and MCPA-Na) increased the extent of damage, lowered the rate of photosynthesis, and differed in their effect on ROS production. The chemicals probably have different mechanisms to exercise their effects: NAC and ASC probably function as antioxidant agents or as precursors of other antioxidant molecules that protect the DNA and photosynthetic apparatus directly from the ROS produced as a result of UV-B radiation, and GPS and MCPA-Na probably disrupt the normal metabolism in S. javanicum to induce the leaking of ROS into the photosynthetic electron transfer pathway following UV-B radiation, and thereby damage the DNA. Such mechanisms have serious implications for the use of environment-friendly herbicides, which, because they can destroy DNA, may prove harmful to soil microorganisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

Salubrinal protects human skin fibroblasts against UVB-induced cell death by blocking endoplasmic reticulum (ER) stress and regulating calcium homeostasis.

PubMed

Ji, Chao; Yang, Bo; Huang, Shu-Ying; Huang, Jin-Wen; Cheng, Bo

2017-12-02

The role of UVB in skin photo damages has been widely reported. Overexposure to UVB will induce severe DNA damages in epidermal cells and cause most cytotoxic symptoms. In the present study, we tested the potential activity of salubrinal, a selective inhibitor of Eukaryotic Initiation Factor 2 (eIF2) -alpha phosphatase, against UV-induced skin cell damages. We first exposed human fibroblasts to UVB radiation and evaluated the cytosolic Ca 2+ level as well as the induction of ER stress. We found that UVB radiation induced the depletion of ER Ca 2+ and increased the expression of ER stress marker including phosphorylated PERK, CHOP, and phosphorylated IRE1α. We then determined the effects of salubrinal in skin cell death induced by UVB radiation. We observed that cells pre-treated with salubrinal had a higher survival rate compared to cells treated with UVB alone. Pre-treatment with salubrinal successfully re-established the ER function and Ca 2+ homeostasis. Our results suggest that salubrinal can be a potential therapeutic agents used in preventing photoaging and photo damages. Copyright © 2017 Elsevier Inc. All rights reserved.

Silymarin Protects Epidermal Keratinocytes from Ultraviolet Radiation-Induced Apoptosis and DNA Damage by Nucleotide Excision Repair Mechanism

PubMed Central

Katiyar, Santosh K.; Mantena, Sudheer K.; Meeran, Syed M.

2011-01-01

Solar ultraviolet (UV) radiation is a well recognized epidemiologic risk factor for melanoma and non-melanoma skin cancers. This observation has been linked to the accumulation of UVB radiation-induced DNA lesions in cells, and that finally lead to the development of skin cancers. Earlier, we have shown that topical treatment of skin with silymarin, a plant flavanoid from milk thistle (Silybum marianum), inhibits photocarcinogenesis in mice; however it is less understood whether chemopreventive effect of silymarin is mediated through the repair of DNA lesions in skin cells and that protect the cells from apoptosis. Here, we show that treatment of normal human epidermal keratinocytes (NHEK) with silymarin blocks UVB-induced apoptosis of NHEK in vitro. Silymarin reduces the amount of UVB radiation-induced DNA damage as demonstrated by reduced amounts of cyclobutane pyrimidine dimers (CPDs) and as measured by comet assay, and that ultimately may lead to reduced apoptosis of NHEK. The reduction of UV radiation-induced DNA damage by silymarin appears to be related with induction of nucleotide excision repair (NER) genes, because UV radiation-induced apoptosis was not blocked by silymarin in NER-deficient human fibroblasts. Cytostaining and dot-blot analysis revealed that silymarin repaired UV-induced CPDs in NER-proficient fibroblasts from a healthy individual but did not repair UV-induced CPD-positive cells in NER-deficient fibroblasts from patients suffering from xeroderma pigmentosum complementation-A disease. Similarly, immunohistochemical analysis revealed that silymarin did not reduce the number of UVB-induced sunburn/apoptotic cells in the skin of NER-deficient mice, but reduced the number of sunburn cells in their wild-type counterparts. Together, these results suggest that silymarin exert the capacity to reduce UV radiation-induced DNA damage and, thus, prevent the harmful effects of UV radiation on the genomic stability of epidermal cells. PMID:21731736

Linalool prevents oxidative stress activated protein kinases in single UVB-exposed human skin cells

PubMed Central

Govindasamy, Kanimozhi; Ramasamy, Karthikeyan; Muthusamy, Ganesan; Shanmugam, Mohana; Thangaiyan, Radhiga; Robert, Beaulah Mary; Ponniresan, Veeramani kandan; Rathinaraj, Pierson

2017-01-01

Ultraviolet-B radiation (285–320 nm) elicits a number of cellular signaling elements. We investigated the preventive effect of linalool, a natural monoterpene, against UVB-induced oxidative imbalance, activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling in HDFa cells. We observed that linalool treatment (30 μM) prevented acute UVB-irradiation (20 mJ/cm2) mediated loss of activities of antioxidant enzymes in HDFa cells. The comet assay results illustrate that linalool significantly prevents UVB-mediated 8-deoxy guanosine formation (oxidative DNA damage) rather than UVB-induced cyclobutane pyrimidine (CPD) formation. This might be due to its ability to prevent UVB-induced ROS formation and to restore the oxidative imbalance of cells. This has been reflected in UVB-induced overexpression of MAPK and NF-κB signaling. We observed that linalool inhibited UVB-induced phosphorylation of ERK1, JNK and p38 proteins of MAPK family. Linalool inhibited UVB-induced activation of NF-κB/p65 by activating IκBa. We further observed that UVB-induced expression of TNF-α, IL6, IL-10, MMP-2 and MMP-9 was modulated by linalool treatment in HDFa cells. Thus, linalool protects the human skin cells from the oxidative damages of UVB radiation and modulates MAPK and NF-κB signaling in HDFa cells. The present findings substantiate that linalool may act as a photoprotective agent against UVB-induced skin damages. PMID:28467450

C/EBPα Expression is Partially Regulated by C/EBPβ in Response to DNA Damage and C/EBPα Deficient Fibroblasts Display an Impaired G1 Checkpoint

PubMed Central

Ranjan, Rakesh; Thompson, Elizabeth A.; Yoon, Kyungsil; Smart, Robert C.

2009-01-01

We observed that C/EBPα is highly inducible in primary fibroblasts by DNA damaging agents that induce strand breaks, alkylate and crosslink DNA as well as those that produce bulky DNA lesions. Fibroblasts deficient in C/EBPα (C/EBPα-/-) display an impaired G1 checkpoint as evidenced by inappropriate entry into S-phase in response to DNA damage and these cells also display an enhanced G1 to S transition in response to mitogens. The induction of C/EBPα by DNA damage in fibroblasts does not require p53. EMSA analysis of nuclear extracts prepared from UVB- and MNNG-treated fibroblasts revealed increased binding of C/EBPβ to a C/EBP consensus sequence and ChIP analysis revealed increased C/EBPβ binding to the C/EBPα promoter. To determine whether C/EBPβ has a role in the regulation of C/EBPα we treated C/EBPβ-/- fibroblasts with UVB or MNNG. We observed C/EBPα induction was impaired in both UVB- and MNNG- treated C/EBPβ-/- fibroblasts. Our study reveals a novel role for C/EBPβ in the regulation of C/EBPα in response to DNA damage and provides definitive genetic evidence that C/EBPα has a critical role in the DNA damage G1 checkpoint. PMID:19581927

Pterostilbene protects against UVB-induced photo-damage through a phosphatidylinositol-3-kinase-dependent Nrf2/ARE pathway in human keratinocytes.

PubMed

Li, Huaping; Jiang, Na; Liang, Bihua; Liu, Qing; Zhang, Erting; Peng, Liqian; Deng, Huiyan; Li, Runxiang; Li, Zhenjie; Zhu, Huilan

2017-11-01

Ultraviolet B (UVB) irradiation is the initial etiological factor for various skin disorders, including erythema, sunburn, photoaging, and photocarcinogenesis. Pterostilbene (Pter) displayed remarkable antioxidant, anti-inflammatory, and anticarcinogenic activities. This study aimed to investigate the effective mechanism of Pter against UVB-induced photodamage in immortalized human keratinocytes. Human keratinocytes were pretreated with Pter (5 and 10 μM) for 24 h prior to UVB irradiation (300 mJ/cm 2 ). Harvested cells were analyzed by MTT, DCFH-DA, comet, western blotting, luciferase promoter, small interference RNA transfection, and quantitative real-time polymerase chain reaction assay. Pter significantly attenuated UVB-induced cell death and reactive oxygen species (ROS) generation, and effectively increased nuclear translocation of NF-E2-related factor-2 (Nrf2), expression of Nrf2-dependent antioxidant enzymes, and DNA repair activity. Moreover, the protective effects of Pter were abolished by small interference RNA-mediated Nrf2 silencing. Furthermore, Pter was also found to induce the phosphorylation of Nrf2 and the known phosphatidylinositol-3-kinase (PI3K) phosphorylated kinase, Akt. The specific inhibitor of PI3K, LY294002, successfully abrogated Pter-induced Nrf2 phosphorylation, activation of Nrf2-antioxidant response element pathway, ROS scavenging ability, and DNA repair activity. The present study indicated that Pter effectively protected against UVB-induced photodamage by increasing endogenous defense mechanisms, scavenging UVB-induced ROS, and aiding in damaged DNA repair through a PI3K-dependent activation of Nrf2/ARE pathway.

The deceptive nature of UVA tanning versus the modest protective effects of UVB tanning on human skin.

PubMed

Miyamura, Yoshinori; Coelho, Sergio G; Schlenz, Kathrin; Batzer, Jan; Smuda, Christoph; Choi, Wonseon; Brenner, Michaela; Passeron, Thierry; Zhang, Guofeng; Kolbe, Ludger; Wolber, Rainer; Hearing, Vincent J

2011-02-01

The relationship between human skin pigmentation and protection from ultraviolet (UV) radiation is an important element underlying differences in skin carcinogenesis rates. The association between UV damage and the risk of skin cancer is clear, yet a strategic balance in exposure to UV needs to be met. Dark skin is protected from UV-induced DNA damage significantly more than light skin owing to the constitutively higher pigmentation, but an as yet unresolved and important question is what photoprotective benefit, if any, is afforded by facultative pigmentation (i.e. a tan induced by UV exposure). To address that and to compare the effects of various wavelengths of UV, we repetitively exposed human skin to suberythemal doses of UVA and/or UVB over 2 weeks after which a challenge dose of UVA and UVB was given. Although visual skin pigmentation (tanning) elicited by different UV exposure protocols was similar, the melanin content and UV-protective effects against DNA damage in UVB-tanned skin (but not in UVA-tanned skin) were significantly higher. UVA-induced tans seem to result from the photooxidation of existing melanin and its precursors with some redistribution of pigment granules, while UVB stimulates melanocytes to up-regulate melanin synthesis and increases pigmentation coverage, effects that are synergistically stimulated in UVA and UVB-exposed skin. Thus, UVA tanning contributes essentially no photoprotection, although all types of UV-induced tanning result in DNA and cellular damage, which can eventually lead to photocarcinogenesis. 2010 John Wiley & Sons A/S. This article is a US Government work and is in the public domain in the USA.

DNA Damage and Repair in Plants under Ultraviolet and Ionizing Radiations

PubMed Central

Gill, Sarvajeet S.; Gill, Ritu; Jha, Manoranjan; Tuteja, Narendra

2015-01-01

Being sessile, plants are continuously exposed to DNA-damaging agents present in the environment such as ultraviolet (UV) and ionizing radiations (IR). Sunlight acts as an energy source for photosynthetic plants; hence, avoidance of UV radiations (namely, UV-A, 315–400 nm; UV-B, 280–315 nm; and UV-C, <280 nm) is unpreventable. DNA in particular strongly absorbs UV-B; therefore, it is the most important target for UV-B induced damage. On the other hand, IR causes water radiolysis, which generates highly reactive hydroxyl radicals (OH•) and causes radiogenic damage to important cellular components. However, to maintain genomic integrity under UV/IR exposure, plants make use of several DNA repair mechanisms. In the light of recent breakthrough, the current minireview (a) introduces UV/IR and overviews UV/IR-mediated DNA damage products and (b) critically discusses the biochemistry and genetics of major pathways responsible for the repair of UV/IR-accrued DNA damage. The outcome of the discussion may be helpful in devising future research in the current context. PMID:25729769

Enhancement of UVB radiation-mediated apoptosis by knockdown of cytosolic NADP+-dependent isocitrate dehydrogenase in HaCaT cells.

PubMed

Lee, Su Jeong; Park, Jeen-Woo

2014-04-01

Ultraviolet B (UVB) radiation induces the production of reactive oxygen species (ROS) that promote apoptotic cell death. We showed that cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) plays an essential role in the control of cellular redox balance and defense against oxidative damage, by supplying NADPH for antioxidant systems. In this study, we demonstrated that knockdown of IDPc expression by RNA interference enhances UVB-induced apoptosis of immortalized human HaCaT keratinocytes. This effect manifested as DNA fragmentation, changes in cellular redox status, mitochondrial dysfunction, and modulation of apoptotic marker expression. Based on our findings, we suggest that attenuation of IDPc expression may protect skin from UVB-mediated damage, by inducing the apoptosis of UV-damaged cells.

Jatropha curcas leaf and bark fractions protect against ultraviolet radiation-B induced DNA damage in human peripheral blood lymphocytes.

PubMed

Sundari, J; Selvaraj, R; Rajendra Prasad, N; Elumalai, R

2013-11-01

The present study is conducted to investigate the antioxidant potential of Jatropha curcas root bark extract (RB4 fraction) and leaf extract (L1 fraction), and to study their effects on UVB-radiation-induced DNA damage in cultured human blood lymphocytes. In this study, J. curcas showed strong antioxidant property in different free radical scavenging systems. Both the fractions effectively scavenged hydroxyl (OH), superoxide anion (O₂(·-)), 1,1-diphenyl-2-picrylhydrazyl (DPPH·) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid radical cation (ABTS(·+)) in a concentration-dependent manner. The IC₅₀ (Inhibitory Concentration 50) values of J. curcas fractions were compared to standard ascorbic acid used in this study. The antioxidant potential of a compound was directly proportional to the photoprotective effect. In this study, human peripheral blood lymphocytes (HPBL) were exposed to UVB-radiation and there was an increase in comet attributes (% tail DNA, tail length, tail movement and Olive tail moment). Jatropha curcas RB4 fraction and L1 fraction treatment before UVB-irradiation significantly decreased the % tail DNA, tail length, tail moment and Olive tail moment in irradiated HPBL. These results suggested that J. curcas exhibited strong antioxidant property and RB4 and L1 fractions protected UVB-radiation-induced DNA damage in HPBL. Copyright © 2013 Elsevier B.V. All rights reserved.

Polyhydroxylated fatty alcohols derived from avocado suppress inflammatory response and provide non-sunscreen protection against UV-induced damage in skin cells.

PubMed

Rosenblat, Gennady; Meretski, Shai; Segal, Joseph; Tarshis, Mark; Schroeder, Avi; Zanin-Zhorov, Alexandra; Lion, Gilead; Ingber, Arieh; Hochberg, Malka

2011-05-01

Exposing skin to ultraviolet (UV) radiation contributes to photoaging and to the development of skin cancer by DNA lesions and triggering inflammatory and other harmful cellular cascades. The present study tested the ability of unique lipid molecules, polyhydroxylated fatty alcohols (PFA), extracted from avocado, to reduce UVB-induced damage and inflammation in skin. Introducing PFA to keratinocytes prior to their exposure to UVB exerted a protective effect, increasing cell viability, decreasing the secretion of IL-6 and PGE(2), and enhancing DNA repair. In human skin explants, treating with PFA reduced significantly UV-induced cellular damage. These results support the idea that PFA can play an important role as a photo-protective agent in UV-induced skin damage.

Differential responses to high- and low-dose ultraviolet-B stress in tobacco Bright Yellow-2 cells

PubMed Central

Takahashi, Shinya; Kojo, Kei H.; Kutsuna, Natsumaro; Endo, Masaki; Toki, Seiichi; Isoda, Hiroko; Hasezawa, Seiichiro

2015-01-01

Ultraviolet (UV)-B irradiation leads to DNA damage, cell cycle arrest, growth inhibition, and cell death. To evaluate the UV-B stress–induced changes in plant cells, we developed a model system based on tobacco Bright Yellow-2 (BY-2) cells. Both low-dose UV-B (low UV-B: 740 J m−2) and high-dose UV-B (high UV-B: 2960 J m−2) inhibited cell proliferation and induced cell death; these effects were more pronounced at high UV-B. Flow cytometry showed cell cycle arrest within 1 day after UV-B irradiation; neither low- nor high-UV-B–irradiated cells entered mitosis within 12 h. Cell cycle progression was gradually restored in low-UV-B–irradiated cells but not in high-UV-B–irradiated cells. UV-A irradiation, which activates cyclobutane pyrimidine dimer (CPD) photolyase, reduced inhibition of cell proliferation by low but not high UV-B and suppressed high-UV-B–induced cell death. UV-B induced CPD formation in a dose-dependent manner. The amounts of CPDs decreased gradually within 3 days in low-UV-B–irradiated cells, but remained elevated after 3 days in high-UV-B–irradiated cells. Low UV-B slightly increased the number of DNA single-strand breaks detected by the comet assay at 1 day after irradiation, and then decreased at 2 and 3 days after irradiation. High UV-B increased DNA fragmentation detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay 1 and 3 days after irradiation. Caffeine, an inhibitor of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) checkpoint kinases, reduced the rate of cell death in high-UV-B–irradiated cells. Our data suggest that low-UV-B–induced CPDs and/or DNA strand-breaks inhibit DNA replication and proliferation of BY-2 cells, whereas larger contents of high-UV-B–induced CPDs and/or DNA strand-breaks lead to cell death. PMID:25954287

Proteomic analysis of UVB-induced protein expression- and redox-dependent changes in skin fibroblasts using lysine- and cysteine-labeling two-dimensional difference gel electrophoresis.

PubMed

Wu, Chieh-Lin; Chou, Hsiu-Chuan; Cheng, Chao-Sheng; Li, Ji-Min; Lin, Szu-Ting; Chen, Yi-Wen; Chan, Hong-Lin

2012-04-03

UVB is the most energetic and DNA-damaging to humans in ultraviolet radiation. Previous research has suggested that exposure to UVB causes skin pathologies because of direct DNA damage and the generation of reactive oxygen species (ROS). However, the detailed molecular mechanisms by which UVB leads to skin cancer have yet to be clarified. In the current study, normal skin fibroblast cells (CCD-966SK) were exposed to various doses of UVB, and the changes in protein expression and thiol reactivity were monitored with lysine- and cysteine-labeling 2D-DIGE and MALDI-TOF mass spectrometry. Our proteomic analysis revealed that 89 identified proteins showed significant changes in protein expression, and 37 in thiol reactivity. Many proteins that are known to be involved in protein folding, redox regulation and nucleotide biosynthesis were up-regulated under UVB irradiation. In contrast, proteins responsible for biosynthesis and protein degradation were down-regulated. In addition, the thiol-reactivity of proteins involving cytoskeleton, metabolism, and signal transduction were altered by UVB. In summary, these UVB-modulated cellular proteins and redox-regulated proteins might play important roles in the early stages of skin cancer formation and photoaging induced by UVB-irradiation. Such proteins might provide a potential target for the rational design of drugs to prevent UVB-induced diseases. Copyright © 2011 Elsevier B.V. All rights reserved.

Photo-protection by 3-bromo-4, 5-dihydroxybenzaldehyde against ultraviolet B-induced oxidative stress in human keratinocytes.

PubMed

Hyun, Yu Jae; Piao, Mei Jing; Zhang, Rui; Choi, Yung Hyun; Chae, Sungwook; Hyun, Jin Won

2012-09-01

Exposure of the skin to ultraviolet B (UVB) radiation leads to epidermal damage and the generation of reactive oxygen species (ROS) in skin cells, including keratinocytes. Therefore, the photo-protective effect of 3-bromo-4, 5-dihydroxybenzaldehyde (BDB) against UVB was assessed in human HaCaT keratinocytes exposed to UVB radiation in vitro. BDB restored cell viability, which decreased upon exposure to UVB radiation. BDB exhibited scavenging activity against 1, 1-diphenyl-2-picrylhydrazyl radicals, intracellular ROS induced by hydrogen peroxide (H(2)O(2)) or UVB radiation, the superoxide anion generated by the xanthine/xanthine oxidase system, and the hydroxyl radical generated by the Fenton reaction (FeSO(4)+H(2)O(2)). Moreover, BDB absorbed UVB and decreased injury resulting from UVB-induced oxidative stress to lipids, proteins and DNA. Finally, BDB reduced UVB-induced apoptosis, as exemplified by fewer apoptotic bodies and a reduction in DNA fragmentation. Taken together, these results suggest that BDB protects human keratinocytes against UVB-induced oxidative stress by scavenging ROS and absorbing UVB rays, thereby reducing injury to cellular components. Copyright © 2012 Elsevier Inc. All rights reserved.

Enhancement of UVB radiation-mediated apoptosis by knockdown of cytosolic NADP+-dependent isocitrate dehydrogenase in HaCaT cells

PubMed Central

Lee, Su Jeong; Park, Jeen-Woo

2014-01-01

Ultraviolet B (UVB) radiation induces the production of reactive oxygen species (ROS) that promote apoptotic cell death. We showed that cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) plays an essential role in the control of cellular redox balance and defense against oxidative damage, by supplying NADPH for antioxidant systems. In this study, we demonstrated that knockdown of IDPc expression by RNA interference enhances UVB-induced apoptosis of immortalized human HaCaT keratinocytes. This effect manifested as DNA fragmentation, changes in cellular redox status, mitochondrial dysfunction, and modulation of apoptotic marker expression. Based on our findings, we suggest that attenuation of IDPc expression may protect skin from UVB-mediated damage, by inducing the apoptosis of UV-damaged cells. [BMB Reports 2014; 47(4): 209-214] PMID:24286310

Antagonizing Effects and Mechanisms of Afzelin against UVB-Induced Cell Damage

PubMed Central

Shin, Seoung Woo; Jung, Eunsun; Kim, Seungbeom; Kim, Jang-Hyun; Kim, Eui-Gyun; Lee, Jongsung; Park, Deokhoon

2013-01-01

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human keratinocytes, resulting in skin inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effects of UV irradiation is essential. Therefore, in this study, we investigated the protective effects of afzelin, one of the flavonoids, against UV irradiation in human keratinocytes and epidermal equivalent models. Spectrophotometric measurements revealed that the afzelin extinction maxima were in the UVB and UVA range, and UV transmission below 376 nm was <10%, indicating UV-absorbing activity of afzelin. In the phototoxicity assay using the 3T3 NRU phototoxicity test (3T3-NRU-PT), afzelin presented a tendency to no phototoxic potential. In addition, in order to investigate cellular functions of afzelin itself, cells were treated with afzelin after UVB irradiation. In human keratinocyte, afzelin effectively inhibited the UVB-mediated increase in lipid peroxidation and the formation of cyclobutane pyrimidine dimers. Afzelin also inhibited UVB-induced cell death in human keratinocytes by inhibiting intrinsic apoptotic signaling. Furthermore, afzelin showed inhibitory effects on UVB-induced release of pro-inflammatory mediators such as interleukin-6, tumor necrosis factor-α, and prostaglandin-E2 in human keratinocytes by interfering with the p38 kinase pathway. Using an epidermal equivalent model exposed to UVB radiation, anti-apoptotic activity of afzelin was also confirmed together with a photoprotective effect at the morphological level. Taken together, our results suggest that afzelin has several cellular activities such as DNA-protective, antioxidant, and anti-inflammatory as well as UV-absorbing activity and may protect human skin from UVB-induced damage by a combination of UV-absorbing and cellular activities. PMID:23626759

Protective Effect of the Ethyl Acetate Fraction of Sargassum muticum Against Ultraviolet B–Irradiated Damage in Human Keratinocytes

PubMed Central

Piao, Mei Jing; Yoon, Weon Jong; Kang, Hee Kyoung; Yoo, Eun Sook; Koh, Young Sang; Kim, Dong Sam; Lee, Nam Ho; Hyun, Jin Won

2011-01-01

The aim of this study was to investigate the cytoprotective properties of the ethyl acetate fraction of Sargassum muticum (SME) against ultraviolet B (UVB)-induced cell damage in human keratinocytes (HaCaT cells). SME exhibited scavenging activity toward the 1,1-diphenyl-2-picrylhydrazyl radicals and hydrogen peroxide (H2O2) and UVB-induced intracellular reactive oxygen species (ROS). SME also scavenged the hydroxyl radicals generated by the Fenton reaction (FeSO4 + H2O2), which was detected using electron spin resonance spectrometry. In addition, SME decreased the level of lipid peroxidation that was increased by UVB radiation, and restored the level of protein expression and the activities of antioxidant enzymes that were decreased by UVB radiation. Furthermore, SME reduced UVB-induced apoptosis as shown by decreased DNA fragmentation and numbers of apoptotic bodies. These results suggest that SME protects human keratinocytes against UVB-induced oxidative stress by enhancing antioxidant activity in cells, thereby inhibiting apoptosis. PMID:22174656

UV-B inhibition of hypocotyl growth in etiolated Arabidopsis thaliana seedlings is a consequence of cell cycle arrest initiated by photodimer accumulation

PubMed Central

Biever, Jessica J.; Brinkman, Doug; Gardner, Gary

2014-01-01

Ultraviolet (UV) radiation is an important constituent of sunlight that determines plant morphology and growth. It induces photomorphogenic responses but also causes damage to DNA. Arabidopsis mutants of the endonucleases that function in nucleotide excision repair, xpf-3 and uvr1-1, showed hypersensitivity to UV-B (280–320nm) in terms of inhibition of hypocotyl growth. SOG1 is a transcription factor that functions in the DNA damage signalling response after γ-irradiation. xpf mutants that carry the sog1-1 mutation showed hypocotyl growth inhibition after UV-B irradiation similar to the wild type. A DNA replication inhibitor, hydroxyurea (HU), also inhibited hypocotyl growth in etiolated seedlings, but xpf-3 was not hypersensitive to HU. UV-B irradiation induced accumulation of the G2/M-specific cell cycle reporter construct CYCB1;1-GUS in wild-type Arabidopsis seedlings that was consistent with the expected accumulation of photodimers and coincided with the time course of hypocotyl growth inhibition after UV-B treatment. Etiolated mutants of UVR8, a recently described UV-B photoreceptor gene, irradiated with UV-B showed inhibition of hypocotyl growth that was not different from that of the wild type, but they lacked UV-B-specific expression of chalcone synthase (CHS), as expected from previous reports. CHS expression after UV-B irradiation was not different in xpf-3 compared with the wild type, nor was it altered after HU treatment. These results suggest that hypocotyl growth inhibition by UV-B light in etiolated Arabidopsis seedlings, a photomorphogenic response, is dictated by signals originating from UV-B absorption by DNA that lead to cell cycle arrest. This process occurs distinct from UVR8 and its signalling pathway responsible for CHS induction. PMID:24591052

Sunlight damage to cellular DNA: Focus on oxidatively generated lesions.

PubMed

Schuch, André Passaglia; Moreno, Natália Cestari; Schuch, Natielen Jacques; Menck, Carlos Frederico Martins; Garcia, Camila Carrião Machado

2017-06-01

The routine and often unavoidable exposure to solar ultraviolet (UV) radiation makes it one of the most significant environmental DNA-damaging agents to which humans are exposed. Sunlight, specifically UVB and UVA, triggers various types of DNA damage. Although sunlight, mainly UVB, is necessary for the production of vitamin D, which is necessary for human health, DNA damage may have several deleterious consequences, such as cell death, mutagenesis, photoaging and cancer. UVA and UVB photons can be directly absorbed not only by DNA, which results in lesions, but also by the chromophores that are present in skin cells. This process leads to the formation of reactive oxygen species, which may indirectly cause DNA damage. Despite many decades of investigation, the discrimination among the consequences of these different types of lesions is not clear. However, human cells have complex systems to avoid the deleterious effects of the reactive species produced by sunlight. These systems include antioxidants, that protect DNA, and mechanisms of DNA damage repair and tolerance. Genetic defects in these mechanisms that have clear harmful effects in the exposed skin are found in several human syndromes. The best known of these is xeroderma pigmentosum (XP), whose patients are defective in the nucleotide excision repair (NER) and translesion synthesis (TLS) pathways. These patients are mainly affected due to UV-induced pyrimidine dimers, but there is growing evidence that XP cells are also defective in the protection against other types of lesions, including oxidized DNA bases. This raises a question regarding the relative roles of the various forms of sunlight-induced DNA damage on skin carcinogenesis and photoaging. Therefore, knowledge of what occurs in XP patients may still bring important contributions to the understanding of the biological impact of sunlight-induced deleterious effects on the skin cells. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Stress-specific p38 MAPK activation is sufficient to drive EGFR endocytosis but not its nuclear translocation.

PubMed

Tomas, Alejandra; Jones, Sylwia; Vaughan, Simon O; Hochhauser, Daniel; Futter, Clare E

2017-08-01

EGF receptor (EGFR) endocytosis is induced by stress in a manner dependent on the p38 MAPK family. Ligand and stresses such as X-rays, reportedly promote nuclear trafficking of endocytosed EGFR for regulation of gene transcription and DNA repair. We fail to detect EGFR endocytosis or nuclear transport following X-ray treatment of HeLa or head and neck cancer cells, despite extensive DNA damage induction. Apparent nuclear staining with EGFR extracellular domain antibody remained present despite reduced/absent EGFR expression, and so did not represent nuclear EGFR. UVB and UVC, but not X-ray or UVA, treatment induced p38 activation and EGFR endocytosis, although all of these stresses induced DNA damage, indicating that DNA damage alone is not sufficient to induce EGFR endocytosis. Increased reactive oxygen species (ROS) levels following UVB treatment, compared to that seen with X-rays, do not alone explain differences in p38 activation. UVB, like UVC, induced EGFR accumulation predominantly in perinuclear endosomes, rather than in the nucleus. Our morphological techniques identifying major changes in receptor distribution do not exclude the possibility that small but biologically relevant amounts of EGFR enter the nucleus. This study highlights the importance and limitations of morphological analyses of receptor distribution in understanding signaling outcome. © 2017. Published by The Company of Biologists Ltd.

Is UV-induced DNA damage greater at higher elevation?

PubMed

Wang, Qing-Wei; Hidema, Jun; Hikosaka, Kouki

2014-05-01

• Although ultraviolet radiation (UV) is known to have negative effects on plant growth, there has been no direct evidence that plants growing at higher elevations are more severely affected by ultraviolet-B (UV-B) radiation, which is known to increase with elevation. We examined damage to DNA, a primary target of UV-B, in the widespread species Polygonum sachalinense (Fallopia sachalinensis) and Plantago asiatica at two elevations.• We sampled leaves of both species at 300 and 1700 m above sea level every 2 h for 11 d across the growing season and determined the level of cyclobutane pyrimidine dimer (CPD), a major product of UV damage to DNA.• The CPD level was significantly influenced by the time of day, date, elevation, and their interactions in both species. The CPD level tended to be higher at noon or on sunny days. DNA damage was more severe at 1700 m than at 300 m: on average, 8.7% greater at high elevation in P. asiatica and 7.8% greater in P. sachalinense Stepwise multiple regression analysis indicated that the CPD level was explained mainly by UV-B and had no significant relationship with other environmental factors such as temperature and photosynthetically active radiation.• UV-induced DNA damage in plants is greater at higher elevations. © 2014 Botanical Society of America, Inc.

Simultaneous detection of ultraviolet B-induced DNA damage using capillary electrophoresis with laser-induced fluorescence.

PubMed

Guthrie, Jeffrey W; Limmer, Robert T; Brooks, Eric A; Wisnewski, Chelsea C; Loggins-Davis, Nnekia D; Bouzid, Abderraouf

2015-01-01

An immunoassay based on CE-LIF was developed for the simultaneous detection of cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts (6-4PPs) in genomic DNA irradiated with UVB or natural sunlight. Human cells were first exposed to varying amounts of UVB or natural sunlight to induce DNA damage. Genomic DNA was extracted and incubated with anti-CPD and anti-6-4PP primary antibodies attached to secondary antibodies with a fluorescent quantum dot (QD) reporter that emitted either red or yellow fluorescence. CE was used to separate the unbound antibodies from those bound to the photoproducts, and LIF with appropriate optical filters was used to separate the fluorescence signals from each QD to individual photomultiplier tubes for simultaneous photoproduct detection. Using this strategy, photoproducts were detected from ∼6 ng (200 ng μL(-1)) of DNA under a low UVB fluence of 65 J m(-2) for CPDs or 195 J m(-2) for 6-4PPs. This assay was also the first to demonstrate the detection of CPDs in human cells after only 15 min of irradiation under natural sunlight. Copyright © 2014 Elsevier B.V. All rights reserved.

Protective effect of 4-coumaric acid from UVB ray damage in the rabbit eye.

PubMed

Lodovici, Maura; Caldini, Silvia; Morbidelli, Lucia; Akpan, Victor; Ziche, Marina; Dolara, Piero

2009-01-08

UV-induced oxidation damage seems to play a major role in a number of specific pathological conditions of intraocular tissues, such as cataract formation and retinal degeneration. Therefore, antioxidant and/or scavenger compounds might protect the eyes from UV-induced cellular damage. We previously reported that 4-coumaric acid (4-CA) is able to protect rabbit corneal-derived cells (SIRC) from UVB-induced oxidation damage. In this study we evaluated the protective effect of 4-CA against UVB-induced cell damage in rabbit cornea in vivo. Twelve male New Zealand albino rabbits were used; four rabbits were used as a control and received vehicle in one eye and 4-CA acid in the contralateral eye; eight rabbits were exposed to UVB rays (79.2mJ/cm(2)) and three days before to UV exposure each animal received 1 drop/day of vehicle in one eye and 1 drop/day of vehicle containing 4-CA (164ng) in the contralateral eye. Corneal and sclera tissues were removed and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) levels were measured. Superoxide dismutase (SOD) and xanthine oxidase (XO) activities were determined in aqueous humour. UVB-induced vessel hyper-reactivity was strongly reduced at 4 and 24h after UVB exposure after local treatment with 4-CA, 8-oxodGuo levels, a marker of oxidative DNA damage, were significantly increased (P<0.05) in sclera and cornea by UVB irradiation, but when 4-CA was administered to the conjunctiva in a buffered solution once a day for 3d before and 6d after UVB exposure, levels of 8-oxodGuo were similar to controls and significantly reduced (P<0.05) compared to UVB-treated corneas. XO activity in the aqueous humour was significantly increased. The administration of 4-CA for 3d before and 6d after UVB irradiation induced a small but significant (P<0.05) reduction of XO compared with control eyes. Our results indicate that the administration of 4-CA protects eye tissues, thus reducing the harmful effect of UVB radiation at low concentration, probably through its free radical scavenging and antioxidant properties. Therefore, 4-CA may be useful in protecting the eye from free radical damage following UVB exposure from sunlight, UV lamps and welding torches.

Cortisol Release in Response to UVB Exposure in Xiphophorus Fish

PubMed Central

Contreras, Adam J.; Boswell, Mikki; Downs, Kevin P.; Pasquali, Amanda; Walter, Ronald B.

2014-01-01

Xiphophorus fishes are comprised of 26 known species. Interspecies hybridization between select species has been utilized to produce experimental models to study melanoma development. Xiphophorus melanoma induction protocols utilize ultraviolet light (UVB) to induce DNA damage and associated downstream tumorigenesis. However, the impact of induced stress caused by the UVB treatment of the experimental animals undergoing tumor induction protocols has not been assessed. Stress is an adaptive physiological response to excessive or unpredictable environmental stimuli. The stress response in fishes may be measured by assay of cortisol released into the water. Here, we present results from investigations of stress response during experimental treatment and UVB exposure in X. maculatus Jp 163 B, X. couchianus, and F1 interspecies hybrids produced from the mating X. maculatus Jp 163 B x X. couchianus. Overall, cortisol release rates for males and females after UVB exposure showed no statistical differences. At lower UVB doses (8 and 16 kJ/m2), X. couchianus exhibited 2 fold higher levels of DNA damage then either X. maculatus or the F1 hybrid. However, based on cortisol release rates, none of the fish types tested induced a primary stress response at the UVB lower doses (8 and 16 kJ/m2). In contrast, at a very high UVB dose (32 kJ/m2) both X. maculatus and the F1 hybrid showed a 5 fold increase in cortisol release rate. To determine the effect of pigmentation on UVB induced stress, wild type and albino X. hellerii were exposed to UVB (32 kJ/m2). Albino X. hellerii exhibited 3.7 fold increase in cortisol release while wild type X. hellerii did not exhibit a significant cortisol response to UVB. Overall, the data suggest the rather low UVB doses often employed in tumour induction protocols do not induce a primary stress response in Xiphophorus fishes. PMID:24625568

Size is an essential parameter in governing the UVB-protective efficacy of silver nanoparticles in human keratinocytes.

PubMed

Palanki, Rohan; Arora, Sumit; Tyagi, Nikhil; Rusu, Lilia; Singh, Ajay P; Palanki, Srinivas; Carter, James E; Singh, Seema

2015-09-15

Ultraviolet (UV) radiation from sun, particularly its UVB component (290-320 nm), is considered the major etiological cause of skin cancer that impacts over 2 million lives in the United States alone. Recently, we reported that polydisperse colloidal suspension of silver nanoparticles (AgNPs) protected the human keratinocytes (HaCaT) against UVB-induced damage, thus indicating their potential for prevention of skin carcinogenesis. Here we sought out to investigate if size controlled the chemopreventive efficacy of AgNPs against UVB-induced DNA damage and apoptosis. Percent cell viability was examined by WST-1 assay after treating the cells with various doses (1-10 μg/mL) of AgNPs of different sizes (10, 20, 40, 60 and 100 nm) for 12 and 24 h. For protection studies, cells were treated with AgNPs of different sizes at a uniform concentration of 1 μg/mL. After 3 h, cells were irradiated with UVB (40 mJ/cm(2)) and dot-blot analysis was performed to detect cyclobutane pyrimidine dimers (CPDs) as an indication of DNA damage. Apoptosis was analyzed by flow cytometry after staining the cells with 7-Amino-Actinomycin (7-AAD) and PE Annexin V. Immunoblot analysis was accomplished by processing the cells for protein extraction and Western blotting using specific antibodies against various proteins. The data show that the pretreatment of HaCaT cells with AgNPs in the size range of 10-40 nm were effective in protecting the skin cells from UVB radiation-induced DNA damage as validated by reduced amounts of CPDs, whereas no protection was observed with AgNPs of larger sizes (60 and 100 nm). Similarly, only smaller size AgNPs (10-40 nm) were effective in protecting the skin cells from UV radiation-induced apoptosis. At the molecular level, UVB -irradiation of HaCaT cells led to marked increase in expression of pro-apoptotic protein (Bax) and decrease in anti-apoptotic proteins (Bcl-2 and Bcl-xL), while it remained largely unaffected in skin cells pretreated with smaller size AgNPs (10-40 nm). Altogether, these findings suggest that size is a critical determinant of the UVB-protective efficacy of AgNPs in human keratinocytes.

Solar ultraviolet radiation induces biological alterations in human skin in vitro: relevance of a well-balanced UVA/UVB protection.

PubMed

Bernerd, Francoise; Marionnet, Claire; Duval, Christine

2012-06-01

Cutaneous damages such as sunburn, pigmentation, and photoaging are known to be induced by acute as well as repetitive sun exposure. Not only for basic research, but also for the design of the most efficient photoprotection, it is crucial to understand and identify the early biological events occurring after ultraviolet (UV) exposure. Reconstructed human skin models provide excellent and reliable in vitro tools to study the UV-induced alterations of the different skin cell types, keratinocytes, fibroblasts, and melanocytes in a dose- and time-dependent manner. Using different in vitro human skin models, the effects of UV light (UVB and UVA) were investigated. UVB-induced damages are essentially epidermal, with the typical sunburn cells and DNA lesions, whereas UVA radiation-induced damages are mostly located within the dermal compartment. Pigmentation can also be obtained after solar simulated radiation exposure of pigmented reconstructed skin model. Those models are also highly adequate to assess the potential of sunscreens to protect the skin from UV-associated damage, sunburn reaction, photoaging, and pigmentation. The results showed that an effective photoprotection is provided by broad-spectrum sunscreens with a potent absorption in both UVB and UVA ranges.

Silymarin inhibits ultraviolet radiation-induced immune suppression through DNA repair-dependent activation of dendritic cells and stimulation of effector T cells

PubMed Central

Vaid, Mudit; Prasad, Ram; Singh, Tripti; Elmets, Craig A.; Xu, Hui; Katiyar, Santosh K.

2013-01-01

Silymarin inhibits UVB-induced immunosuppression in mouse skin. To identify the molecular mechanisms underlying this effect, we used an adoptive transfer approach in which dendritic cells (DCs) from the draining lymph nodes of donor mice that had been UVB-exposed and sensitized to 2,4,-dinitrofluorobenzene (DNFB) were transferred into naïve recipient mice. The contact hypersensitivity (CHS) response of the recipient mice to DNFB was then measured. When DCs were obtained from UVB-exposed donor mice that were not treated with silymarin, the CHS response was suppressed confirming the role of DCs in the UVB-induced immunosuppression. Silymarin treatment of UVB-exposed donor mice relieved this suppression of the CHS response in the recipients. Silymarin treatment was associated with rapid repair of UVB-induced cyclobutane pyrimidine dimers (CPDs) in DCs and silymarin treatment did not prevent UV-induced immunosuppression in XPA-deficient mice which are unable to repair UV-induced DNA damage. The CHS response in mice receiving DCs from silymarin-treated UV-exposed donor mice also was associated with enhanced secretion of Th1-type cytokines and stimulation of T cells. Adoptive transfer of T cells revealed that transfer of either CD8+ or CD4+ cells from silymarin-treated, UVB-exposed donors resulted in enhancement of the CHS response. Cell culture study showed enhanced secretion of IL-2 and IFNγ by CD8+ T cells, and reduced secretion of Th2 cytokines by CD4+ cells, obtained from silymarin-treated UVB-exposed mice. These data suggest that DNA repair-dependent functional activation of DCs, a reduction in CD4+ regulatory T-cell activity, and stimulation of CD8+ effector T cells contribute to silymarin-mediated inhibition of UVB-induced immunosuppression. PMID:23395695

Protective effect of 3,4-dihydroxybenzoic acid isolated from Cladophora wrightiana Harvey against ultraviolet B radiation-induced cell damage in human HaCaT keratinocytes.

PubMed

Cha, Ji Won; Piao, Mei Jing; Kim, Ki Cheon; Zheng, Jian; Yao, Cheng Wen; Hyun, Chang Lim; Kang, Hee Kyoung; Yoo, Eun Sook; Koh, Young Sang; Lee, Nam Ho; Ko, Mi Hee; Hyun, Jin Won

2014-03-01

The aim of the present study was to elucidate the protective properties of 3,4-dihydroxybenzoic acid (DBA) isolated from Cladophora wrightiana Harvey (a green alga) against ultraviolet B (UVB)-induced damage to human HaCaT keratinocytes. DBA exhibited scavenging actions against the 1,1-diphenyl-2-picrylhydrazyl radical, the superoxide anion, and the hydroxyl radical. Furthermore, DBA decreased the levels of intracellular reactive oxygen species generated by hydrogen peroxide or UVB treatment of the cells. DBA also decreased the UVB-augmented levels of phospho-histone H2A.X and the extent of comet tail formation, which are both indications of DNA damage. In addition, the compound safeguarded keratinocytes from UVB-induced injury by reversing the production of apoptotic bodies, overturning the disruption of mitochondrial membrane potential, increasing the expression of the anti-apoptotic protein, B-cell lymphoma 2, and decreasing the expression of the pro-apoptotic proteins, Bcl-2-associated X and cleaved caspase-3. Taken together, these results demonstrate that DBA isolated from a green alga protects human keratinocytes against UVB-induced oxidative stress and apoptosis.

UVA-induced protection of skin through the induction of heme oxygenase-1.

PubMed

Xiang, Yuancai; Liu, Gang; Yang, Li; Zhong, Julia Li

2011-12-01

UVA (320-400 nm) and UVB (290-320 nm) are the major components of solar UV irradiation, which is associated with various pathological conditions. UVB causes direct damage to DNA of epidermal cells and is mainly responsible for erythema, immunosuppression, photoaging, and skin cancer. UVA has oxidizing properties that can cause damage or enhance UVB damaging effects on skin. On the other hand, UVA can also lead to high levels of heme oxygenase-1 (HO-1) expression of cells that can provide an antioxidant effect on skin as well as anti-inflammatory properties in mammals and rodents. Therefore, this review focuses on the potential protection of UVA wavebands for the skin immune response, instead of mechanisms that underlie UVA-induced damage. Also, the role of HO-1 in UVA-mediated protection against UVB-induced immunosuppression in skin will be summarized. Thus, this review facilitates further understanding of potential beneficial mechanisms of UVA irradiation, and using the longer UVA (UVA1, 340-400 nm) in combination with HO-1 for phototherapy and skin protection against sunlight exposure.

Antagonist effects of veratric acid against UVB-induced cell damages.

PubMed

Shin, Seoung Woo; Jung, Eunsun; Kim, Seungbeom; Lee, Kyung-Eun; Youm, Jong-Kyung; Park, Deokhoon

2013-05-10

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human epidermis, resulting in inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effect of UV irradiation is essential. In recent years naturally occurring herbal compounds such as phenolic acids, flavonoids, and high molecular weight polyphenols have gained considerable attention as beneficial protective agents. The simple phenolic veratric acid (VA, 3,4-dimethoxybenzoic acid) is one of the major benzoic acid derivatives from vegetables and fruits and it also occurs naturally in medicinal mushrooms which have been reported to have anti-inflammatory and anti-oxidant activities. However, it has rarely been applied in skin care. This study, therefore, aimed to explore the possible roles of veratric acid in protection against UVB-induced damage in HaCaT cells. Results showed that veratric acid can attenuate cyclobutane pyrimidine dimers (CPDs) formation, glutathione (GSH) depletion and apoptosis induced by UVB. Furthermore, veratric acid had inhibitory effects on the UVB-induced release of the inflammatory mediators such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of veratric acid on human skin. Overall, results demonstrated significant benefits of veratric acid on the protection of keratinocyte against UVB-induced injuries and suggested its potential use in skin photoprotection.

Protective effects of grape stem extract against UVB-induced damage in C57BL mice skin.

PubMed

Che, Denis Nchang; Xie, Guang Hua; Cho, Byoung Ok; Shin, Jae Young; Kang, Hyun Ju; Jang, Seon Il

2017-08-01

Humans have become exposed to another form of a trait which is ultraviolet B (UVB) radiation reaching the earth's surface. This has become a major source of oxidative stress that ultimately leads to inflammation, DNA damage, photoaging and pigmentation disorders etc. Although several studies have shown the photo-protective role of different grape parts like the fruits and seeds, little or no data demonstrating the in vivo photo-protective role of grape stem, which is the most discarded part of the grape are available. We evaluated the protective influence of grape stem extract against UVB-induced oxidative damage in C57BL mice characterized by epidermal hyperplasia, pigmentation, collagen degradation and inflammation. Grape stem extract was administered topically 1week before UVB irradiation (120mJ/cm 2 ) and continued until the termination of the experiment. A group of non-irradiated mice and a group of irradiated mice topically administered with propylene were used as a negative and positive control. Epidermal thickness, pigmentation, erythema, mast cell and neutrophil infiltration, collagen degradation and COX-2, Nrf2, and HO-1 expressions were evaluated. Grape stem extract markedly recovered skin damage induced by the UVB radiation through the prevention of epidermal hyperplasia, pigmentation, erythema, mast cell and neutrophil infiltrations, collagen degradation and COX-2, Nrf2, and HO-1 expressions. Our study demonstrated for the first time in C57BL mice that grape stem extract reduces UVB-induced oxidative damage and hence can play a protective role in skin photo-damage. Copyright © 2017. Published by Elsevier B.V.

Time-Restricted Feeding Shifts the Skin Circadian Clock and Alters UVB-Induced DNA Damage.

PubMed

Wang, Hong; van Spyk, Elyse; Liu, Qiang; Geyfman, Mikhail; Salmans, Michael L; Kumar, Vivek; Ihler, Alexander; Li, Ning; Takahashi, Joseph S; Andersen, Bogi

2017-08-01

The epidermis is a highly regenerative barrier protecting organisms from environmental insults, including UV radiation, the main cause of skin cancer and skin aging. Here, we show that time-restricted feeding (RF) shifts the phase and alters the amplitude of the skin circadian clock and affects the expression of approximately 10% of the skin transcriptome. Furthermore, a large number of skin-expressed genes are acutely regulated by food intake. Although the circadian clock is required for daily rhythms in DNA synthesis in epidermal progenitor cells, RF-induced shifts in clock phase do not alter the phase of DNA synthesis. However, RF alters both diurnal sensitivity to UVB-induced DNA damage and expression of the key DNA repair gene, Xpa. Together, our findings indicate regulation of skin function by time of feeding and emphasize a link between circadian rhythm, food intake, and skin health. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Chondracanthus tenellus (Harvey) hommersand extract protects the human keratinocyte cell line by blocking free radicals and UVB radiation-induced cell damage.

PubMed

Piao, Mei Jing; Hyun, Yu Jae; Oh, Tae-Heon; Kang, Hee Kyoung; Yoo, Eun Sook; Koh, Young Sang; Lee, Nam Ho; Suh, In Soo; Hyun, Jin Won

2012-12-01

The aim of this study was to investigate the protective effects of the ethanol extract of the red algae Chondracanthus tenellus (Harvey) Hommersand (CTE) on cultured human keratinocyte cell line. The cellular protection conferred by CTE was evidenced by the ability of the extract to absorb ultraviolet B (UVB; 280-320 nm) and to scavenge the radical 1,1-diphenyl-2-picrylhydrazyl, as well as intracellular reactive oxygen species (ROS), induced by either hydrogen peroxide (H(2)O(2)) or UVB radiation. In addition, both superoxide anion generated by the xanthine/xanthine oxidase system and hydroxyl radical generated by the Fenton reaction (FeSO(4) + H(2)O(2)) were scavenged by CTE, as confirmed using electron spin resonance spectrometry. In the human keratinocyte cell line, CTE decreased the degree of injury resulting from UVB-induced oxidative stress to lipids, proteins, and DNA. CTE-treated cells also showed a reduction in UVB-induced apoptosis, as exemplified by fewer apoptotic bodies and less DNA fragmentation. Taken together, these results suggest that CTE confers protection on the human keratinocyte cell line against UVB-induced oxidative stress by absorbing UVB ray and scavenging ROS, thereby reducing injury to cellular constituents.

Genoprotective effect of Phyllanthus orbicularis extract against UVA, UVB and solar radiation.

PubMed

Vernhes Tamayo, Marioly; Schuch, André Passaglia; Yagura, Teiti; Baly Gil, Luis; Menck, Carlos Frederico Martins; Sánchez-Lamar, Angel

2018-05-16

One approach to protect the human skin against harmful effects of solar ultraviolet (UV) radiation is to use natural products as photoprotectors. In this work, the extract from specie Phyllanthus orbicularis K was evaluated as a protective agent against the photodamage by UVB, UVA artificial lamps and environmental sunlight exposure. The plasmid DNA solutions were exposed to radiations using the DNA-dosimeter system in presence of plant extract. The DNA repair enzymes, E. coli Formamidopyrimidine-DNA glycosylase (Fpg) and T4 bacteriophage endonuclease V (T4-endo V), were employed to discriminate oxidized DNA damage and cyclobutane pyrimidine dimers (CPD) respectively. The supercoiled and relaxed forms of DNA were separated through electrophoretic migration in agarose gels. These DNA forms were quantified to determine strands break, representing the types of lesion levels. The results showed that, in presence of P. orbicularis extract, the CPD and oxidative damage were reduced in irradiated DNA samples. The photoprotective effect of extract was more evident for UVB and sunlight radiation than for UVA. This work documents the UV absorbing properties of P. orbicularis aqueous extract and opens up new vistas in its characterization as protective agent against DNA damage induced by environmental sunlight radiation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Apigenin prevents ultraviolet-B radiation induced cyclobutane pyrimidine dimers formation in human dermal fibroblasts.

PubMed

Britto, S Mary; Shanthakumari, D; Agilan, B; Radhiga, T; Kanimozhi, G; Prasad, N Rajendra

2017-09-01

Exposure to solar ultraviolet-B (UVB) radiation leads to the formation of cyclobutane pyrimidine dimers (CPDs). We investigated the protective effect of apigenin against UVB-induced CPDs formation in human dermal fibroblasts cells (HDFa). For this purpose, HDFa cells were treated with apigenin (15μM) prior to UVB irradiation (20mJ/cm 2 ); DNA damage and subsequent molecular end points were observed. Exposure to UVB radiation increased significant CPDs formation in HDFa cells and the frequencies of CPDs were reduced by treatment with apigenin (15μM). UVB-induced CPDs downregulates the expression of nucleotide excision repair (NER) genes such as xeroderma pigmentosum complementation group C, B, G and F (XPC, XPB, XPG and XPF), transcription factor II human (TFIIH) and excision repair cross-complementation group 1 (ERCC1) in HDFa cells. Conversely, apigenin treatment restored UVB-induced loss of NER proteins in HDFa cells, which indicates its preventive effect against CPDs formation. Besides, single low dose UVB-exposure induced nuclear fragmentation, apoptotic frequency and apoptotic proteins expression (Bax and Caspase-3) have been prevented by the apigenin pretreatment. Furthermore, apigenin exhibits strong UV absorbance property and showed 10.08 SPF value. Thus, apigenin can protect skin cells against UVB-induced CPDs formation probably through its sunscreen effect. Hence, apigenin can be considered as an effective protective agent against UV induced skin damages. Copyright © 2017 Elsevier B.V. All rights reserved.

Protective Effect of Tropical Highland Blackberry Juice (Rubus adenotrichos Schltdl.) Against UVB-Mediated Damage in Human Epidermal Keratinocytes and in a Reconstituted Skin Equivalent Model

PubMed Central

Calvo-Castro, Laura; Syed, Deeba N.; Chamcheu, Jean C.; Vilela, Fernanda M. P.; Pérez, Ana M.; Vaillant, Fabrice; Rojas, Miguel; Mukhtar, Hasan

2014-01-01

Solar ultraviolet (UV) radiation, particularly its UVB (280–320 nm) spectrum, is the primary environmental stimulus leading to skin carcinogenesis. Several botanical species with antioxidant properties have shown photochemopreventive effects against UVB damage. Costa Rica’s tropical highland blackberry (Rubus adenotrichos) contains important levels of phenolic compounds, mainly ellagitannins and anthocyanins, with strong antioxidant properties. In this study, we examined the photochemopreventive effect of R. adenotrichos blackberry juice (BBJ) on UVB-mediated responses in human epidermal keratinocytes and in a three-dimensional (3D) reconstituted normal human skin equivalent (SE). Pretreatment (2 h) and posttreatment (24 h) of normal human epidermal keratinocytes (NHEKs) with BBJ reduced UVB (25 mJ cm−2)-mediated (1) cyclobutane pyrimidine dimers (CPDs) and (2) 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) formation. Furthermore, treatment of NHEKs with BBJ increased UVB-mediated (1) poly(ADP-ribose) polymerase cleavage and (2) activation of caspases 3, 8 and 9. Thus, BBJ seems to alleviate UVB-induced effects by reducing DNA damage and increasing apoptosis of damaged cells. To establish the in vivo significance of these findings to human skin, immunohistochemistry studies were performed in a 3D SE model, where BBJ was also found to decrease CPDs formation. These data suggest that BBJ may be developed as an agent to ameliorate UV-induced skin damage. PMID:23711186

Protective effect of tropical highland blackberry juice (Rubus adenotrichos Schltdl.) against UVB-mediated damage in human epidermal keratinocytes and in a reconstituted skin equivalent model.

PubMed

Calvo-Castro, Laura; Syed, Deeba N; Chamcheu, Jean C; Vilela, Fernanda M P; Pérez, Ana M; Vaillant, Fabrice; Rojas, Miguel; Mukhtar, Hasan

2013-01-01

Solar ultraviolet (UV) radiation, particularly its UVB (280-320 nm) spectrum, is the primary environmental stimulus leading to skin carcinogenesis. Several botanical species with antioxidant properties have shown photochemopreventive effects against UVB damage. Costa Rica's tropical highland blackberry (Rubus adenotrichos) contains important levels of phenolic compounds, mainly ellagitannins and anthocyanins, with strong antioxidant properties. In this study, we examined the photochemopreventive effect of R. adenotrichos blackberry juice (BBJ) on UVB-mediated responses in human epidermal keratinocytes and in a three-dimensional (3D) reconstituted normal human skin equivalent (SE). Pretreatment (2 h) and posttreatment (24 h) of normal human epidermal keratinocytes (NHEKs) with BBJ reduced UVB (25 mJ cm(-2))-mediated (1) cyclobutane pyrimidine dimers (CPDs) and (2) 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation. Furthermore, treatment of NHEKs with BBJ increased UVB-mediated (1) poly(ADP-ribose) polymerase cleavage and (2) activation of caspases 3, 8 and 9. Thus, BBJ seems to alleviate UVB-induced effects by reducing DNA damage and increasing apoptosis of damaged cells. To establish the in vivo significance of these findings to human skin, immunohistochemistry studies were performed in a 3D SE model, where BBJ was also found to decrease CPDs formation. These data suggest that BBJ may be developed as an agent to ameliorate UV-induced skin damage. © 2013 The American Society of Photobiology.

Differential effects of topical vitamin E and C E Ferulic® treatments on ultraviolet light B-induced cutaneous tumor development in Skh-1 mice.

PubMed

Burns, Erin M; Tober, Kathleen L; Riggenbach, Judith A; Kusewitt, Donna F; Young, Gregory S; Oberyszyn, Tatiana M

2013-01-01

Because of the ever-increasing incidence of ultraviolet light B (UVB)-induced skin cancer, considerable attention is being paid to prevention through the use of both sunscreens and after sun treatments, many of which contain antioxidants. Vitamin E is included as an antioxidant in many sunscreens and lotions currently on the market. Studies examining the efficacy of vitamin E as a topical preventative agent for UVB-induced skin cancer have yielded conflicting results. A likely contributor to differences in study outcome is the stability of vitamin E in the particular formulation being tested. In the current study we examined the effects of topical vitamin E alone as well as vitamin E combined with vitamin C and ferulic acid in a more stable topical formula (C E Ferulic®). Mice were exposed to UVB for 10 weeks in order to induce skin damage. Then, before the appearance of any cutaneous lesions, mice were treated for 15 weeks with a topical antioxidant, without any further UVB exposure. We found that topical C E Ferulic decreased tumor number and tumor burden and prevented the development of malignant skin tumors in female mice with chronically UVB-damaged skin. In contrast, female mice chronically exposed to UVB and treated topically with vitamin E alone showed a trend towards increased tumor growth rate and exhibited increased levels of overall DNA damage, cutaneous proliferation, and angiogenesis compared to vehicle-treated mice. Thus, we have demonstrated that topical 5% alpha tocopherol may actually promote carcinogenesis when applied on chronically UVB-damaged skin while treating with a more stable antioxidant compound may offer therapeutic benefits.

Molecular response of nasal mucosa to therapeutic exposure to broad-band ultraviolet radiation

PubMed Central

Mitchell, David; Paniker, Lakshmi; Sanchez, Guillermo; Bella, Zsolt; Garaczi, Edina; Szell, Marta; Hamid, Qutayba; Kemeny, Lajos; Koreck, Andrea

2010-01-01

Abstract Ultraviolet radiation (UVR) phototherapy is a promising new treatment for inflammatory airway diseases. However, the potential carcinogenic risks associated with this treatment are not well understood. UV-specific DNA photoproducts were used as biomarkers to address this issue. Radioimmunoassay was used to quantify cyclobutane pyrimidine dimers (CPDs) and (6–4) photoproducts in DNA purified from two milieus: nasal mucosa samples from subjects exposed to intranasal phototherapy and human airway (EpiAirway™) and human skin (EpiDerm™) tissue models. Immunohistochemistry was used to detect CPD formation and persistence in human nasal biopsies and human tissue models. In subjects exposed to broadband ultraviolet radiation, DNA damage frequencies were determined prior to as well as immediately after treatment and at increasing times post-treatment. We observed significant levels of DNA damage immediately after treatment and efficient removal of the damage within a few days. No residual damage was observed in human subjects exposed to multiple UVB treatments several weeks after the last treatment. To better understand the molecular response of the nasal epithelium to DNA damage, parallel experiments were conducted in EpiAirway and EpiDerm model systems. Repair rates in these two tissues were very similar and comparable to that observed in human skin. The data suggest that the UV-induced DNA damage response of respiratory epithelia is very similar to that of the human epidermis and that nasal mucosa is able to efficiently repair UVB induced DNA damage. PMID:18671762

Photoprotective Properties of Isothiocyanate and Nitrile Glucosinolate Derivatives From Meadowfoam (Limnanthes alba) Against UVB Irradiation in Human Skin Equivalent

PubMed Central

Carpenter, Evan L.; Le, Mai N.; Miranda, Cristobal L.; Reed, Ralph L.; Stevens, Jan F.; Indra, Arup K.; Ganguli-Indra, Gitali

2018-01-01

Exposure to ultraviolet B (UVB) irradiation of the skin leads to numerous dermatological concerns including skin cancer and accelerated aging. Natural product glucosinolate derivatives, like sulforaphane, have been shown to exhibit chemopreventive and photoprotective properties. In this study, we examined meadowfoam (Limnanthes alba) glucosinolate derivatives, 3-methoxybenzyl isothiocyanate (MBITC) and 3-methoxyphenyl acetonitrile (MPACN), for their activity in protecting against the consequences of UV exposure. To that end, we have exposed human primary epidermal keratinocytes (HPEKs) and 3D human skin reconstructed in vitro (EpiDermTM FT-400) to UVB insult and investigated whether MBITC and MPACN treatment ameliorated the harmful effects of UVB damage. Activity was determined by the compounds’ efficacy in counteracting UVB-induced DNA damage, matrix-metalloproteinase (MMP) expression, and proliferation. We found that in monolayer cultures of HPEK, MBITC and MPACN did not protect against a UVB-induced loss in proliferation and MBITC itself inhibited cell proliferation. However, in human reconstructed skin-equivalents, MBITC and MPACN decrease epidermal cyclobutane pyrimidine dimers (CPDs) and significantly reduce total phosphorylated γH2A.X levels. Both MBITC and MPACN inhibit UVB-induced MMP-1 and MMP-3 expression indicating their role to prevent photoaging. Both compounds, and MPACN in particular, showed activity against UVB-induced proliferation as indicated by fewer epidermal PCNA+ cells and prevented UVB-induced hyperplasia as determined by a reduction in reconstructed skin epidermal thickness (ET). These data demonstrate that MBITC and MPACN exhibit promising anti-photocarcinogenic and anti-photoaging properties in the skin microenvironment and could be used for therapeutic interventions. PMID:29867483

Photoprotective Properties of Isothiocyanate and Nitrile Glucosinolate Derivatives From Meadowfoam (Limnanthes alba) Against UVB Irradiation in Human Skin Equivalent.

PubMed

Carpenter, Evan L; Le, Mai N; Miranda, Cristobal L; Reed, Ralph L; Stevens, Jan F; Indra, Arup K; Ganguli-Indra, Gitali

2018-01-01

Exposure to ultraviolet B (UVB) irradiation of the skin leads to numerous dermatological concerns including skin cancer and accelerated aging. Natural product glucosinolate derivatives, like sulforaphane, have been shown to exhibit chemopreventive and photoprotective properties. In this study, we examined meadowfoam ( Limnanthes alba ) glucosinolate derivatives, 3-methoxybenzyl isothiocyanate (MBITC) and 3-methoxyphenyl acetonitrile (MPACN), for their activity in protecting against the consequences of UV exposure. To that end, we have exposed human primary epidermal keratinocytes (HPEKs) and 3D human skin reconstructed in vitro (EpiDerm TM FT-400) to UVB insult and investigated whether MBITC and MPACN treatment ameliorated the harmful effects of UVB damage. Activity was determined by the compounds' efficacy in counteracting UVB-induced DNA damage, matrix-metalloproteinase (MMP) expression, and proliferation. We found that in monolayer cultures of HPEK, MBITC and MPACN did not protect against a UVB-induced loss in proliferation and MBITC itself inhibited cell proliferation. However, in human reconstructed skin-equivalents, MBITC and MPACN decrease epidermal cyclobutane pyrimidine dimers (CPDs) and significantly reduce total phosphorylated γH2A.X levels. Both MBITC and MPACN inhibit UVB-induced MMP-1 and MMP-3 expression indicating their role to prevent photoaging. Both compounds, and MPACN in particular, showed activity against UVB-induced proliferation as indicated by fewer epidermal PCNA+ cells and prevented UVB-induced hyperplasia as determined by a reduction in reconstructed skin epidermal thickness (ET). These data demonstrate that MBITC and MPACN exhibit promising anti-photocarcinogenic and anti-photoaging properties in the skin microenvironment and could be used for therapeutic interventions.

Dietary proanthocyanidins prevent ultraviolet radiation-induced non-melanoma skin cancer through enhanced repair of damaged DNA-dependent activation of immune sensitivity.

PubMed

Katiyar, Santosh K; Pal, Harish C; Prasad, Ram

2017-10-01

Numerous plant products have been used to prevent and manage a wide variety of diseases for centuries. These products are now considered as promising options for the development of more effective and less toxic alternatives to the systems of medicine developed primarily in developed countries in the modern era. Grape seed proanthocyanidins (GSPs) are of great interest due to their anti-carcinogenic effects that have been demonstrated using various tumor models including ultraviolet (UV) radiation-induced non-melanoma skin cancer. In a pre-clinical mouse model supplementation of a control diet (AIN76A) with GSPs at concentrations of 0.2% and 0.5% (w/w) significantly inhibits the growth and multiplicity of UVB radiation-induced skin tumors. In this review, we summarize the evidence that this inhibition of UVB-induced skin tumor development by dietary GSPs is mediated by a multiplicity of coordinated effects including: (i) Promotion of the repair of damaged DNA by nuclear excision repair mechanisms, and (ii) DNA repair-dependent stimulation of the immune system following the functional activation of dendritic cells and effector T cells. Dietary GSPs hold promise for the development of an effective alternative strategy for the prevention of excessive solar UVB radiation exposure-induced skin diseases including the risk of non-melanoma skin cancer in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Role of p53 in silibinin-mediated inhibition of ultraviolet B radiation-induced DNA damage, inflammation and skin carcinogenesis.

PubMed

Rigby, Cynthia M; Roy, Srirupa; Deep, Gagan; Guillermo-Lagae, Ruth; Jain, Anil K; Dhar, Deepanshi; Orlicky, David J; Agarwal, Chapla; Agarwal, Rajesh

2017-01-01

Non-melanoma skin cancers (NMSC) are a growing problem given that solar ultraviolet B (UVB) radiation exposure is increasing most likely due to depletion of the atmospheric ozone layer and lack of adequate sun protection. Better preventive methods are urgently required to reduce UV-caused photodamage and NMSC incidence. Earlier, we have reported that silibinin treatment activates p53 and reduces photodamage and NMSC, both in vitro and in vivo; but whether silibinin exerts its protective effects primarily through p53 remains unknown. To address this question, we generated p53 heterozygous (p53 +/- ) and p53 knockout (p53 -/- ) mice on SKH-1 hairless mouse background, and assessed silibinin efficacy in both short- and long-term UVB exposure experiments. In the chronic UVB-exposed skin tumorigenesis study, compared to p53 +/+ mice, p53 +/- mice developed skin tumors earlier and had higher tumor number, multiplicity and volume. Silibinin topical treatment significantly reduced the tumor number, multiplicity and volume in p53 +/+ mice but silibinin' protective efficacy was significantly compromised in p53 +/- mice. Additionally, silibinin treatment failed to inhibit precursor skin cancer lesions in p53 -/- mice but improved the survival of the mice. In short-term studies, silibinin application accelerated the removal of UVB-induced DNA damage in p53 +/+ mice while its efficacy was partially compromised in p53 -/- mice. Interestingly, silibinin treatment also inhibited the UVB-induced inflammatory markers in skin tissue. These results further confirmed that absence of the p53 allele predisposes mice to photodamage and photocarcinogenesis, and established that silibinin mediates its protection against UVB-induced photodamage, inflammation and photocarcinogenesis partly through p53 activation. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Role of p53 in silibinin-mediated inhibition of ultraviolet B radiation-induced DNA damage, inflammation and skin carcinogenesis

PubMed Central

Rigby, Cynthia M.; Roy, Srirupa; Deep, Gagan; Guillermo-Lagae, Ruth; Jain, Anil K.; Dhar, Deepanshi; Orlicky, David J.; Agarwal, Chapla; Agarwal, Rajesh

2017-01-01

Non-melanoma skin cancers (NMSC) are a growing problem given that solar ultraviolet B (UVB) radiation exposure is increasing most likely due to depletion of the atmospheric ozone layer and lack of adequate sun protection. Better preventive methods are urgently required to reduce UV-caused photodamage and NMSC incidence. Earlier, we have reported that silibinin treatment activates p53 and reduces photodamage and NMSC, both in vitro and in vivo; but whether silibinin exerts its protective effects primarily through p53 remains unknown. To address this question, we generated p53 heterozygous (p53+/−) and p53 knockout (p53−/−) mice on SKH-1 hairless mouse background, and assessed silibinin efficacy in both short- and long-term UVB exposure experiments. In the chronic UVB-exposed skin tumorigenesis study, compared to p53+/+ mice, p53+/− mice developed skin tumors earlier and had higher tumor number, multiplicity and volume. Silibinin topical treatment significantly reduced the tumor number, multiplicity and volume in p53+/+ mice but silibinin’ protective efficacy was significantly compromised in p53+/− mice. Additionally, silibinin treatment failed to inhibit precursor skin cancer lesions in p53−/− mice but improved the survival of the mice. In short-term studies, silibinin application accelerated the removal of UVB-induced DNA damage in p53+/+ mice while its efficacy was partially compromised in p53−/− mice. Interestingly, silibinin treatment also inhibited the UVB-induced inflammatory markers in skin tissue. These results further confirmed that absence of the p53 allele predisposes mice to photodamage and photocarcinogenesis, and established that silibinin mediates its protection against UVB-induced photodamage, inflammation and photocarcinogenesis partly through p53 activation. PMID:27729375

A Comparative Analysis of the Photo-Protective Effects of Soy Isoflavones in Their Aglycone and Glucoside Forms

PubMed Central

Iovine, Barbara; Iannella, Maria Luigia; Gasparri, Franco; Giannini, Valentina; Monfrecola, Giuseppe; Bevilacqua, Maria Assunta

2012-01-01

Isoflavones exist in nature predominantly as glucosides such as daidzin or genistin and are rarely found in their corresponding aglycone forms daidzein and genistein. The metabolism and absorption of isoflavones ingested with food is well documented, but little is known about their use as topical photo-protective agents. The aim of this study was to investigate in a comparative analysis the photo-protective effects of isoflavones in both their aglycone and glucoside forms. In human skin fibroblasts irradiated with 60 mJ/cm2 ultraviolet B (UVB), we measured the expression levels of COX-2 and Gadd45, which are involved in inflammation and DNA repair, respectively. We also determined the cellular response to UVB-induced DNA damage using the comet assay. Our findings suggest that both the isoflavone glucosides at a specific concentration and combination with an aglycone mixture exerted an anti-inflammatory and photo-protective effect that prevented 41% and 71% of UVB-induced DNA damage, respectively. The advantages of using either isoflavone glucosides or an aglycone mixture in applications in the field of dermatology will depend on their properties and their different potential uses. PMID:23211668

Molecular mechanisms of UVB-induced senescence of dermal fibroblasts and its relevance for photoaging of the human skin.

PubMed

Cavinato, Maria; Jansen-Dürr, Pidder

2017-08-01

Due to its ability to cross the epidermis and reach the upper dermis where it causes cumulative DNA damage and increased oxidative stress, UVB is considered the most harmful component of sunlight to the skin. The consequences of chronic exposition to UVB are related to photoaging and photocarcinogenesis. There are limitations to the study of human skin aging and for this reason the use of models is required. Human dermal fibroblasts submitted to mild and repeated doses of UVB are considered a versatile model to study UVB effects in the process of skin photoaging, which depends on the accumulation of senescent cells, in particular in the dermis. Here we provide updated information about the current model of UVB-induced senescence with special emphasis on the process of protein quality control. Copyright © 2017 Elsevier Inc. All rights reserved.

Solar UV radiation-induced DNA Bipyrimidine photoproducts: formation and mechanistic insights.

PubMed

Cadet, Jean; Grand, André; Douki, Thierry

2015-01-01

This review chapter presents a critical survey of the main available information on the UVB and UVA bipyrimidine photoproducts which constitute the predominant recipient classes of photo-induced DNA damage. Evidence is provided that UVB irradiation of isolated DNA in aqueous solutions and in cells gives rise to the predominant generation of cis-syn cyclobutane pyrimidine dimers (CPDs) and, to a lesser extent, of pyrimidine (6-4) pyrimidone photoproducts (6-4PPs), the importance of which is strongly primary sequence dependent. A notable change in the photoproduct distribution is observed when DNA either in the dry or in desiccated microorganisms is exposed to UVC or UVB photons with an overwhelming formation of 5-(α-thymidyl)-5,6-dihydrothymidine, also called spore photoproduct (dSP), at the expense of CPDs and 6-4PPs. UVA irradiation of isolated and cellular DNA gives rise predominantly to bipyrimidine photoproducts with the overwhelming formation of thymine-containing cyclobutane pyrimidine dimers at the exclusion of 6-4PPs. UVA photons have been shown to modulate the distribution of UVB dimeric pyrimidine photoproducts by triggering isomerization of the 6-4PPs into related Dewar valence isomers. Mechanistic aspects of the formation of bipyrimidine photoproducts are discussed in the light of recent photophysical and theoretical studies.

The combined effects of UV-B radiation and herbicides on photosynthesis, antioxidant enzymes and DNA damage in two bloom-forming cyanobacteria.

PubMed

Chen, Lanzhou; Xie, Mu; Bi, Yonghong; Wang, Gaohong; Deng, Songqiang; Liu, Yongding

2012-06-01

In this study, we investigated the combined effects of UV-B irradiation and herbicides (glyphosate, GPS; 2-Methyl-4-chlorophenoxyacetic acid, MCPA-Na; 3-(3,4-dichlorophenyl)-1,1-dimethylurea, DCMU) and the antioxidant (ascorbic acid, ASC) on photosynthesis, antioxidant enzymes and DNA damage in two bloom-forming cyanobacteria, Anabaena sp. and Microcystis viridis. UV-B irradiance increased reactive oxygen species (ROS) production, which decreased chlorophyll a fluorescence yield, pigment content and superoxide dismutase (SOD) activity, and increased malondialdehyde (MDA) content and caused serious DNA damage. The degree of these damages was aggravated by the addition of DCMU, GPS and MCPA, and was partially mitigated by the addition of ASC. During the recovery process, the degree and mechanism in restoring DNA damage and photosynthesis inhibition were different by the removal of UV-B and herbicides (DCMU, GPS and MCPA) in both cyanobacteria. These results suggest that the combination of UV-B and exogenous herbicides have detrimental effects on cyanobacterial metabolism through either a ROS-mediated process or by affecting the electron transport chain, and may cause the shifts in the phytoplankton community. Copyright © 2012 Elsevier Inc. All rights reserved.

Inhibition of ultraviolet light-induced oxidative events in the skin and internal organs of hairless mice by isoflavone genistein.

PubMed

Wei, Huachen; Zhang, Xueshu; Wang, Yan; Lebwohl, Mark

2002-11-08

We have previously demonstrated that soybean isoflavone genistein inhibits ultraviolet-B (UVB)-induced skin tumorigenesis in hairless mice. In the present study, we further investigated the possible mechanism(s) of action whereby genistein inhibits photocarcinogenesis with focuses on UVB-induced oxidative events, including hydrogen peroxide (H(2)O(2)) production, lipid peroxidation (as represented by malondialdehyde, MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in vivo. We demonstrated that subacute exposure to UVB substantially increased the level of H(2)O(2), lipid peroxides, and 8-OHdG in skin of hairless mice. In addition, chronic exposure to low-dose UVB (0.9-1.2 kJ/m(2) for 20 weeks) substantially increased the levels of 8-OHdG not only in the epidermis, but also in the internal organs such as liver, brain, and spleen of mice with exception of kidney. However, genistein did not affect the level of UVB-induced pyrimidine dimmers in the same UVB exposed mouse skin, indicating selective inhibition of oxidative DNA damage by genistein. Induction of H(2)O(2) was independent of UVB fluences whereas the levels of MDA and 8-OHdG were induced in an UVB fluence-dependent manner. The results suggest that H(2)O(2) be generated as an acute cutaneous response to UVB irradiation, while MDA and 8-OHdG are accumulated with increasing UVB exposure and more closely related to chronic effects of UVB radiation. Pre-treatment of animals with 10 micromol of genistein 1 h prior to UVB exposure significantly inhibited UVB-induced H(2)O(2) and MDA in skin and 8-OHdG in epidermis as well as internal organs. Suppression of 8-OHdG formation by genistein has been corroborated in purified DNA irradiated with UVA and B. In summary, our results suggest that UVB irradiation elicit a series of oxidative events, which can be substantially inhibited by isoflavonoid genistein through either direct quenching of reactive oxygen species or indirect antiinflammatory effects. Thus, the antioxidative properties of genistein may explain for the mechanisms of anti-photocarcinogenic action of genistein.

UVR2 ensures transgenerational genome stability under simulated natural UV-B in Arabidopsis thaliana

PubMed Central

Willing, Eva-Maria; Piofczyk, Thomas; Albert, Andreas; Winkler, J. Barbro; Schneeberger, Korbinian; Pecinka, Ales

2016-01-01

Ground levels of solar UV-B radiation induce DNA damage. Sessile phototrophic organisms such as vascular plants are recurrently exposed to sunlight and require UV-B photoreception, flavonols shielding, direct reversal of pyrimidine dimers and nucleotide excision repair for resistance against UV-B radiation. However, the frequency of UV-B-induced mutations is unknown in plants. Here we quantify the amount and types of mutations in the offspring of Arabidopsis thaliana wild-type and UV-B-hypersensitive mutants exposed to simulated natural UV-B over their entire life cycle. We show that reversal of pyrimidine dimers by UVR2 photolyase is the major mechanism required for sustaining plant genome stability across generations under UV-B. In addition to widespread somatic expression, germline-specific UVR2 activity occurs during late flower development, and is important for ensuring low mutation rates in male and female cell lineages. This allows plants to maintain genome integrity in the germline despite exposure to UV-B. PMID:27905394

Wavelength dependence of biological damage induced by UV radiation on bacteria.

PubMed

Santos, Ana L; Oliveira, Vanessa; Baptista, Inês; Henriques, Isabel; Gomes, Newton C M; Almeida, Adelaide; Correia, António; Cunha, Ângela

2013-01-01

The biological effects of UV radiation of different wavelengths (UVA, UVB and UVC) were assessed in nine bacterial isolates displaying different UV sensitivities. Biological effects (survival and activity) and molecular markers of oxidative stress [DNA strand breakage (DSB), generation of reactive oxygen species (ROS), oxidative damage to proteins and lipids, and the activity of antioxidant enzymes catalase and superoxide dismutase] were quantified and statistically analyzed in order to identify the major determinants of cell inactivation under the different spectral regions. Survival and activity followed a clear wavelength dependence, being highest under UVA and lowest under UVC. The generation of ROS, as well as protein and lipid oxidation, followed the same pattern. DNA damage (DSB) showed the inverse trend. Multiple stepwise regression analysis revealed that survival under UVA, UVB and UVC wavelengths was best explained by DSB, oxidative damage to lipids, and intracellular ROS levels, respectively.

Coenzyme Q0 Enhances Ultraviolet B-Induced Apoptosis in Human Estrogen Receptor-Positive Breast (MCF-7) Cancer Cells.

PubMed

Wang, Hui-Min; Yang, Hsin-Ling; Thiyagarajan, Varadharajan; Huang, Tzu-Hsiang; Huang, Pei-Jane; Chen, Ssu-Ching; Liu, Jer-Yuh; Hsu, Li-Sung; Chang, Hsueh-Wei; Hseu, You-Cheng

2017-09-01

Coenzyme Q 0 (CoQ 0 ; 2,3-dimethoxy-5-methyl-1,4-benzoquinone), a major active constituent of Antrodia camphorata, has been shown to inhibit human triple-negative breast cancer (MDA-MB-231) cells through induction of apoptosis and cell-cycle arrest. Ecological studies have suggested a possible association between ultraviolet B (UVB) radiation and reduction in the risk of breast cancer. However, the underlying mechanism of the combination of CoQ 0 and UVB in human estrogen receptor-positive breast cancer (MCF-7) remains unclear. In this study, the possible effect of CoQ 0 on inducing apoptosis in MCF-7 cells under exposure to low-dose UVB (0.05 J/cm 2 ) has been investigated. CoQ 0 treatment (0-35 µM, for 24-72 hours) inhibits moderately the growth of breast cancer MCF-7 cells, and the cell viability was significantly decreased when the cells were pretreated with UVB irradiation. It was noted that there was a remarkable accumulation of subploid cells, the so-called sub-G1 peak, in CoQ 0 -treated cells by using flow cytometric analysis, which suggests that the viability reduction observed after treatment may result from apoptosis induction in MCF-7 cells. CoQ 0 caused an elevation of reactive oxygen species, as indicated by dichlorofluorescein fluorescence, and UVB pretreatment significantly increased CoQ 0 -induced reactive oxygen species generation in MCF-7 cells. In addition, cells were exposed to CoQ 0 , and the induction of DNA damage was evaluated by single-cell gel electrophoresis (comet assay). CoQ 0 -induced DNA damage was remarkably enhanced by UVB pretreatment. Furthermore, CoQ 0 induced apoptosis in MCF-7 cells, which was associated with PARP degradation, Bcl-2/Bax dysregulation, and p53 expression as shown by western blot. Collectively, these findings suggest that CoQ 0 might be an important supplemental agent for treating patients with breast cancer.

Hydrocaffeic and p-coumaric acids, natural phenolic compounds, inhibit UV-B damage in WKD human conjunctival cells in vitro and rabbit eye in vivo.

PubMed

Larrosa, Mar; Lodovici, Maura; Morbidelli, Lucia; Dolara, Piero

2008-10-01

This paper studied the effect on UV-B ocular damage of 10microM hydrocaffeic acid (HCAF) alone and as a mixture (MIX) (5 microM HCAF+5 microM p-coumaric acid). Since ocular UV-B damage is mediated by reactive oxygen species, the aim was to test if HCAF and MIX could reduce oxidation damage in human conjunctival cells (WKD) in vitro and in cornea and sclera of rabbits in vivo. After UVB irradiation (44 J/m(2)) of WKD cells, 8-oxodG levels in DNA were markedly increased and this effect was attenuated by HCAF and MIX. Rabbit eyes were treated by application of HCAF and MIX drops before UV-B exposure (79 J/m(2)). Corneal and scleral DNA oxidation damage, xanthine-oxidase (XO) activity and malondialdehyde levels (MDA) in corneal tissue and prostaglandin E(2) (PGE(2)) in the aqueous humour were reduced by HCAF alone and in combination with p-coumaric acid, showing their potential as a topical treatment against UV-B damage.

Faster DNA Repair of Ultraviolet-Induced Cyclobutane Pyrimidine Dimers and Lower Sensitivity to Apoptosis in Human Corneal Epithelial Cells than in Epidermal Keratinocytes

PubMed Central

Mallet, Justin D.; Bastien, Nathalie; Gendron, Sébastien P.; Rochette, Patrick J.

2016-01-01

Absorption of UV rays by DNA generates the formation of mutagenic cyclobutane pyrimidine dimers (CPD) and pyrimidine (6–4) pyrimidone photoproducts (6-4PP). These damages are the major cause of skin cancer because in turn, they can lead to signature UV mutations. The eye is exposed to UV light, but the cornea is orders of magnitude less prone to UV-induced cancer. In an attempt to shed light on this paradox, we compared cells of the corneal epithelium and the epidermis for UVB-induced DNA damage frequency, repair and cell death sensitivity. We found similar CPD levels but a 4-time faster UVB-induced CPD, but not 6-4PP, repair and lower UV-induced apoptosis sensitivity in corneal epithelial cells than epidermal. We then investigated levels of DDB2, a UV-induced DNA damage recognition protein mostly impacting CPD repair, XPC, essential for the repair of both CPD and 6-4PP and p53 a protein upstream of the genotoxic stress response. We found more DDB2, XPC and p53 in corneal epithelial cells than in epidermal cells. According to our results analyzing the protein stability of DDB2 and XPC, the higher level of DDB2 and XPC in corneal epithelial cells is most likely due to an increased stability of the protein. Taken together, our results show that corneal epithelial cells have a better efficiency to repair UV-induced mutagenic CPD. On the other hand, they are less prone to UV-induced apoptosis, which could be related to the fact that since the repair is more efficient in the HCEC, the need to eliminate highly damaged cells by apoptosis is reduced. PMID:27611318

UV-B susceptibility and photoreactivation in embryonic development of the two-spotted spider mite, Tetranychus urticae.

PubMed

Yoshioka, Yoshio; Gotoh, Tetsuo; Suzuki, Takeshi

2018-05-14

Developmental errors are often induced in the embryos of many organisms by environmental stress. Ultraviolet-B radiation (UV-B) is one of the most serious environmental stressors in embryonic development. Here, we investigated susceptibility to UV-B (0.5 kJ m -2 ) in embryos of the two-spotted spider mite, Tetranychus urticae, to examine the potential use of UV-B in control of this important agricultural pest worldwide. Peak susceptibility to UV-B (0% hatchability) was found in T. urticae eggs 36-48 h after oviposition at 25 °C, which coincides with the stages of morphogenesis forming the germ band and initial limb primordia. However, hatchability recovered to ~ 80% when eggs irradiated with UV-B were subsequently exposed to visible radiation (VIS) at 10.2 kJ m -2 , driving photoreactivation (the photoenzymatic repair of DNA damage). The recovery effect decreased to 40-70% hatchability, depending on the embryonic developmental stage, when VIS irradiation was delayed for 4 h after the end of exposure to UV-B. Thus UV-B damage to T. urticae embryos is critical, particularly in the early stages of morphogenesis, and photoreactivation functions to mitigate UV-B damage, even in the susceptible stages, but immediate VIS irradiation is needed after exposure to UV-B. These findings suggest that nighttime irradiation with UV-B can effectively kill T. urticae eggs without subsequent photoreactivation and may be useful in the physical control of this species.

Effects of UV Rays and Thymol/Thymus vulgaris L. Extract in an ex vivo Human Skin Model: Morphological and Genotoxicological Assessment.

PubMed

Cornaghi, Laura; Arnaboldi, Francesca; Calò, Rossella; Landoni, Federica; Baruffaldi Preis, William Franz; Marabini, Laura; Donetti, Elena

2016-01-01

Ultraviolet (UV) radiation is the major environmental factor affecting functions of the skin. Compounds rich in polyphenols, such as Thymus vulgaris leaf extract and thymol, have been proposed for the prevention of UV-induced skin damage. We compared the acute effects induced by UVA and UVB rays on epidermal morphology and proliferation, cytotoxicity, and genotoxicity. Normal human skin explants were obtained from young healthy women (n = 7) after informed consent and cultured at the air-liquid interface overnight. After 24 h, the samples were divided in 2 groups: the former exposed to UVA (16 or 24 J/cm2) and the latter irradiated with UVB (0.24 or 0.72 J/cm2). One hour after the end of irradiation, supernatants were collected for evaluation of the lactate dehydrogenase activity. Twenty-four hours after UVB exposure, biopsies were processed for light and transmission electron microscopy analysis, proliferation, cytotoxicity, and genotoxicity. UVB and UVA rays induced early inhibition of cell proliferation and DNA damage compared to controls. In particular, UVB rays were always more cytotoxic and genotoxic than UVA ones. For this reason, we evaluated the effect of either T. vulgaris L. extract (1.82 µg/ml) or thymol (1 µg/ml) on all samples treated for 1 h before UVB irradiation. While Thymus had a protective action for all of the endpoints evaluated, the action of the extract was less pronounced on epidermal proliferation and morphological features. The results presented in this study could be the basis for investigating the mechanism of thymol and T. vulgaris L. extract against the damage induced by UV radiation. © 2016 S. Karger AG, Basel.

Survival and SOS response induction in ultraviolet B irradiated Escherichia coli cells with defective repair mechanisms.

PubMed

Prada Medina, Cesar Augusto; Aristizabal Tessmer, Elke Tatjana; Quintero Ruiz, Nathalia; Serment-Guerrero, Jorge; Fuentes, Jorge Luis

2016-06-01

Purpose In this paper, the contribution of different genes involved in DNA repair for both survival and SOS induction in Escherichia coli mutants exposed to ultraviolet B radiation (UVB, [wavelength range 280-315 nm]) was evaluated. Materials and methods E. coli strains defective in uvrA, oxyR, recO, recN, recJ, exoX, recB, recD or xonA genes were used to determine cell survival. All strains also had the genetic sulA::lacZ fusion, which allowed for the quantification of SOS induction through the SOS Chromotest. Results Five gene products were particularly important for survival, as follows: UvrA > RecB > RecO > RecJ > XonA. Strains defective in uvrA and recJ genes showed elevated SOS induction compared with the wild type, which remained stable for up to 240 min after UVB-irradiation. In addition, E. coli strains carrying the recO or recN mutation showed no SOS induction. Conclusions The nucleotide excision and DNA recombination pathways were equally used to repair UVB-induced DNA damage in E. coli cells. The sulA gene was not turned off in strains defective in UvrA and RecJ. RecO protein was essential for processing DNA damage prior to SOS induction. In this study, the roles of DNA repair proteins and their contributions to the mechanisms that induce SOS genes in E. coli are proposed.

NADPH Oxidase-1 Plays a Key Role in Keratinocyte Responses to UV Radiation and UVB-Induced Skin Carcinogenesis.

PubMed

Raad, Houssam; Serrano-Sanchez, Martin; Harfouche, Ghida; Mahfouf, Walid; Bortolotto, Doriane; Bergeron, Vanessa; Kasraian, Zeinab; Dousset, Lea; Hosseini, Mohsen; Taieb, Alain; Rezvani, Hamid Reza

2017-06-01

The nicotinamide adenine dinucleotide phosphate oxidase (NOX) family enzymes are involved in several physiological functions. However, their roles in keratinocyte responses to UV radiation have not been clearly elucidated. This study shows that, among other NOX family members, UVB irradiation results in a biphasic activation of NOX1 that plays a critical role in defining keratinocyte fate through the modulation of the DNA damage response network. Indeed, suppression of both bursts of UVB-induced NOX1 activation by using a specific peptide inhibitor of NOX1 (InhNOX1) is associated with increased nucleotide excision repair efficiency and reduction of apoptosis, which is finally translated into decreased photocarcinogenesis. On the contrary, when only the second peak of UVB-induced NOX1 activation is blocked, both nucleotide excision repair efficiency and apoptosis are decreased. Our results show that inhibition of NOX1 activation could be a promising target for the prevention and treatment of UVB-induced skin cancer in nucleotide excision repair-proficient and -deficient patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemoprevention of Skin Cancer with 1,1-Bis (3′-Indolyl)-1-(Aromatic) Methane Analog through Induction of the Orphan Nuclear Receptor, NR4A2 (Nurr1)

PubMed Central

Shah, Punit P.; Patel, Apurva R.; Godugu, Chandraiah; Safe, Stephen; Katiyar, Santosh K.; Singh, Mandip

2013-01-01

Background The objective of this study was to demonstrate the anti-skin cancer and chemopreventive potential of 1,1-bis(3′-indolyl)-1-(p-chlorophenyl methane) (DIM-D) using an in vitro model. Methods In vitro cell cytotoxicity and viability assays were carried out in A431 human epidermoid carcinoma cell line and normal human epidermal keratinocytes (NHEK) respectively by crystal violet staining. Apoptosis induction in A431 cells (DIM-D treated) and NHEK cells pretreated with DIM-D (2 hr) prior to UVB irradiation, were assessed. The accumulation of reactive oxygen species (ROS) in DIM-D pretreated NHEK cells (2 hr) prior to UVB exposure was also determined. Immunocytochemistry and western blot analysis was performed to determine cleaved caspase 3 and DNA damage markers in DIM-D treated A431 cells and in DIM-D pretreated NHEK cells prior to UVB irradiation. Results The IC50 values of DIM-D were 68.7±7.3, 48.3±10.1 and 11.5±3.1 μM whilst for Epigallocatechin gallate (EGCG) were 419.1±8.3, 186.1±5.2 and 56.7±3.1 μM for 24, 48 and 72 hr treatments respectively. DIM-D exhibited a significantly (p<0.05) greater induction of DNA fragmentation in A431 cells compared to EGCG with percent cell death of 38.9. In addition, DIM-D induced higher expression in A431 cells compared to EGCG of cleaved caspase 3 (3.0-fold vs. 2.4-fold changes), Nurr1 (2.7-fold vs. 1.7-fold changes) and NFκB (1.3-fold vs. 1.1-fold changes). DIM-D also exhibited chemopreventive activity in UVB-irradiated NHEK cells by significantly (p<0.05) reducing UVB-induced ROS formation and apoptosis compared to EGCG. Additionally, DIM-D induced expression of Nurr1 but reduced expression of 8-OHdG significantly in UVB-irradiated NHEK cells compared to EGCG and UV only. Conclusion Our results suggest that DIM-D exhibits Nurr1-dependent transactivation in the induction of apoptosis in A431 cells and it protects NHEK cells against UVB-induced ROS formation and DNA damage. PMID:23950896

Bioactive grape proanthocyanidins enhance immune reactivity in UV-irradiated skin through functional activation of dendritic cells in mice

PubMed Central

Vaid, Mudit; Singh, Tripti; Prasad, Ram; Elmets, Craig A.; Xu, Hui; Katiyar, Santosh K.

2013-01-01

Ultraviolet (UV) radiation-induced immunosuppression has been implicated in skin carcinogenesis. Grape seed proanthocyanidins (GSPs) have anti-skin carcinogenic effects in mice and GSPs-fed mice exhibit a reduction in UV-induced suppression of allergic contact hypersensitivity (CHS), a prototypic T cell-mediated response. Here, we report that dietary GSPs did not inhibit UVB-induced suppression of CHS in xeroderma pigmentosum complementation group A (XPA)-deficient mice, which lack nucleotide excision repair mechanisms. GSPs enhanced repair of UVB-induced DNA damage (cyclobutane pyrimidine dimers) in wild-type, but not XPA-deficient, dendritic cells (DCs). Co-culture of CD4+ T cells with DCs from UVB-irradiated wild-type mice resulted in suppression of T-cell proliferation and secretion of Th-1 type cytokines that was ameliorated when the DCs were obtained from GSPs-fed mice; whereas, DCs obtained from GSPs-fed XPA-KO mice failed to restore T-cell proliferation. In adoptive transfer experiments, donor DCs were positively selected from the draining lymph nodes of UVB-exposed donor mice that were sensitized to 2,4, dinitrofluorobenzene were transferred into naïve recipient mice and the CHS response assessed. Naïve recipients that received DCs from UVB-exposed wild-type donors that had been fed GSPs exhibited a full CHS response, whereas no significant CHS was observed in mice that received DCs from XPA-KO mice fed GSPs. These results suggest that GSPs prevent UVB-induced immunosuppression through DNA repair-dependent functional activation of dendritic cells in mice. PMID:23321928

Stimulatory effect of oral administration of tea, coffee or caffeine on UVB-induced apoptosis in the epidermis of SKH-1 mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Conney, Allan H.; Zhou, Sherry; Lee Maojung

Oral administration of green tea or a caffeine solution, but not decaffeinated green tea, inhibits UVB-induced complete carcinogenesis in SKH-1 mice. Oral administration of green tea, coffee or a caffeine solution for 2 weeks enhanced UVB-induced increases in apoptosis in the epidermis, but these treatments had no effect in non-UVB treated normal epidermis. Our results suggest that administration of green tea, coffee and caffeine may inhibit UVB-induced carcinogenesis - at least in part - by enhancing UVB-induced apoptosis. Plasma levels of caffeine observed after its oral administration at cancer-preventive dose levels were within the range observed in moderate coffee drinkers.more » Topical applications of caffeine to mice previously treated with UVB for 20 weeks (high risk mice without tumors) inhibited the formation of tumors and stimulated apoptosis in the tumors but not in areas of the epidermis away from tumors. The selective effects of caffeine administration to stimulate UVB-induced apoptosis or apoptosis in tumors but not in normal epidermis or in areas of the epidermis away from tumors is of considerable interest, but the reasons for the selective effects of caffeine on apoptosis in DNA damaged tissues are unknown. Further studies are needed to determine mechanisms of these effects of caffeine and to determine the effects of caffeine administration on sunlight-induced actinic keratoses and squamous cell carcinomas in humans.« less

Investigating the role of melanin in UVA/UVB- and hydrogen peroxide-induced cellular and mitochondrial ROS production and mitochondrial DNA damage in human melanoma cells.

PubMed

Swalwell, Helen; Latimer, Jennifer; Haywood, Rachel M; Birch-Machin, Mark A

2012-02-01

Skin cancer incidence is dramatically increasing worldwide, with exposure to ultraviolet radiation (UVR) a predominant factor. The UVA component initiates oxidative stress in human skin, although its exact role in the initiation of skin cancer, particularly malignant melanoma, remains unclear and is controversial because there is evidence for a melanin-dependent mechanism in UVA-linked melanoma studies. Nonpigmented (CHL-1, A375), moderately pigmented (FM55, SKmel23), and highly pigmented (FM94, hyperpigmented FM55) human melanoma cell lines have been used to investigate UVA-induced production of reactive oxygen species using FACS analysis, at both the cellular (dihydrorhodamine-123) and the mitochondrial (MitoSOX) level, where most cellular stress is generated. For the first time, downstream mtDNA damage (utilizing a quantitative long-PCR assay) has been investigated. Using UVA, UVB, and H(2)O(2) as cellular stressors, we have explored the dual roles of melanin as a photoprotector and photosensitizer. The presence of melanin has no influence over cellular oxidative stress generation, whereas, in contrast, melanin protects against mitochondrial superoxide generation and mtDNA damage (one-way ANOVA with post hoc Tukey's analysis, P<0.001). We show that if melanin binds directly to DNA, it acts as a direct photosensitizer of mtDNA damage during UVA irradiation (P<0.001), providing evidence for the dual roles of melanin. Copyright © 2011 Elsevier Inc. All rights reserved.

Flavonols Protect Against UV Radiation-Induced Thymine Dimer Formation in an Artificial Skin Mimic.

PubMed

Maini, Sabia; Fahlman, Brian M; Krol, Ed S

2015-01-01

Exposure of skin to ultraviolet light has been shown to have a number of deleterious effects including photoaging, photoimmunosuppression and photoinduced DNA damage which can lead to the development of skin cancer. In this paper we present a study on the ability of three flavonols to protect EpiDerm™, an artificial skin mimic, against UV-induced damage. EpiDerm™ samples were treated with flavonol in acetone and exposed to UVA (100 kJ/m(2) at 365 nm) and UVB (9000 J/m(2) at 310 nm) radiation. Secretion of matrix metalloproteinase-1 (MMP-1) and tumor necrosis factor-α (TNF-a) were determined by ELISA, cyclobutane pyrimidine dimers were quantified using LC-APCI-MS. EpiDerm™ treated topically with quercetin significantly decreased MMP-1 secretion induced by UVA (100 µM) or UVB (200 µM) and TNF-a secretion was significantly reduced at 100 µM quercetin for both UVA and UVB radiation. In addition, topically applied quercetin was found to be photostable over the duration of the experiment. EpiDerm™ samples were treated topically with quercetin, kaempferol or galangin (52 µM) immediately prior to UVA or UVB exposure, and the cyclobutane thymine dimers (T-T (CPD)) were quantified using an HPLC-APCI MS/MS method. All three flavonols significantly decreased T-T (CPD) formation in UVB irradiated EpiDerm™, however no effect could be observed for the UVA irradiation experiments as thymine dimer formation was below the limit of quantitation. Our results suggest that flavonols can provide protection against UV radiation-induced skin damage through both antioxidant activity and direct photo-absorption. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

UV and ionizing radiations induced DNA damage, differences and similarities

NASA Astrophysics Data System (ADS)

Ravanat, Jean-Luc; Douki, Thierry

2016-11-01

Both UV and ionizing radiations damage DNA. Two main mechanisms, so-called direct and indirect pathways, are involved in the degradation of DNA induced by ionizing radiations. The direct effect of radiation corresponds to direct ionization of DNA (one electron ejection) whereas indirect effects are produced by reactive oxygen species generated through water radiolysis, including the highly reactive hydroxyl radicals, which damage DNA. UV (and visible) light damages DNA by again two distinct mechanisms. UVC and to a lesser extend UVB photons are directly absorbed by DNA bases, generating their excited states that are at the origin of the formation of pyrimidine dimers. UVA (and visible) light by interaction with endogenous or exogenous photosensitizers induce the formation of DNA damage through photosensitization reactions. The excited photosensitizer is able to induce either a one-electron oxidation of DNA (type I) or to produce singlet oxygen (type II) that reacts with DNA. In addition, through an energy transfer from the excited photosensitizer to DNA bases (sometime called type III mechanism) formation of pyrimidine dimers could be produced. Interestingly it has been shown recently that pyrimidine dimers are also produced by direct absorption of UVA light by DNA, even if absorption of DNA bases at these wavelengths is very low. It should be stressed that some excited photosensitizers (such as psoralens) could add directly to DNA bases to generate adducts. The review will described the differences and similarities in terms of damage formation (structure and mechanisms) between these two physical genotoxic agents.

UV-B-Induced Erythema in Human Skin: The Circadian Clock Is Ticking.

PubMed

Sarkar, Soumyadeep; Gaddameedhi, Shobhan

2018-02-01

Acute exposure of skin to UV-B causes DNA damage and sunburn erythema in both mice and humans. Previous studies documented time-of-day-related differences in sunburn responses after UV-B exposure in mice. Because humans are diurnal and mice are nocturnal, the circadian rhythm in human skin was hypothesized to be in opposite phase to the rhythm in mice. A study by Nikkola et al. demonstrates that humans are more prone to sunburn erythema after evening exposure to solar UV-B radiation as compared with morning exposure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Bioactive grape proanthocyanidins enhance immune reactivity in UV-irradiated skin through functional activation of dendritic cells in mice.

PubMed

Vaid, Mudit; Singh, Tripti; Prasad, Ram; Elmets, Craig A; Xu, Hui; Katiyar, Santosh K

2013-03-01

Ultraviolet (UV) radiation-induced immunosuppression has been implicated in skin carcinogenesis. Grape seed proanthocyanidins (GSPs) have anti-skin carcinogenic effects in mice and GSPs-fed mice exhibit a reduction in UV-induced suppression of allergic contact hypersensitivity (CHS), a prototypic T-cell-mediated response. Here, we report that dietary GSPs did not inhibit UVB-induced suppression of CHS in xeroderma pigmentosum complementation group A (XPA)-deficient mice, which lack nucleotide excision repair mechanisms. GSPs enhanced repair of UVB-induced DNA damage (cyclobutane pyrimidine dimers) in wild-type, but not XPA-deficient, dendritic cells (DC). Co-culture of CD4(+) T cells with DCs from UVB-irradiated wild-type mice resulted in suppression of T-cell proliferation and secretion of T-helper (TH) 1-type cytokines that was ameliorated when the DCs were obtained from GSP-fed mice, whereas DCs obtained from GSP-fed XPA-KO mice failed to restore T-cell proliferation. In adoptive transfer experiments, donor DCs were positively selected from the draining lymph nodes of UVB-exposed donor mice that were sensitized to 2,4,-dinitrofluorobenzene were transferred into naïve recipient mice and the CHS response assessed. Naïve recipients that received DCs from UVB-exposed wild-type donors that had been fed GSPs exhibited a full CHS response, whereas no significant CHS was observed in mice that received DCs from XPA-KO mice fed GSPs. These results suggest that GSPs prevent UVB-induced immunosuppression through DNA repair-dependent functional activation of dendritic cells in mice. Cancer Prev Res; 6(3); 242-52. ©2013 AACR. ©2013 AACR.

Flavonoids Derived from Abelmoschus esculentus Attenuates UV-B Induced Cell Damage in Human Dermal Fibroblasts Through Nrf2-ARE Pathway.

PubMed

Patwardhan, Juilee; Bhatt, Purvi

2016-05-01

Ultraviolet-B (UV-B) radiation is a smaller fraction of the total radiation reaching the Earth but leads to extensive damage to the deoxyribonucleic acid (DNA) and other biomolecules through formation of free radicals altering redox homeostasis of the cell. Abelmoschus esculentus (okra) has been known in Ayurveda as antidiabetic, hypolipidemic, demulscent, antispasmodic, diuretic, purgative, etc. The aim of this study is to evaluate the protective effect of flavonoids from A. esculentus against UV-B-induced cell damage in human dermal fibroblasts. UV-B protective activity of ethyl acetate (EA) fraction of okra was studied against UV-B-induced cytotoxicity, antioxidant regulation, oxidative DNA damage, intracellular reactive oxygen species (ROS) generation, apoptotic morphological changes, and regulation of heme oxygenase-1 (HO-1) gene through nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway. Flavonoid-rich EA fraction depicted a significant antioxidant potential also showing presence of rutin. Pretreatment of cells with EA fraction (10-30 μg/ml) prevented UV-B-induced cytotoxicity, depletion of endogenous enzymatic antioxidants, oxidative DNA damage, intracellular ROS production, apoptotic changes, and overexpression of Nrf2 and HO-1. Our study demonstrated for the 1(st) time that EA fraction of okra may reduce oxidative stress through Nrf2-ARE pathway as well as through endogenous enzymatic antioxidant system. These results suggested that flavonoids from okra may be considered as potential UV-B protective agents and may also be formulated into herbal sunscreen for topical application. Flavonoid-enriched ethyl acetate (EA) fraction from A. esculentus protected against ultraviolet-B (UV-B)-induced oxidative DNA damageEA fraction prevented UV-B-induced cytotoxicity, depletion of endogenous enzymatic antioxidants, and intracellular reactive oxygen species productionEA fraction could reduce oxidative stress through the Nrf2-ARE PathwayEA fraction was found to be nongenotoxic and prevented apoptotic changes. Flavonoids from Abelmoschus esculentus protected from ultraviolet-B-induced damageThey were capable of reducing oxidative stress through Nrf2-ARE PathwayThey are nongenotoxic and do not possess mutagenic potentialFlavonoids from A. esculentus can be studied and explored further for its topical application as sunscreen. Abbreviations used: ABTS: 2,2'-azino-bis-(3-ethylbenzothiazoline -6-sulphonic acid), AO: Acridine orange, Analysis of variance, ARE: Antioxidant response elements, BSA: Bovine serum albumin, CAPE: Caffeic acid phenethyl ester, CAT: Catalase, DCFH-DA: 2',7'-dichlorofluorescein diacetate, DMEM: Dulbecco's modified eagle's medium, DMSO: dimethyl sulfoxide, DNA: Deoxyribonucleic acid, DPBS: Dulbecco's phosphate-buffered saline, DPPH: 2,2-diphenyl-1-picryl hydrazyl, ECL: Enhanced chemiluminescence, EDTA: Ethylenediaminetetraacetic acid, ELISA: Enzyme-linked immunosorbent assay, EtBr: Ethidium bromide, FBS: Fetal bovine serum, FE Fraction: Flavonoid-enriched fraction, FRAP: Ferric reducing antioxidant power, GPx: Glutathione peroxidase, GR: Glutathione reductase, GST: Glutathione-S-transferase, GSH: Reduced glutathione, GSSG: Oxidized glutathione, HDF: Human dermal fibroblast adult cells, HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid, HRP: Horseradish peroxidase, HO-1: Heme oxygenase-1, HPTLC: High-performance thin layer chromatography, Keap-1: Kelch-like ECH-associated protein-1, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, NaCl: sodium chloride, NFDM: nonfat dry milk, Nrf2: Nuclear factor E2-related factor 2, NQO1: NAD (P) H: Quinine oxidoreductase 1, OH: Hydroxyl ions, PBST: Phosphate-buffered saline with 0.1% tween 20, PCR: Polymerase chain reaction, PMSF: Phenylmethanesulfonyl fluoride, Rf: Retention factor, ROS: Reactive oxygen species, rRNA: Ribosomal ribonucleic acid, SDS: Sodium dodecyl sulfate, SOD: Superoxide dismutase, TLC: Thin layer chromatography, TLC-DPPH: Thin layer chromatography-2,2-diphenyl-1-picryl hydrazyl, UV: Ultraviolet, UV-A: Ultraviolet-A, UV-B: Ultraviolet-B, UV-C: Ultraviolet-C, qPCR: Quantitative polymerase chain reaction.

Inhibition of Ultraviolet B-Induced Expression of the Proinflammatory Cytokines TNF-α and VEGF in the Cornea by Fucoxanthin Treatment in a Rat Model.

PubMed

Chen, Shiu-Jau; Lee, Ching-Ju; Lin, Tzer-Bin; Liu, Hsiang-Jui; Huang, Shuan-Yu; Chen, Jia-Zeng; Tseng, Kuang-Wen

2016-01-07

Ultraviolet B (UVB) irradiation is the most common cause of radiation damage to the eyeball and is a risk factor for human corneal damage. We determined the protective effect of fucoxanthin, which is a carotenoid found in common edible seaweed, on ocular tissues against oxidative UVB-induced corneal injury. The experimental rats were intravenously injected with fucoxanthin at doses of 0.5, 5 mg/kg body weight/day or with a vehicle before UVB irradiation. Lissamine green for corneal surface staining showed that UVB irradiation caused serious damage on the corneal surface, including severe epithelial exfoliation and deteriorated epithelial smoothness. Histopathological lesion examination revealed that levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF), significantly increased. However, pretreatment with fucoxanthin inhibited UVB radiation-induced corneal disorders including evident preservation of corneal surface smoothness, downregulation of proinflammatory cytokine expression, and decrease of infiltrated polymorphonuclear leukocytes from UVB-induced damage. Moreover, significant preservation of the epithelial integrity and inhibition of stromal swelling were also observed after UVB irradiation in fucoxanthin-treated groups. Pretreatment with fucoxanthin may protect against UVB radiation-induced corneal disorders by inhibiting expression of proinflammatory factors, TNF-α, and VEGF and by blocking polymorphonuclear leukocyte infiltration.

Development of a high-throughput screening system for identification of novel reagents regulating DNA damage in human dermal fibroblasts.

PubMed

Bae, Seunghee; An, In-Sook; An, Sungkwan

2015-09-01

Ultraviolet (UV) radiation is a major inducer of skin aging and accumulated exposure to UV radiation increases DNA damage in skin cells, including dermal fibroblasts. In the present study, we developed a novel DNA repair regulating material discovery (DREAM) system for the high-throughput screening and identification of putative materials regulating DNA repair in skin cells. First, we established a modified lentivirus expressing the luciferase and hypoxanthine phosphoribosyl transferase (HPRT) genes. Then, human dermal fibroblast WS-1 cells were infected with the modified lentivirus and selected with puromycin to establish cells that stably expressed luciferase and HPRT (DREAM-F cells). The first step in the DREAM protocol was a 96-well-based screening procedure, involving the analysis of cell viability and luciferase activity after pretreatment of DREAM-F cells with reagents of interest and post-treatment with UVB radiation, and vice versa. In the second step, we validated certain effective reagents identified in the first step by analyzing the cell cycle, evaluating cell death, and performing HPRT-DNA sequencing in DREAM-F cells treated with these reagents and UVB. This DREAM system is scalable and forms a time-saving high-throughput screening system for identifying novel anti-photoaging reagents regulating DNA damage in dermal fibroblasts.

Regenerative and reparative effects of human chorion-derived stem cell conditioned medium on photo-aged epidermal cells

PubMed Central

Li, Qiankun; Chen, Yan; Ma, Kui; Zhao, Along; Zhang, Cuiping; Fu, Xiaobing

2016-01-01

ABSTRACT Epidermal cells are an important regenerative source for skin wound healing. Aged epidermal cells have a low ability to renew themselves and repair skin injury. Ultraviolet (UV) radiation, particularly UVB, can cause photo-aging of the skin by suppressing the viability of human epidermal cells. A chorion-derived stem cell conditioned medium (CDSC-CNM) is thought to have regenerative properties. This study aimed to determine the regenerative effects of CDSC-CNM on UVB-induced photo-aged epidermal cells. Epidermal cells were passaged four times and irradiated with quantitative UVB, and non-irradiated cells served as a control group. Cells were then treated with different concentrations of CDSC-CNM. Compared to the non-irradiated group, the proliferation rates and migration rates of UVB-induced photo-aged epidermal cells significantly decreased (p < 0.05) with increasing intracellular radical oxygen species (ROS) generation and DNA damage. After treatment with CDSC-CNM, photo-aged epidermal cells significantly improved their viability, and their ROS generation and DNA damage decreased. The secretory factors in CDSC-CNM, including epidermal growth factor (EGF), transforming growth factor-β (TGF-β), interleukin (IL)-6, and IL-8 and the related signaling pathway protein levels, increased compared to the control medium (CM). The potential regenerative and reparative effects of CDSC-CNM indicate that it may be a candidate material for the treatment of prematurely aged skin. The functions of the secretory factors and the mechanisms of CDSC-CNM therapy deserve further attention. PMID:27097375

Drug delivery strategies for chemoprevention of UVB-induced skin cancer: A review.

PubMed

Bagde, Arvind; Mondal, Arindam; Singh, Mandip

2018-01-01

Annually, more skin cancer cases are diagnosed than the collective incidence of the colon, lung, breast, and prostate cancer. Persistent contact with sunlight is a primary cause for all the skin malignancies. UVB radiation induces reactive oxygen species (ROS) production in the skin which eventually leads to DNA damage and mutation. Various delivery approaches for the skin cancer treatment/prevention have been evolving and are directed toward improvements in terms of delivery modes, therapeutic agents, and site-specificity of therapeutics delivery. The effective chemoprevention activity achieved is based on the efficiency of the delivery system used and the amount of the therapeutic molecule deposited in the skin. In this article, we have discussed different studies performed specifically for the chemoprevention of UVB-induced skin cancer. Ultra-flexible nanocarriers, transethosomes nanocarriers, silica nanoparticles, silver nanoparticles, nanocapsule suspensions, microemulsion, nanoemulsion, and polymeric nanoparticles which have been used so far to deliver the desired drug molecule for preventing the UVB-induced skin cancer. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The repair of low dose UV light-induced damage to human skin DNA in condition of trace amount Mg 2+

NASA Astrophysics Data System (ADS)

Gao, Fang; Guo, Zhouyi; Zheng, Changchun; Wang, Rui; Liu, Zhiming; Meng, Pei; Zhai, Juan

2008-12-01

Ultraviolet light-induced damage to human skin DNA was widely investigated. The primary mechanism of this damage contributed to form cyclobutane pyrimidine dimmers (CPDs). Although the distribution of UV light-induced CPDs within a defined sequence is similar, the damage in cellular environment which shields the nuclear DNA was higher than that in organism in apparent dose. So we use low UVB light as main study agent. Low dose UV-irradiated HDF-a cells (Human Dermal Fibroblasts-adult cells) which is weaker than epidermic cells were cultured with DMEM at different trace amount of Mg2+ (0mmol/L , 0.1mmol/L , 0.2mmol/L, 0.4mmol/L, 0.8mmol/L, 1.2mmol/L) free-serum DMEM and the repair of DNA strands injured were observed. Treat these cells with DNA strand breaks detection, photoproducts detection and the repair of photoproducts detection. Then quantitate the role of trace amount Mg2+ in repair of UV light-induced damage to human skin. The experiment results indicated that epidermic cells have capability of resistance to UV-radiation at a certain extent. And Mg2+ can regulate the UV-induced damage repair and relative vitality. It can offer a rationale and experiment data to relieve UV light-induced skin disease.

The ethyl acetate fraction of Sargassum muticum attenuates ultraviolet B radiation-induced apoptotic cell death via regulation of MAPK- and caspase-dependent signaling pathways in human HaCaT keratinocytes.

PubMed

Piao, Mei Jing; Kim, Ki Cheon; Zheng, Jian; Yao, Cheng Wen; Cha, Ji Won; Boo, Sun Jin; Yoon, Weon Jong; Kang, Hee Kyoung; Yoo, Eun Sook; Koh, Young Sang; Ko, Mi Hee; Lee, Nam Ho; Hyun, Jin Won

2014-09-01

Our previous work demonstrated that an ethyl acetate extract derived from Sargassum muticum (Yendo) Fenshol (SME) protected human HaCaT keratinocytes against ultraviolet B (UVB)-induced oxidative stress by increasing antioxidant activity in the cells, thereby inhibiting apoptosis. The aim of the current study was to further elucidate the anti-apoptotic mechanism of SME against UVB-induced cell damage. The expression levels of several apoptotic-associated and mitogen-activated kinase (MAPK) signaling proteins were determined by western blot analysis of UVB-irradiated HaCaT cells with or without prior SME treatment. In addition, the loss of mitochondrial membrane potential (Δψm) was detected using flow cytometry or confocal microscopy and the mitochondria membrane-permeate dye, JC-1. Apoptosis was assessed by quantifying DNA fragmentation and apoptotic body formation. Furthermore, cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. SME absorbed electromagnetic radiation in the UVB range (280-320 nm) of the UV/visible light spectrum. SME also increased Bcl-2 and Mcl-1 expression in UVB-irradiated cells and decreased the Bax expression. Moreover, SME inhibited the UVB-induced disruption of mitochondrial membrane potential and prevented UVB-mediated increases in activated caspase-9 and caspase-3 (an apoptotic initiator and executor, respectively) levels. Notably, treatment with a pan-caspase inhibitor enhanced the anti-apoptotic effects of SME in UVB-irradiated cells. Finally, SME reduced the UVB-mediated phosphorylation of p38 MAPK and JNK, and prevented the UVB-mediated dephosphorylation of Erk1/2 and Akt. The present results indicate that SME safeguards HaCaT keratinocytes from UVB-mediated apoptosis by inhibiting a caspase-dependent signaling pathway.

Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pratheeshkumar, Poyil; Son, Young-Ok; Wang, Xin

Skin cancer is one of the most commonly diagnosed cancers in the United States. Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is present in various vegetables and fruits especially in edible berries, and displays potent antioxidant and anticarcinogenic properties. In this study, we have assessed the in vivo effects of C3G on UVB irradiation induced chronic inflammatory responses in SKH-1 hairless mice, a well-established model for UVB-induced skin carcinogenesis. Here, we show that C3G inhibited UVB-induced skin damage and inflammation in SKH-1 hairless mice. Our results indicatemore » that C3G inhibited glutathione depletion, lipid peroxidation and myeloperoxidation in mouse skin by chronic UVB exposure. C3G significantly decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-6 and TNF-α, associated with cutaneous inflammation. Likewise, UVB-induced inflammatory responses were diminished by C3G as observed by a remarkable reduction in the levels of phosphorylated MAP kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, C3G also decreased UVB-induced cyclooxygenase-2 (COX-2), PGE{sub 2} and iNOS levels, which are well-known key mediators of inflammation and cancer. Treatment with C3G inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mice skin. Immunofluorescence assay revealed that topical application of C3G inhibited the expression of 8-hydroxy-2′-deoxyguanosine, proliferating cell nuclear antigen, and cyclin D1 in chronic UVB exposed mouse skin. Collectively, these data indicates that C3G can provide substantial protection against the adverse effects of UVB radiation by modulating UVB-induced MAP kinase and NF-κB signaling pathways. - Highlights: • C3G inhibited UVB-induced oxidative damage and inflammation. • C3G inhibited UVB-induced COX-2, iNOS and PGE{sub 2} production. • C3G inhibited UVB-induced elevated proinflammatory cytokine level. • C3G inhibited UVB-induced p38 MAP kinase signaling. • C3G inhibited UVB-induced NF-κB activation.« less

Protection of human keratinocytes from UVB-induced inflammation using root extract of Lithospermum erythrorhizon.

PubMed

Ishida, Takahiro; Sakaguchi, Ikuyo

2007-05-01

UVB irradiation is an important inducer of biological changes in skin and can activate inflammatory reactions and apoptotic pathways, leading to skin damage. A root extract of Lithospermum erythrorhizon (SK), which has naphthoquinone pigments containing shikonin and shikonin derivatives, is known for its anti-inflammatory, anti-bacterial, and anti-tumor activity, and for its scavenging of reactive oxygen species. However, the effect of SK against UV damage is not clear. The aim of this study was to evaluate the efficacy of SK against UVB induced damage in normal human epidermal keratinocytes (NHEK). UVB-irradiated NHEK showed decreased cell viability, increased production of interleukin (IL)-1alpha, IL-6, IL-8, and tumor necrosis factor-alpha, and induced apoptosis. In an apoptosis pathway assay, UVB-irradiated NHEK showed increased caspase-3 activity, p53 and its phosphorylation at serine 15 compared with non-irradiated cells. All these effects induced by UVB irradiation were clearly inhibited by treatment with SK before and after UVB irradiation for 24 h. It is suggested that SK can protect epidermal cells against harmful effects of UVB irradiation and that SK treatment is probably beneficial for photoprotection of the skin.

Lycium barbarum Polysaccharides Protect Rat Corneal Epithelial Cells against Ultraviolet B-Induced Apoptosis by Attenuating the Mitochondrial Pathway and Inhibiting JNK Phosphorylation.

PubMed

Du, Shaobo; Han, Biao; Li, Kang; Zhang, Xuan; Sha, Xueli; Gao, Lan

2017-01-01

Lycium barbarum polysaccharides (LBPs) have been shown to play a key role in protecting the eyes by reducing the apoptosis induced by certain types of damage. However, it is not known whether LBPs can protect damaged corneal cells from apoptosis. Moreover, no reports have focused on the role of LBPs in guarding against ultraviolet B- (UVB-) induced apoptosis. The present study aimed to investigate the protective effect and underlying mechanism of LBPs against UVB-induced apoptosis in rat corneal epithelial (RCE) cells. The results showed that LBPs significantly prevented the loss of cell viability and inhibited cell apoptosis induced by UVB in RCE cells. LBPs also inhibited UVB-induced loss of mitochondrial membrane potential, downregulation of Bcl-2 , and upregulation of Bax and caspase-3. Finally, LBPs attenuated the phosphorylation of c-Jun NH 2 -terminal kinase (JNK) triggered by UVB. In summary, LBPs protect RCE cells against UVB-induced damage and apoptosis, and the underlying mechanism involves the attenuation of the mitochondrial apoptosis pathway and the inhibition of JNK phosphorylation.

Effect of Thai banana (Musa AA group) in reducing accumulation of oxidation end products in UVB-irradiated mouse skin.

PubMed

Leerach, Nontaphat; Yakaew, Swanya; Phimnuan, Preeyawass; Soimee, Wichuda; Nakyai, Wongnapa; Luangbudnark, Witoo; Viyoch, Jarupa

2017-03-01

Chronic UVB exposure causes skin disorders and cancer through DNA strand breaks and oxidation of numerous functional groups of proteins and lipids in the skin. In this study, we investigated the effects of Thai banana (Musa AA group, "Khai," and Musa ABB group, "Namwa") on the prevention of UVB-induced skin damage when fed to male ICR mice. Mice were orally fed banana (Khai or Namwa) fruit pulps at dose of 1mg/g body weight/day for 12weeks. The shaved backs of the mice were irradiated with UVB for 12weeks. The intensity dose of UVB-exposure was increased from 54mJ/cm 2 /exposure at week 1 to 126mJ/cm 2 /exposure at week 12. A significant increase in skin thickness, lipid peroxidation, protein oxidation end products, and expression of MMP-1 was observed in UVB-irradiated mouse skin. A reduction in the accumulation of oxidation end products was found in the skin of UVB-irradiated mice receiving Khai. This occurred in conjunction with a reduction in MMP-1 expression, inhibition of epidermal thickening, and induction of γ-GCS expression. The dietary intake of Khai prevented skin damage from chronic UVB exposure by increased γ-GCS expression and reduced oxidation end products included carbonyls, malondialdehyde and 4-hydroxynonenal. Copyright © 2017 Elsevier B.V. All rights reserved.

In vitro protective effect of a Jacquez grapes wine extract on UVB-induced skin damage.

PubMed

Tomaino, A; Cristani, M; Cimino, F; Speciale, A; Trombetta, D; Bonina, F; Saija, A

2006-12-01

Several studies have shown that UV radiation on the skin results in the formation of reactive oxygen species (ROS) that interact with proteins, lipids and DNA, thus altering cellular functions. The epidermis is composed mainly of keratinocytes, rich in ROS detoxifying enzymes and in low-molecular-mass antioxidant molecules. However, the increased generation of ROS can overwhelm the natural defences against oxidative stress. Therefore treatment of the skin with products containing plant-derived antioxidant ingredients may be a useful strategy for the prevention of UV-mediated cutaneous damage. In the present study we have investigated the in vitro capability of a Jacquez grapes wine extract (containing a significant level of proanthocyanidins, together with lower amounts of anthocyanins and hydroxycinnamic acids; JW-E), to protect skin against UVB-induced oxidative damage by using a three-dimensional tissue culture model of human epidermis. The endpoints of our experiments were cell viability, release of interleukin-1alpha and prostaglandin E(2) (well-known mediators of cutaneous inflammatory processes), accumulation in the epidermis of malondialdehyde/4-hydroxynonenal and protein carbonyl groups (derived by the oxidative damage respectively of lipids and proteins) and tissue redox balance (expressed by the levels of reduced glutathione, oxidized glutathione, glutathione peroxidase and glutathione reductase). Taken together, our findings demonstrate that the JW-E is an efficient botanical mixture able to prevent skin oxidative damage induced by UV-B exposure and may thus be a potential promising candidate as a skin photoprotective agent.

Blackberry extract inhibits UVB-induced oxidative damage and inflammation through MAP kinases and NF-κB signaling pathways in SKH-1 mice skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Divya, Sasidharan Padmaja; Wang, Xin; Pratheeshkumar, Poyil

Extensive exposure of solar ultraviolet-B (UVB) radiation to skin induces oxidative stress and inflammation that play a crucial role in the induction of skin cancer. Photochemoprevention with natural products represents a simple but very effective strategy for the management of cutaneous neoplasia. In this study, we investigated whether blackberry extract (BBE) reduces chronic inflammatory responses induced by UVB irradiation in SKH-1 hairless mice skin. Mice were exposed to UVB radiation (100 mJ/cm{sup 2}) on alternate days for 10 weeks, and BBE (10% and 20%) was applied topically a day before UVB exposure. Our results show that BBE suppressed UVB-induced hyperplasiamore » and reduced infiltration of inflammatory cells in the SKH-1 hairless mice skin. BBE treatment reduced glutathione (GSH) depletion, lipid peroxidation (LPO), and myeloperoxidase (MPO) in mouse skin by chronic UVB exposure. BBE significantly decreased the level of pro-inflammatory cytokines IL-6 and TNF-α in UVB-exposed skin. Likewise, UVB-induced inflammatory responses were diminished by BBE as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, BBE also reduced inflammatory mediators such as cyclooxygenase-2 (COX-2), prostaglandin E{sub 2} (PGE{sub 2}), and inducible nitric oxide synthase (iNOS) levels in UVB-exposed skin. Treatment with BBE inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mouse skin. Immunohistochemistry analysis revealed that topical application of BBE inhibited the expression of 8-oxo-7, 8-dihydro-2′-deoxyguanosine (8-oxodG), cyclobutane pyrimidine dimers (CPD), proliferating cell nuclear antigen (PCNA), and cyclin D1 in UVB-exposed skin. Collectively, these data indicate that BBE protects from UVB-induced oxidative damage and inflammation by modulating MAP kinase and NF-κB signaling pathways. - Highlights: • Blackberry extract inhibits UVB-induced glutathione depletion. • Blackberry extract inhibits UVB-induced lipid peroxidation. • Blackberry extract inhibits UVB-induced myeloperoxidase activity. • Blackberry extract diminishes UVB-induced inflammatory responses. • Blackberry extract prevents skin from oxidative damage and inflammation by UVB.« less

Blocking RhoA/ROCK inhibits the pathogenesis of pemphigus vulgaris by suppressing oxidative stress and apoptosis through TAK1/NOD2-mediated NF-κB pathway.

PubMed

Liang, Junqin; Zeng, Xuewen; Halifu, Yilinuer; Chen, Wenjing; Hu, Fengxia; Wang, Peng; Zhang, Huan; Kang, Xiaojing

2017-12-01

Oxidative stress and apoptosis play critical roles in pemphigus vulgaris (PV). The main aim of the present study was to investigate the effects of RhoA/ROCK signaling on UVB-induced oxidative damage, and to delineate the molecular mechanisms involved in the UVB-mediated inflammatory and apoptotic response. In HaCaT cells, we observed that blockage of RhoA/ROCK signaling with the inhibitor CT04 or Y27632 greatly inhibited the UVB-mediated increase in intracellular reactive oxygen species (ROS). Additionally, inhibition of RhoA/ROCK signaling reduced UVB-induced apoptosis, as exemplified by a reduction in DNA fragmentation, and also elevated anti-apoptotic Bcl-2 protein, concomitant with reduced levels of pro-apoptotic protein Bax, caspase-3 cleavage and decreased PARP-1 protein. The release of inflammatory mediators TNF-α, IL-1β, and IL-6 was also attenuated. Mechanically, we observed that blockage of RhoA/ROCK repressed the TAK1/NOD2-mediated NF-κB pathway in HaCaT cells exposed to UVB. Taken together, these data reveal that RhoA/ROCK signaling is one of the regulators contributing to oxidative damage and apoptosis in human keratinocytes, suggesting that RhoA/ROCK signaling has strong potential to be used as a useful therapeutic target in skin diseases including PV.

Impacts of UVB radiation on food consumption of forest specialist tadpoles.

PubMed

Londero, James Eduardo Lago; Dos Santos, Caroline Peripolli; Segatto, Ana Lúcia Anversa; Passaglia Schuch, André

2017-09-01

Solar ultraviolet radiation B (UVB) is an important environmental stressor for amphibian populations due to its genotoxicity, especially in early developmental stages. Nonetheless, there is an absence of works focused on the UVB effects on tadpoles' food consumption efficiency. In this work, we investigated the effects of the exposure to a low environmental-simulated dose of UVB radiation on food consumption of tadpoles of the forest specialist Hypsiboas curupi [Hylidae, Anura] species. After UVB treatment tadpoles were divided and exposed to a visible light source or kept in the dark, in order to indirectly evaluate the efficiency of DNA repair performed by photolyases and nucleotide excision repair (NER), respectively. The body mass and the amount of food in tadpoles' guts were verified in both conditions and these data were complemented by the micronuclei frequency in blood cells. Furthermore, the keratinized labial tooth rows were analyzed in order to check for possible UVB-induced damage in this structure. Our results clearly show that the body weight decrease induced by UVB radiation occurs due to the reduction of tadpoles' food consumption. This behavior is directly correlated with the genotoxic impact of UVB light, since the micronuclei frequency significantly increased after treatments. Surprisingly, the results indicate that photoreactivation treatment was ineffective to restore the food consumption activity and body weight values, suggesting a low efficiency of photolyases enzymes in this species. In addition, UVB treatments induced a higher number of breaks in the keratinized labial tooth rows, which could be also associated with the decrease of food consumption. This work contributes to better understand the process of weight loss observed in tadpoles exposed to UVB radiation and emphasizes the susceptibility of forest specialist amphibian species to sunlight-induced genotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

The optical effect of a semiconductor laser on protecting wheat from UV-B radiation damage.

PubMed

Qiu, Zong-Bo; Zhu, Xin-Jun; Li, Fang-Min; Liu, Xiao; Yue, Ming

2007-07-01

Lasers have been widely used in the field of biology along with the development of laser technology, but the mechanism of the bio-effect of lasers is not explicit. The objective of this paper was to test the optical effect of a laser on protecting wheat from UV-B damage. A patent instrument was employed to emit semiconductor laser (wavelength 650 nm) and incoherent red light, which was transformed from the semiconductor laser. The wavelength, power and lightfleck diameter of the incoherent red light are the same as those of the semiconductor laser. The semiconductor laser (wavelength 650 nm, power density 3.97 mW mm(-2)) and incoherent red light (wavelength 650 nm, power density 3.97 mW mm(-2)) directly irradiated the embryo of wheat seeds for 3 min respectively, and when the seedlings were 12-day-old they were irradiated by UV-B radiation (10.08 kJ m(-2)) for 12 h in the dark. Changes in the concentration of malondialdehyde (MDA), hydrogen peroxide (H(2)O(2)), glutathione (GSH), ascorbate (AsA), carotenoids (CAR), the production rate of superoxide radical (O(2)(-)), the activities of peroxidase (POD), catalase (CAT), superoxide dismutase (SOD) and the growth parameters of seedlings (plant height, leaf area and fresh weight) were measured to test the optical effect of the laser. The results showed that the incoherent red light treatment could not enhance the activities of SOD, POD and CAT and the concentration of AsA and CAR. When the plant cells were irradiated by UV-B, the incoherent red light treatment could not eliminate active oxygen and prevent lipid peroxidation in wheat. The results also clearly demonstrate that the plant DNA was damaged by UV-B radiation and semiconductor laser irradiance had the capability to protect plants from UV-B-induced DNA damage, while the incoherent red light could not. This is the first investigation reporting the optical effect of a semiconductor laser on protecting wheat from UV-B radiation damage.

Oxidative stress-induced protein damage inhibits DNA repair and determines mutation risk and anticancer drug effectiveness

PubMed Central

McAdam, Elizabeth; Brem, Reto; Karran, Peter

2016-01-01

The relationship between sun exposure and non-melanoma skin cancer risk is well established. Solar ultraviolet radiation (UV; wavelengths 280-400 nm) is firmly implicated in skin cancer development. Nucleotide excision repair (NER) protects against cancer by removing potentially mutagenic DNA lesions induced by UVB (280-320 nm). How the 20-fold more abundant UVA (320-400 mn) component of solar UV radiation increases skin cancer risk is not understood. We demonstrate here that the contribution of UVA to the effects of UV radiation on cultured human cells is largely independent of its ability to damage DNA. Instead, the effects of UVA reflect the induction of oxidative stress that causes extensive protein oxidation. Because NER proteins are among those damaged, UVA irradiation inhibits NER and increases the cells’ susceptibility to mutation by UVB. NER inhibition is a common consequence of oxidative stress. Exposure to chemical oxidants, treatment with drugs that deplete cellular antioxidants, and interventions that interfere with glucose metabolism to disrupt the supply of cellular reducing power all inhibit NER. Tumor cells are often in a condition of oxidative stress and one effect of the NER inhibition that results from stress-induced protein oxidation is an increased sensitivity to the anticancer drug cisplatin. Statement of implication: Since NER is both a defence against cancer a significant determinant of cell survival after treatment with anticancer drugs, its attenuation by protein damage under conditions of oxidative-stress has implications for both cancer risk and for the effectiveness of anticancer therapy. PMID:27106867

UV-B radiation-induced oxidative stress and p38 signaling pathway involvement in the benthic copepod Tigriopus japonicus.

PubMed

Kim, Bo-Mi; Rhee, Jae-Sung; Lee, Kyun-Woo; Kim, Min-Jung; Shin, Kyung-Hoon; Lee, Su-Jae; Lee, Young-Mi; Lee, Jae-Seong

2015-01-01

Ultraviolet B (UV-B) radiation presents an environmental hazard to aquatic organisms. To understand the molecular responses of the intertidal copepod Tigriopus japonicus to UV-B radiation, we measured the acute toxicity response to 96 h of UV-B radiation, and we also assessed the intracellular reactive oxygen species (ROS) levels, glutathione (GSH) content, and antioxidant enzyme (GST, GR, GPx, and SOD) activities after 24 h of exposure to UV-B with LD50 and half LD50 values. Also, expression patterns of p53 and hsp gene families with phosphorylation of p38 MAPK were investigated in UV-B-exposed copepods. We found that the ROS level, GSH content, and antioxidant enzyme activity levels were increased with the transcriptional upregulation of antioxidant-related genes, indicating that UV-B induces oxidative stress by generating ROS and stimulating antioxidant enzymatic activity as a defense mechanism. Additionally, we found that p53 expression was significantly increased after UV-B irradiation due to increases in the phosphorylation of the stress-responsive p38 MAPK, indicating that UV-B may be responsible for inducing DNA damage in T. japonicus. Of the hsp family genes, transcriptional levels of hsp20, hsp20.7, hsp70, and hsp90 were elevated in response to a low dose of UV-B radiation (9 kJ m(-2)), suggesting that these hsp genes may be involved in cellular protection against UV-B radiation. In this paper, we performed a pathway-oriented mechanistic analysis in response to UV-B radiation, and this analysis provides a better understanding of the effects of UV-B in the intertidal benthic copepod T. japonicus. Copyright © 2014 Elsevier Inc. All rights reserved.

Photosensitized rose Bengal-induced phototoxicity on human melanoma cell line under natural sunlight exposure.

PubMed

Srivastav, Ajeet K; Mujtaba, Syed Faiz; Dwivedi, Ashish; Amar, Saroj K; Goyal, Shruti; Verma, Ankit; Kushwaha, Hari N; Chaturvedi, Rajnish K; Ray, Ratan Singh

2016-03-01

Rose Bengal (RB) is an anionic water-soluble xanthene dye, which used for many years to assess eye cornea and conjunctiva damage. RB showed strong absorption maxima (λmax) under visible light followed by UV-B and UV-A. RB under sunlight exposure showed a time-dependent photodegradation. Our results show that photosensitized RB generates (1)O2 via Type-II photodynamic pathway and induced DNA damage under sunlight/UV-R exposure. 2'dGuO degradation, micronuclei formation, and single- and double-strand breakage were the outcome of photogenotoxicity caused by RB. Quenching studies with NaN3 advocate the involvement of (1)O2 in RB photogenotoxicity. RB induced linoleic acid photoperoxidation, which was parallel to (1)O2-mediated DNA damage. Oxidative stress in A375 cell line (human melanoma cell line) was detected through DCF-DA assay. Photosensitized RB decreased maximum cellular viability under sunlight followed by UV-B and UV-A exposures. Apoptosis was detected as a pattern of cell death through the increased of caspase-3 activity, decreased mitochondrial membrane potential, and PS translocation through inner to outer plasma membrane. Increased cytosolic levels of Bax also advocate the apoptotic cell death. We propose a p53-mediated apoptosis via increased expression of Bax gene and protein. Thus, the exact mechanism behind RB phototoxicity was the involvement of (1)O2, which induced oxidative stress-mediated DNA and membrane damage, finally apoptotic cell death under natural sunlight exposure. The study suggests that after the use of RB, sunlight exposure may avoid to prevent from its harmful effects. Copyright © 2015. Published by Elsevier B.V.

Protective effect of rare earth against oxidative stress under ultraviolet-B radiation.

PubMed

Wang, Lihong; Huang, Xiaohua; Zhou, Qing

2009-04-01

The effects of lanthanum (III) (La(III)) in protecting soybean leaves against oxidative stress induced by ultraviolet-B (UV-B) radiation were investigated. The increase in contents of hydrogen peroxide (H(2)O(2)) and superoxide (O2*-) due to UV-B radiation suggested oxidative stress. The increase in the content of malondialdehyde (MDA) and the decrease in the index of unsaturated fatty acid (IUFA) indicated oxidative damage on cell membrane induced by UV-B radiation. La(III) partially reversed UV-B-radiation-induced damage of plant growth. The reduction in the contents of H(2)O(2), O2*-, and MDA and increase in the content of IUFA, compared with UV-B treatment, also indicated that La(III) alleviated the oxidative damage induced by UV-B radiation. The increase in the activities of superoxide dismutase and peroxidase and the contents of ascorbate, carotenoids, and flavonoids were observed in soybean leaves with La(III) + UV-B treatment, compared with UV-B treatment. Our data suggested that La(III) could protect soybean plants from UV-B-radiation-induced oxidative stress by reacting with reactive oxygen species directly or by improving the defense system of plants.

Whey peptides prevent chronic ultraviolet B radiation-induced skin aging in melanin-possessing male hairless mice.

PubMed

Kimura, Yoshiyuki; Sumiyoshi, Maho; Kobayashi, Toshiya

2014-01-01

Whey proteins or peptides exhibit various actions, including an antioxidant action, an anticancer action, and a protective action against childhood asthma and atopic syndrome. The effects of orally administered whey peptides (WPs) on chronic ultraviolet B (UVB) radiation-induced cutaneous changes, including changes in cutaneous thickness, elasticity, wrinkle formation, etc., have not been examined. In this study, we studied the preventive effects of WPs on cutaneous aging induced by chronic UVB irradiation in melanin-possessing male hairless mice (HRM). UVB (36-180 mJ/cm(2)) was irradiated to the dorsal area for 17 wk in HRM, and the measurements of cutaneous thickness and elasticity in UVB irradiated mice were performed every week. WPs (200 and 400 mg/kg, twice daily) were administered orally for 17 wk. WPs inhibited the increase in cutaneous thickness, wrinkle formation, and melanin granules and the reduction in cutaneous elasticity associated with photoaging. Furthermore, it has been reported that UVB irradiation-induced skin aging is closely associated with the increase in expression of matrix metalloproteinase (MMP), vascular endothelial growth factor (VEGF), Ki-67-, and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells. WPs also prevented increases in the expression of MMP-2 and pro-MMP-9, VEGF, and Ki-67- and 8-OHdG-positive cells induced by chronic UVB irradiation. It was found that WPs prevent type IV collagen degradation, angiogenesis, proliferation, and DNA damage caused by UVB irradiation. Overall, these results demonstrate the considerable benefit of WPs for protection against solar UV-irradiated skin aging as a supplemental nutrient.

Protective Role of Mitochondrial Peroxiredoxin III against UVB-Induced Apoptosis of Epidermal Keratinocytes.

PubMed

Baek, Jin Young; Park, Sujin; Park, Jiyoung; Jang, Ji Yong; Wang, Su Bin; Kim, Sin Ri; Woo, Hyun Ae; Lim, Kyung Min; Chang, Tong-Shin

2017-06-01

UVB light induces generation of reactive oxygen species, ultimately leading to skin cell damage. Mitochondria are a major source of reactive oxygen species in UVB-irradiated skin cells, with increased levels of mitochondrial reactive oxygen species having been implicated in keratinocyte apoptosis. Peroxiredoxin III (PrxIII) is the most abundant and potent H 2 O 2 -removing enzyme in the mitochondria of most cell types. Here, the protective role of PrxIII against UVB-induced apoptosis of epidermal keratinocytes was investigated. Mitochondrial H 2 O 2 levels were differentiated from other types of ROS using mitochondria-specific fluorescent H 2 O 2 indicators. Upon UVB irradiation, PrxIII-knockdown HaCaT human keratinocytes and PrxIII-deficient (PrxIII -/- ) mouse primary keratinocytes exhibited enhanced accumulation of mitochondrial H 2 O 2 compared with PrxIII-expressing controls. Keratinocytes lacking PrxIII were subsequently sensitized to apoptosis through mitochondrial membrane potential loss, cardiolipin oxidation, cytochrome c release, and caspase activation. Increased UVB-induced epidermal tissue damage in PrxIII -/- mice was attributable to increased caspase-dependent keratinocyte apoptosis. Our findings show that mitochondrial H 2 O 2 is a key mediator in UVB-induced apoptosis of keratinocytes and that PrxIII plays a critical role in protecting epidermal keratinocytes against UVB-induced apoptosis through eliminating mitochondrial H 2 O 2 . These findings support the concept that reinforcing mitochondrial PrxIII defenses may help prevent UVB-induced skin damage such as inflammation, sunburn, and photoaging. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

[Effect of flavin adenine dinucleotide on ultraviolet B induced damage in cultured human corneal epithelial cells].

PubMed

Sakamoto, Asuka; Nakamura, Masatsugu

2012-01-01

This study evaluated the effects of flavin adenine dinucleotide (FAD) on ultraviolet B (UV-B)-induced damage in cultured human corneal epithelial (HCE-T) cells. The cultured HCE-T cells were treated with 0.003125-0.05% FAD before exposure to 80 mJ/cm2 UV-B. Cell viability was measured 24 h after UV-B irradiation using the MTS assay. Reactive oxygen species (ROS) were detected 30 min after UV-B irradiation using 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester. Apoptosis was evaluated 4 h after UV-B irradiation in the caspase-3/7 activity assay. UV-B irradiation reduced cell viability and stimulated ROS production and caspase-3/7 activity in HCE-T cells. Pretreatment of UV-B irradiated HCE-T cells with FAD significantly attenuated cell viability reduction and inhibited the stimulation of both ROS production and caspase-3/7 activity due to UV-B exposure compared with those with vehicle (0% FAD). These results clarified that FAD inhibits ROS-mediated apoptosis by UV-B irradiation in HCE-T cells and suggest that FAD may be effective as a radical scavenger in UV-B-induced corneal damage.

Artificial and Solar UV Radiation Induces Strand Breaks and Cyclobutane Pyrimidine Dimers in Bacillus subtilis Spore DNA

PubMed Central

Slieman, Tony A.; Nicholson, Wayne L.

2000-01-01

The loss of stratospheric ozone and the accompanying increase in solar UV flux have led to concerns regarding decreases in global microbial productivity. Central to understanding this process is determining the types and amounts of DNA damage in microbes caused by solar UV irradiation. While UV irradiation of dormant Bacillus subtilis endospores results mainly in formation of the “spore photoproduct” 5-thyminyl-5,6-dihydrothymine, genetic evidence indicates that an additional DNA photoproduct(s) may be formed in spores exposed to solar UV-B and UV-A radiation (Y. Xue and W. L. Nicholson, Appl. Environ. Microbiol. 62:2221–2227, 1996). We examined the occurrence of double-strand breaks, single-strand breaks, cyclobutane pyrimidine dimers, and apurinic-apyrimidinic sites in spore DNA under several UV irradiation conditions by using enzymatic probes and neutral or alkaline agarose gel electrophoresis. DNA from spores irradiated with artificial 254-nm UV-C radiation accumulated single-strand breaks, double-strand breaks, and cyclobutane pyrimidine dimers, while DNA from spores exposed to artificial UV-B radiation (wavelengths, 290 to 310 nm) accumulated only cyclobutane pyrimidine dimers. DNA from spores exposed to full-spectrum sunlight (UV-B and UV-A radiation) accumulated single-strand breaks, double-strand breaks, and cyclobutane pyrimidine dimers, whereas DNA from spores exposed to sunlight from which the UV-B component had been removed with a filter (“UV-A sunlight”) accumulated only single-strand breaks and double-strand breaks. Apurinic-apyrimidinic sites were not detected in spore DNA under any of the irradiation conditions used. Our data indicate that there is a complex spectrum of UV photoproducts in DNA of bacterial spores exposed to solar UV irradiation in the environment. PMID:10618224

Baicalin Scavenged Reactive Oxygen Species and Protected Human Keratinocytes Against UVB-induced Cytotoxicity.

PubMed

Chang, Wen-Shin; Lin, En-Yuan; Hsu, Shih-Wei; Hu, Pei-Shin; Chuang, Chin-Liang; Liao, Cheng-Hsi; Fu, Chun-Kai; Su, Chung-Hao; Gong, Chi-Li; Hsiao, Chieh-Lun; Bau, DA-Tian; Tsai, Chia-Wen

Ultraviolet B (UVB), with a wavelength of 280-320 nm, represents one of the most important environmental factors for skin disorders, including sunburn, hyperpigmentation, solar keratosis, solar elastosis and skin cancer. Therefore, protection against excessive UVA-induced damage is useful for prevention of sunburn and other human diseases. Baicalin, a major component of traditional Chinese medicine Scutellaria baicalensis, has been reported to possess antioxidant and cytostatic capacities. In this study, we examined whether baicalin is also capable of protecting human keratinocytes from UVB irradiation. The results showed that baicalin effectively scavenged reactive oxygen species (ROS) elevated within 4 h after UVB radiation and reversed the UVB-suppressed cell viability and UVB-induced apoptosis after 24 h. Our results demonstrated the utility of baicalin to complement the contributions of traditional Chinese medicine in UVB-induced damage to skin and suggested their potential application as pharmaceutical agents in long-term sun-shining injury prevention. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Developmental reprogramming by UV-B radiation in plants.

PubMed

Dotto, Marcela; Casati, Paula

2017-11-01

Plants are extremely plastic organisms with the ability to adapt and respond to the changing environmental conditions surrounding them. Sunlight is one of the main resources for plants, both as a primary energy source for photosynthesis and as a stimulus that regulates different aspects of their growth and development. UV-B comprises wavelengths that correspond to a high energy region of the solar spectrum capable of reaching the biosphere, influencing plant growth. It is currently believed that plants are able to acclimate when growing under the influence of this radiation and perceive it as a signal, without stress signs. Nonetheless, many UV-B induced changes are elicited after DNA damage occurs as a consequence of exposure. In this review we focus on the influence of UV-B on leaf, flower and root development and emphasize the limited understanding of the molecular mechanisms for most of this developmental processes affected by UV-B documented over the years of research in this area. Copyright © 2017 Elsevier B.V. All rights reserved.

Dandelion Extracts Protect Human Skin Fibroblasts from UVB Damage and Cellular Senescence

PubMed Central

Yang, Yafan; Li, Shuangshuang

2015-01-01

Ultraviolet (UV) irradiation causes damage in skin by generating excessive reactive oxygen species (ROS) and induction of matrix metalloproteinases (MMPs), leading to skin photoageing. Dandelion extracts have long been used for traditional Chinese medicine and native American medicine to treat cancers, hepatitis, and digestive diseases; however, less is known on the effects of dandelion extracts in skin photoageing. Here we found that dandelion leaf and flower extracts significantly protect UVB irradiation-inhibited cell viability when added before UVB irradiation or promptly after irradiation. Dandelion leaf and flower extracts inhibited UVB irradiation-stimulated MMP activity and ROS generation. Dandelion root extracts showed less action on protecting HDFs from UVB irradiation-induced MMP activity, ROS generation, and cell death. Furthermore, dandelion leaf and flower but not root extracts stimulated glutathione generation and glutathione reductase mRNA expression in the presence or absence of UVB irradiation. We also found that dandelion leaf and flower extracts help absorb UVB irradiation. In addition, dandelion extracts significantly protected HDFs from H2O2-induced cellular senescence. In conclusion, dandelion extracts especially leaf and flower extracts are potent protective agents against UVB damage and H2O2-induced cellular senescence in HDFs by suppressing ROS generation and MMP activities and helping UVB absorption. PMID:26576225

Cellular defense against UVB-induced phototoxicity by cytosolic NADP(+)-dependent isocitrate dehydrogenase.

PubMed

Jo, Seung-Hee; Lee, So-Hyun; Chun, Hang Suk; Lee, Su Min; Koh, Ho-Jin; Lee, Sung-Eun; Chun, Jang-Soo; Park, Jeen-Woo; Huh, Tae-Lin

2002-03-29

Ultraviolet (UV) radiation is known as a major cause of skin photoaging and photocarcinogenesis. Many harmful effects of UV radiation are associated with the generation of reactive oxygen species. Recently, we have shown that NADP(+)-dependent isocitrate dehydrogenase is involved in the supply of NADPH needed for GSH production against cellular oxidative damage. In this study we investigated the role of cytosolic form of NADP(+)-dependent isocitrate dehydrogenase (IDPc) against UV radiation-induced cytotoxicity by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 2.3-fold higher and 39% lower, respectively, than that in the parental cells carrying the vector alone. Upon exposure to UVB (312 nm), the cells with low levels of IDPc became more sensitive to cell killing. Lipid peroxidation, protein oxidation, oxidative DNA damage, and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly overexpressed IDPc exhibited enhanced resistance against UV radiation, compared to the control cells. The data indicate that IDPc plays an important role in cellular defense against UV radiation-induced oxidative injury. (c)2002 Elsevier Science (USA).

Naringin protects ultraviolet B-induced skin damage by regulating p38 MAPK signal pathway.

PubMed

Ren, Xiaolin; Shi, Yuling; Zhao, Di; Xu, Mengyu; Li, Xiaolong; Dang, Yongyan; Ye, Xiyun

2016-05-01

Naringin is a bioflavonoid and has free radical scavenging and anti-inflammatory properties. We examined the effects of naringin on skin after ultraviolet radiation B (UVB) irradiation and the signal pathways by in vitro and in vivo assay. HaCaT cells pretreated with naringin significantly inhibited UVB induced-cell apoptosis and production of intracellular reactive oxygen species (ROS). The expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) in HaCaT cells pretreated with naringin were decreased compared with the only UVB group. Also, the activation of p38 induced by UVB in HaCaT cells was reversed by naringin treatments. The inhibition function of naringin on p38 activity was more obvious than JNK. In vivo, topical treatments with naringin prevented the increase of epidermal thickness, IL-6 production, cell apoptosis and the overexpression of COX-2 in BALB/c mice skin irradiated with UVB. Naringin treatment also markedly blocked the activation of p38 in response to UVB stimulation in the mouse skin. Naringin can effectively protect against UVB-induced keratinocyte apoptosis and skin damage by inhibiting ROS production, COX-2 overexpression and strong inflammation reactions. It seemed that naringin played its role against UVB-induced skin damage through inhibition of mitogen-activated protein kinase (MAPK)/p38 activation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

UVB Induces a Genome-Wide Acting Negative Regulatory Mechanism That Operates at the Level of Transcription Initiation in Human Cells

PubMed Central

Gyenis, Ákos; Umlauf, David; Újfaludi, Zsuzsanna; Boros, Imre; Ye, Tao; Tora, Làszlò

2014-01-01

Faithful transcription of DNA is constantly threatened by different endogenous and environmental genotoxic effects. Transcription coupled repair (TCR) has been described to stop transcription and quickly remove DNA lesions from the transcribed strand of active genes, permitting rapid resumption of blocked transcription. This repair mechanism has been well characterized in the past using individual target genes. Moreover, numerous efforts investigated the fate of blocked RNA polymerase II (Pol II) during DNA repair mechanisms and suggested that stopped Pol II complexes can either backtrack, be removed and degraded or bypass the lesions to allow TCR. We investigated the effect of a non-lethal dose of UVB on global DNA-bound Pol II distribution in human cells. We found that the used UVB dose did not induce Pol II degradation however surprisingly at about 93% of the promoters of all expressed genes Pol II occupancy was seriously reduced 2–4 hours following UVB irradiation. The presence of Pol II at these cleared promoters was restored 5–6 hours after irradiation, indicating that the negative regulation is very dynamic. We also identified a small set of genes (including several p53 regulated genes), where the UVB-induced Pol II clearing did not operate. Interestingly, at promoters, where Pol II promoter clearance occurs, TFIIH, but not TBP, follows the behavior of Pol II, suggesting that at these genes upon UVB treatment TFIIH is sequestered for DNA repair by the TCR machinery. In agreement, in cells where the TCR factor, the Cockayne Syndrome B protein, was depleted UVB did not induce Pol II and TFIIH clearance at promoters. Thus, our study reveals a UVB induced negative regulatory mechanism that targets Pol II transcription initiation on the large majority of transcribed gene promoters, and a small subset of genes, where Pol II escapes this negative regulation. PMID:25058334

Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin.

PubMed

Pratheeshkumar, Poyil; Son, Young-Ok; Wang, Xin; Divya, Sasidharan Padmaja; Joseph, Binoy; Hitron, John Andrew; Wang, Lei; Kim, Donghern; Yin, Yuanqin; Roy, Ram Vinod; Lu, Jian; Zhang, Zhuo; Wang, Yitao; Shi, Xianglin

2014-10-01

Skin cancer is one of the most commonly diagnosed cancers in the United States. Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is present in various vegetables and fruits especially in edible berries, and displays potent antioxidant and anticarcinogenic properties. In this study, we have assessed the in vivo effects of C3G on UVB irradiation induced chronic inflammatory responses in SKH-1 hairless mice, a well-established model for UVB-induced skin carcinogenesis. Here, we show that C3G inhibited UVB-induced skin damage and inflammation in SKH-1 hairless mice. Our results indicate that C3G inhibited glutathione depletion, lipid peroxidation and myeloperoxidation in mouse skin by chronic UVB exposure. C3G significantly decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-6 and TNF-α, associated with cutaneous inflammation. Likewise, UVB-induced inflammatory responses were diminished by C3G as observed by a remarkable reduction in the levels of phosphorylated MAP kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, C3G also decreased UVB-induced cyclooxygenase-2 (COX-2), PGE2 and iNOS levels, which are well-known key mediators of inflammation and cancer. Treatment with C3G inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mice skin. Immunofluorescence assay revealed that topical application of C3G inhibited the expression of 8-hydroxy-2'-deoxyguanosine, proliferating cell nuclear antigen, and cyclin D1 in chronic UVB exposed mouse skin. Collectively, these data indicates that C3G can provide substantial protection against the adverse effects of UVB radiation by modulating UVB-induced MAP kinase and NF-κB signaling pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

Cyanidin-3-Glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signalling pathways in SKH-1 hairless mice skin

PubMed Central

Pratheeshkumar, Poyil; Son, Young-Ok; Wang, Xin; Divya, Sasidharan Padmaja; Joseph, Binoy; Hitron, John Andrew; Wang, Lei; Kim, Donghern; Yin, Yuanqin; Roy, Ram Vinod; Lu, Jian; Zhang, Zhuo; Wang, Yitao; Shi, Xianglin

2015-01-01

Skin cancer is one of the most commonly diagnosed cancers in the United States. Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Cyanidin-3-Glucoside (C3G), a member of the anthocyanin family, is present in various vegetables and fruits especially in edible berries, and displays potent antioxidant and anticarcinogenic properties. In this study, we have assessed the in vivo effects of C3G on UVB irradiation induced chronic inflammatory responses in SKH-1 hairless mice, a well-established model for UVB-induced skin carcinogenesis. Here, we show that C3G inhibited UVB-induced skin damage and inflammation in SKH-1 hairless mice. Our results indicate that C3G inhibited glutathione depletion, lipid peroxidation and myeloperoxidation in mouse skin by chronic UVB exposure. C3G significantly decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-6 and TNF-α, associated with cutaneous inflammation. Likewise, UVB-induced inflammatory responses were diminished by C3G as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, C3G also decreased UVB-induced cyclooxygenase-2 (COX-2), PGE2 and iNOS levels, which are well-known key mediators of inflammation and cancer. Treatment with C3G inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mice skin. Immunofluorescence assay revealed that topical application of C3G inhibited the expression of 8-hydroxy-2′-deoxyguanosine, proliferating cell nuclear antigen, and cyclin D1 in chronic UVB exposed mouse skin. Collectively, these data indicates that C3G can provide substantial protection against the adverse effects of UVB radiation by modulating UVB-induced MAP kinase and NF-κB signaling pathways. PMID:25062774

Ultraviolet-B Protective Effect of Flavonoids from Eugenia caryophylata on Human Dermal Fibroblast Cells.

PubMed

Patwardhan, Juilee; Bhatt, Purvi

2015-10-01

The exposure of skin to ultraviolet-B (UV-B) radiations leads to deoxyribonucleic acid (DNA) damage and can induce production of free radicals which imbalance the redox status of the cell and lead to increased oxidative stress. Clove has been traditionally used for its analgesic, anti-inflammatory, anti-microbial, anti-viral, and antiseptic effects. To evaluate the UV-B protective activity of flavonoids from Eugenia caryophylata (clove) buds on human dermal fibroblast cells. Protective ability of flavonoid-enriched (FE) fraction of clove was studied against UV-B induced cytotoxicity, anti-oxidant regulation, oxidative DNA damage, intracellular reactive oxygen species (ROS) generation, apoptotic morphological changes, and regulation of heme oxygenase-1 (HO-1) gene through nuclear factor E2-related factor 2 antioxidant response element (Nrf2 ARE) pathway. FE fraction showed a significant antioxidant potential. Pretreatment of cells with FE fraction (10-40 μg/ml) reversed the effects of UV-B induced cytotoxicity, depletion of endogenous enzymatic antioxidants, oxidative DNA damage, intracellular ROS production, apoptotic changes, and overexpression of Nrf2 and HO-1. The present study demonstrated for the first time that the FE fraction from clove could confer UV-B protection probably through the Nrf2-ARE pathway, which included the down-regulation of Nrf2 and HO-1. These findings suggested that the flavonoids from clove could potentially be considered as UV-B protectants and can be explored further for its topical application to the area of the skin requiring protection. Pretreatment of human dermal fibroblast with flavonoid-enriched fraction of Eugenia caryophylata attenuated effects of ultraviolet-B radiationsIt also conferred protection through nuclear factor E2-related factor 2-antioxidant response pathway and increased tolerance of cells against oxidative stressFlavonoid-enriched fraction can be explored further for topical application to the skin as a ultraviolet-B protectant. Abbreviations used: ABTS: 2,2'-azino-bis-(3-ethylbenzothiazoline- 6-sulphonic acid), AO: Acridine orange, Analysis of variance, ARE: Antioxidant response elements, BSA: Bovine serum albumin, CAPE: Caffeic acid phenethyl ester, CAT: Catalase, DCFH-DA: 2',7'-dichlorofluorescein diacetate, DMEM: Dulbecco's Modified Eagle's Medium, DMSO: Dimethyl sulfoxide, DNA: Deoxyribonucleic acid, DPBS: Dulbecco's phosphate buffered saline, DPPH: 2,2-diphenyl-1-picrylhydrazyl, ECL: Enhanced chemiluminescence, EDTA: Ethylenediaminetetraacetic acid, ELISA: Enzyme-linked immunesorbent assay, EtBr: Ethidium bromide, FBS: Fetal bovine serum, FE fraction: Flavonoid-enriched fraction, FRAP: Ferric reducing antioxidant power, GPx: Glutathione peroxidase, GR: Glutathione reductase, GST: Glutathione-S-transferase, GSH: Reduced glutathione, GSSG: Oxidized glutathione, HDF: Human dermal fibroblast, HEPES: 4-(2-hydroxyethyl)-1-piperazineethanesulphonic acid, HRP: Horseradish peroxidase, HO-1: Heme oxygenase-1, HPTLC: High-performance thin layer chromatography, Keap-1: Kelch-like ECH-associated protein-1, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, NaCl: Sodium chloride, NFDM: Nonfat dry milk, Nrf2: Nuclear factor E2-related factor 2, NQO1: NAD (P) H: Quinine oxidoreductase 1, OH: Hydroxyl ions, PBST: Phosphate buffered saline with 0.1% tween 20, PCR: Polymerase chain reaction, PMSF: Phenylmethanesulfonyl fluoride, Rf: Retention factor, ROS: Reactive oxygen species, rRNA: Ribosomal ribonucleic acid, SDS: Sodium dodecyl sulfate, SOD: Superoxide dismutase, TLC: Thin layer chromatography, TLC-DPPH: Thin layer chromatography-2,2-diphenyl-1-picrylhydrazyl, UV: Ultraviolet, UV-A: Ultraviolet-A, UV-B: Ultraviolet-B, UV-C: Ultraviolet-C, and qPCR: Quantitative polymerase chain reaction.

Wild chrysanthemum extract prevents UVB radiation-induced acute cell death and photoaging.

PubMed

Sun, Sujiao; Jiang, Ping; Su, Weiting; Xiang, Yang; Li, Jian; Zeng, Lin; Yang, Shuangjuan

2016-03-01

Wild chrysanthemum (Chrysanthemum indicum L.) is traditionally used in folk medicine as an anti-inflammatory agent. It is also used in the southwest plateau region of China to prevent ultraviolet-induced skin damage. However, the role and mechanism by which wild chrysanthemum prevents UV-induced skin damage and photoaging have never been investigated in vitro. In the present study, we found that aqueous extracts from wild chrysanthemum strongly reduced high-dose UVB-induced acute cell death of human immortalized keratinocytic HaCat cells. Wild chrysanthemum extract was also demonstrated to reduce low-dose UVB-induced expression of the photoaging-related matrix metalloproteinases MMP-2 and MMP-9. The ROS level elevated by UVB irradiation was strongly attenuated by wild chrysanthemum extract. Further study revealed that wild chrysanthemum extract reduced UVB-triggered ERK1/2 and p38 MAPK phosphorylation and their protective role, which is partially dependent on inhibiting p38 activation. These results suggest that wild chrysanthemum extract can protect the skin from UVB-induced acute skin damage and photoaging by reducing the intracellular reactive oxygen species (ROS) level and inhibiting p38 MAPK phosphorylation. The present study confirmed the protective role of wild chrysanthemum against UV-induced skin disorders in vitro and indicated the possible mechanism. Further study to identify the active components in wild chrysanthemum extract would be useful for developing new drugs for preventing and treating skin diseases, including skin cancer and photoaging, induced by UV irradiation.

Topical treatment with pterostilbene, a natural phytoalexin, effectively protects hairless mice against UVB radiation-induced skin damage and carcinogenesis.

PubMed

Sirerol, J Antoni; Feddi, Fatima; Mena, Salvador; Rodriguez, María L; Sirera, Paula; Aupí, Miguel; Pérez, Salvador; Asensi, Miguel; Ortega, Angel; Estrela, José M

2015-08-01

The aim of our study was to investigate in the SKH-1 hairless mouse model the effect of pterostilbene (Pter), a natural dimethoxy analog of resveratrol (Resv), against procarcinogenic ultraviolet B radiation (UVB)-induced skin damage. Pter prevented acute UVB (360 mJ/cm(2))-induced increase in skin fold, thickness, and redness, as well as photoaging-associated skin wrinkling and hyperplasia. Pter, but not Resv, effectively prevented chronic UVB (180 mJ/cm(2), three doses/week for 6 months)-induced skin carcinogenesis (90% of Pter-treated mice did not develop skin carcinomas, whereas a large number of tumors were observed in all controls). This anticarcinogenic effect was associated with (a) maintenance of skin antioxidant defenses (i.e., glutathione (GSH) levels, catalase, superoxide, and GSH peroxidase activities) close to control values (untreated mice) and (b) an inhibition of UVB-induced oxidative damage (using as biomarkers 8-hydroxy-2'-deoxyguanosine, protein carbonyls, and isoprostanes). The molecular mechanism underlying the photoprotective effect elicited by Pter was further evaluated using HaCaT immortalized human keratinocytes and was shown to involve potential modulation of the Nrf2-dependent antioxidant response. Copyright © 2015 Elsevier Inc. All rights reserved.

Pharmacological activities of an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts in UVB-induced oxidative stress and inflammation of human corneal cells.

PubMed

Bigagli, Elisabetta; Cinci, Lorenzo; D'Ambrosio, Mario; Luceri, Cristina

2017-08-01

Ultraviolet B (UVB) exposure is a risk factor for corneal damage resulting in oxidative stress, inflammation and cell death. The aim of this study was to investigate the potential protective effects of a commercial eye drop (Dacriovis™) containing Matricaria chamomilla and Euphrasia officinalis extracts on human corneal epithelial cells (HCEC-12) against UVB radiation-induced oxidative stress and inflammation as well as the underlying mechanisms. The antioxidant potential of the eye drops was evaluated by measuring the ferric reducing antioxidant power and the total phenolic content by Folin-Ciocalteu reagent. HCEC-12 cells were exposed to UVB radiation and treated with the eye drops at various concentrations. Cell viability, wound healing assay, reactive oxygen species (ROS) levels, protein and lipid oxidative damage and COX-2, IL-1β, iNOS, SOD-2, HO-1 and GSS gene expression, were assessed. Eye drops were able to protect corneal epithelial cells from UVB-induced cell death and ameliorated the wound healing; the eye drops exhibited a strong antioxidant activity, decreasing ROS levels and protein and lipid oxidative damage. Eye drops also exerted anti-inflammatory activities by decreasing COX-2, IL-1β, iNOS expression, counteracted UVB-induced GSS and SOD-2 expression and restored HO-1 expression to control levels. These findings suggest that an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts exerts positive effects against UVB induced oxidative stress and inflammation and may be useful in protecting corneal epithelial cells from UVB exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Photoprotective effects of topical ginseng leaf extract using Ultraflo L against UVB-induced skin damage in hairless mice.

PubMed

Hong, Yang Hee; Lee, Hyun-Sun; Jung, Eun Young; Han, Sung-Hee; Park, Yooheon; Suh, Hyung Joo

2017-10-01

Abnormal activation of matrix metalloproteinases (MMPs) plays an important role in UV-induced wrinkle formation, which is a major dermatological problem. This formation occurs due to the degeneration of the extracellular matrix (ECM). In this study, we investigated the cutaneous photoprotective effects of Ultraflo L treated ginseng leaf (UTGL) in hairless mice. SKH-1 hairless mice (6 weeks of age) were randomly divided into four groups (8 mice/group). UTGL formulation was applied topically to the skin of the mice for 10 weeks. The normal control group received nonvehicle and was not irradiated with UVB. The UV control (UVB) group received nonvehicle and was exposed to gradient-UVB irradiation. The groups (GA) receiving topical application of UTGL formulation were subjected to gradient-UVB irradiation on 0.5 mg/cm 2 [GA-low (GA-L)] and 1.0 mg/cm 2 [(GA-high (GA-H)] of dorsal skin area, respectively. We found that topical treatment with UTGL attenuated UVB-induced epidermal thickness and impairment of skin barrier function. Additionally, UTGL suppressed the expression of MMP-2, -3, and -13 induced by UVB irradiation. Our results show that topical application of UTGL protects the skin against UVB-induced damage in hairless mice and suggest that UTGL can act as a potential agent for preventing and/or treating UVB-induced photoaging. UTGL possesses sunscreen properties and may exhibit photochemoprotective activities inside the skin of mice. Therefore, UTGL could be used as a potential therapeutic agent to protect the skin against UVB-induced photoaging.

Blackberry extract inhibits UVB-induced oxidative damage and inflammation through MAP kinases and NF-κB signaling pathways in SKH-1 mice skin.

PubMed

Divya, Sasidharan Padmaja; Wang, Xin; Pratheeshkumar, Poyil; Son, Young-Ok; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Hitron, John Andrew; Wang, Lei; Asha, Padmaja; Shi, Xianglin; Zhang, Zhuo

2015-04-01

Extensive exposure of solar ultraviolet-B (UVB) radiation to skin induces oxidative stress and inflammation that play a crucial role in the induction of skin cancer. Photochemoprevention with natural products represents a simple but very effective strategy for the management of cutaneous neoplasia. In this study, we investigated whether blackberry extract (BBE) reduces chronic inflammatory responses induced by UVB irradiation in SKH-1 hairless mice skin. Mice were exposed to UVB radiation (100 mJ/cm(2)) on alternate days for 10 weeks, and BBE (10% and 20%) was applied topically a day before UVB exposure. Our results show that BBE suppressed UVB-induced hyperplasia and reduced infiltration of inflammatory cells in the SKH-1 hairless mice skin. BBE treatment reduced glutathione (GSH) depletion, lipid peroxidation (LPO), and myeloperoxidase (MPO) in mouse skin by chronic UVB exposure. BBE significantly decreased the level of pro-inflammatory cytokines IL-6 and TNF-α in UVB-exposed skin. Likewise, UVB-induced inflammatory responses were diminished by BBE as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, BBE also reduced inflammatory mediators such as cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and inducible nitric oxide synthase (iNOS) levels in UVB-exposed skin. Treatment with BBE inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mouse skin. Immunohistochemistry analysis revealed that topical application of BBE inhibited the expression of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG), cyclobutane pyrimidine dimers (CPD), proliferating cell nuclear antigen (PCNA), and cyclin D1 in UVB-exposed skin. Collectively, these data indicate that BBE protects from UVB-induced oxidative damage and inflammation by modulating MAP kinase and NF-κB signaling pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Protective role of integrin-linked kinase against oxidative stress and in maintenance of genomic integrity

PubMed Central

Im, Michelle; Dagnino, Lina

2018-01-01

The balance between the production of reactive oxygen species and activation of antioxidant pathways is essential to maintain a normal redox state in all tissues. Oxidative stress caused by excessive oxidant species generation can cause damage to DNA and other macromolecules, affecting cell function and viability. Here we show that integrin-linked kinase (ILK) plays a key role in eliciting a protective response to oxidative damage in epidermal cells. Inactivation of the Ilk gene causes elevated levels of intracellular oxidant species (IOS) and DNA damage in the absence of exogenous oxidative insults. In ILK-deficient cells, excessive IOS production can be prevented through inhibition of NADPH oxidase activity, with a concomitant reduction in DNA damage. Additionally, ILK is necessary for DNA repair processes following UVB-induced damage, as ILK-deficient cells show a significantly impaired ability to remove cyclobutane pyrimidine dimers following irradiation. Thus, ILK is essential to maintain cellular redox balance and, in its absence, epidermal cells become more susceptible to oxidative damage through mechanisms that involve IOS production by NADPH oxidase activity. PMID:29568383

Protective role of integrin-linked kinase against oxidative stress and in maintenance of genomic integrity.

PubMed

Im, Michelle; Dagnino, Lina

2018-03-02

The balance between the production of reactive oxygen species and activation of antioxidant pathways is essential to maintain a normal redox state in all tissues. Oxidative stress caused by excessive oxidant species generation can cause damage to DNA and other macromolecules, affecting cell function and viability. Here we show that integrin-linked kinase (ILK) plays a key role in eliciting a protective response to oxidative damage in epidermal cells. Inactivation of the Ilk gene causes elevated levels of intracellular oxidant species (IOS) and DNA damage in the absence of exogenous oxidative insults. In ILK-deficient cells, excessive IOS production can be prevented through inhibition of NADPH oxidase activity, with a concomitant reduction in DNA damage. Additionally, ILK is necessary for DNA repair processes following UVB-induced damage, as ILK-deficient cells show a significantly impaired ability to remove cyclobutane pyrimidine dimers following irradiation. Thus, ILK is essential to maintain cellular redox balance and, in its absence, epidermal cells become more susceptible to oxidative damage through mechanisms that involve IOS production by NADPH oxidase activity.

Saponins from Tribulus terrestris L. protect human keratinocytes from UVB-induced damage.

PubMed

Sisto, Margherita; Lisi, Sabrina; D'Amore, Massimo; De Lucro, Raffaella; Carati, Davide; Castellana, Donatello; La Pesa, Velia; Zuccarello, Vincenzo; Lofrumento, Dario D

2012-12-05

Chronic exposure to solar UVB radiation damages skin, increasing the risk to develop cancer. Hence the identification of compounds with a photoprotective efficacy is essential. This study examined the role of saponins derived from Tribulus terrestris L. (TT) on the modulation of apoptosis in normal human keratinocytes (NHEK) exposed to physiological doses of UVB and to evaluate their antitumoral properties. In NHEK, TT saponins attenuate UVB-induced programmed cell death through inhibition of intrinsic apoptotic pathway. In squamous cell carcinomas (SCC) TT saponins do not make the malignant keratinocytes more resistant to UVB and determine an enhanced apoptotic response. The photoprotective effect of TT saponins is tightly correlated to the enhancement of NER genes expression and the block of UVB-mediated NF-κB activation. Collectively, our study shows experimental evidence that TT has a preventive efficacy against UVB-induced carcinogenesis and the molecular knowledge on the mechanisms through which TT saponins regulate cell death suggests great potential for TT to be developed into a new medicine for cancer patients. Copyright © 2012 Elsevier B.V. All rights reserved.

UV-B-induced DNA damage and repair in the mouse lens.

PubMed

Mesa, Rosana; Bassnett, Steven

2013-10-17

Epidemiologic studies have linked UV-B exposure to development of cortical cataracts, but the underlying molecular mechanism(s) is unresolved. Here, we used a mouse model to examine the nature and distribution of DNA photolesions produced by ocular UV-B irradiation. Anesthetized mice, eye globes, or isolated lenses were exposed to UV-B. Antibodies specific for 6-4 photoproducts (6-4 PPs) or cyclobutane pyrimidine dimers (CPDs) were used to visualize DNA adducts. Illumination of intact globes with UV-B-induced 6-4 PP and CPD formation in cells of the cornea, anterior iris, and central lens epithelium. Photolesions were not detected in retina or lens cells situated in the shadow of the iris. Photolesions in lens epithelial cells were produced with radiant exposures significantly below the minimal erythemal dose. Lens epithelial cells rapidly repaired 6-4 PPs, but CPD levels did not markedly diminish, even over extended postirradiation recovery periods in vitro or in vivo. The repair of 6-4 PPs did not depend on the proliferative activity of the epithelial cells, since the repair rate in the mitotically-active germinative zone (GZ) was indistinguishable from that of quiescent cells in the central epithelium. Even relatively modest exposures to UV-B produced 6-4 PP and CPD photolesions in lens epithelial cells. Cyclobutane pyrimidine dimer lesions were particularly prevalent and were repaired slowly if at all. Studies on sun-exposed skin have established a causal connection between photolesions and so-called UV-signature mutations. If similar mechanisms apply in the lens, it suggests that somatic mutations in lens epithelial cells may contribute to the development of cortical cataracts.

Involvement of the Extrinsic and Intrinsic Pathways in Ultraviolet B-Induced Apoptosis of Corneal Epithelial Cells

PubMed Central

Ubels, John L.; Glupker, Courtney D.; Schotanus, Mark P.; Haarsma, Loren D.

2015-01-01

The goal of this study was to elucidate the pathway by which UVB initiates efflux of K+ and subsequently apoptosis in human corneal limbal epithelial (HCLE) cells. The initial focus of the study was on the extrinsic pathway involving Fas. HCLE cells transfected with Fas siRNA were exposed to 80–150 mJ/cm2 UVB and incubated in culture medium with 5.5 mM K+. Knock down of Fas resulted in limited reduction in UVB-induced caspase-8 and -3 activity. Patch-clamp recordings showed no difference in UVB-induced normalized K+ currents between Fas transfected and control cells. Knockdown of caspase-8 had no effect on the activation of caspase-3 following UVB exposure, while a caspase-8 inhibitor completely eliminated UVB activation of caspase-3. This suggests that caspase-8 is a robust enzyme, able to activate caspase-3 via residual caspase-8 present after knockdown, and that caspase-8 is directly involved in the UVB activation of caspase-3. Inhibition of caspase-9 significantly decreased the activation of caspases-8 and -3 in response to UVB. Knockdown of Apaf-1, required for activation of caspase-9, resulted in a significant reduction in UVB-induced activation of caspases-9, -8, and -3. Knockdown of Apaf-1 also inhibited intrinsic and UVB-induced levels of apoptosis, as determined by DNA fragmentation measured by TUNEL assay. In UVB exposed cultures treated with caspase-3 inhibitor, the percentage of apoptotic cells was reduced to control levels, confirming the necessity of caspase-3 activation in DNA fragmentation. The lack of effect of Fas knockdown on K+ channel activation, as well as the limited effect on activation of caspases-8 and -3, strongly suggest that Fas and the extrinsic pathway is not of primary importance in the initiation of apoptosis in response to UVB in HCLE cells. Inhibition of caspase-8 and -3 activation following inhibition of caspase-9, as well as reduction in activation of caspases-9, -8, and -3 and DNA fragmentation in response to Apaf-1 knockdown support the conclusion that the intrinsic pathway is more important in UVB-induced apoptosis in HCLE cells. PMID:26559338

Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal pigment epithelial cells: A potential role for reducing UVB light-induced retinal damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Chao-Peng; Yao, Jin; Tao, Zhi-Fu

Highlights: •UVB irradiation induces RPE autophagy. •EGCG treatment represses UVB-mediated autophagy. •EGCG regulates UVB-mediated autophagy through mTOR signaling pathway. •EGCG sensitizes RPE cells to UVB-induced damage in an autophagy-dependent manner. -- Abstract: Autophagy is an intracellular catabolic process involved in protein and organelle degradation via the lysosomal pathway that has been linked in the pathogenesis of age-related macular degeneration (AMD). UVB irradiation-mediated degeneration of the macular retinal pigment epithelial (RPE) cells is an important hallmark of AMD, which is along with the change in RPE autophagy. Thus, pharmacological manipulation of RPE autophagy may offer an alternative therapeutic target in AMD.more » Here, we found that epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, plays a regulatory role in UVB irradiation-induced autophagy in RPE cells. UVB irradiation results in a marked increase in the amount of LC3-II protein in a dose-dependent manner. EGCG administration leads to a significant reduction in the formation of LC3-II and autophagosomes. mTOR signaling activation is required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation is significantly impaired by rapamycin administration. Moreover, EGCG significantly alleviates the toxic effects of UVB irradiation on RPE cells in an autophagy-dependent manner. Collectively, our study reveals a novel role of EGCG in RPE autophagy. EGCG may be exploited as a potential therapeutic reagent for the treatment of pathological conditions associated with abnormal autophagy.« less

Photoprotective Potential of Penta-O-Galloyl-β-DGlucose by Targeting NF-κB and MAPK Signaling in UVB Radiation-Induced Human Dermal Fibroblasts and Mouse Skin.

PubMed

Kim, Byung-Hak; Choi, Mi Sun; Lee, Hyun Gyu; Lee, Song-Hee; Noh, Kum Hee; Kwon, Sunho; Jeong, Ae Jin; Lee, Haeri; Yi, Eun Hee; Park, Jung Youl; Lee, Jintae; Joo, Eun Young; Ye, Sang-Kyu

2015-11-01

Exposure of the skin to ultraviolet radiation can cause skin damage with various pathological changes including inflammation. In the present study, we identified the skin-protective activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (pentagalloyl glucose, PGG) in ultraviolet B (UVB) radiation-induced human dermal fibroblasts and mouse skin. PGG exhibited antioxidant activity with regard to intracellular reactive oxygen species (ROS) generation as well as ROS and reactive nitrogen species (RNS) scavenging. Furthermore, PGG exhibited anti-inflammatory activity, inhibiting the activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, resulting in inhibition of the expression of pro-inflammatory mediators. Topical application of PGG followed by chronic exposure to UVB radiation in the dorsal skin of hairless mice resulted in a significant decrease in the progression of inflammatory skin damages, leading to inhibited activation of NF-κB signaling and expression of pro-inflammatory mediators. The present study demonstrated that PGG protected from skin damage induced by UVB radiation, and thus, may be a potential candidate for the prevention of environmental stimuli-induced inflammatory skin damage.

Altered DNA Methylation and Expression Profiles of 8-Oxoguanine DNA Glycosylase 1 in Lens Tissue from Age-related Cataract Patients.

PubMed

Wang, Yong; Li, Fei; Zhang, Guowei; Kang, Lihua; Qin, Bai; Guan, Huaijin

2015-01-01

Oxidative stress and DNA damage contribute to the pathogenesis of age-related cataract (ARC). Most oxidative DNA lesions are repaired via the base excision repair (BER) proteins including 8-oxoguanine DNA glycosylase 1 (OGG1). This study examined DNA methylation of CpG islands upstream of OGG1 and their relation to the gene expression in lens cortex from ARC patients. The clinical case-control study consisted of 15 cortical type of ARC patients and 15 age-matched non-ARC controls who received transparent lens extraction due to vitreoretinal diseases. OGG1 expression in lens cortex was analyzed by qRT-PCR and Western blot. The localization and the proportion of cells positive for OGG1 were determined by immunofluorescence. Bisulfite-sequencing PCR (BSP) was performed to evaluate the methylation status of CpG islands near OGG1 in DNA extracted from lens cortex. To test relationship between the methylation and the expression of the gene of interest, 5-Aza-2'-deoxycytidine (5-Aza-dC) was used to induce demethylation of cultured human lens epithelium B-3 (HLE B-3). To test the role of OGG1 in the repair of cellular damage, HLE B-3 was transfected with OGG1 vector, followed by ultraviolet radiation b (UVB) exposure to induce apoptosis. The mRNA and protein levels of OGG1 were significantly reduced in the lens cortex of ARC. Immunofluorescence showed that the proportion of OGG1-positive cells decreased significantly in ARC cortex in comparison with the control. The CpG island in first exon of OGG1 displayed hypermethylation in the DNA extracted from the lens cortex of ARC. Treatment of HLEB-3 cells with 5-Aza-dC upregulated OGG1 expression. UVB-induced apoptosis was attenuated after transfection with OGG1. A reduced OGG1 expression was correlated with hypermethylation of a CpG island of OGG1 in lens cortex of ARC. The role of epigenetic change in OGG1 gene in the susceptibility to oxidative stress induced cortical ARC is warranted to further study.

Protective effect of fermented Cyclopia intermedia against UVB-induced damage in HaCaT human keratinocytes.

PubMed

Im, A-Rang; Yeon, Sung Hum; Lee, Jung Seung; Um, Key An; Ahn, Young-Joon; Chae, Sungwook

2016-07-29

The fermented leaves and stems of Cyclopia intermedia are used to brew honeybush tea, a herbal tea indigenous to South Africa. The aim of this study was to evaluate the protective effect of fermented honeybush extracts (FH ex) and scale-up fermented honeybush extracts (SFH ex) against ultraviolet B (UVB)-induced damage in HaCaT keratinocytes. To this end, we examined UVB-induced cell viability, antioxidant enzymes, and inflammatory mediators in HaCaT cells. UVB significantly decreased HaCaT cell viability, whereas FH ex and SFH ex did not exhibit cytotoxic effects and increased the viability of the HaCaT cells. To further investigate the protective effects of FH ex on UVB-induced oxidative stress in HaCaT cells, the activities of superoxide dismutase (SOD), catalase (CAT), matrix metalloproteinases (MMPs), pro-inflammatory cytokines and skin barrier function in terms of involucrin, filaggrin, and loricrin were analyzed. UVB-induced treatment reduced the activity of antioxidant enzymes and skin barrier function, while FH ex or SFH ex increased their activity. These results suggest that FH ex exerted cytoprotective activity against UVB-induced oxidative stress in HaCaT cells through stimulation of antioxidant enzymes activities. Furthermore, FH ex and SFH ex suppressed the UVB-induced expression of inflammatory mediators, such as IL-1β, IL-6, and IL-8, at mRNA level together with down regulation of matrix metalloproteinase (MMPs). In addition, FH ex and SFH ex reversed the phosphorylation of mitogen-activated protein kinase (MAPK) induced by UVB-irradiation. Notably, FH ex and SFH ex markedly inhibited UVB-induced activation of ERK, p38, and JNK. Thus, this agent exhibits anti-oxidative and -inflammatory effects via lowering ROS production, suppressing p38, ERK, and JNK activation, and down-regulating expression of MMPs. These findings suggest that FH ex and SFH ex can be used as a skin anti-photoaging agent.

Photoactivated UVR8-COP1 Module Determines Photomorphogenic UV-B Signaling Output in Arabidopsis

PubMed Central

Ouyang, Xinhao; Chen, Liangbi; Deng, Xing Wang

2014-01-01

In Arabidopsis, ultraviolet (UV)-B-induced photomorphogenesis is initiated by a unique photoreceptor UV RESISTANCE LOCUS 8 (UVR8) which utilizes its tryptophan residues as internal chromophore to sense UV-B. As a result of UV-B light perception, the UVR8 homodimer shaped by its arginine residues undergoes a conformational switch of monomerization. Then UVR8 associates with the CONSTITUTIVELY PHOTOMORPHOGENIC 1-SUPPRESSOR OF PHYA (COP1-SPA) core complex(es) that is released from the CULLIN 4-DAMAGED DNA BINDING PROTEIN 1 (CUL4-DDB1) E3 apparatus. This association, in turn, causes COP1 to convert from a repressor to a promoter of photomorphogenesis. It is not fully understood, however, regarding the biological significance of light-absorbing and dimer-stabilizing residues for UVR8 activity in photomorphogenic UV-B signaling. Here, we take advantage of transgenic UVR8 variants to demonstrate that two light-absorbing tryptophans, W233 and W285, and two dimer-stabilizing arginines, R286 and R338, play pivotal roles in UV-B-induced photomorphogenesis. Mutation of each residue results in alterations in UV-B light perception, UVR8 monomerization and UVR8-COP1 association in response to photomorphogenic UV-B. We also identify and functionally characterize two constitutively active UVR8 variants, UVR8W285A and UVR8R338A, whose photobiological activities are enhanced by the repression of CUL4, a negative regulator in this pathway. Based on our molecular and biochemical evidence, we propose that the UVR8-COP1 affinity in plants critically determines the photomorphogenic UV-B signal transduction coupling with UVR8-mediated UV-B light perception. PMID:24651064

Rapamycin Protects Skin Fibroblasts from Ultraviolet B-Induced Photoaging by Suppressing the Production of Reactive Oxygen Species.

PubMed

Qin, Dengke; Ren, Runjian; Jia, Chuanlong; Lu, Yongzhou; Yang, Qingjian; Chen, Liang; Wu, Xinyuan; Zhu, Jingjing; Guo, Yu; Yang, Ping; Zhou, Yiqun; Zhu, Ningwen; Bi, Bo; Liu, Tianyi

2018-01-01

Ultraviolet B (UVB) irradiation alters multiple molecular pathways in the skin, thereby inducing skin photoaging. Murine dermal fibroblasts (MDFs) were subjected to a series of 4 sub-cytotoxic UVB doses (120 mJ/cm2), resulting in changes in cell shape, DNA damage, cell cycle arrest, extracellular matrix variations, reactive oxygen species (ROS) generation, and alterations in major intracellular antioxidant and cellular autophagy levels. Rapamycin (RAPA) is a new macrolide immunosuppressive agent that is primarily used in oncology, cardiology, and transplantation medicine and has been found to extend the lifespan of genetically heterogeneous mice. Several studies have shown that RAPA may have anti-aging effects in cells and organisms. Thus, in this study, we explored the effects and mechanisms of RAPA against the photoaging process using a well-established cellular photoaging model. We developed a stress-induced premature senescence (SIPS) model through repeated exposure of MDFs to ultraviolet B (UVB) irradiation. The cells were cultured in the absence or presence of RAPA for 48 h. Senescent phenotypes were assessed by examining cell viability, cell morphology, senescence-associated β-galactosidase (SA-β-gal) expression, cell cycle progression, intracellular ROS production, matrix metalloproteinase (MMP) synthesis and degradation, extracellular matrix (ECM) component protein expression, alterations in major intracellular antioxidant levels, and the cellular autophagy level. Compared with the UVB group, pretreatment with RAPA (5 µM) significantly decreased the staining intensity and percentage of SA-β-gal-positive cells and preserved the elongated cell shape. Moreover, cells pretreated with RAPA showed inhibition of the reduction in the type I collagen content by blocking the UVB-induced upregulation of MMP expression. RAPA also decreased photoaging cell cycle arrest and downregulated p53 and p21 expression. RAPA application significantly attenuated irradiation-induced ROS release by modulating intracellular antioxidants and increasing the autophagy level. Our study demonstrated that RAPA elicited oxidative damage in vitro by reducing ROS accumulation in photoaged fibroblasts. The anti-aging effect can be attributed to the maintenance of normal antioxidant and cellular autophagy levels. However, determination of the definitive mechanism requires further study. © 2018 The Author(s). Published by S. Karger AG, Basel.

Mitochondrial telomerase reverse transcriptase binds to and protects mitochondrial DNA and function from damage.

PubMed

Haendeler, Judith; Dröse, Stefan; Büchner, Nicole; Jakob, Sascha; Altschmied, Joachim; Goy, Christine; Spyridopoulos, Ioakim; Zeiher, Andreas M; Brandt, Ulrich; Dimmeler, Stefanie

2009-06-01

The enzyme telomerase and its catalytic subunit the telomerase reverse transcriptase (TERT) are important for maintenance of telomere length in the nucleus. Recent studies provided evidence for a mitochondrial localization of TERT. Therefore, we investigated the exact localization of TERT within the mitochondria and its function. Here, we demonstrate that TERT is localized in the matrix of the mitochondria. TERT binds to mitochondrial DNA at the coding regions for ND1 and ND2. Binding of TERT to mitochondrial DNA protects against ethidium bromide-induced damage. TERT increases overall respiratory chain activity, which is most pronounced at complex I and dependent on the reverse transcriptase activity of the enzyme. Moreover, mitochondrial reactive oxygen species are increased after genetic ablation of TERT by shRNA. Mitochondrially targeted TERT and not wild-type TERT revealed the most prominent protective effect on H(2)O(2)-induced apoptosis. Lung fibroblasts from 6-month-old TERT(-/-) mice (F2 generation) showed increased sensitivity toward UVB radiation and heart mitochondria exhibited significantly reduced respiratory chain activity already under basal conditions, demonstrating the protective function of TERT in vivo. Mitochondrial TERT exerts a novel protective function by binding to mitochondrial DNA, increasing respiratory chain activity and protecting against oxidative stress-induced damage.

Nanoencapsulation of rice bran oil increases its protective effects against UVB radiation-induced skin injury in mice.

PubMed

Rigo, Lucas Almeida; da Silva, Cássia Regina; de Oliveira, Sara Marchesan; Cabreira, Thaíssa Nunes; de Bona da Silva, Cristiane; Ferreira, Juliano; Beck, Ruy Carlos Ruver

2015-06-01

Excessive UV-B radiation by sunlight produces inflammatory and oxidative damage of skin, which can lead to sunburn, photoaging, and cancer. This study evaluated whether nanoencapsulation improves the protective effects of rice bran oil against UVB radiation-induced skin damage in mice. Lipid-core nanocapsules containing rice bran oil were prepared, and had mean size around 200 nm, negative zeta potential (∼-9 mV), and low polydispersity index (<0.20). In order to allow application on the skin, a hydrogel containing the nanoencapsulated rice bran oil was prepared. This formulation was able to prevent ear edema induced by UVB irradiation by 60 ± 9%, when compared with a hydrogel containing LNC prepared with a mixture of medium chain triglycerides instead of rice bran oil. Protein carbonylation levels (biomarker of oxidative stress) and NF-κB nuclear translocation (biomarker of pro-inflammatory and carcinogenesis response) were reduced (81% and 87%, respectively) in animals treated with the hydrogel containing the nanoencapsulated rice bran oil. These in vivo results demonstrate the beneficial effects of nanoencapsulation to improve the protective properties of rice bran oil on skin damage caused by UVB exposure. Copyright © 2015 Elsevier B.V. All rights reserved.

The interplay of UV and cutaneous papillomavirus infection in skin cancer development

PubMed Central

Stephan, Sonja; Braspenning-Wesch, Ilona; Mikulec, Julita; Niebler, Martina; Gröne, Hermann-Josef; Flechtenmacher, Christa; Akgül, Baki

2017-01-01

Cutaneous human papillomaviruses (HPVs) are considered as cofactors for non-melanoma skin cancer (NMSC) development, especially in association with UVB. Extensively studied transgenic mouse models failed to mimic all aspects of virus-host interactions starting from primary infection to the appearance of a tumor. Using the natural model Mastomys coucha, which reflects the human situation in many aspects, we provide the first evidence that only UVB and Mastomys natalensis papillomavirus (MnPV) infection strongly promote NMSC formation. Using UVB exposures that correspond to UV indices of different geographical regions, irradiated animals developed either well-differentiated keratinizing squamous cell carcinomas (SCCs), still supporting productive infections with high viral loads and transcriptional activity, or poorly differentiated non-keratinizing SCCs almost lacking MnPV DNA and in turn, early and late viral transcription. Intriguingly, animals with the latter phenotype, however, still showed strong seropositivity, clearly verifying a preceding MnPV infection. Of note, the mere presence of MnPV could induce γH2AX foci, indicating that viral infection without prior UVB exposure can already perturb genome stability of the host cell. Moreover, as shown both under in vitro and in vivo conditions, MnPV E6/E7 expression also attenuates the excision repair of cyclobutane pyrimidine dimers upon UVB irradiation, suggesting a viral impact on the DNA damage response. While mutations of Ras family members (e.g. Hras, Kras, and Nras) were absent, the majority of SCCs harbored—like in humans—Trp53 mutations especially at two hot-spots in the DNA-binding domain, resulting in a loss of function that favored tumor dedifferentiation, counter-selective for viral maintenance. Such a constellation provides a reasonable explanation for making continuous viral presence dispensable during skin carcinogenesis as observed in patients with NMSC. PMID:29190285

Assessment of DNA damage as a tool to measure UV-B tolerance in soybean lines differing in foliar flavonoid composition

USDA-ARS?s Scientific Manuscript database

Continued stratospheric ozone depletion and the resultant increase in ultraviolet-B radiation (UV-B) raises a concern for a potential decrease in crop yields and impacts on agricultural and natural ecosystems. Although the implementation of regulations that minimize inputs of chlorofluorocarbons in...

8-Oxo-2'-deoxyguanosine ameliorates UVB-induced skin damage in hairless mice by scavenging reactive oxygen species and inhibiting MMP expression.

PubMed

Lee, Jin-Ku; Ko, Seong-Hee; Ye, Sang-Kyu; Chung, Myung-Hee

2013-04-01

Skin is uniquely vulnerable to damage caused by reactive oxygen species (ROS), which are most commonly produced in response to ultraviolet (UV) light. ROS generated at injury sites play an important role in modulating the inflammatory response. Besides inhibiting Rac, 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) has also shown notable antioxidant action. We tested whether 8-oxo-dG could protect skin from UVB-induced damage by scavenging ROS. HaCaT cells and hairless mice were irradiated with 15 and 180 mJ/cm(2) narrow-spectrum UVB, respectively. ROS generation was detected through incubation with DCFDA and confocal microscopy. Western blot analyses and immunohistochemistry were performed to verify the activities of ERK, JNK, p38, ATF-2, and c-Jun, and the expression of matrix metalloproteinases (MMPs), in UVB-irradiated HaCaT cells and murine skin. Hydrogen peroxide production and protein carbonyl concentrations were measured in UVB-damaged mouse skin. MMP-1 and MMP-9 expression in UVB-irradiated HaCaT cells was measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). In UVB-irradiated HaCaT cells, 8-oxo-dG inhibited ROS production, subsequent activation of mitogen-activated protein kinase (MAPK), ATF-2, and c-Jun, and MMP expression. It also prevented UV-induced skin reactions in hairless mice, inhibiting the increase in protein carbonyl content, activation of MAPKs, ATF-2, and c-Jun, the increases in MMP-9 and -13 expression, and epidermal hyperplasia. 8-oxo-dG can be considered an endogenous antioxidant and its potent antioxidant activity might be a beneficial property that could be exploited to protect skin from ROS-associated photodamage. Copyright © 2013. Published by Elsevier Ireland Ltd.

Plant extracts and natural compounds used against UVB-induced photoaging.

PubMed

Cavinato, Maria; Waltenberger, Birgit; Baraldo, Giorgia; Grade, Carla V C; Stuppner, Hermann; Jansen-Dürr, Pidder

2017-08-01

Skin is continuously exposed to a variety of environmental stresses, including ultraviolet (UV) radiation. UVB is an inherent component of sunlight that crosses the epidermis and reaches the upper dermis, leading to increased oxidative stress, activation of inflammatory response and accumulation of DNA damage among other effects. The increase in UVB radiation on earth due to the destruction of stratospheric ozone poses a major environmental threat to the skin, increasing the risk of damage with long-term consequences, such as photoaging and photocarcinogenesis. Extracts from plants and natural compounds have been historically used in traditional medicine in the form of teas and ointments but the effect of most of these compounds has yet to be verified. Regarding the increasing concern of the population with issues related to quality of life and appearance, the cosmetic market for anti-aging and photoprotective products based on natural compounds is continuously growing, and there is increasing requirement of expansion on research in this field. In this review we summarized the most current and relevant information concerning plant extracts and natural compounds that are able to protect or mitigate the deleterious effects caused by photoaging in different experimental models.

Skin protection against UVA-induced iron damage by multiantioxidants and iron chelating drugs/prodrugs.

PubMed

Reelfs, Olivier; Eggleston, Ian M; Pourzand, Charareh

2010-03-01

In humans, prolonged sunlight exposure is associated with various pathological states. The continuing drive to develop improved skin protection involves not only approaches to reduce DNA damage by solar ultraviolet B (UVB) but also the development of methodologies to provide protection against ultraviolet A (UVA), the oxidising component of sunlight. Furthermore identification of specific cellular events following ultraviolet (UV) irradiation is likely to provide clues as to the mechanism of the development of resulting pathologies and therefore strategies for protection. Our discovery that UVA radiation, leads to an immediate measurable increase in 'labile' iron in human skin fibroblasts and keratinocytes provides a new insight into UVA-induced skin damage, since iron is a catalyst of biological oxidations. The main purpose of this overview is to bring together some of the new findings related to mechanisms underlying UVA-induced iron release and to discuss novel approaches based on the use of multiantioxidants and light-activated caged-iron chelators for efficient protection of skin cells against UVA-induced iron damage.

DNA damage in lens epithelium of cataract patients in vivo and ex vivo.

PubMed

Øsnes-Ringen, Oyvind; Azqueta, Amaia O; Moe, Morten C; Zetterström, Charlotta; Røger, Magnus; Nicolaissen, Bjørn; Collins, Andrew R

2013-11-01

DNA damage has been described in the human cataractous lens epithelium, and oxidative stress generated by UV radiation and endogenous metabolic processes has been suggested to play a significant role in the pathogenesis of cataract. In this study, the aim was to explore the quality and relative quantity of DNA damage in lens epithelium of cataract patients in vivo and after incubation in a cell culture system. Capsulotomy specimens were analysed, before and after 1 week of ex vivo cultivation, using the comet assay to measure DNA strand breaks, oxidized purine and pyrimidine bases and UV-induced cyclobutane pyrimidine dimers. DNA strand breaks were barely detectable, oxidized pyrimidines and pyrimidine dimers were present at low levels, whereas there was a relatively high level of oxidized purines, which further increased after cultivation. The observed levels of oxidized purines in cataractous lens epithelium may support a theory consistent with light damage and oxidative stress as mediators of molecular damage to the human lens epithelium. Damage commonly associated with UV-B irradiation was relatively low. The levels of oxidized purines increased further in a commonly used culture system. This is of interest considering the importance and versatility of ex vivo systems in studies exploring the pathogenesis of cataract. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

Solar UV-B radiation and ethylene play a key role in modulating effective defenses against Anticarsia gemmatalis larvae in field-grown soybean.

PubMed

Dillon, Francisco M; Tejedor, M Daniela; Ilina, Natalia; Chludil, Hugo D; Mithöfer, Axel; Pagano, Eduardo A; Zavala, Jorge A

2018-02-01

Solar UV-B radiation has been reported to enhance plant defenses against herbivore insects in many species. However, the mechanism and traits involved in the UV-B mediated increment of plant resistance are unknown in crops species, such as soybean. Here, we studied defense-related responses in undamaged and Anticarsia gemmatalis larvae-damaged leaves of two soybean cultivars grown under attenuated or full solar UV-B radiation. We determined changes in jasmonates, ethylene (ET), salicylic acid, trypsin protease inhibitor activity, flavonoids, and mRNA expression of genes related with defenses. ET emission induced by Anticarsia gemmatalis damage was synergistically increased in plants grown under solar UV-B radiation and was positively correlated with malonyl genistin concentration, trypsin proteinase inhibitor activity and expression of IFS2, and the pathogenesis protein PR2, while was negatively correlated with leaf consumption. The precursor of ET, aminocyclopropane-carboxylic acid, applied exogenously to soybean was sufficient to strongly induce leaf isoflavonoids. Our results showed that in field-grown soybean isoflavonoids were regulated by both herbivory and solar UV-B inducible ET, whereas flavonols were regulated by solar UV-B radiation only and not by herbivory or ET. Our study suggests that, although ET can modulate UV-B-mediated priming of inducible plant defenses, some plant defenses, such as isoflavonoids, are regulated by ET alone. © 2017 John Wiley & Sons Ltd.

Solar UV-B radiation modulates chemical defenses against Anticarsia gemmatalis larvae in leaves of field-grown soybean.

PubMed

Dillon, Francisco M; Chludil, Hugo D; Zavala, Jorge A

2017-09-01

Although it is well known that solar ultraviolet B (UV-B) radiation enhances plant defenses, there is less knowledge about traits that define insect resistance in field-grown soybean. Here we study the effects of solar UV-B radiation on: a) the induction of phenolic compounds and trypsin proteinase inhibitors (TPI) in soybean undamaged leaves or damaged by Anticarsia gemmatalis neonates during six days, and b) the survival and mass gain of A. gemmatalis larvae that fed on soybean foliage. Two soybean cultivars (cv.), Charata and Williams, were grown under plastic with different transmittance to solar UV-B radiation, which generated two treatments: ambient UV-B (UVB+) and reduced UV-B (UVB-) radiation. Solar UV-B radiation decreased survivorship by 30% and mass gain by 45% of larvae that fed on cv. Charata, but no effect was found in those larvae that fed on cv. Williams. TPI activity and malonyl genistin were induced by A. gemmatalis damage in both cultivars, but solar UV-B radiation and damage only synergistically increased the induction of these compounds in cv. Williams. Although TPI activity and genistein derivatives were induced by herbivory, these results did not explain the differences found in survivorship and mass gain of larvae that fed on cv. Charata. However, we found a positive association between lower larval performance and the presence of two quercetin triglycosides and a kaempferol triglycoside in foliage of cv. Charata, which were identified by HPLC-DAD/MS 2 . We conclude that exclusion of solar UV-B radiation reduce resistance to A. gemmatalis, due to a reduction in flavonol concentration in a cultivar that has low levels of genistein derivatives like cv. Charata. Copyright © 2017 Elsevier Ltd. All rights reserved.

Responses of He-Ne laser on agronomic traits and the crosstalk between UVR8 signaling and phytochrome B signaling pathway in Arabidopsis thaliana subjected to supplementary ultraviolet-B (UV-B) stress.

PubMed

Gao, Limei; Li, Yongfeng; Shen, Zhihua; Han, Rong

2018-05-01

UV-B acclimation effects and UV-B damage repair induced by a 632.8-nm He-Ne laser were investigated in Arabidopsis thaliana plants in response to supplementary UV-B stress. There was an increasing trend in growth parameters in the combination-treated plants with He-Ne laser and UV-B light compared to those stressed with enhanced UV-B light alone during different developmental stages of plants. The photosynthetic efficiency (Pn) and survival rates of seedlings were significantly higher in the combination treatments than UV-B stress alone. The expression of UVR8, phytochrome B (PhyB), and their mediated signal responsive genes such as COP1, HY5, and CHS were also significantly upregulated in plants with the laser irradiation compared with other groups without the laser. Levels of flavonol accumulation in leaves and capsule yield of He-Ne laser-treated plants were increased. The phyB-9 mutants were more sensitive to enhanced UV-B stress and had no obvious improvements in plant phenotypic development and physiological damage caused by enhanced UV-B stress after He-Ne laser irradiation. Our results suggested that UVR8 and its mediated signaling pathway via interaction with COP1 can be induced by He-Ne laser, and these processes were dependent on cytoplasmic PhyB levels in plant cells, which might be one of the most important mechanisms of He-Ne laser on UV-B protection and UV-B damage repair. These current data have also elucidated that the biostimulatory effects of He-Ne laser on Arabidopsis thaliana plants would happen not only during the early growth stage but also during the entire late developmental stage.

Epidermal Rac1 regulates the DNA damage response and protects from UV-light-induced keratinocyte apoptosis and skin carcinogenesis

PubMed Central

Deshmukh, Jayesh; Pofahl, Ruth; Haase, Ingo

2017-01-01

Non-melanoma skin cancer (NMSC) is the most common type of cancer. Increased expression and activity of Rac1, a small Rho GTPase, has been shown previously in NMSC and other human cancers; suggesting that Rac1 may function as an oncogene in skin. DMBA/TPA skin carcinogenesis studies in mice have shown that Rac1 is required for chemically induced skin papilloma formation. However, UVB radiation by the sun, which causes DNA damage, is the most relevant cause for NMSC. A potential role of Rac1 in UV-light-induced skin carcinogenesis has not been investigated so far. To investigate this, we irradiated mice with epidermal Rac1 deficiency (Rac1-EKO) and their controls using a well-established protocol for long-term UV-irradiation. Most of the Rac1-EKO mice developed severe skin erosions upon long-term UV-irradiation, unlike their controls. These skin erosions in Rac1-EKO mice healed subsequently. Surprisingly, we observed development of squamous cell carcinomas (SCCs) within the UV-irradiation fields. This shows that the presence of Rac1 in the epidermis protects from UV-light-induced skin carcinogenesis. Short-term UV-irradiation experiments revealed increased UV-light-induced apoptosis of Rac1-deficient epidermal keratinocytes in vitro as well as in vivo. Further investigations using cyclobutane pyrimidine dimer photolyase transgenic mice revealed that the observed increase in UV-light-induced keratinocyte apoptosis in Rac1-EKO mice is DNA damage dependent and correlates with caspase-8 activation. Furthermore, Rac1-deficient keratinocytes showed reduced levels of p53, γ-H2AX and p-Chk1 suggesting an attenuated DNA damage response upon UV-irradiation. Taken together, our data provide direct evidence for a protective role of Rac1 in UV-light-induced skin carcinogenesis and keratinocyte apoptosis probably through regulating mechanisms of the DNA damage response and repair pathways. PMID:28277539

Epidermal Rac1 regulates the DNA damage response and protects from UV-light-induced keratinocyte apoptosis and skin carcinogenesis.

PubMed

Deshmukh, Jayesh; Pofahl, Ruth; Haase, Ingo

2017-03-09

Non-melanoma skin cancer (NMSC) is the most common type of cancer. Increased expression and activity of Rac1, a small Rho GTPase, has been shown previously in NMSC and other human cancers; suggesting that Rac1 may function as an oncogene in skin. DMBA/TPA skin carcinogenesis studies in mice have shown that Rac1 is required for chemically induced skin papilloma formation. However, UVB radiation by the sun, which causes DNA damage, is the most relevant cause for NMSC. A potential role of Rac1 in UV-light-induced skin carcinogenesis has not been investigated so far. To investigate this, we irradiated mice with epidermal Rac1 deficiency (Rac1-EKO) and their controls using a well-established protocol for long-term UV-irradiation. Most of the Rac1-EKO mice developed severe skin erosions upon long-term UV-irradiation, unlike their controls. These skin erosions in Rac1-EKO mice healed subsequently. Surprisingly, we observed development of squamous cell carcinomas (SCCs) within the UV-irradiation fields. This shows that the presence of Rac1 in the epidermis protects from UV-light-induced skin carcinogenesis. Short-term UV-irradiation experiments revealed increased UV-light-induced apoptosis of Rac1-deficient epidermal keratinocytes in vitro as well as in vivo. Further investigations using cyclobutane pyrimidine dimer photolyase transgenic mice revealed that the observed increase in UV-light-induced keratinocyte apoptosis in Rac1-EKO mice is DNA damage dependent and correlates with caspase-8 activation. Furthermore, Rac1-deficient keratinocytes showed reduced levels of p53, γ-H2AX and p-Chk1 suggesting an attenuated DNA damage response upon UV-irradiation. Taken together, our data provide direct evidence for a protective role of Rac1 in UV-light-induced skin carcinogenesis and keratinocyte apoptosis probably through regulating mechanisms of the DNA damage response and repair pathways.

Mutagenesis during plant responses to UVB radiation.

PubMed

Holá, M; Vágnerová, R; Angelis, K J

2015-08-01

We tested an idea that induced mutagenesis due to unrepaired DNA lesions, here the UV photoproducts, underlies the impact of UVB irradiation on plant phenotype. For this purpose we used protonemal culture of the moss Physcomitrella patens with 50% of apical cells, which mimics actively growing tissue, the most vulnerable stage for the induction of mutations. We measured the UVB mutation rate of various moss lines with defects in DNA repair (pplig4, ppku70, pprad50, ppmre11), and in selected clones resistant to 2-Fluoroadenine, which were mutated in the adenosine phosphotrasferase gene (APT), we analysed induced mutations by sequencing. In parallel we followed DNA break repair and removal of cyclobutane pyrimidine dimers with a half-life τ = 4 h 14 min determined by comet assay combined with UV dimer specific T4 endonuclease V. We show that UVB induces massive, sequence specific, error-prone bypass repair that is responsible for a high mutation rate owing to relatively slow, though error-free, removal of photoproducts by nucleotide excision repair (NER). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Response of Two Legumes to Two Ultraviolet-B Radiation Regimes

NASA Technical Reports Server (NTRS)

Levy, Daniel L.; Skiles, J. W.

2000-01-01

Depletion of the stratospheric ozone layer has been directly linked to increased levels of UV radiation at the earth's surface. The purpose of this study was to evaluate the responses of soybean (Glycine max) and alfalfa (Medicago sativa) to increased UV-B radiation (280-320 nm). Soybean and alfalfa were grown successively in a growth chamber that provided UV-B intensities 45% above nominal summer field levels. Mylar-D (UVB opaque) and mono-acetate (UV-B transparent) films were used to establish the two UV-B treatments. Soybean grown under increased UV showed 21% smaller internodal lengths and higher concentrations of UV-B absorbing pigments (i.e. flavonoids) compared to plants grown under no UV. Significant results for alfalfa included 22% greater leaf flavonoid concentration under increased UV, 14% greater leaf chlorophyll concentration under no UV, and 32% greater above-ground biomass with no UV. These leguminous species possess mechanisms that protect against UV-B damage as indicated by increases in foliar concentrations of UV-B absorbing compounds. Alfalfa appears to be more sensitive to UV-B damage than soybean. Remote sensing of chlorophyll fluorescence may offer a means of monitoring UV-induced plant stress and damage.

Protective effect of Schizandrin B against damage of UVB irradiated skin cells depend on inhibition of inflammatory pathways.

PubMed

Gao, Chenguang; Chen, Hong; Niu, Cong; Hu, Jie; Cao, Bo

2017-01-02

Schizandrin B is extracted from Schisandra chinensis (Turcz.) Baill. This study evaluated the photoprotective effect of Schizandrin B on oxidative stress injury of the skin caused by UVB-irradiation and the molecular mechanism of the photoprotective effect of Schizandrin B, and we firstly found that Schizandrin B could block Cox-2, IL-6 and IL-18 signal pathway to protect damage of skin cells given by UVB-irradiation. In the research, we found that Schizandrin B can attenuate the UVB-induced toxicity on keratinocytes and dermal fibroblasts in human body, and can outstandingly eliminated intracellular ROS produced by UVB-irradiation. These results demonstrate that Schizandrin B can regulate the function of decreasing intracellular SOD's activity and increasing the expression level of MDA in HaCaT cells result from the guidance of UVB, and it markedly reduced the production of inflammatory factors such as Cox-2, IL-6 or IL-18, decreased the expression level of MMP-1, and interdicted degradation process of collagens in UVB-radiated cells. Therefore, skin keratinocytes can be effectively protected from UVB-radiated damage by Schizandrin B, and UVB-irradiation caused inflammatory responses can be inhibited by attenuating process of ROS generating.

Protection against UVB-induced oxidative stress in human skin cells and skin models by methionine sulfoxide reductase A.

PubMed

Pelle, Edward; Maes, Daniel; Huang, Xi; Frenkel, Krystyna; Pernodet, Nadine; Yarosh, Daniel B; Zhang, Qi

2012-01-01

Environmental trauma to human skin can lead to oxidative damage of proteins and affect their activity and structure. When methionine becomes oxidized to its sulfoxide form, methionine sulfoxide reductase A (MSRA) reduces it back to methionine. We report here the increase in MSRA in normal human epidermal keratinocytes (NHEK) after ultraviolet B (UVB) radiation, as well as the reduction in hydrogen peroxide levels in NHEK pre-treated with MSRA after exposure. Further, when NHEK were pre-treated with a non-cytotoxic pentapeptide containing methionine sulfoxide (metSO), MSRA expression increased by 18.2%. Additionally, when the media of skin models were supplemented with the metSO pentapeptide and then exposed to UVB, a 31.1% reduction in sunburn cells was evident. We conclude that the presence of MSRA or an externally applied peptide reduces oxidative damage in NHEK and skin models and that MSRA contributes to the protection of proteins against UVB-induced damage in skin.

Extract of Punica granatum inhibits skin photoaging induced by UVB irradiation.

PubMed

Park, Hye Min; Moon, Eunjung; Kim, Ae-Jung; Kim, Mi Hyun; Lee, Sanghee; Lee, Jung Bok; Park, Yong Kon; Jung, Hyuk-Sang; Kim, Yoon-Bum; Kim, Sun Yeou

2010-03-01

Punica granatum (pomegranate) is kind of a fruit consumed fresh or in beverage. It has been widely used in traditional medicine in various parts of the world. In this study, we examined the efficacy of a Punica granatum (PG) extract in protecting skin against UVB-induced damage using cultured human skin fibroblasts. A Korean red PG sample was used, and its effects classified according to if the PG source originated from the rind, seed and fruit. The polyphenol content of PG, which is known to prevent other adverse cutaneous effects of UV irradiation, was measured by GC-MS. The protective effects of PG on UVB-induced skin photoaging were examined by determining the level of procollagen type I and MMP-1 after UVB irradiation. Based on the GC-MS quantitative analysis, catechin, quercetin, kaempferol, and equol were the predominant compounds detected in PG. In the changes of expression of procollagen type I and MMP-1 in UV irradiated human skin fibroblasts treated PG, especially extract prepared from rind, the synthesis of collagen was increased and the expression of MMP-1 was decreased. The major polyphenols in PG, particularly catechin, play a significant role in its photoprotective effects on UVB-induced skin damage.

[The role of free radicals in the UV-induced skin damage. Photo-aging].

PubMed

Emri, Gabriella; Horkay, Irén; Remenyik, Eva

2006-04-23

The natural (intrinsic) ageing of the skin is enhanced by environmental factors (extrinsic ageing). One of the most important exogenous factors is the solar UV exposure, which results in photo-aging. Besides this, epidemiological and experimental data show a rapid increase in the incidence of human skin cancers, which is also in relation to the increased sunlight exposure of the skin. In the background of these processes there are cell biological effects, photochemical reactions, membrane receptor changes, lipid- and protein modifications, DNA-damage induced by UV. The qualities and quantities of them are wavelength dependent. The UVB photons are absorbed mostly by the DNA of the epidermal keratinocytes, therefore this spectrum is more relevant for photocarcinogenesis. The effect of UVA-irradiation is mainly manifested in the induction of free radicals, which have not only DNA-damaging, but also immunomodulating effect, which also can influence on tumour development. Furthermore, the free radicals cause dermal connective tissue damage as well via activating transcription factors, inducing matrix metalloproteinases, diminishing the procollagen I and fibrillin-1 synthesis. These processes are augmented by mitochondrial DNA mutations, protein oxidation, apoptosis induction. Therefore the enzymes neutralising free radicals and antioxidant molecules, respectively, have an important role in the defence mechanisms. In the therapy of photo-aging the local retinoids lived up to expectations, but the clinical effectiveness of antioxidant vitamins is lower than expected. The most important factor in the prevention of the photo-aging and photocarcinogenesis is the sun protection at present.

Nitric oxide alleviates oxidative damage induced by enhanced ultraviolet-B radiation in cyanobacterium.

PubMed

Xue, Lingui; Li, Shiweng; Sheng, Hongmei; Feng, Huyuan; Xu, Shijian; An, Lizhe

2007-10-01

To study the role of nitric oxide (NO) on enhanced ultraviolet-B (UV-B) radiation (280-320 nm)-induced damage of Cyanobacterium, the growth, pigment content, and antioxidative activity of Spirulina platensis-794 cells were investigated under enhanced UV-B radiation and under different chemical treatments with or without UV-B radiation for 6 h. The changes in chlorophyll-a, malondialdehyde content, and biomass confirmed that 0.5 mM: sodium nitroprusside (SNP), a donor of nitric oxide (NO), could markedly alleviate the damage caused by enhanced UV-B. Specifically, the biomass and the chlorophyll-a content in S. platensis-794 cells decreased 40% and 42%, respectively under enhanced UV-B stress alone, but they only decreased 10% and 18% in the cells treated with UV-B irradiation and 0.5 mM: SNP. Further experiments suggested that NO treatment significantly increased the activities of superoxide dismutase (SOD) and catalase (CAT), and decreased the accumulation of O (2)(-) in enhanced UV-B-irradiated cells. SOD and CAT activity increased 0.95- and 6.73-fold, respectively. The accumulation of reduced glutathione (GSH) increased during treatment with 0.5 mM: SNP in normal S. platensis cells, but SNP treatment could inhibit the increase of GSH in enhanced UV-B-stressed S. platensis cells. Thus, these results suggest that NO can strongly alleviate oxidative damage caused by UV-B stress by increasing the activities of SOD, peroxidase, CAT, and the accumulation of GSH, and by eliminating O (2)(-) in S. platensis-794 cells. In addition, the difference of NO origin between plants and cyanobacteria are discussed.

UV-B Radiation Contributes to Amphibian Population Declines

NASA Astrophysics Data System (ADS)

Blaustein, Andrew

2007-05-01

UV-B (280-315 nm) radiation is the most significant biologically damaging radiation at the terrestrial surface. At the organismal level, UV-B radiation can slow growth rates, cause immune dysfunction and result in sublethal damage. UV-B radiation can lead to mutations and cell death. Over evolutionary time, UV radiation has been an important stressor on living organisms. Natural events, including impacts from comets and asteroids, volcanic activity, supernova explosions and solar flares, can cause large-scale ozone depletion with accompanying increases in UV radiation. However, these natural events are transient. Moreover, the amount of ozone damage due to natural events depends upon a number of variables, including the magnitude of the event. This is different from modern-day human-induced production of chlorofluorocarbons (CFCs) and other chemicals that deplete stratospheric ozone continuously, resulting in long-term increases in UV-B radiation at the surface of the earth. We will briefly review the effects of UV-B exposure in one group of aquatic organisms_amphibians. UV-B has been implicated as a possible factor contributing to global declines and range reductions in amphibian populations.

Preventive effects of β-thujaplicin against UVB-induced MMP-1 and MMP-3 mRNA expressions in skin fibroblasts.

PubMed

Cherng, Jong Yuh; Chen, Li Yin; Shih, Mei Fen

2012-01-01

Solar UV radiation damages human skin by affecting skin tone and resiliency and leads to premature aging (photoaging). The skin damage is caused by the activation of the AP-1 transcription factor, which increases matrix metalloproteinase (MMP) expression and collagen degradation. An increase of interleukin (IL)-6 is also correlated with the activation of MMP-1 expression. β-thujaplicin has shown both acaricidal and antimicrobial activities. Also, β-thujaplicin has been shown to be protective against apoptosis due to the oxidative effects of UV irradiation. However, the effect of β-thujaplicin on UVB-induced MMPs had not been investigated. In this study, after UVB exposure, MMP-1 and IL-6 production in human skin fibroblasts was examined in the presence of β-thujaplicin, vitamin C, and vitamin E. The expression of MMP-1, MMP-3, tissue inhibitor of metalloproteinase (TIMP-1, TIMP-3) and procollagen mRNA was also investigated. Results showed that UVB-induced MMP-1 production was suppressed by the β-thujaplicin treatment in a dose-dependent manner, but not by vitamin C and vitamin E. β-thujaplicin also prevented the up-regulation of MMP-1 and MMP-3 mRNA. Moreover, the UVB-suppressed procollagen gene expression was restored to normal by β-thujaplicin. Neither UVB nor β-thujaplicin affected the mRNA expression of TIMP-1 and TIMP-3. The IL-6 production induced by UVB was lower in β-thujaplicin treated fibroblasts than in the controls. In conclusion, this study shows the capability of β-thujaplicin in preventing MMP-1 production due to UVB irradiation via inhibition of MMP gene expression. Importantly, the UVB-suppressed procollagen gene expression can be restored to normal by β-thujaplicin. These findings indicate that β-thujaplicin is a promising and potent agent to inhibit UVB-induced MMP-1 and MMP-3 gene expression in skin fibroblasts.

UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling

PubMed Central

Moore, Carlene; Cevikbas, Ferda; Pasolli, H. Amalia; Chen, Yong; Kong, Wei; Kempkes, Cordula; Parekh, Puja; Lee, Suk Hee; Kontchou, Nelly-Ange; Yeh, Iwei; Jokerst, Nan Marie; Fuchs, Elaine; Steinhoff, Martin; Liedtke, Wolfgang B.

2013-01-01

At our body surface, the epidermis absorbs UV radiation. UV overexposure leads to sunburn with tissue injury and pain. To understand how, we focus on TRPV4, a nonselective cation channel highly expressed in epithelial skin cells and known to function in sensory transduction, a property shared with other transient receptor potential channels. We show that following UVB exposure mice with induced Trpv4 deletions, specifically in keratinocytes, are less sensitive to noxious thermal and mechanical stimuli than control animals. Exploring the mechanism, we find that epidermal TRPV4 orchestrates UVB-evoked skin tissue damage and increased expression of the proalgesic/algogenic mediator endothelin-1. In culture, UVB causes a direct, TRPV4-dependent Ca2+ response in keratinocytes. In mice, topical treatment with a TRPV4-selective inhibitor decreases UVB-evoked pain behavior, epidermal tissue damage, and endothelin-1 expression. In humans, sunburn enhances epidermal expression of TRPV4 and endothelin-1, underscoring the potential of keratinocyte-derived TRPV4 as a therapeutic target for UVB-induced sunburn, in particular pain. PMID:23929777

UVB radiation generates sunburn pain and affects skin by activating epidermal TRPV4 ion channels and triggering endothelin-1 signaling.

PubMed

Moore, Carlene; Cevikbas, Ferda; Pasolli, H Amalia; Chen, Yong; Kong, Wei; Kempkes, Cordula; Parekh, Puja; Lee, Suk Hee; Kontchou, Nelly-Ange; Yeh, Iwei; Ye, Iwei; Jokerst, Nan Marie; Fuchs, Elaine; Steinhoff, Martin; Liedtke, Wolfgang B

2013-08-20

At our body surface, the epidermis absorbs UV radiation. UV overexposure leads to sunburn with tissue injury and pain. To understand how, we focus on TRPV4, a nonselective cation channel highly expressed in epithelial skin cells and known to function in sensory transduction, a property shared with other transient receptor potential channels. We show that following UVB exposure mice with induced Trpv4 deletions, specifically in keratinocytes, are less sensitive to noxious thermal and mechanical stimuli than control animals. Exploring the mechanism, we find that epidermal TRPV4 orchestrates UVB-evoked skin tissue damage and increased expression of the proalgesic/algogenic mediator endothelin-1. In culture, UVB causes a direct, TRPV4-dependent Ca(2+) response in keratinocytes. In mice, topical treatment with a TRPV4-selective inhibitor decreases UVB-evoked pain behavior, epidermal tissue damage, and endothelin-1 expression. In humans, sunburn enhances epidermal expression of TRPV4 and endothelin-1, underscoring the potential of keratinocyte-derived TRPV4 as a therapeutic target for UVB-induced sunburn, in particular pain.

Repression of Growth Regulating Factors by the MicroRNA396 Inhibits Cell Proliferation by UV-B Radiation in Arabidopsis Leaves[C][W

PubMed Central

Casadevall, Romina; Rodriguez, Ramiro E.; Debernardi, Juan M.; Palatnik, Javier F.; Casati, Paula

2013-01-01

Because of their sessile lifestyle, plants are continuously exposed to solar UV-B radiation. Inhibition of leaf growth is one of the most consistent responses of plants upon exposure to UV-B radiation. In this work, we investigated the role of GROWTH-REGULATING FACTORs (GRFs) and of microRNA miR396 in UV-B–mediated inhibition of leaf growth in Arabidopsis thaliana plants. We demonstrate that miRNA396 is upregulated by UV-B radiation in proliferating tissues and that this induction is correlated with a decrease in GRF1, GRF2, and GRF3 transcripts. Induction of miR396 results in inhibition of cell proliferation, and this outcome is independent of the UV-B photoreceptor UV resistance locus 8, as well as ATM AND RAD3–RELATED and the mitogen-activated protein kinase MPK6, but is dependent on MPK3. Transgenic plants expressing an artificial target mimic directed against miR396 (MIM396) with a decrease in the endogenous microRNA activity or plants expressing miR396-resistant copies of several GRFs are less sensitive to this inhibition. Consequently, at intensities that can induce DNA damage in Arabidopsis plants, UV-B radiation limits leaf growth by inhibiting cell division in proliferating tissues, a process mediated by miR396 and GRFs. PMID:24076976

Protective Effect of Mangifera indica Linn., Cocos nucifera Linn., and Averrhoa carambola Linn. Extracts against Ultraviolet B-Induced Damage in Human Keratinocytes.

PubMed

Ronpirin, Chalinee; Pattarachotanant, Nattaporn; Tencomnao, Tewin

2016-01-01

This study was aimed at investigating the antioxidant activity of Mangifera indica Linn., Cocos nucifera Linn., and Averrhoa carambola Linn. and their biological effect on human keratinocytes affected by the ultraviolet B (UVB), a major cause of cell damage and skin cancer through induction of DNA damage, production of reactive oxygen species (ROS), and apoptosis. The richest antioxidant activity was found in ethanol fraction of M. indica (21.32 ± 0.66 mg QE/g dry weight), while the lowest one was found in aqueous fractions of M. indica and C. nucifera (1.76 ± 2.10 and 1.65 ± 0.38 mg QE/g dry weight, respectively). Ethanol and aqueous fractions of A. carambola (250 µg/mL) significantly reduced the number of apoptotic cells. The expression of cleaved caspase 3 in UVB-treated group was significantly greater than that in untreated group. Both fractions of A. carambola (50, 100, and 250 µg/mL) significantly decreased the expression of cleaved caspase 3. Regarding the induction of DNA repair, ethanol (100 and 250 µg/mL) and aqueous (50, 100 and 250 µg/mL) fractions of A. carambola significantly decreased the percentage of cyclobutane pyrimidine dimers (CPD). Taken together, our results suggest that both fractions of A. carambola may be potentially developed for dermal applications.

Polypeptide from Chlamys farreri inhibits UVB-induced apoptosis of HaCaT cells via iNOS/NO and HSP90

NASA Astrophysics Data System (ADS)

Zhang, Zhengyang; Liu, Xiaojin; Liu, Tuo; Yan, Lin; Wang, Yuejun; Wang, Chunbo

2009-09-01

Polypeptide from Chlamys farreri (PCF) is a novel marine bioactive product that was isolated from the gonochoric Chinese scallop Chlamys farreri, and was found to be an effective antioxidant in our recent studies. In this study, we investigated the effect of PCF on ultraviolet B (UVB)-induced apoptosis of HaCaT cells and the intracellular signaling pathways involved. Pretreatment with the inducible nitric oxide synthase (iNOS) inhibitor S-methylisothiourea sulfate inhibited UVB-induced apoptosis, indicating that iNOS and NO play important roles in apoptosis. On the other hand, the inhibition of UVB-induced apoptosis in the immortalized keratinocyte (HaCaT) cells by PCF was estimated using a DNA ladder. PCF treatment inhibited UVB-induced iNOS activation, as determined by RT-PCR, NO production, as determined by ESR, and up-regulated heat shock protein (HSP) 90 activation, as determined by Western blotting. Our results indicate that iNOS and NO are involved in UVB-induced apoptosis of HaCaT cells and the protective effect of PCF against UVB irradiation is exerted by suppressing the expression of iNOS, followed by inhibition of NO release and enhanced activation of HSP90.

Effect of UVB radiation exposure in the expression of genes and proteins related to apoptosis in freshwater prawn embryos.

PubMed

Schramm, Heloísa; Jaramillo, Michael L; Quadros, Thaline de; Zeni, Eliane C; Müller, Yara M R; Ammar, Dib; Nazari, Evelise M

2017-10-01

Our previous studies showed that embryos of the freshwater prawn Macrobrachium olfersii exposed to ultraviolet B (UVB) radiation exhibited DNA damage, excessive ROS production, mitochondrial dysfunction and increased hsp70 expression, which are able, independently or together, to induce apoptosis. Thus, we attempted to elucidate some key apoptosis-related genes (ARG) and apoptosis-related proteins (ARP) and their expression during different stages of embryonic development, as well as to characterize the chronology of ARG expression and ARP contents after UVB radiation insult. We demonstrate that p53, Bax and Caspase3 genes are active in the embryonic cells at early embryonic developmental stages, and that the Bcl2 gene is active from the mid-embryonic stage. After UVB radiation exposure, we found an increase in ARP such as p53 and Bak after 3h of exposure. Moreover, an increase in ARG transcript levels for p53, Bax, Bcl2 and Caspase3 was observed at 6h after UVB exposure. Then, after 12h of UVB radiation exposure, an increase in Caspase3 gene expression and protein was observed, concomitantly with an increased number of apoptotic cells. Our data reveal that ARG and ARP are developmentally regulated in embryonic cells of M. olfersii and that UVB radiation causes apoptosis after 12h of exposure. Overall, we demonstrate that embryonic cells of M. olfersii are able to active the cell machinery against environmental changes, such as increased incidence of UVB radiation in aquatic ecosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

A comparative study of baby immature and adult shoots of Aloe vera on UVB-induced skin photoaging in vitro.

PubMed

Hwang, Eunson; Kim, Su Hyeon; Lee, Sarah; Lee, Choong Hwan; Do, Seon-Gil; Kim, Jinwan; Kim, Sun Yeou

2013-12-01

Ultraviolet (UV) irradiation induces photo-damage of the skin, which in turn causes depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkle formations are associated with collagen synthesis and matrix metalloproteinase (MMP) expression. The production of type I procollagen is regulated by transforming growth factor-β1 (TGF-β1) expression; the activation of MMP is also correlated with an increase of interleukin-6 (IL-6). Aloe barbadensis M. (Aloe vera) is widely used in cosmetic and pharmaceutical products. In this study, we examined whether baby aloe shoot extract (BAE, immature aloe extract), which is from the one-month-old shoots of Aloe vera, and adult aloe shoot extract (AE), which is from the four-month-old shoots of Aloe vera, have a protective effect on UVB-induced skin photoaging in normal human dermal fibroblasts (NHDFs). The effects of BAE and AE on UVB-induced photoaging were tested by measuring the levels of reactive oxygen species, MMP-1, MMP-3, IL-6, type I procollagen, and TGF-β1 after UVB irradiation. We found that NHDF cells treated with BAE after UVB-irradiation suppressed MMP-1, MMP-3, and IL-6 levels compared to the AE-treated cells. Furthermore, BAE treatment elevated type I procollagen and TGF-β1 levels. Our results suggest that BAE may potentially protect the skin from UVB-induced damage more than AE. Copyright © 2013 John Wiley & Sons, Ltd.

Expression of Nudix hydrolase genes in barley under UV irradiation

NASA Astrophysics Data System (ADS)

Tanaka, Sayuri; Sugimoto, Manabu; Kihara, Makoto

Seed storage and cultivation should be necessary to self-supply foods when astronauts would stay and investigate during long-term space travel and habitation in the bases on the Moon and Mars. Thought the sunlight is the most importance to plants, both as the ultimate energy source and as an environmental signal regulating growth and development, UV presenting the sunlight can damage many aspects of plant processes at the physiological and DNA level. Especially UV-C, which is eliminated by the stratospheric ozone layer, is suspected to be extremely harmful and give a deadly injury to plants in space. However, the defense mechanism against UV-C irradiation damage in plant cells has not been clear. In this study, we investigated the expression of Nudix hydrolases, which defense plants from biotic / abiotic stress, in barley under UV irradiation. The genes encoding the amino acid sequences, which show homology to those of 28 kinds of Nudix hydrolases in Arabidopsis thaliana, were identified in the barley full-length cDNA library. BLAST analysis showed 14 kinds of barley genes (HvNUDX1-14), which encode the Nudix motif sequence. A phylogenetic tree showed that HvNUDX1, HvNUDX7, HvNUDX9 and HvNUDX11 belonged to the ADP-ribose pyrophosphohydrolase, ADP-sugar pyrophosphohydrolase, NAD(P)H pyrophosphohydrolase and FAD pyrophosphohydrolase subfamilies, respectively, HvNUDX3, HvNUDX6, and HvNUDX8 belonged to the Ap _{n}A pyrophosphohydrolase subfamilies, HvNUDX5 and HvNUDX14 belonged to the coenzyme A pyrophosphohydrolase subfamilies, HvNUDX12 and HvNUDX13 belonged to the Ap _{4}A pyrophosphohydrolase subfamilies. Induction of HvNUDX genes by UV-A (340nm), UV-B (312nm), and UV-C (260nm) were analyzed by quantitative RT-PCR. The results showed that HvNUDX4 was induced by UV-A and UV-B, HvNUDX6 was induced by UV-B and UV-C, and HvNUDX7 and HvNUDX14 were induced by UV-C, significantly. Our results suggest that the response of HvNUDXs to UV irradiation is different by UV wavelength, and UV-C induced 4 genes of HvNUDX.

Long non-coding RNA HULC promotes UVB-induced injury by up-regulation of BNIP3 in keratinocytes.

PubMed

Zhao, Li; Man, Yigang; Liu, Shumei

2018-08-01

Ultraviolet radiation b (UVB) is a common high-energy radiation which can lead to cell damage and even skin cancer. The mechanisms of lncRNAs in various diseases have attracted much attention of researchers. Herein, we investigated the effects and regulations of lncRNA highly up-regulated in liver cancer (HULC) on UVB-induced injury in HaCaT cells. The HaCaT cells were exposed to UVB at a wavelength of 280-320 nm. Cell viability was detected at different times (0, 3, 6, 12 and 24 h) after UVB treatment. Cells were transfected with sh-HULC, pc-HULC, sh-BNIP3 (Bcl-2 interacting protein 3) or pc-BNIP3, respectively. ZM 39,923 HCl was used as JAK/STAT(1/3) inhibitor. Cell viability and apoptosis were tested by trypan blue dye and flow cytometry analysis, respectively. The expression levels of autophagy-related factors were analyzed by Western blot assay. The expression changes of HULC and BNIP3 were measured by qRT-PCR. We found that UVB decreased cell viability, increased apoptosis and autophagy, and up-regulated the expression of HULC in HaCaT cells. Overexpression of HULC reduced cell viability, enhanced apoptosis and autophagy, and up-regulated BNIP3 expression by activating JAK/STAT(1/3) signaling pathway. Finally, BNIP3 suppression increased cell viability, reduced apoptosis and autophagy via the deactivation of mTOR signaling pathway. The results demonstrated that lncRNA HULC up-regulated BNIP3 and activated JAK/STAT(1/3) signaling pathway to accelerate UVB-induced cell damage in HaCaT cells. This study provides a possible target for the clinical treatment of UVB-induced keratinocyte injury. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Redox proteomic evaluation of oxidative modification and recovery in a 3D reconstituted human skin tissue model exposed to UVB.

PubMed

Dyer, J M; Haines, S R; Thomas, A; Wang, W; Walls, R J; Clerens, S; Harland, D P

2017-04-01

Exposure to UV in humans resulting in sunburn triggers a complex series of events that are a mix of immediate and delayed damage mediation and healing. While studies on the effects of UV exposure on DNA damage and repair have been reported, changes in the oxidative modification of skin proteins are poorly understood at the molecular level, despite the important role played by structural proteins in skin tissue, and the effect of the integrity of these proteins on skin appearance and health. Proteomic molecular mapping of oxidation was here applied to try to enhance understanding of skin damage and recovery from oxidative damage and UVB exposure. A redox proteomic-based approach was applied to evaluating skin protein modification when exposed to varying doses of UVB after initial oxidative stress, via tracking changes in protein oxidation during the healing process in vitro using a full-thickness reconstituted human skin tissue model. Bioassays and structural evaluation confirmed that our cultured skin tissues underwent a normal physiological response to UVB exposure. A set of potential skin marker peptides was generated, for use in tracking skin protein oxidative modification. Exposure to UVB after thermal oxidative stress was found to result in higher levels of skin protein oxidation than a non-irradiated control for up to seven days after exposure. Recovery of the skin proteins from oxidative stress, as assessed by the overall protein oxidation levels, was found to be impaired by UVB exposure. Oxidative modification was largely observed in skin structural proteins. Exposure of skin proteins to UVB exacerbates oxidative damage to structural skin proteins, with higher exposure levels leading to increasingly impaired recovery from this damage. This has potential implications for the functional performance of the proteins and inter-related skin health and cosmetic appearance. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Different susceptibility of cells of porcine skin and internal organs to ultraviolet A-induced breaking of nuclear DNA.

PubMed

Brozyna, Anna; Chwirot, Barbara W

2005-01-01

There is a continuously growing interest in medical applications of ultraviolet radiation (UV-A and long-wavelength UV-B) especially for laser surgery, phototherapy and photodiagnostics of human internal organs. UV-B and UV-A radiation is potentially mutagenic, however, there has been very little information published to date concerning the significance of possible deleterious action of such photons on cells of internal tissues. The aim of this study is to compare the sensitivities of skin cells to those of internal organs upon exposure to UV-A. To assess this sensitivity we have determined the UV-A dose-dependent frequency of nuclear DNA breaks detected with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) technique. The materials for the study were macroscopic samples of porcine skin, colon and esophagus. The UV-A dose ranged from 0.1 to 1000 mJ/cm2, which is similar to doses received by cells in regions examined with laser-induced fluorescence or by cells surrounding areas subject to a laser ablation. To reduce the influence of DNA repair processes the tissue samples were kept at a low temperature during the irradiation and were deep frozen immediately after completing the irradiation procedure. The cells of the internal organs are much more susceptible to UV-A-induced breaking of DNA than the skin cells. The percentage fractions and the spatial distributions of the damaged cells and the characteristics of the UV-A dose dependence seem to vary by type of internal organ.

Molecular Mechanisms of Ultraviolet Radiation-Induced DNA Damage and Repair

PubMed Central

Rastogi, Rajesh P.; Richa; Kumar, Ashok; Tyagi, Madhu B.; Sinha, Rajeshwar P.

2010-01-01

DNA is one of the prime molecules, and its stability is of utmost importance for proper functioning and existence of all living systems. Genotoxic chemicals and radiations exert adverse effects on genome stability. Ultraviolet radiation (UVR) (mainly UV-B: 280–315 nm) is one of the powerful agents that can alter the normal state of life by inducing a variety of mutagenic and cytotoxic DNA lesions such as cyclobutane-pyrimidine dimers (CPDs), 6-4 photoproducts (6-4PPs), and their Dewar valence isomers as well as DNA strand breaks by interfering the genome integrity. To counteract these lesions, organisms have developed a number of highly conserved repair mechanisms such as photoreactivation, base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR). Additionally, double-strand break repair (by homologous recombination and nonhomologous end joining), SOS response, cell-cycle checkpoints, and programmed cell death (apoptosis) are also operative in various organisms with the expense of specific gene products. This review deals with UV-induced alterations in DNA and its maintenance by various repair mechanisms. PMID:21209706

Rapid repair of UVA-induced oxidized purines and persistence of UVB-induced dipyrimidine lesions determine the mutagenicity of sunlight in mouse cells

PubMed Central

Besaratinia, Ahmad; Kim, Sang-in; Pfeifer, Gerd P.

2009-01-01

Despite the predominance of UVA relative to UVB in terrestrial sunlight, solar mutagenesis in humans and rodents is characterized by mutations specific for UVB. We have investigated the kinetics of repair of UVA- and UVB-induced DNA lesions in relation to mutagenicity in transgenic mouse fibroblasts irradiated with equilethal doses of UVA and UVB in comparison to SSL. We have also analyzed mutagenesis-derived carcinogenesis in sunlight-associated human skin cancers by compiling the published data on mutation types found in crucial genes in non-melanoma and melanoma skin cancers. Here, we demonstrate a resistance to repair of UVB-induced CPDs together with rapid removal of UVA-induced oxidized purines in the genome overall and in the cII transgene of SSL-irradiated cells. The spectra of mutation induced by both UVB- and SSL-irradiation in this experimental system are characterized by significant increases in relative frequency of C to T transitions at dipyrimidines, which are the established signature mutation of CPDs. This type of mutation is also the predominant mutation found in human non-melanoma and melanoma tumor samples in the TP53, CDKN2, PTCH, and protein kinase genes. The prevailing role of UVB over UVA in solar mutagenesis in our test system can be ascribed to different kinetics of repair for lesions induced by the respective UV-irradiation. PMID:18326785

Ultraviolet A within Sunlight Induces Mutations in the Epidermal Basal Layer of Engineered Human Skin

PubMed Central

Huang, Xiao Xuan; Bernerd, Françoise; Halliday, Gary Mark

2009-01-01

The ultraviolet B (UVB) waveband within sunlight is an important carcinogen; however, UVA is also likely to be involved. By ascribing mutations to being either UVB or UVA induced, we have previously shown that human skin cancers contain similar numbers of UVB- and UVA-induced mutations, and, importantly, the UVA mutations were at the base of the epidermis of the tumors. To determine whether these mutations occurred in response to UV, we exposed engineered human skin (EHS) to UVA, UVB, or a mixture that resembled sunlight, and then detected mutations by both denaturing high-performance liquid chromatography and DNA sequencing. EHS resembles human skin, modeling differential waveband penetration to the basal, dividing keratinocytes. We administered only four low doses of UV exposure. Both UVA and UVB induced p53 mutations in irradiated EHS, suggesting that sunlight doses that are achievable during normal daily activities are mutagenic. UVA- but not UVB-induced mutations predominated in the basal epidermis that contains dividing keratinocytes and are thought to give rise to skin tumors. These studies indicate that both UVA and UVB at physiological doses are mutagenic to keratinocytes in EHS. PMID:19264911

The effects of quercetin-loaded PLGA-TPGS nanoparticles on ultraviolet B-induced skin damages in vivo.

PubMed

Zhu, Xianbing; Zeng, Xiaowei; Zhang, Xudong; Cao, Wei; Wang, Yilin; Chen, Houjie; Wang, Teng; Tsai, Hsiang-I; Zhang, Ran; Chang, Danfeng; He, Shuai; Mei, Lin; Shi, Xiaojun

2016-04-01

Ultraviolet (UV) radiation has deleterious effects on living organisms, and functions as a tumor initiator and promoter. Multiple natural compounds, like quercetin, have been shown the protective effects on UV-induced damage. However, quercetin is extremely hydrophobic and limited by its poor percutaneous permeation and skin deposition. Here, we show that quercetin-loaded PLGA-TPGS nanoparticles could overcome low hydrophilicity of quercetin and improve its anti-UVB effect. Quercetin-loaded NPs can significantly block UVB irradiation induced COX-2 up-expression and NF-kB activation in Hacat cell line. Moreover, PLGA-TPGS NPs could efficiently get through epidermis and reach dermis. Treatment of mice with quercetin-loaded NPs also attenuates UVB irradiation-associated macroscopic and histopathological changes in mice skin. These results demonstrated that copolymer PLGA-TPGS could be used as drug nanocarriers against skin damage and disease. The findings provide an external use of PLGA-TPGS nanocarriers for application in the treatment of skin diseases. Skin is the largest organ in the body and is subjected to ultraviolet (UV) radiation damage daily from the sun. Excessive exposure has been linked to the development of skin cancer. Hence, topically applied agents can play a major role in skin protection. In this article, the authors developed quercetin-loaded PLGA-TPGS nanoparticles and showed their anti-UVB effect. Copyright © 2015 Elsevier Inc. All rights reserved.

Moderate salt treatment alleviates ultraviolet-B radiation caused impairment in poplar plants

NASA Astrophysics Data System (ADS)

Ma, Xuan; Ou, Yong-Bin; Gao, Yong-Feng; Lutts, Stanley; Li, Tao-Tao; Wang, Yang; Chen, Yong-Fu; Sun, Yu-Fang; Yao, Yin-An

2016-09-01

The effects of moderate salinity on the responses of woody plants to UV-B radiation were investigated using two Populus species (Populus alba and Populus russkii). Under UV-B radiation, moderate salinity reduced the oxidation pressure in both species, as indicated by lower levels of cellular H2O2 and membrane peroxidation, and weakened the inhibition of photochemical efficiency expressed by O-J-I-P changes. UV-B-induced DNA lesions in chloroplast and nucleus were alleviated by salinity, which could be explained by the higher expression levels of DNA repair system genes under UV-B&salt condition, such as the PHR, DDB2, and MutSα genes. The salt-induced increase in organic osmolytes proline and glycine betaine, afforded more efficient protection against UV-B radiation. Therefore moderate salinity induced cross-tolerance to UV-B stress in poplar plants. It is thus suggested that woody plants growing in moderate salted condition would be less affected by enhanced UV-B radiation than plants growing in the absence of salt. Our results also showed that UV-B signal genes in poplar plants PaCOP1, PaSTO and PaSTH2 were quickly responding to UV-B radiation, but not to salt. The transcripts of PaHY5 and its downstream pathway genes (PaCHS1, PaCHS4, PaFLS1 and PaFLS2) were differently up-regulated by these treatments, but the flavonoid compounds were not involved in the cross-tolerance since their concentration increased to the same extent in both UV-B and combined stresses.

Long-term uvb forecasting on the basis of spectral and broad-band measurements

NASA Astrophysics Data System (ADS)

Bérces, A.; Gáspár, S.; Kovács, G.; Rontó, G.

2003-04-01

The stratospheric ozone concentration has been investigated by several methods, e.g. determinations of the ozone layer using a network of ground based spectrophotometers, of the Dobson and the Brewer types. These data indicate significant decrease of the ozone layer superimposed by much larger seasonal changes at specific geographical locations. The stratospheric ozone plays an important role in the attenuation of the short-wavelength components of the solar spectrum, thus the consequence of the decreased ozone layer is an increased UVB level. Various pyranometers measuring the biological effect of environmental UV radiation have been constructed with spectral sensitivities close to the erythema action spectrum defined by the CIE. Using these erythemally weighted broad-band instruments to detect the tendency of UVB radiation controversial data have been found. To quantify the biological risk due to environmental UV radiation it is reasonable to weight the solar spectrum by the spectral sensitivity of the DNA damage taking into account the high DNA-sensitivity at the short wavelength range of the solar spectrum. Various biological dosimeters have been developed e.g. polycrystalline uracil thin layer. These are usually simple biological systems or components of them. Their UV sensitivity is a consequence of the DNA-damage. Biological dosimeters applied for long-term monitoring are promising tools for the assessment of the biological hazard. Simultaneous application of uracil dosimeters and Robertson-Berger meters can be useful to predict the increasing tendency of the biological UV exposure more precisely. The ratio of the biologically effective dose obtained by the uracil dosimeter (a predominately UVB effect) and by the Robertson-Berger meter (insensitive to changes below 300 nm) is a sensitive method for establishing changes in UVB irradiance due to changes in ozone layer.

The effect of actinoquinol with hyaluronic acid in eye drops on the optical properties and oxidative damage of the rabbit cornea irradiated with UVB rays.

PubMed

Čejka, Čestmír; Luyckx, Jacques; Ardan, Taras; Pláteník, Jan; Širc, Jakub; Michálek, Jiří; Čejková, Jitka

2010-01-01

Irradiation of the cornea with UVB rays leads to its oxidative damage, swelling and increased light absorption. We investigated changes in the corneal optics (evaluated by changes of corneal hydration and light absorption) and microscopical disturbances of corneas irradiated with UVB rays as influenced by eye drops containing actinoquinol with hyaluronic acid. Rabbit corneas were irradiated with a daily dose of 0.5 or 1.01 J cm(-2) of UVB rays (312 nm) for 4 days. During irradiation, the eye drops were applied on the right eye and buffered saline (or hyaluronic acid) on the left eye. On day 5 the rabbits were sacrificed and the corneas examined spectrophotometrically for light absorption. The corneal thickness (hydration) was measured using a pachymeter. Corneas of some other rabbits were examined immunohistochemically. After buffered saline treatment UVB rays evoked changes in the corneal optics and induced oxidative damage of the corneas. After actinoquinol-hyaluronic acid application, these changes were diminished. Hyaluronic acid alone was less effective. In conclusion, actinoquinol-hyaluronic acid eye drops decreased changes in corneal optics and suppressed oxidative damage in the UVB-irradiated cornea. However, the effective corneal protection by these eye drops was limited to the lower UVB dose. © 2010 The Authors. Journal Compilation. The American Society of Photobiology.

Photosensitized 2-amino-3-hydroxypyridine-induced mitochondrial apoptosis via Smac/DIABLO in human skin cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goyal, Shruti; Amar, Saroj Kumar; Academy of Scientific and Innovative Research

The popularity of hair dyes use has been increasing regularly throughout the world as per the demand of hair coloring fashion trends and other cosmetic products. 2-Amino-3-hydroxypyridine (A132) is widely used as a hair dye ingredient around the world. We are reporting first time the phototoxicity mechanism of A132 under ambient environmental UV-B radiation. It showed maximum absorption in UV-B region (317 nm) and forms a photoproduct within an hour exposure of UV-B irradiation. Photocytotoxicity of A132 in human keratinocytes (HaCaT) was measured by mitochondrial (MTT), lysosomal (NRU) and LDH assays which illustrated the significant reduction in cell viability. Themore » role of reactive oxygen species (ROS) generation for A132 phototoxicity was established photo- chemically as well as intracellularly. Noteworthy, formation of tail DNA (comet assay), micronuclei and cyclobutane pyrimidine dimers (CPDs) (immunocytochemistry) formation confirmed the photogenotoxic potential of dye. Cell cycle study (sub-G1peak) and staining with EB/AO revealed the cell cycle arrest and apoptosis. Further, mitochondrial mediated apoptosis was corroborated by reduced MMP, release of cytochrome c and upregulation of caspase-3. Release of mitochondrial Smac/DIABLO in cytoplasm demonstrated the caspase dependent apoptotic cell death by photolabile A132 dye. In-addition increased Bax/Bcl2 ratio again proved the apoptosis. Thus, study suggests that A132 induces photogenotoxicity, phototoxicity and apoptotic cell death through the involvement of Smac/DIABLO in mitochondrial apoptosis via caspase dependent manner. Therefore, the long term use of A132 dye and sunlight exposure jointly increased the oxidative stress in skin which causes premature hair loss, damage to progenitor cells of hair follicles. - Highlights: • Photodegradation of A132 and formation of novel photoproduct • Involvement of ROS in A132 phototoxicity • Role of ROS in DNA damage, CPD and micronuclei formation • Release of Smac/DIABLO from mitochondria during apoptosis • Caspase 3 dependent apoptotic cell death.« less

Ultra-violet B (UVB)-induced skin cell death occurs through a cyclophilin D intrinsic signaling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ji, Chao; Yang, Bo; Yang, Zhi

Highlights: Black-Right-Pointing-Pointer UVB radiated skin keratinocytes show cyclophilin D (Cyp-D) upregulation. Black-Right-Pointing-Pointer NAC inhibits UVB induced Cyp-D expression, while H{sub 2}O{sub 2} facilitates it. Black-Right-Pointing-Pointer Cyp-D-deficient cells are significantly less susceptible to UVB induced cell death. Black-Right-Pointing-Pointer Over-expression of Cyp-D causes spontaneous keratinocytes cell death. -- Abstract: UVB-induced skin cell damage involves the opening of mitochondrial permeability transition pore (mPTP), which leads to both apoptotic and necrotic cell death. Cyclophilin D (Cyp-D) translocation to the inner membrane of mitochondrion acts as a key component to open the mPTP. Our Western-Blot results in primary cultured human skin keratinocytes and in HaCaTmore » cell line demonstrated that UVB radiation and hydrogen peroxide (H{sub 2}O{sub 2}) induced Cyp-D expression, which was inhibited by anti-oxidant N-acetyl cysteine (NAC). We created a stable Cyp-D deficiency skin keratinocytes by expressing Cyp-D-shRNA through lentiviral infection. Cyp-D-deficient cells were significantly less susceptible than their counterparts to UVB- or H{sub 2}O{sub 2}-induced cell death. Further, cyclosporine A (Cs-A), a Cyp-D inhibitor, inhibited UVB- or H{sub 2}O{sub 2}-induced keratinocytes cell death. Reversely, over-expression of Cyp-D in primary keratinocytes caused spontaneous keratinocytes cell death. These results suggest Cyp-D's critical role in UVB/oxidative stress-induced skin cell death.« less

Daily Ingestion of Aloe Vera Gel Powder Containing Aloe Sterols Prevents Skin Photoaging in OVX Hairless Mice.

PubMed

Yao, Ruiqing; Tanaka, Miyuki; Misawa, Eriko; Saito, Marie; Nabeshima, Kazumi; Yamauchi, Koji; Abe, Fumiaki; Yamamoto, Yuki; Furukawa, Fukumi

2016-10-12

Estrogen deficiencies associated with menopause accelerate spontaneous skin aging and stimulate the ultraviolet (UV) irradiation-induced photoaging of skin. However, food compositions with the potential to ameliorate the UV irradiation-induced acceleration of skin aging with menopause have not yet been investigated in detail. In the present study, we examined the ability of plant sterols derived from Aloe vera gel to prevent the UV irradiation-induced acceleration of skin aging in ovariectomized mice. Skin transepidermal water loss (TEWL) was significantly higher in the ovariectomy group than in the sham operation group following UVB irradiation, whereas skin elasticity was significantly lower. Ultraviolet B (UVB) irradiation induced greater reductions in skin hyaluronic acid levels and more severe collagen fiber damage in the derims in the ovariectomy group than in the sham group. The intake of AVGP significantly ameliorated this acceleration in skin aging by reducing the expression of matrix metalloproteinases (MMPs) and increasing that of epidermal growth factor (EGF) and hyaluronan synthase (HAS) in the skin. These results indicate that AVGP supplementation prevents skin damage induced by UVB irradiation and ovariectomy in part by inhibiting damage to the extracellular matrix. © 2016 Institute of Food Technologists®.

Sun exposure: what molecular photodermatology tells us about its good and bad sides.

PubMed

Krutmann, Jean; Morita, Akimichi; Chung, Jin Ho

2012-03-01

The health consequences of sun exposure have concerned mankind for more than 100 years. Recent molecular studies in photodermatology have greatly advanced our understanding of this important topic. We will illustrate this progress by focusing on the following selected topics: (i) the nature of the DNA damage-independent part of the UVB response of human skin and the role of the arylhydrocarbon receptor in cutaneous biology, (ii) the contribution of wavelengths beyond the UV spectrum to solar radiation-induced skin damage, (iii) the emerging evidence that subcutaneous fat is a target tissue for sunlight, and (iv) the most recent insight into the mode of action of phototherapy.

Protective Effect of Mangifera indica Linn., Cocos nucifera Linn., and Averrhoa carambola Linn. Extracts against Ultraviolet B-Induced Damage in Human Keratinocytes

PubMed Central

Ronpirin, Chalinee; Pattarachotanant, Nattaporn

2016-01-01

This study was aimed at investigating the antioxidant activity of Mangifera indica Linn., Cocos nucifera Linn., and Averrhoa carambola Linn. and their biological effect on human keratinocytes affected by the ultraviolet B (UVB), a major cause of cell damage and skin cancer through induction of DNA damage, production of reactive oxygen species (ROS), and apoptosis. The richest antioxidant activity was found in ethanol fraction of M. indica (21.32 ± 0.66 mg QE/g dry weight), while the lowest one was found in aqueous fractions of M. indica and C. nucifera (1.76 ± 2.10 and 1.65 ± 0.38 mg QE/g dry weight, respectively). Ethanol and aqueous fractions of A. carambola (250 µg/mL) significantly reduced the number of apoptotic cells. The expression of cleaved caspase 3 in UVB-treated group was significantly greater than that in untreated group. Both fractions of A. carambola (50, 100, and 250 µg/mL) significantly decreased the expression of cleaved caspase 3. Regarding the induction of DNA repair, ethanol (100 and 250 µg/mL) and aqueous (50, 100 and 250 µg/mL) fractions of A. carambola significantly decreased the percentage of cyclobutane pyrimidine dimers (CPD). Taken together, our results suggest that both fractions of A. carambola may be potentially developed for dermal applications. PMID:27057195

UVB-Induced Senescence of Human Dermal Fibroblasts Involves Impairment of Proteasome and Enhanced Autophagic Activity.

PubMed

Cavinato, Maria; Koziel, Rafal; Romani, Nikolaus; Weinmüllner, Regina; Jenewein, Brigitte; Hermann, Martin; Dubrac, Sandrine; Ratzinger, Gudrun; Grillari, Johannes; Schmuth, Matthias; Jansen-Dürr, Pidder

2017-05-01

In the current study, we have extended previous findings aiming at a better understanding of molecular mechanisms underlying UVB-induced senescence of diploid human dermal fibroblasts (HDFs), an experimental model to study the process of photoaging in the skin. We provide evidence that the inhibition of proteasomal degradation of damaged proteins and the activation of autophagosome formation are early events in UVB-induced senescence of HDFs, dependent on UVB-induced accumulation of reactive oxygen species. Our data suggest that autophagy is required for the establishment of the senescent phenotype in UVB-treated HDFs and that inhibition of autophagy is sufficient to change the cell fate from senescence to cell death by apoptosis. Studies in reconstructed skin equivalents revealed that UVB irradiation triggers hallmarks of autophagy induction in the dermal layer. These findings have potential implications for fundamental as well as translational research into skin aging, in particular photoaging. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

UVB-induced mutagenesis in hairless {lambda}lacZ-transgenic mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frijhoff, A.F.W.; Rebel, H.; Mientjes, E.J.

UVB-induced mutagenesis was studied in hairless 40.6 transgenic mice (Muta{trademark}Mouse), which contain the {lambda}gt1OlacZ shuttle vector as a target for mutagenesis. Mice were exposed at the dorsal side to either single doses of 200, 500, 800, or 1000 J/m{sup 2} UVB or to two successive irradiations of either 200 and 800 J/m{sup 2} UVB, with intervals of 1,3, or 5 days, or to 800 and 200 J/m{sup 2} UVB with a 5-day interval. At 23 days after the last exposure, lacZ mutant frequencies (MF) were determined in the epidermis. The lacZ MF increased linearly with increasing dose of UVB. Themore » mutagenic effect of two successive irradiations appeared to be additive. The UV-induced mutation spectrum was dominated by G:C{r_arrow}A:T transitions at dipyrimidine sites. DNA-sequence analysis of spontaneously mutated phages showed a diverse spectrum consisting of insertions, deletions and G:C {r_arrow} A:T transitions at CpG sites. the results indicate that the hairless {lambda}lacZ-transgenic mouse is a suitable in vivo model for studying UVB-induced mutations. 29 refs., 5 tabs.« less

Terrestrial ecosystems, increased solar ultraviolet radiation, and interactions with other climate change factors.

PubMed

Caldwell, M M; Bornman, J F; Ballaré, C L; Flint, S D; Kulandaivelu, G

2007-03-01

There have been significant advances in our understanding of the effects of UV-B radiation on terrestrial ecosystems, especially in the description of mechanisms of plant response. A further area of highly interesting research emphasizes the importance of indirect UV radiation effects on plants, pathogens, herbivores, soil microbes and ecosystem processes below the surface. Although photosynthesis of higher plants and mosses is seldom affected by enhanced or reduced UV-B radiation in most field studies, effects on growth and morphology (form) of higher plants and mosses are often manifested. This can lead to small reductions in shoot production and changes in the competitive balance of different species. Fungi and bacteria are generally more sensitive to damage by UV-B radiation than are higher plants. However, the species differ in their UV-B radiation sensitivity to damage, some being affected while others may be very tolerant. This can lead to changes in species composition of microbial communities with subsequent influences on processes such as litter decomposition. Changes in plant chemical composition are commonly reported due to UV-B manipulations (either enhancement or attenuation of UV-B in sunlight) and may lead to substantial reductions in consumption of plant tissues by insects. Although sunlight does not penetrate significantly into soils, the biomass and morphology of plant root systems of plants can be modified to a much greater degree than plant shoots. Root mass can exhibit sizeable declines with more UV-B. Also, UV-B-induced changes in soil microbial communities and biomass, as well as altered populations of small invertebrates have been reported and these changes have important implications for mineral nutrient cycling in the soil. Many new developments in understanding the underlying mechanisms mediating plant response to UV-B radiation have emerged. This new information is helpful in understanding common responses of plants to UV-B radiation, such as diminished growth, acclimation responses of plants to UV-B radiation and interactions of plants with consumer organisms such as insects and plant pathogens. The response to UV-B radiation involves both the initial stimulus by solar radiation and transmission of signals within the plants. Resulting changes in gene expression induced by these signals may have elements in common with those elicited by other environmental factors, and generate overlapping functional (including acclimation) responses. Concurrent responses of terrestrial systems to the combination of enhanced UV-B radiation and other global change factors (increased temperature, CO2, available nitrogen and altered precipitation) are less well understood. Studies of individual plant responses to combinations of factors indicate that plant growth can be augmented by higher CO2 levels, yet many of the effects of UV-B radiation are usually not ameliorated by the elevated CO2. UV-B radiation often increases both plant frost tolerance and survival under extreme high temperature conditions. Conversely, extreme temperatures sometimes influence the UV-B radiation sensitivity of plants directly. Plants that endure water deficit stress effectively are also likely to be tolerant of high UV-B flux. Biologically available nitrogen is exceeding historical levels in many regions due to human activities. Studies show that plants well supplied with nitrogen are generally more sensitive to UV-B radiation. Technical issues concerning the use of biological spectral weighting functions (BSWFs) have been further elucidated. The BSWFs, which are multiplication factors assigned to different wavelengths giving an indication of their relative biological effectiveness, are critical to the proper conduct and interpretation of experiments in which organisms are exposed to UV radiation, both in the field and in controlled environment facilities. The characteristics of BSWFs vary considerably among different plant processes, such as growth, DNA damage, oxidative damage and induction of changes in secondary chemicals. Thus, use of a single BSWF for plant or ecosystem response is not appropriate. This brief review emphasizes progress since the previous report toward the understanding of solar ultraviolet radiation effects on terrestrial systems as it relates to ozone column reduction and the interaction of climate change factors.

Plasma lipoproteins as mediators of the oxidative stress induced by UV light in human skin: a review of biochemical and biophysical studies on mechanisms of apolipoprotein alteration, lipid peroxidation, and associated skin cell responses.

PubMed

Filipe, Paulo; Morlière, Patrice; Silva, João N; Mazière, Jean-Claude; Patterson, Larry K; Freitas, João P; Santus, R

2013-01-01

There are numerous studies concerning the effect of UVB light on skin cells but fewer on other skin components such as the interstitial fluid. This review highlights high-density lipoprotein (HDL) and low-density lipoprotein (LDL) as important targets of UVB in interstitial fluid. Tryptophan residues are the sole apolipoprotein residues absorbing solar UVB. The UVB-induced one-electron oxidation of Trp produces (•)Trp and (•)O2 (-) radicals which trigger lipid peroxidation. Immunoblots from buffered solutions or suction blister fluid reveal that propagation of photooxidative damage to other residues such as Tyr or disulfide bonds produces intra- and intermolecular bonds in apolipoproteins A-I, A-II, and B100. Partial repair of phenoxyl tyrosyl radicals (TyrO(•)) by α -tocopherol is observed with LDL and HDL on millisecond or second time scales, whereas limited repair of α -tocopherol by carotenoids occurs in only HDL. More effective repair of Tyr and α -tocopherol is observed with the flavonoid, quercetin, bound to serum albumin, but quercetin is less potent than new synthetic polyphenols in inhibiting LDL lipid peroxidation or restoring α -tocopherol. The systemic consequences of HDL and LDL oxidation and the activation and/or inhibition of signalling pathways by oxidized LDL and their ability to enhance transcription factor DNA binding activity are also reviewed.

Development of UV-B screening compounds in response to variation in ambient levels of UV-B radiation

NASA Astrophysics Data System (ADS)

Sullivan, Joe H.; Xu, Chenping; Gao, Wei; Slusser, James R.

2005-08-01

The induction of UV-B screening compounds in response to exposure to UV-B radiation is a commonly reported response and is generally considered to be an adaptive response of plants for protection from UVinduced damage. However, a number of questions remain to be answered including the importance of qualitative and localization differences among species in providing protection, indirect consequences of changes in leaf secondary chemistry on ecological processes and the dose response of metabolite accumulation. In this study we utilized UV monitoring data provided on site by the USDA UV-B Monitoring and Research Program to monitor the changes in UV-screening compounds in soybeans under a range of UV-B levels due to natural variation in ambient UV-B radiation. Soybean cultivars Essex, Clark and Clark-magenta, an isoline of Clark that produces minimal levels of flavonols, were grown beneath shelters covered either with polyester to block most UV-B radiation or teflon which is nearly transparent in the UV range and harvested at regular intervals for pigment and protein analysis. Daily levels of weighted UV-B varied from <1 to >7 kJ m-2. Increases in UV-screening compounds showed a positive dose response to UV-B radiation in all cultivars with Essex showing the steepest dose response. UV-A also induced screening compounds in all species The hydroxycinnimates of the magenta isoline showed a steep dose response to UV-A and a rather constant (non dose specific) but small additional increment in response to UV-B. The Clark isoline, which produced primarily the flavonol quercetin, showed a dose response to UV-B intermediate between that of Clark-magenta and Essex. All three cultivars show similar tolerance to UV-B in field conditions indicating that UV-induced pigment production is adequate to protect them from excessive UV-B damage.

Protective effects of Aloe sterols against UVB-induced photoaging in hairless mice.

PubMed

Misawa, Eriko; Tanaka, Miyuki; Saito, Marie; Nabeshima, Kazumi; Yao, Ruiqing; Yamauchi, Kouji; Abe, Fumiaki; Yamamoto, Yuki; Furukawa, Fukumi

2017-03-01

Aloe vera is a traditional medical plant whose gel has been widely used in skin care. Previously, we have identified Aloe sterols from Aloe vera as active ingredients. This study investigated the protective effects of Aloe sterols without polysaccharides, against ultraviolet B (UVB)-induced skin photoaging in mice using Aloe vera gel extract (AVGE) obtained by supercritical fluid extraction. Aloe vera gel extract was supplemented in the diet (12 or 120 ppm), and HR-1 hairless mice were exposed to UVB irradiation for 7 weeks. Skin measurements and histological and analytical studies were performed. Repeated UVB irradiation induced rough wrinkling of skin with water content reduction and hyperkeratosis. AVGE administration resulted in the significant improvement of UVB-induced skin dryness, epidermal thickness, and wrinkle formation. The AVGE group also suppressed the degenerations of dermal collagen fibers and the appearance of cutaneous apoptosis cells induced by UVB. Furthermore, AVGE administration reduced the excess elevation of pro-inflammatory cytokines (IL-1β and TNF-α) and matrix metalloproteinases (MMP-2, MMP-9, MMP-12, and MMP-13) in UVB-exposed skin. The dietary ingestion of Aloe sterols protected against chronic UVB damage in mouse skin, and our results suggest that Aloe sterols may prevent skin photoaging through the anti-inflammation and MMP regulation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Feasibility of Ionization-Mediated Pathway for Ultraviolet-Induced Melanin Damage.

PubMed

Mandal, Mukunda; Das, Tamal; Grewal, Baljinder K; Ghosh, Debashree

2015-10-22

Melanin is the pigment found in human skin that is responsible for both photoprotection and photodamage. Recently there have been reports that greater photodamage of DNA occurs when cells containing melanin are irradiated with ultraviolet (UV) radiation, thus suggesting that the photoproducts of melanin cause DNA damage. Photoionization processes have also been implicated in the photodegradation of melanin. However, not much is known about the oxidation potential of melanin and its monomers. In this work we calculate the ionization energies of monomers, dimers, and few oligomers of eumelanin to estimate the threshold energy required for the ionization of eumelanin. We find that this threshold is within the UV-B region for eumelanin. We also look at the charge and spin distributions of the various ionized states of the monomers that are formed to understand which of the ionization channels might favor monomerization from a covalent dimer.

UV-Induced Molecular Signaling Differences in Melanoma and Non-melanoma Skin Cancer.

PubMed

Liu-Smith, Feng; Jia, Jinjing; Zheng, Yan

2017-01-01

There are three major types of skin cancer: melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC and SCC are often referred to as non-melanoma skin cancer (NMSC). NMSCs are relatively non-lethal and curable by surgery, hence are not reportable in most cancer registries all over the world. Melanoma is the deadliest skin cancer. Its incidence rate (case number) is about 1/10th of that for NMSC, yet its death toll is ~8 fold higher than NMSC.Melanomas arise from melanocytes which are normally located on the basement membrane with dendrites extending into the epidermal keratinocytes. A major known function of melanocytes is to produce pigments which are enclosed by lipid membrane (termed melanosomes) and distribute them into keratinocytes, thus give different shade of skin colors. BCCs arise from basal cells, which are a layer of cells located at the deepest part of epidermis. Basal cells are recently considered to be skin stem cells as they are constantly proliferating and generating keratinocytes which are continuously pushed to the surface and eventually become a dead layer of stratum corneum. Squamous cells are the keratinocytes which resembles fish scale shape, ie, those initiated from basal cells and differentiated into squamous cells. Both basal cells and squamous cells belong to keratinocytes, therefore sometimes BCC and SCC are termed keratinocyte cancer.These three types of cancer share many characteristics, yet they are very different from etiology to progression. One shared characteristic of skin cancer is that, according to the current views, they all are caused by solar or artificial ultraviolet radiation (UVR). UVA and UVB from solar UVR are the major UV bands reaching the earth surface. Both UV types cause DNA damage and immune suppression which play crucial roles in skin carcinogenesis. UVB can be directly absorbed by DNA molecules and thus causes UV-signature DNA damages; UVA, on the other hand, may function through inducing cellular ROS which then causes oxidative DNA damages [1-4]. This chapter will discuss the molecular signaling differences of UVR in melanoma and NMSC.

Protective effects of citrus and rosemary extracts on UV-induced damage in skin cell model and human volunteers.

PubMed

Pérez-Sánchez, A; Barrajón-Catalán, E; Caturla, N; Castillo, J; Benavente-García, O; Alcaraz, M; Micol, V

2014-07-05

Ultraviolet radiation absorbed by the epidermis is the major cause of various cutaneous disorders, including photoaging and skin cancers. Although topical sunscreens may offer proper skin protection, dietary plant compounds may significantly contribute to lifelong protection of skin health, especially when unconsciously sun UV exposed. A combination of rosemary and citrus bioflavonoids extracts was used to inhibit UV harmful effects on human HaCaT keratinocytes and in human volunteers after oral intake. Survival of HaCaT cells after UVB radiation was higher in treatments using the combination of extracts than in those performed with individual extracts, indicating potential synergic effects. The combination of extracts also decreased UVB-induced intracellular radical oxygen species (ROS) and prevented DNA damage in HaCaT cells by comet assay and decreased chromosomal aberrations in X-irradiated human lymphocytes. The oral daily consumption of 250 mg of the combination by human volunteers revealed a significant minimal erythema dose (MED) increase after eight weeks (34%, p<0.05). Stronger protection was achieved after 12 weeks (56%, p<0.01). The combination of citrus flavonoids and rosemary polyphenols and diterpenes may be considered as an ingredient for oral photoprotection. Their mechanism of action may deserve further attention. Copyright © 2014 Elsevier B.V. All rights reserved.

Photoreactivation in Paramecium tetraurelia under conditions of various degrees of ozone layer depletion.

PubMed

Takahashi, Akihisa; Kumatani, Toshihiro; Usui, Saori; Tsujimura, Ryoko; Seki, Takaharu; Morimoto, Kouichi; Ohnishi, Takeo

2005-01-01

Photoreactivation (PR) is an efficient survival mechanism that helps protect cells against the harmful effects of solar-ultraviolet (UV) radiation. The PR mechanism involves photolyase, just one enzyme, and can repair DNA damage, such as cyclobutane-pyrimidine dimers (CPD) induced by near-UV/blue light, a component of sunlight. Although the balance of near-UV/blue light and far-UV light reaching the Earth's surface could be altered by the atmospheric ozone layer's depletion, experiments simulating this environmental change and its possible effects on life have not yet been performed. To quantify the strength of UVB in sunlight reaching the Earth's surface, we measured the number of CPD generated in plasmid DNA after UVB irradiation or exposure to sunlight. To simulate the increase of solar-UV radiation resulting from the ozone layer depletion, Paramecium tetraurelia was exposed to UVB and/or sunlight in clear summer weather. PR recovery after exposure to sunlight was complete at a low dose rate of 0.2 J/m2 x s, but was less efficient when the dose rate was increased by a factor of 2.5 to 0.5 J/m2 x s. It is suggested that solar-UV radiation would not influence the cell growth of P. tetraurelia for the reason of high PR activity even when the ozone concentration was decreased 30% from the present levels.

Z-ligustilide ameliorated ultraviolet B-induced oxidative stress and inflammatory cytokine production in human keratinocytes through upregulation of Nrf2/HO-1 and suppression of NF-κB pathway.

PubMed

Wu, Zhouwei; Uchi, Hiroshi; Morino-Koga, Saori; Shi, Weimin; Furue, Masutaka

2015-09-01

Ultraviolet B (UVB), a harmful environmental factor, is responsible for a variety of skin disorders including skin inflammation through reactive oxygen species (ROS) and inflammatory mediator production. Here, we investigated the effect of Z-ligustilide (Z-lig), an active ingredient isolated from the medicinal plants Cnidium officinale and Angelica acutiloba, on UVB-induced ROS generation and inflammatory mediator production in normal human epidermal keratinocytes (NHEKs) as well as its underlying mechanisms. Z-lig significantly rescued UVB-induced NHEKs damage in a dosage-dependent manner. Pretreatment of NHEKs with Z-lig inhibited UVB-induced ROS production in NHEKs. Both silencing the nuclear factor E2-related factor 2 (Nrf2) and the supplement of tin protoporphyrin IX (SnPP), a haeme oxygenase-1 (HO-1) inhibitor, cancelled the inhibitory effect of Z-lig on UVB-induced ROS upregulation in NHEKs. Moreover, pretreatment of NHEKs with Z-lig reduced UVB-induced nuclear factor kappa B (NF-κB)-dependent inflammatory mediators (IL-6, IL-8 and MCP-1) production at both mRNA and protein level. In the presence of Z-lig, UVB-induced NF-κB subunit p65 nuclear translocation was abolished, and the IκBα degradation was suppressed. Taken together, these findings suggest that Z-lig can suppress UVB-induced ROS generation through Nrf2/HO-1 upregulation and inflammation by suppressing the NF-κB pathway, suggesting that Z-lig may be beneficial in protecting skin from UVB exposure. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dietary eicosapentaenoic acid prevents systemic immunosuppression in mice induced by UVB radiation.

PubMed

Moison, R M; Beijersbergen Van Henegouwen, G M

2001-07-01

Moison, R. M. W. and Beijersbergen van Henegouwen, G. M. J. Dietary Eicosapentaenoic Acid Prevents Systemic Immunosuppression in Mice Induced by UVB Radiation. Radiat. Res. 156, 36-44 (2001). Reactive oxygen species (ROS) contribute to the immunosuppression induced by UVB radiation. Omega-3 fatty acids in fish oil, e.g. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can modulate immunoresponsiveness, but because of their susceptibility to ROS-induced damage, they can also challenge the epidermal antioxidant defense system. The influence of dietary supplementation with different omega-3 fatty acids on systemic immunosuppression induced in mice by UVB radiation was studied using the contact hypersensitivity response to trinitrochlorobenzene. In an attempt to study the mechanisms involved, UVB-radiation-induced changes in epidermal antioxidant status were also studied. Mice received high-fat (25% w/w) diets enriched with either oleic acid (control diet), EPA, DHA, or EPA + DHA (MaxEPA). Immunosuppression induced by UVB radiation was 53% in mice fed the oleic acid diet and 69% in mice fed the DHA diet. In contrast, immunosuppression was only 4% and 24% in mice fed the EPA and MaxEPA diets, respectively. Increased lipid peroxidation and decreased vitamin E levels (P < 0.05) were found in unirradiated mice fed the MaxEPA and DHA diets. For all diets, exposure to UVB radiation increased lipid peroxidation (P < 0.05), but levels of glutathione (P < 0.05) and vitamin C (P > 0.05) decreased only in the mice given fish oil. UVB irradiation did not influence vitamin E levels. In conclusion, dietary EPA, but not DHA, protects against UVB-radiation-induced immunosuppression in mice. The degree of protection appears to be related to the amount of EPA incorporated and the ability of the epidermis to maintain an adequate antioxidant level after irradiation.

Orally administered betaine reduces photodamage caused by UVB irradiation through the regulation of matrix metalloproteinase-9 activity in hairless mice.

PubMed

Im, A-Rang; Lee, Hee Jeong; Youn, Ui Joung; Hyun, Jin Won; Chae, Sungwook

2016-01-01

Betaine is widely distributed in plants, microorganisms, in several types of food and in medical herbs, including Lycium chinense. The administration of 100 mg betaine/kg body weight/day is an effective strategy for preventing ultraviolet irradiation‑induced skin damage. The present study aimed to determine the preventive effects of betaine on ultraviolet B (UVB) irradiation‑induced skin damage in hairless mice. The mice were divided into three groups: Control (n=5), UVB‑treated vehicle (n=5) and UVB‑treated betaine (n=5) groups. The level of irradiation was progressively increased between 60 mJ/cm2 per exposure at week 1 (one minimal erythematous dose = 60 mJ/cm2) and 90 mJ/cm2 per exposure at week 7. The formation of wrinkles significantly increased following UVB exposure in the UVB‑treated vehicle group. However, treatment with betaine suppressed UVB‑induced wrinkle formation, as determined by the mean length, mean depth, number, epidermal thickness and collagen damage. Furthermore, oral administration of betaine also inhibited the UVB‑induced expression of mitogen‑activated protein kinase kinase (MEK), extracellular signal‑regulated kinase (ERK), and matrix metalloproteinase‑9 (MMP‑9). These findings suggested that betaine inhibits UVB‑induced skin damage by suppressing increased expression of MMP‑9 through the inhibition of MEK and ERK.

Fisetin Regulates Nrf2 Expression and the Inflammation-Related Signaling Pathway to Prevent UVB-Induced Skin Damage in Hairless Mice.

PubMed

Wu, Po-Yuan; Lyu, Jia-Ling; Liu, Yi-Jung; Chien, Ting-Yi; Hsu, Hao-Cheng; Wen, Kuo-Ching; Chiang, Hsiu-Mei

2017-10-10

Chronic ultraviolet (UV) exposure may cause skin damage, disrupt skin barrier function, and promote wrinkle formation. UV induces oxidative stress and inflammation, which results in extracellular matrix degradation in the dermis and epidermal hyperplasia. Our previous study demonstrated that fisetin exerts photoprotective activity by inhibiting mitogen-activated protein kinase/activator protein-1/matrix metalloproteinases (MMPs) activation. In this study, fisetin was applied topically to investigate its antiphotodamage effects in hairless mice. The erythema index (a* values) and transepidermal water loss were evaluated to assess skin damage, and immunohistochemical staining was conducted to elucidate the photoprotective mechanism of fisetin. The results revealed that the topical application of fisetin reduced UVB-induced increase in the a* value and wrinkle formation. In addition, fisetin inhibited epidermal hyperplasia and increased the collagen content in the dermis. Fisetin exerted photoprotective activity by inhibiting the expression of MMP-1, MMP-2, and cyclooxygenase-2 and increasing the expression of nuclear factor erythroid 2-related factor. Furthermore, fisetin increased the expression of filaggrin to prevent UVB-induced barrier function disruption. Altogether, the present results provide evidence of the effects and mechanisms of fisetin's antiphotodamage and antiphotoinflammation activities.

Fisetin Regulates Nrf2 Expression and the Inflammation-Related Signaling Pathway to Prevent UVB-Induced Skin Damage in Hairless Mice

PubMed Central

Wu, Po-Yuan; Lyu, Jia-Ling; Chien, Ting-Yi; Hsu, Hao-Cheng; Wen, Kuo-Ching

2017-01-01

Chronic ultraviolet (UV) exposure may cause skin damage, disrupt skin barrier function, and promote wrinkle formation. UV induces oxidative stress and inflammation, which results in extracellular matrix degradation in the dermis and epidermal hyperplasia. Our previous study demonstrated that fisetin exerts photoprotective activity by inhibiting mitogen-activated protein kinase/activator protein-1/matrix metalloproteinases (MMPs) activation. In this study, fisetin was applied topically to investigate its antiphotodamage effects in hairless mice. The erythema index (a* values) and transepidermal water loss were evaluated to assess skin damage, and immunohistochemical staining was conducted to elucidate the photoprotective mechanism of fisetin. The results revealed that the topical application of fisetin reduced UVB-induced increase in the a* value and wrinkle formation. In addition, fisetin inhibited epidermal hyperplasia and increased the collagen content in the dermis. Fisetin exerted photoprotective activity by inhibiting the expression of MMP-1, MMP-2, and cyclooxygenase-2 and increasing the expression of nuclear factor erythroid 2-related factor. Furthermore, fisetin increased the expression of filaggrin to prevent UVB-induced barrier function disruption. Altogether, the present results provide evidence of the effects and mechanisms of fisetin’s antiphotodamage and antiphotoinflammation activities. PMID:28994699

Oral Supplementation with Cocoa Extract Reduces UVB-Induced Wrinkles in Hairless Mouse Skin.

PubMed

Kim, Jong-Eun; Song, Dasom; Kim, Junil; Choi, Jina; Kim, Jong Rhan; Yoon, Hyun-Sun; Bae, Jung-Soo; Han, Mira; Lee, Sein; Hong, Ji Sun; Song, Dayoung; Kim, Seong-Jin; Son, Myoung-Jin; Choi, Sang-Woon; Chung, Jin Ho; Kim, Tae-Aug; Lee, Ki Won

2016-05-01

Cacao beans contain various bioactive phytochemicals that could modify the pathogeneses of certain diseases. Here, we report that oral administration of cacao powder (CP) attenuates UVB-induced skin wrinkling by the regulation of genes involved in dermal matrix production and maintenance. Transcriptome analysis revealed that 788 genes are down- or upregulated in the CP supplemented group, compared with the UVB-irradiated mouse skin controls. Among the differentially expressed genes, cathepsin G and serpin B6c play important roles in UVB-induced skin wrinkle formation. Gene regulatory network analysis also identified several candidate regulators responsible for the protective effects of CP supplementation against UVB-induced skin damage. CP also elicited antiwrinkle effects via inhibition of UVB-induced matrix metalloproteinases-1 expression in both the human skin equivalent model and human dermal fibroblasts. Inhibition of UVB-induced activator protein-1 via CP supplementation is likely to affect the expression of matrix metalloproteinases-1. CP supplementation also downregulates the expression of cathepsin G in human dermal fibroblasts. 5-(3',4'-Dihydroxyphenyl)-γ-valerolactone, a major in vivo metabolite of CP, showed effects similar to CP supplementation. These results suggest that cacao extract may offer a protective effect against photoaging by inhibiting the breakdown of dermal matrix, which leads to an overall reduction in wrinkle formation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Apoptosis of Corneal Epithelial Cells Caused by Ultraviolet B-induced Loss of K+ is Inhibited by Ba2+

PubMed Central

Glupker, Courtney D.; Boersma, Peter M.; Schotanus, Mark P.; Haarsma, Loren D.; Ubels, John L.

2017-01-01

UVB exposure at ambient outdoor levels triggers rapid K+ loss and apoptosis in human corneal limbal epithelial (HCLE) cells cultured in medium containing 5.5 mM K+, but considerably less apoptosis occurs when the medium contains the high K+ concentration that is present in tears (25 mM). Since Ba2+ blocks several K+ channels, we tested whether Ba2+-sensitive K+ channels are responsible for some or all of the UVB-activated K+ loss and subsequent activation of the caspase cascade and apoptosis. Corneal epithelial cells in culture were exposed to UVB at 80 or 150 mJ/cm2. Patch-clamp recording was used to measure UVB-induced K+ currents. Caspase-activity and TUNEL assays were performed on HCLE cells exposed to UVB followed by incubation in the presence or absence of Ba2+. K+ currents were activated in HCLE cells following UVB-exposure. These currents were reversibly blocked by 5 mM Ba2+. When HCLE cells were incubated with 5 mM Ba2+ after exposure to UVB, activation of caspases-9, -8, and -3 and DNA fragmentation were significantly decreased. The data confirm that UVB-induced K+ current activation and loss of intracellular K+ leads to activation of the caspase cascade and apoptosis. Extracellular Ba2+ inhibits UVB-induced apoptosis by preventing loss of intracellular K+ when K+ channels are activated. Ba2+ therefore has effects similar to elevated extracellular K+ in protecting HCLE cells from UVB-induced apoptosis. This supports our overall hypothesis that elevated K+ in tears contributes to protection of the corneal epithelium from adverse effects of ambient outdoor UVB. PMID:27189864

Isoprene emission aids recovery of photosynthetic performance in transgenic Nicotiana tabacum following high intensity acute UV-B exposure.

PubMed

Centritto, Mauro; Haworth, Matthew; Marino, Giovanni; Pallozzi, Emanuele; Tsonev, Tsonko; Velikova, Violeta; Nogues, Isabel; Loreto, Francesco

2014-09-01

Isoprene emission by terrestrial plants is believed to play a role in mitigating the effects of abiotic stress on photosynthesis. Ultraviolet-B light (UV-B) induces damage to the photosynthetic apparatus of plants, but the role of isoprene in UV-B tolerance is poorly understood. To investigate this putative protective role, we exposed non-emitting (NE) control and transgenic isoprene emitting (IE) Nicotiana tabacum (tobacco) plants to high intensity UV-B exposure. Methanol emissions increased with UV-B intensity, indicating oxidative damage. However, isoprene emission was unaffected during exposure to UV-B radiation, but declined in the 48 h following UV-B treatment at the highest UV-B intensities of 9 and 15 Wm(-2). Photosynthesis and the performance of photosystem II (PSII) declined to similar extents in IE and NE plants following UV-B exposure, suggesting that isoprene emission did not ameliorate the immediate impact of UV-B on photosynthesis. However, after the stress, photosynthesis and PSII recovered in IE plants, which maintained isoprene formation, but not in NE plants. Recovery of IE plants was also associated with elevated antioxidant levels and cycling; suggesting that both isoprene formation and antioxidant systems contributed to reinstating the integrity and functionality of cellular membranes and photosynthesis following exposure to excessive levels of UV-B radiation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of UVC, UVB, UVA and a solar simulator on the survival of mouse melanoma cell lines differing in melanin content

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hill, H.Z.; Hill, G.J.; Cieszka, K.

These studies were designed to determine the survival of cells that vary in constitutive pigment levels after exposure to different UV wave lengths. The lamps employed emitted UVC (near monochromatic 254 nm), UVB (Philips TL01-88.7% of UV output is UVB), UVA (Philips HPW125-89% of output is at 365 nm) and Westinghouse FS20 (broad band UVB and UVA). Dish lids were used to cut off UVC in the UVB and FS20 experiments and 0.25 inch plate glass was used to cut off UVB in the UVA experiments. UVC photons interact with putative intracellular photosensitizers which in turn convert O{sub 2} tomore » active oxygen species which damage DNA to produce strand breaks, cross links and base damage. UVB acts by both mechanisms. The two cell lines studied were Cloudman S91/I3 (3.6 pg melanin/cell) and the closely related S91/amel (1.2 pg melanin/cell). Attached cells were covered with Ca{sup ++} and Mg{sup ++} free PBS and irradiated in the cold. Colonies were scored after 2 weeks. The two cell lines exhibit similar survival kinetics after UVC. S91/IE is more sensitive to killing by either UVB (TL01) or UVA. However, S91/amel cells are more sensitive to killing by UVB plus UVA (FS20). It is clear that UV of different qualities can interact to produce effects that would not be predicted based on responses to monochromatic wave lengths.« less

Effects of UV-B radiation on the isoflavone accumulation and physiological-biochemical changes of soybean during germination: Physiological-biochemical change of germinated soybean induced by UV-B.

PubMed

Ma, Meng; Wang, Pei; Yang, Runqiang; Gu, Zhenxin

2018-06-01

In this study, the effects of UV-B radiation on the isoflavones accumulation, physiological and nutritional quality, water status, and characteristics of proteins in germinated soybeans were investigated. The results showed that isoflavones content in soybeans increased with appropriate intensity and time of UV-B radiation and decreased with excessive treatment. Fresh weight, length, free amino acids, reducing sugar contents and bulk water (T 23 ) in germinated soybeans decreased with increasing radiation time, indicating that UV-B inhibited the growth and nutrients metabolism of soybean during germination. Cell damage was detected in germinated soybeans with excessive UV-B radiation, as shown by the black spots in cotyledons and the increased intercellular water determined by LF-NMR. Germination resulted in an increase in random coil structures, while UV-B radiation induced no obvious changes in FT-IR spectrum and protein conformation of soybeans. Both UV-B radiation and germination caused the increase in soluble proteins, especially in 1.0-75.0 kDa fraction. Copyright © 2018 Elsevier Ltd. All rights reserved.

Increased susceptibility to in vitro ultraviolet B radiation in fibroblasts and lymphocytes cultured from systemic lupus erythematosus patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Golan, T.D.; Foltyn, V.; Roueff, A.

1991-02-01

Sunlight is known to induce exacerbations of systemic lupus erythematosus (SLE) but its mechanism remains unclear. We have previously reported that ultraviolet A (UVA) exposure induces an increase in total DNA synthesis (DS) in vitro but a decrease in unscheduled DNA repair synthesis (UDRS) of splenocytes of murine SLE strains. In order to investigate whether similar observations are characteristic of human SLE, peripheral blood lymphocytes (PBL) and dermal fibroblast (DF) cultures of 20 patients and 15 matched controls were exposed in vitro to UVA or UVB at different doses. Thirteen (65%) SLE DF cultures exposed to UVB light (12-24 J/m2)more » showed an increase in DS compared to paired unirradiated cultures. In contrast, UVB-irradiated DF from normal individuals had no significant increase in DS following UVB irradiation. When SLE DF were exposed to higher doses of UVB (48-96 J/m2), 90% of cultures showed a decrease in DS compared to only 20% in the control group. All of the SLE DF cultures showed a decrease of their unscheduled DNA repair capacity following UVB (24-48 J/m2) irradiation whereas no UDRS was apparent in 74% of controls under the same conditions. Similar findings regarding UDRS were observed in SLE PBL cultures and were also confirmed by autoradiography. UVA exposure (0-3840 J/m2) had no effect on DS nor on UDRS in DF or PBL cultured from SLE and controls. The relevance of these in vitro findings to the in vivo pathogenesis of the disease is discussed.« less

UV-B photoreceptor-mediated protection of the photosynthetic machinery in Chlamydomonas reinhardtii

PubMed Central

Allorent, Guillaume; Lefebvre-Legendre, Linnka; Chappuis, Richard; Kuntz, Marcel; Truong, Thuy B.; Niyogi, Krishna K.; Goldschmidt-Clermont, Michel

2016-01-01

Life on earth is dependent on the photosynthetic conversion of light energy into chemical energy. However, absorption of excess sunlight can damage the photosynthetic machinery and limit photosynthetic activity, thereby affecting growth and productivity. Photosynthetic light harvesting can be down-regulated by nonphotochemical quenching (NPQ). A major component of NPQ is qE (energy-dependent nonphotochemical quenching), which allows dissipation of light energy as heat. Photodamage peaks in the UV-B part of the spectrum, but whether and how UV-B induces qE are unknown. Plants are responsive to UV-B via the UVR8 photoreceptor. Here, we report in the green alga Chlamydomonas reinhardtii that UVR8 induces accumulation of specific members of the light-harvesting complex (LHC) superfamily that contribute to qE, in particular LHC Stress-Related 1 (LHCSR1) and Photosystem II Subunit S (PSBS). The capacity for qE is strongly induced by UV-B, although the patterns of qE-related proteins accumulating in response to UV-B or to high light are clearly different. The competence for qE induced by acclimation to UV-B markedly contributes to photoprotection upon subsequent exposure to high light. Our study reveals an anterograde link between photoreceptor-mediated signaling in the nucleocytosolic compartment and the photoprotective regulation of photosynthetic activity in the chloroplast. PMID:27930292

UV-B photoreceptor-mediated protection of the photosynthetic machinery in Chlamydomonas reinhardtii.

PubMed

Allorent, Guillaume; Lefebvre-Legendre, Linnka; Chappuis, Richard; Kuntz, Marcel; Truong, Thuy B; Niyogi, Krishna K; Ulm, Roman; Goldschmidt-Clermont, Michel

2016-12-20

Life on earth is dependent on the photosynthetic conversion of light energy into chemical energy. However, absorption of excess sunlight can damage the photosynthetic machinery and limit photosynthetic activity, thereby affecting growth and productivity. Photosynthetic light harvesting can be down-regulated by nonphotochemical quenching (NPQ). A major component of NPQ is qE (energy-dependent nonphotochemical quenching), which allows dissipation of light energy as heat. Photodamage peaks in the UV-B part of the spectrum, but whether and how UV-B induces qE are unknown. Plants are responsive to UV-B via the UVR8 photoreceptor. Here, we report in the green alga Chlamydomonas reinhardtii that UVR8 induces accumulation of specific members of the light-harvesting complex (LHC) superfamily that contribute to qE, in particular LHC Stress-Related 1 (LHCSR1) and Photosystem II Subunit S (PSBS). The capacity for qE is strongly induced by UV-B, although the patterns of qE-related proteins accumulating in response to UV-B or to high light are clearly different. The competence for qE induced by acclimation to UV-B markedly contributes to photoprotection upon subsequent exposure to high light. Our study reveals an anterograde link between photoreceptor-mediated signaling in the nucleocytosolic compartment and the photoprotective regulation of photosynthetic activity in the chloroplast.

UV-blocking spectacle lens protects against UV-induced decline of visual performance.

PubMed

Liou, Jyh-Cheng; Teng, Mei-Ching; Tsai, Yun-Shan; Lin, En-Chieh; Chen, Bo-Yie

2015-01-01

Excessive exposure to sunlight may be a risk factor for ocular diseases and reduced visual performance. This study was designed to examine the ability of an ultraviolet (UV)-blocking spectacle lens to prevent visual acuity decline and ocular surface disorders in a mouse model of UVB-induced photokeratitis. Mice were divided into 4 groups (10 mice per group): (1) a blank control group (no exposure to UV radiation), (2) a UVB/no lens group (mice exposed to UVB rays, but without lens protection), (3) a UVB/UV400 group (mice exposed to UVB rays and protected using the CR-39™ spectacle lens [UV400 coating]), and (4) a UVB/photochromic group (mice exposed to UVB rays and protected using the CR-39™ spectacle lens [photochromic coating]). We investigated UVB-induced changes in visual acuity and in corneal smoothness, opacity, and lissamine green staining. We also evaluated the correlation between visual acuity decline and changes to the corneal surface parameters. Tissue sections were prepared and stained immunohistochemically to evaluate the structural integrity of the cornea and conjunctiva. In blank controls, the cornea remained undamaged, whereas in UVB-exposed mice, the corneal surface was disrupted; this disruption significantly correlated with a concomitant decline in visual acuity. Both the UVB/UV400 and UVB/photochromic groups had sharper visual acuity and a healthier corneal surface than the UVB/no lens group. Eyes in both protected groups also showed better corneal and conjunctival structural integrity than unprotected eyes. Furthermore, there were fewer apoptotic cells and less polymorphonuclear leukocyte infiltration in corneas protected by the spectacle lenses. The model established herein reliably determines the protective effect of UV-blocking ophthalmic biomaterials, because the in vivo protection against UV-induced ocular damage and visual acuity decline was easily defined.

Efficacy of marigold extract-loaded formulations against UV-induced oxidative stress.

PubMed

Fonseca, Yris Maria; Catini, Carolina Dias; Vicentini, Fabiana T M C; Cardoso, Juliana Cordeiro; Cavalcanti De Albuquerque Junior, Ricardo Luiz; Vieira Fonseca, Maria José

2011-06-01

The present study investigated the potential use of topical formulations containing marigold extract (ME) (Calendula officinalis extract) against ultraviolet (UV)B irradiation-induced skin damage. The physical and functional stabilities, as well as the skin penetration capacity, of the different topical formulations developed were evaluated. In addition, the in vivo capacity to prevent/treat the UVB irradiation-induced skin damage, in hairless mice, of the formulation with better skin penetration capacity was investigated. All of the formulations were physically and functionally stable. The gel formulation [Formulation 3 (F3)] was the most effective for the topical delivery of ME, which was detected as 0.21 μg/cm(2) of narcissin and as 0.07 μg/cm(2) of the rutin in the viable epidermis. This formulation was able to maintain glutathione reduced levels close to those of nonirradiated animals, but did not affect the gelatinase-9 and myeloperoxidase activities increased by exposure to UVB irradiation. In addition, F3 reduced the histological skin changes induced by UVB irradiation that appear as modifications of collagen fibrils. Therefore, the photoprotective effect in hairless mice achieved with the topical application of ME in gel formulation is most likely associated with a possible improvement in the collagen synthesis in the subepidermal connective tissue. Copyright © 2010 Wiley-Liss, Inc.

Interference of silibinin with IGF-1R signalling pathways protects human epidermoid carcinoma A431 cells from UVB-induced apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Weiwei; Otkur, Wuxiyar; Li, Lingzhi

Highlights: ► Silibinin protects A431 cells from UVB irradiation-induced apoptosis. ► Up-regulation of the IGF-1R-JNK/ERK pathways by UVB induces cell apoptosis. ► Silibinin inhibits IGF-1R pathways to repress caspase-8-mediated apoptosis. -- Abstract: Ultraviolet B (UVB) from sunlight is a major cause of cutaneous lesion. Silibinin, a traditional hepatic protectant, elicits protective effects against UVB-induced cellular damage. In A431 cells, the insulin-like growth factor-1 receptor (IGF-1R) was markedly up-regulated by UVB irradiation. The activation of the IGF-1R signalling pathways contributed to apoptosis of the cells rather than rescuing the cells from death. Up-regulated IGF-1R stimulated downstream mitogen-activated protein kinases (MAPKs), suchmore » as c-Jun N-terminal kinases (JNK) and extracellular signal-regulated protein kinases 1/2 (ERK1/2). The subsequent activation of caspase-8 and caspase-3 led to apoptosis. The activation of IGF-1R signalling pathways is the cause of A431 cell death. The pharmacological inhibitors and the small interfering RNA (siRNA) targeting IGF-1R suppressed the downstream activation of JNK/ERK-caspases to help the survival of the UVB-irradiated A431 cells. Indeed, silibinin treatment suppressed the IGF-1R-JNK/ERK pathways and thus protected the cells from UVB-induced apoptosis.« less

Reactive oxygen-mediated damage to a human DNA replication and repair protein.

PubMed

Montaner, Beatriz; O'Donovan, Peter; Reelfs, Olivier; Perrett, Conal M; Zhang, Xiaohong; Xu, Yao-Zhong; Ren, Xiaolin; Macpherson, Peter; Frith, David; Karran, Peter

2007-11-01

Ultraviolet A (UVA) makes up more than 90% of incident terrestrial ultraviolet radiation. Unlike shorter wavelength UVB, which damages DNA directly, UVA is absorbed poorly by DNA and is therefore considered to be less hazardous. Organ transplant patients treated with the immunosuppressant azathioprine frequently develop skin cancer. Their DNA contains 6-thioguanine-a base analogue that generates DNA-damaging singlet oxygen ((1)O(2)) when exposed to UVA. Here, we show that this (1)O(2) damages proliferating cell nuclear antigen (PCNA), the homotrimeric DNA polymerase sliding clamp. It causes covalent oxidative crosslinking between the PCNA subunits through a histidine residue in the intersubunit domain. Crosslinking also occurs after treatment with higher-although still moderate-doses of UVA alone or with chemical oxidants. Chronic accumulation of oxidized proteins is linked to neurodegenerative disorders and ageing. Our findings identify oxidative damage to an important DNA replication and repair protein as a previously unrecognized hazard of acute oxidative stress.

Long non-coding RNA HOTAIR promotes UVB-induced apoptosis and inflammatory injury by up-regulation of PKR in keratinocytes.

PubMed

Liu, Guo; Zhang, Wenhao

2018-06-11

Excessive exposure to ultraviolet (UV) rays can cause damage of the skin and may induce cancer, immunosuppression, photoaging, and inflammation. The long non-coding RNA (lncRNA) HOX antisense intergenic RNA (HOTAIR) is involved in multiple human biological processes. However, its role in UVB-induced keratinocyte injury is unclear. This study was performed to investigate the effects of HOTAIR in UVB-induced apoptosis and inflammatory injury in human keratinocytes (HaCaT cells). Quantitative real-time polymerase chain reaction was performed to analyze the expression levels of HOTAIR, PKR, TNF-α, and IL-6. Cell viability was measured using trypan blue exclusion method and cell apoptosis using flow cytometry and western blot. ELISA was used to measure the concentrations of TNF-α and IL-6. Western blot was used to measure the expression of PKR, apoptosis-related proteins, and PI3K/AKT and NF-κB pathway proteins. UVB induced HaCaT cell injury by inhibiting cell viability and promoting cell apoptosis and expressions of IL-6 and TNF-α. UVB also promoted the expression of HOTAIR. HOTAIR suppression increased cell viability and decreased apoptosis and expression of inflammatory factors in UVB-treated cells. HOTAIR also promoted the expression of PKR. Overexpression of HOTAIR decreased cell viability and increased cell apoptosis and expression of inflammatory factors in UVB-treated cells by upregulating PKR. Overexpression of PKR decreased cell viability and promoted cell apoptosis in UVB-treated cells. Overexpression of PKR activated PI3K/AKT and NF-κB pathways. Our findings identified an essential role of HOTAIR in promoting UVB-induced apoptosis and inflammatory injury by up-regulating PKR in keratinocytes.

Generation of novel covalent RNA-protein complexes in cells by ultraviolet B irradiation: implications for autoimmunity.

PubMed

Andrade, Felipe; Casciola-Rosen, Livia A; Rosen, Antony

2005-04-01

To determine whether ultraviolet B (UVB) irradiation induces novel modifications in autoantigens targeted during experimental photoinduced epidermal damage. To search for novel UVB-induced autoantigen modifications, lysates made from UVB-irradiated human keratinocytes or HeLa cells were immunoblotted using human autoantibodies that recognize ribonucleoprotein autoantigens. Novel autoantigen structures identified were further characterized using nucleases and RNA hybridization. Human sera that recognize U1-70 kd (U1-70K) and La by immunoblotting also recognized multiple novel species when they were used to immunoblot lysates of UVB-irradiated keratinocytes or HeLa cells. These species were not present in control cells and were not observed when apoptosis was induced by Fas ligation or cytotoxic lymphocyte granule contents. Biochemical analysis using multiple assays revealed that these novel UVB-induced molecular species result from the covalent crosslinking between the U1 RNA and the hYRNA molecules with their associated proteins, including U1-70K, La, and likely components of the Sm particle. These data demonstrate that UVB irradiation of live cells can directly induce covalent RNA-protein complexes, which are recognized by human autoantibodies. As previously described for other autoantigens, these covalent complexes of RNA and proteins may have important consequences in terms of antigen capture and processing.

Potential for tyndalized Lactobacillus acidophilus as an effective component in moisturizing skin and anti-wrinkle products.

PubMed

Im, A-Rang; Kim, Hui Seong; Hyun, Jin Won; Chae, Sungwook

2016-08-01

It is widely accepted that ultraviolet (UV) irradiation induces skin damage. In the present study, a UVB-induced hairless mouse model of skin photoaging was developed to determine whether tyndalized Lactobacillus acidophilus was able to significantly enhance the repair of photodamaged skin. To evaluate the effects of tyndalized L. acidophilus on UVB-induced skin-wrinkle formation in vivo , HR-1 hairless male mice were exposed to UVB radiation and orally administered tyndalized L. acidophilus . Compared with the control group, the UVB irradiation mice displayed a significant increase in transepidermal water loss and a reduction in skin hydration. In mice with UVB-induced photodamage, the effacement of the fine wrinkles by tyndalized L. acidophilus was correlated with dermal collagen synthesis, accompanied by histological changes. Furthermore, western blotting was performed to investigate the protein expression levels of matrix metalloproteinases (MMPs) and mitogen-activated protein kinase. Notably, orally administered tyndalized L. acidophilus reduced the expression levels of MMP-1 and MMP-9. Based upon the aforementioned results, it was determined that tyndalized L. acidophilus effectively inhibited the wrinkle formation induced by UVB irradiation, and that this may be attributed to the downregulation of MMPs. Therefore, tyndalized L. acidophilus may be considered a potential agent for preventing skin photoaging and wrinkle formation.

Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice

PubMed Central

Martinez, Renata M.; Pinho-Ribeiro, Felipe A.; Steffen, Vinicius S.; Silva, Thais C. C.; Caviglione, Carla V.; Bottura, Carolina; Fonseca, Maria J. V.; Vicentini, Fabiana T. M. C.; Vignoli, Josiane A.; Baracat, Marcela M.; Georgetti, Sandra R.; Verri, Waldiceu A.; Casagrande, Rubia

2016-01-01

Naringenin (NGN) exhibits anti-inflammatory and antioxidant activities, but it remains undetermined its topical actions against ultraviolet B (UVB)-induced inflammation and oxidative stress in vivo. The purpose of this study was to evaluate the physicochemical and functional antioxidant stability of NGN containing formulations, and the effects of selected NGN containing formulation on UVB irradiation-induced skin inflammation and oxidative damage in hairless mice. NGN presented ferric reducing power, ability to scavenge 2,2′-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) and hydroxyl radical, and inhibited iron-independent and dependent lipid peroxidation. Among the three formulations containing NGN, only the F3 kept its physicochemical and functional stability over 180 days. Topical application of F3 in mice protected from UVB-induced skin damage by inhibiting edema and cytokine production (TNF-α, IL-1β, IL-6, and IL-10). Furthermore, F3 inhibited superoxide anion and lipid hydroperoxides production and maintained ferric reducing and ABTS scavenging abilities, catalase activity, and reduced glutathione levels. In addition, F3 maintained mRNA expression of cellular antioxidants glutathione peroxidase 1, glutathione reductase and transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), and induced mRNA expression of heme oxygenase-1. In conclusion, a formulation containing NGN may be a promising approach to protecting the skin from the deleterious effects of UVB irradiation. PMID:26741806

UVB Radiation Delays Tribolium castaneum Metamorphosis by Influencing Ecdysteroid Metabolism.

PubMed

Sang, Wen; Yu, Lin; He, Li; Ma, Wei-Hua; Zhu, Zhi-Hui; Zhu, Fen; Wang, Xiao-Ping; Lei, Chao-Liang

2016-01-01

Ultraviolet B (UVB) radiation is an important environmental factor. It is generally known that UVB exhibits high genotoxicity due to causing DNA damage, potentially leading to skin carcinogenesis and aging in mammals. However, little is known about the effects of UVB on the development and metamorphosis of insects, which are the most abundant terrestrial animals. In the present study, we performed dose-response analyses of the effects UVB irradiation on Tribolium castaneum metamorphosis, assessed the function of the T. castaneum prothoracicotropic hormone gene (Trcptth), and analyzed ecdysteroid pathway gene expression profile and ecdysterone titers post-UVB irradiation. The results showed that UVB not only caused death of T. castaneum larvae, but also delayed larval-pupal metamorphosis and reduced the size and emergence rate of pupae. In addition, we verified the function of Trcptth, which is responsible for regulating metamorphosis. It was also found that the expression profiles of Trcptth as well as ecdysteroidogenesis and response genes were influenced by UVB radiation. Therefore, a disturbance pulse of ecdysteroid may be involved in delaying development under exposure to irradiation. To our knowledge, this is the first report indicating that UVB can influence the metamorphosis of insects. This study will contribute to a better understanding of the impact of UVB on signaling mechanisms in insect metamorphosis.

Pterocarpus santalinus L. Regulated Ultraviolet B Irradiation-induced Procollagen Reduction and Matrix Metalloproteinases Expression Through Activation of TGF-β/Smad and Inhibition of the MAPK/AP-1 Pathway in Normal Human Dermal Fibroblasts.

PubMed

Gao, Wei; Lin, Pei; Hwang, Eunson; Wang, Yushuai; Yan, Zhengfei; Ngo, Hien T T; Yi, Tae-Hoo

2018-01-01

Ultraviolet light-induced reactive oxygen species (ROS) damage human skin and prematurely cause aging. A growing body of research is focusing on considering plants and plant-derived compounds as antiphotoaging therapeutic material. Pterocarpus santalinus L., as an Indian traditional medicine, possesses antidiabetic, anti-inflammatory and antioxidative effects. Here, we studied the antiphotoaging effects of ethanolic extract of P. santalinus L. heartwood (EPS) on ultraviolet radiation B (UVB)-irradiated normal human dermal fibroblasts (NHDFs). Results showed that EPS significantly inhibited the upregulation of matrix metalloproteinases and IL-6 caused by UVB irradiation, and suppressed UVB-induced phosphorylation of extracellular signal-regulated kinase, Jun N-terminal kinase and p38, as well as the activation of AP-1 transcription factors. Further study indicated that UVB-induced production of MMP-1 and IL-6 could be inhibited by PD 98059 (an ERK inhibitor) and SP600125 (A JNK inhibitor), implied that EPS inhibited UVB-induced MMP-1 and IL-6 secretion by inactivating MAPK signaling pathway. In addition, EPS possessed an excellent antioxidant activity, which could increase cytoprotective antioxidants such as HO-1, NQ-O1 expression by facilitating the nuclear accumulation of Nrf2. Treatment of NHDFs with EPS also recovered UVB-induced procollagen type I reduction by activating TGF-β/Smad pathway. These findings demonstrated that EPS had a potential effect against UVB-induced skin photoaging. © 2017 The American Society of Photobiology.

Conversion from CUL4-based COP1–SPA E3 apparatus to UVR8–COP1–SPA complexes underlies a distinct biochemical function of COP1 under UV-B

PubMed Central

Huang, Xi; Ouyang, Xinhao; Yang, Panyu; Lau, On Sun; Chen, Liangbi; Wei, Ning; Deng, Xing Wang

2013-01-01

The evolutionarily conserved CONSTITUTIVE PHOTOMORPHOGENESIS 1 (COP1) is a RING and WD40 protein that functions as a substrate receptor of CULLIN4–DAMAGED DNA BINDING PROTEIN 1 (CUL4–DDB1)–based E3 ubiquitin ligases in both plants and animals. In Arabidopsis, COP1 is a central repressor of photomorphogenesis in the form of COP1–SUPPRESSOR OF PHYA (SPA) complex(es). CUL4–DDB1–COP1–SPA suppresses the photomorphogenic program by targeting the transcription factor ELONGATED HYPOCOTYL 5 for degradation. Intriguingly, under photomorphogenic UV-B light, COP1 reverses its repressive role and promotes photomorphogenesis. However, the mechanism by which COP1 is functionally switched is still obscure. Here, we demonstrate that UV-B triggers the physical and functional disassociation of the COP1–SPA core complex(es) from CUL4–DDB1 and the formation of a unique complex(es) containing the UV-B receptor UV RESISTANCE LOCUS 8 (UVR8). The establishment of this UV-B–dependent COP1 complex(es) is associated with its positive modulation of ELONGATED HYPOCOTYL 5 stability and activity, which sheds light on the mechanism of COP1’s promotive action in UV-B–induced photomorphogenesis. PMID:24067658

UV-B photoreceptor-mediated protection of the photosynthetic machinery in Chlamydomonas reinhardtii

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allorent, Guillaume; Lefebvre-Legendre, Linnka; Chappuis, Richard

Life on earth is dependent on the photosynthetic conversion of light energy into chemical energy. However, absorption of excess sunlight can damage the photosynthetic machinery and limit photosynthetic activity, thereby affecting growth and productivity. Photosynthetic light harvesting can be down-regulated by nonphotochemical quenching (NPQ). A major component of NPQ is qE (energy-dependent nonphotochemical quenching), which allows dissipation of light energy as heat. Photodamage peaks in the UV-B part of the spectrum, but whether and how UV-B induces qE are unknown. Plants are responsive to UV-B via the UVR8 photoreceptor. Here in this paper, we report in the green alga Chlamydomonasmore » reinhardtii that UVR8 induces accumulation of specific members of the light-harvesting complex (LHC) superfamily that contribute to qE, in particular LHC Stress-Related 1 (LHCSR1) and Photosystem II Subunit S (PSBS). The capacity for qE is strongly induced by UV-B, although the patterns of qE-related proteins accumulating in response to UV-B or to high light are clearly different. The competence for qE induced by acclimation to UV-B markedly contributes to photoprotection upon subsequent exposure to high light. Our study reveals an anterograde link between photoreceptor-mediated signaling in the nucleocytosolic compartment and the photoprotective regulation of photosynthetic activity in the chloroplast.« less

UV-B photoreceptor-mediated protection of the photosynthetic machinery in Chlamydomonas reinhardtii

DOE PAGES

Allorent, Guillaume; Lefebvre-Legendre, Linnka; Chappuis, Richard; ...

2016-12-05

Life on earth is dependent on the photosynthetic conversion of light energy into chemical energy. However, absorption of excess sunlight can damage the photosynthetic machinery and limit photosynthetic activity, thereby affecting growth and productivity. Photosynthetic light harvesting can be down-regulated by nonphotochemical quenching (NPQ). A major component of NPQ is qE (energy-dependent nonphotochemical quenching), which allows dissipation of light energy as heat. Photodamage peaks in the UV-B part of the spectrum, but whether and how UV-B induces qE are unknown. Plants are responsive to UV-B via the UVR8 photoreceptor. Here in this paper, we report in the green alga Chlamydomonasmore » reinhardtii that UVR8 induces accumulation of specific members of the light-harvesting complex (LHC) superfamily that contribute to qE, in particular LHC Stress-Related 1 (LHCSR1) and Photosystem II Subunit S (PSBS). The capacity for qE is strongly induced by UV-B, although the patterns of qE-related proteins accumulating in response to UV-B or to high light are clearly different. The competence for qE induced by acclimation to UV-B markedly contributes to photoprotection upon subsequent exposure to high light. Our study reveals an anterograde link between photoreceptor-mediated signaling in the nucleocytosolic compartment and the photoprotective regulation of photosynthetic activity in the chloroplast.« less

An LED-based UV-B irradiation system for tiny organisms: System description and demonstration experiment to determine the hatchability of eggs from four Tetranychus spider mite species from Okinawa.

PubMed

Suzuki, Takeshi; Yoshioka, Yoshio; Tsarsitalidou, Olga; Ntalia, Vivi; Ohno, Suguru; Ohyama, Katsumi; Kitashima, Yasuki; Gotoh, Tetsuo; Takeda, Makio; Koveos, Dimitris S

2014-03-01

We developed a computer-based system for controlling the photoperiod and irradiance of UV-B and white light from a 5×5 light-emitting diode (LED) matrix (100×100mm). In this system, the LED matrix was installed in each of four irradiation boxes and controlled by pulse-width modulators so that each box can independently emit UV-B and white light at irradiances of up to 1.5 and 4.0Wm(-2), respectively, or a combination of both light types. We used this system to examine the hatchabilities of the eggs of four Tetranychus spider mite species (T. urticae, T. kanzawai, T. piercei and T. okinawanus) collected from Okinawa Island under UV-B irradiation alone or simultaneous irradiation with white light for 12hd(-1) at 25°C. Although no eggs of any species hatched under the UV-B irradiation, even when the irradiance was as low as 0.02Wm(-2), the hatchabilities increased to >90% under simultaneous irradiation with 4.0Wm(-2) white light. At 0.06Wm(-2) UV-B, T. okinawanus eggs hatched (15% hatchability) under simultaneous irradiation with white light, whereas other species showed hatchabilities <1%. These results suggest that photolyases activated by white light may reduce UV-B-induced DNA damage in spider mite eggs and that the greater UV-B tolerance of T. okinawanus may explain its dominance on plants in seashore environments, which have a higher risk of exposure to reflected UV-B even on the undersurface of leaves. Our system will be useful for further examination of photophysiological responses of tiny organisms because of its ability to precisely control radiation conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of Galla chinensis extracts on UVB-irradiated MMP-1 production in hairless mice.

PubMed

Sun, Zheng-wang; Hwang, Eunson; Lee, Hyun Ji; Lee, Tae Youp; Song, Hyun Geun; Park, Sang-Yong; Shin, Heon-Sub; Lee, Don-Gil; Yi, Tae Hoo

2015-01-01

Galla chinensis (GAC) is a natural traditional Chinese medicine that has been widely used in folk medicine. Although GAC compounds (mainly gallic acid and methyl gallate) possess strong antiviral, antibacterial, anticancer, and antioxidant activities, there is no report regarding topical or oral administration of GAC compounds on UVB irradiation-induced photoaging in hairless mice (SKH: HR-1). In the present study, we examined cell viability, intracellular reactive oxygen species (ROS), matrix metalloproteinase-1 (MMP-1), and interleukin-6 (IL-6) in skin fibroblasts and keratinocytes induced by UVB in vitro. We also studied skin damage by measuring skin thickness, elasticity, wrinkling and levels of protein MMP-1, elastin, procollagen type I, and transforming growth factor-β1 (TGF-β1) in hairless mouse skin chronically irradiated by UVB in vivo. GAC treatment significantly prevented skin photoaging by reducing the levels of ROS, MMP-1, and IL-6 and promoting production of elastin, procollagen type I, and TGF-β1. According to the results of H&E staining and Masson's trichrome staining, GAC reduced skin thickness and wrinkle formation while it increased skin elasticity. The effects of GAC on UVB-induced skin photoaging may be due to suppressed MMP-1 expression. These findings could be referenced for the development of new agents that target UVB-induced photoaging.

Photochemoprotective effect of a fraction of a partially purified extract of Byrsonima crassifolia leaves against UVB-induced oxidative stress in fibroblasts and hairless mice.

PubMed

de Souza, Rebeca Oliveira; de Assis Dias Alves, Geórgia; Aguillera, Ana Luiza Scarano; Rogez, Hervé; Fonseca, Maria José Vieira

2018-01-01

Ultraviolet B (UVB) irradiation increases the risk of various skin disorders, leading to inflammation and oxidative stress and thereby increasing the risk of skin photoaging and carcinogenesis. The use of photochemoprotectors such as natural products with antioxidant and anti-inflammatory properties represents a strategy for preventing UVB-induced skin damage. We investigated the photochemoprotective effect of a fraction of a partially purified extract of Byrsonima crassifolia leaves (BCF) on fibroblasts and hairless mice exposed to UVB radiation. The mixture of phenolic compounds in BCF prevented the decrease in reduced glutathione (GSH) levels in fibroblast cultures induced by UVB radiation more than some of their individual standards ((+)-catechin (CAT), epigallocatechin gallate and quercetin 3-O-β-d-glucopyranoside). Prepared gel formulations increased skin antioxidant activity, and BCF components and the CAT standard were retained in the HRS/J hairless mice epidermis 2h after application. Topical treatment with the BCF or CAT formulations (1%) significantly reduced the decrease in GSH levels and decreased myeloperoxidase activity and the secretion of pro-inflammatory cytokines IL-1β and IL-6 induced by UVB radiation (P<0.05), indicating that both BCF and CAT had anti-inflammatory effects. BCF inhibited UVB-induced metalloproteinase (MMP)-9 secretion/activity, whereas CAT had no effect on MMP-9 activity in the skin of treated animals. These results therefore suggest that BCF can be used as a photochemoprotective agent and antioxidant in the prevention/treatment of inflammation and oxidative stress of the skin induced by UVB radiation. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-wrinkle effects of Sargassum muticum ethyl acetate fraction on ultraviolet B-irradiated hairless mouse skin and mechanistic evaluation in the human HaCaT keratinocyte cell line

PubMed Central

Song, Jae Hyoung; Piao, Mei Jing; Han, Xia; Kang, Kyoung Ah; Kang, Hee Kyoung; Yoon, Weon Jong; Ko, Mi Hee; Lee, Nam Ho; Lee, Mi Young; Chae, Sungwook; Hyun, Jin Won

2016-01-01

The present study investigated the photoprotective properties of the ethyl acetate fraction of Sargassum muticum (SME) against ultraviolet B (UVB)-induced skin damage and photoaging in a mouse model. HR-1 strain hairless male mice were divided into three groups: An untreated control group, a UVB-irradiated vehicle group and a UVB-irradiated SME group. The UVB-irradiated mice in the SME group were orally administered with SME (100 mg/kg body weight in 0.1 ml water per day) and then exposed to radiation at a dose of 60–120 mJ/cm2. Wrinkle formation and skin damage were evaluated by analysis of skin replicas, epidermal thickness and collagen fiber integrity in the dermal connective tissue. The mechanism underlying the action of SME was also investigated in the human HaCaT keratinocyte cell line following exposure of the cells to UVB at a dose of 30 mJ/cm2. The protein expression levels and activity of matrix metalloproteinase-1 (MMP-1), and the binding of activator protein-1 (AP-1) to the MMP-1 promoter were assessed in the HaCaT cells using western blot analysis, an MMP-1 fluorescent assay and a chromatin immune-precipitation assay, respectively. The results showed that the mean length and depth of the wrinkles in the UVB-exposed hairless mice were significantly improved by oral administration of SME, which also prevented the increase in epidermal thickness triggered by UVB irradiation. Furthermore, a marked increase in collagen bundle formation was observed in the UVB-treated mice with SME administration. SME pretreatment also significantly inhibited the UVB-induced upregulation in the expression and activity of MMP-1 in the cultured HaCaT keratinocytes, and the UVB-enhanced association of AP-1 with the MMP-1 promoter. These results suggested that SME may be useful as an anti-photoaging resource for the skin. PMID:27573915

Thread Embedding Acupuncture Inhibits Ultraviolet B Irradiation-Induced Skin Photoaging in Hairless Mice.

PubMed

Kim, Yoon-Jung; Kim, Ha-Neui; Shin, Mi-Sook; Choi, Byung-Tae

2015-01-01

Thread embedding acupuncture (TEA) is an acupuncture treatment applied to many diseases in Korean medical clinics because of its therapeutic effects by continuous stimulation to tissues. It has recently been used to enhance facial skin appearance and antiaging, but data from evidence-based medicine are limited. To investigate whether TEA therapy can inhibit skin photoaging by ultraviolet B (UVB) irradiation, we performed analyses for histology, histopathology, in situ zymography and western blot analysis in HR-1 hairless mice. TEA treatment resulted in decreased wrinkle formation and skin thickness (Epidermis; P = 0.001 versus UV) in UVB irradiated mice and also inhibited degradation of collagen fibers (P = 0.010 versus normal) by inhibiting proteolytic activity of gelatinase matrix-metalloproteinase-9 (MMP-9). Western blot data showed that activation of c-Jun N-terminal kinase (JNK) induced by UVB (P = 0.002 versus normal group) was significantly inhibited by TEA treatment (P = 0.005 versus UV) with subsequent alleviation of MMP-9 activation (P = 0.048 versus UV). These results suggest that TEA treatment can have anti-photoaging effects on UVB-induced skin damage by maintenance of collagen density through regulation of expression of MMP-9 and related JNK signaling. Therefore, TEA therapy may have potential roles as an alternative treatment for protection against skin damage from aging.

Thread Embedding Acupuncture Inhibits Ultraviolet B Irradiation-Induced Skin Photoaging in Hairless Mice

PubMed Central

Kim, Yoon-Jung; Kim, Ha-Neui; Shin, Mi-Sook; Choi, Byung-Tae

2015-01-01

Thread embedding acupuncture (TEA) is an acupuncture treatment applied to many diseases in Korean medical clinics because of its therapeutic effects by continuous stimulation to tissues. It has recently been used to enhance facial skin appearance and antiaging, but data from evidence-based medicine are limited. To investigate whether TEA therapy can inhibit skin photoaging by ultraviolet B (UVB) irradiation, we performed analyses for histology, histopathology, in situ zymography and western blot analysis in HR-1 hairless mice. TEA treatment resulted in decreased wrinkle formation and skin thickness (Epidermis; P = 0.001 versus UV) in UVB irradiated mice and also inhibited degradation of collagen fibers (P = 0.010 versus normal) by inhibiting proteolytic activity of gelatinase matrix-metalloproteinase-9 (MMP-9). Western blot data showed that activation of c-Jun N-terminal kinase (JNK) induced by UVB (P = 0.002 versus normal group) was significantly inhibited by TEA treatment (P = 0.005 versus UV) with subsequent alleviation of MMP-9 activation (P = 0.048 versus UV). These results suggest that TEA treatment can have anti-photoaging effects on UVB-induced skin damage by maintenance of collagen density through regulation of expression of MMP-9 and related JNK signaling. Therefore, TEA therapy may have potential roles as an alternative treatment for protection against skin damage from aging. PMID:26185518

Protective effects of antioxidin-RL from Odorrana livida against ultraviolet B-irradiated skin photoaging.

PubMed

Qin, Di; Lee, Wen-Hui; Gao, Zhiqin; Zhang, Weifen; Peng, Meiyu; Sun, Tongyi; Gao, Yuanyuan

2018-03-01

The unavoidable daily exposure of the skin to ultraviolet (UV) B radiation is proven to have deleterious effects. The action mechanism of antioxidin-RL, an antioxidant peptide purified from skin secretions of frog Odorrana livida with amino acid sequence of AMRLTYNRPCIYAT, is well characterized by NMR titration and mutation based on ABTS + scavenging activities. In order to explore the protective effects of antioxidin-RL against UVB-irradiated skin photoaging, cell uptake assay was used to detect the location of antioxidin-RL molecules serving various biological functions in the cells. The protective effects of antioxidin-RL on UVB-induced response were examined in vitro and in vivo. Results showed that antioxidin-RL successfully penetrated the cell membrane and exerted a positive effect on cell migration. It also effectively inhibited the UVB-induced excessive production of ROS and prevented oxidative damage to DNAs and proteins. Moreover, the mRNA expressions of MMP-1, VEGF, COX-2, and pro-inflammatory cytokines, such as IL-6 and TNF-α in antioxidin-RL-treated HaCaT and HSF cells were significantly down-regulated whereas those of FGF, procollagen type I and TGF-β1 up-regulated. Antioxidin-RL effectively prevented UVB-induced erythema on mouse skin, thereby inhibiting UVB-induced skin thickening and inflammation and increasing collagen deposition as demonstrated by in vivo experiments. Hence, the novel antioxidant peptide antioxidin-RL can effectively reduce UVB-induced skin reactions in vivo and in vitro, providing potential molecules against UVB-induced inflammation and photoaging. Copyright © 2018 Elsevier Inc. All rights reserved.

Role of root UV-B sensing in Arabidopsis early seedling development.

PubMed

Tong, Hongyun; Leasure, Colin D; Hou, Xuewen; Yuen, Gigi; Briggs, Winslow; He, Zheng-Hui

2008-12-30

All sun-exposed organisms are affected by UV-B [(UVB) 280-320 nm], an integral part of sunlight. UVB can cause stresses or act as a developmental signal depending on its fluence levels. In plants, the mechanism by which high-fluence-rate UVB causes damages and activates DNA-repair systems has been extensively studied. However, little is known about how nondamaging low-fluence-rate UVB is perceived to regulate plant morphogenesis and development. Here, we report the identification of an Arabidopsis mutant, root UVB sensitive 1 (rus1), whose primary root is hypersensitive to very low-fluence-rate (VLF) UVB. Under standard growth-chamber fluorescent white light, rus1 displays stunted root growth and fails to form postembryonic leaves. Experiments with different monochromatic light sources showed that rus1 phenotypes can be rescued if the seedlings are allowed to grow in light conditions with minimum UVB. We determined that roots, not other organs, perceive the UVB signal. Genetic and molecular analyses confirmed that the root light-sensitive phenotypes are independent of all other known plant photoreceptors. Three rus1 alleles have been identified and characterized. A map-based approach was used to identify the RUS1 locus. RUS1 encodes a protein that contains DUF647 (domain of unknown function 647), a domain highly conserved in eukaryotes. Our results demonstrate a root VLF UVB-sensing mechanism that is involved in Arabidopsis early seedling morphogenesis and development.

Phenolics from Castanea sativa leaves and their effects on UVB-induced damage.

PubMed

Cerulli, Antonietta; Masullo, Milena; Mari, Angela; Balato, Anna; Filosa, Rosanna; Lembo, Serena; Napolitano, Assunta; Piacente, Sonia

2018-05-01

The phytochemical investigation of the methanol extract of the leaves of Castanea sativa Mill., source of the Italian PGI (Protected Geographical Indication) product 'Marrone di Roccadaspide' (Campania region) afforded as main compounds crenatin (1), chestanin (2), gallic acid (3), cretanin (4), 5-O-p-coumaroylquinic acid (5), p-methylgallic acid (6) and quercetin-3-O-glucoside (7). To quantify the isolated compounds a LC-ESI(QqQ)MS method working with a very sensitive and selective mass tandem experiment called Multiple Reaction Monitoring (MRM) has been developed. Moreover the antioxidant capacity by TEAC assay and the ability of compounds 1-7 to protect HaCaT human keratinocytes from UVB-induced damage has been investigated.

Induction of IL-10 gene expression in human keratinocytes by UVB exposure in vivo and in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Enk, C.D.; Blauvelt, A.; Katz, S.I.

Numerous studies have demonstrated that ultraviolet B (UVB) irradiation has profound effects on the skin and systemic immune systems. Because many of the effects of UVB result in suppression of contact sensitivity responses and because IL-10 induces a Th2 rather than a Th1 response, we sought to determine whether UVB irradiation induces IL-10 transcription and subsequent protein secretion by human epidermal cells. Skin of nine volunteers was exposed to UVB or sham irradiation, and epidermal cell suspensions were prepared from suction blister roofs 24 h thereafter. mRNA was extracted using oligo dT-coated magnetic beads, and IL-10 cDNA was amplified withmore » a sensitive RT-PCR technique. We found that IL-10 was constitutively expressed by epidermal cells in 5 of 9 volunteers and that IL-10 message was up-regulated by UVB exposure in all experiments. Since epidermis consists of a heterogeneous cell population with distinct cytokine profiles, we determined whether UVB caused enhanced IL-10 transcription and protein secretion in human keratinocyte cultures. In these experiments, IL-10 was constitutively expressed by keratinocytes and UVB up-regulated IL-10 gene expression in a dose-dependent manner 24 h after in vitro irradiation, coinciding with IL-10 protein secretion into the culture supernatants. Taken together, the findings indicate that UVB irradiation induces IL-10 in human keratinocytes and suggest that keratinocyte-derived IL-10 may be an important component of the immunosuppression that results from UVB irradiation. 55 refs., 5 figs.« less

Effects of a turmeric extract (Curcuma longa) on chronic ultraviolet B irradiation-induced skin damage in melanin-possessing hairless mice.

PubMed

Sumiyoshi, Maho; Kimura, Yoshiyuki

2009-12-01

Turmeric (the rhizomes of Curcuma longa L., Zingiberacease) is widely used as a dietary pigment and spice, and has been traditionally used for the treatment of inflammation, skin wounds and hepatic disorders in Ayurvedic, Unani and Chinese medicine. Although the topical application or oral administration of turmeric is used to improve skin trouble, there is no evidence to support this effect. The aim of this study was to clarify whether turmeric prevents chronic ultraviolet B (UVB)-irradiated skin damage. We examined the effects of a turmeric extract on skin damage including changes in skin thickness and elasticity, pigmentation and wrinkling caused by long-term, low-dose ultraviolet B irradiation in melanin-possessing hairless mice. The extract (at 300 or 1000 mg/kg, twice daily) prevented an increase in skin thickness and a reduction in skin elasticity induced by chronic UVB exposure. It also prevented the formation of wrinkles and melanin (at 1000 mg/kg, twice daily) as well as increases in the diameter and length of skin blood vessels and in the expression of matrix metalloproteinase-2 (MMP-2). Prevention of UVB-induced skin aging by turmeric may be due to the inhibition of increases in MMP-2 expression caused by chronic irradiation.

Determining the Location of DNA Modification and Mutation Caused by UVB Light in Skin Cancer

DTIC Science & Technology

2014-09-01

14 Appendices……………………………………………………………………………14 2 Introduction Ultraviolet ( UV ) light damages skin cells by causing the formation of...dimers on adjacent pyrimidines in DNA. The two main forms of damage caused by UV light are cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6...caused by UV damage in tumor suppressor genes such as p53 have been found in the majority of skin cancers. Many studies have focused on these and

On the history of phyto-photo UV science (not to be left in skoto toto and silence).

PubMed

Björn, Lars Olof

2015-08-01

This review of the history of ultraviolet photobiology focuses on the effects of UV-B (280-315 nm) radiation on terrestrial plants. It describes the early history of ultraviolet photobiology, the discovery of DNA as a major ultraviolet target and the discovery of photoreactivation and photolyases, and the later identification of Photosystem II as another important target for damage to plants by UV-B radiation. Some experimental techniques are briefly outlined. The insight that the ozone layer was thinning spurred the interest in physiological and ecological effects of UV-B radiation and resulted in an exponential increase over time in the number of publications and citations until 1998, at which time it was realized by the research community that the Montreal Protocol regulating the pollution of the atmosphere with ozone depleting substances was effective. From then on, the publication and citation rate has continued to rise exponentially, but with an abrupt change to lower exponents. We have now entered a phase when more emphasis is put on the "positive" effects of UV-B radiation, and with more emphasis on regulation than on damage and inhibition. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Magnolol reduces UVB-induced photodamage by regulating matrix metalloproteinase activity.

PubMed

Im, A-Rang; Song, Jae Hyoung; Lee, Mi Young; Chae, Sungwook

2015-01-01

In this study, we evaluated the anti-photoaging activity of magnolol in UV-irradiated hairless mice, and hypothesized that magnolol would prevent photoaging in these animals. The inhibitory effect of magnolol on wrinkle formation was determined by analyzing the skin replica, histologically examining the epidermal thickness, and identifying damage to the collagen fibers. The protective effects of magnolol on UVB-induced skin photoaging were examined by determining the level of MMPs and mitogen-activated protein kinases (MAPKs). Exposure to UVB radiation significantly increased skin thickness and wrinkle grade, but magnolol treatment significantly reduced the average length and depth of wrinkles, and this was correlated with the inhibition of collagen fiber loss. The magnolol-treated group had remarkably decreased activity levels of MMP-1, -9, and -13 compared to the corresponding levels in the vehicle-treated UVB-irradiated group. These results indicate that magnolol prevents skin photoaging in UVB-irradiated hairless mice. Copyright © 2014 Elsevier B.V. All rights reserved.

Arabidopsis FHY3 and HY5 Positively Mediate Induction of COP1 Transcription in Response to Photomorphogenic UV-B Light[C][W][OA

PubMed Central

Huang, Xi; Ouyang, Xinhao; Yang, Panyu; Lau, On Sun; Li, Gang; Li, Jigang; Chen, Haodong; Deng, Xing Wang

2012-01-01

As sessile organisms, higher plants have evolved the capacity to sense and interpret diverse light signals to modulate their development. In Arabidopsis thaliana, low-intensity and long-wavelength UV-B light is perceived as an informational signal to mediate UV-B–induced photomorphogenesis. Here, we report that the multifunctional E3 ubiquitin ligase, CONSTITUTIVE PHOTOMORPHOGENESIS1 (COP1), a known key player in UV-B photomorphogenic responses, is also a UV-B–inducible gene. Two transcription factors, FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and ELONGATED HYPOCOTYL5 (HY5), directly bind to distinct regulatory elements within the COP1 promoter, which are essential for the induction of the COP1 gene mediated by photomorphogenic UV-B signaling. Absence of FHY3 results in impaired UV-B–induced hypocotyl growth and reduced tolerance against damaging UV-B. Thus, FHY3 positively regulates UV-B–induced photomorphogenesis by directly activating COP1 transcription, while HY5 promotes COP1 expression via a positive feedback loop. Furthermore, FHY3 and HY5 physically interact with each other, and this interaction is diminished by UV-B. Together, our findings reveal that COP1 gene expression in response to photomorphogenic UV-B is controlled by a combinatorial regulation of FHY3 and HY5, and this UV-B–specific working mode of FHY3 and HY5 is distinct from that in far-red light and circadian conditions. PMID:23150635

Histological study on the effect of electrolyzed reduced water-bathing on UVB radiation-induced skin injury in hairless mice.

PubMed

Yoon, Kyung Su; Huang, Xue Zhu; Yoon, Yang Suk; Kim, Soo-Ki; Song, Soon Bong; Chang, Byung Soo; Kim, Dong Heui; Lee, Kyu Jae

2011-01-01

Electrolyzed reduced water (ERW), functional water, has various beneficial effects via antioxidant mechanism in vivo and in vitro. However there is no study about beneficial effects of ERW bathing. This study aimed to determine the effect of ERW bathing on the UVB-induced skin injury in hairless mice. For this purpose, mice were irradiated with UVB to cause skin injury, followed by individually taken a bath in ERW (ERW-bathing) and tap water (TW-bathing) for 21 d. We examined cytokines profile in acute period, and histological and ultrastructural observation of skin in chronic period. We found that UVB-mediated skin injury of ERW-bathing group was significantly low compared to TW control group in the early stage of experiment. Consistently, epidermal thickening as well as the number of dermal mast cell was significantly lowered in ERW-bathing group. Defection of corneocytes under the scanning electron microscope was less observed in ERW-bathing group than in TW-bathing group. Further, the level of interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-12p70 in ERW group decreased whereas those of IL-10 increased. Collectively, our data indicate that ERW-bathing significantly reduces UVB-induced skin damage through influencing pro-/anti-inflammatory cytokine balance in hairless mice. This suggests that ERW-bathing has a positive effect on acute UVB-mediated skin disorders. This is the first report on bathing effects of ERW in UVB-induced skin injury.

Protective effect of cerium ion against ultraviolet B radiation-induced water stress in soybean seedlings.

PubMed

Mao, Chun Xia; Chen, Min Min; Wang, Lei; Zou, Hua; Liang, Chan Juan; Wang, Li Hong; Zhou, Qing

2012-06-01

Effects of cerium ion (Ce(III)) on water relations of soybean seedlings (Glycine max L.) under ultraviolet B radiation (UV-B, 280-320 nm) stress were investigated under laboratory conditions. UV-B radiation not only affected the contents of two osmolytes (proline, soluble sugar) in soybean seedlings, but also inhibited the transpiration in soybean seedlings by decreasing the stomatal density and conductance. The two effects caused the inhibition in the osmotic and metabolic absorption of water, which decreased the water content and the free water/bound water ratio. Obviously, UV-B radiation led to water stress, causing the decrease in the photosynthesis in soybean seedlings. The pretreatment with 20 mg L(-1) Ce(III) could alleviate UV-B-induced water stress by regulating the osmotic and metabolic absorption of water in soybean seedlings. The alleviated effect caused the increase in the photosynthesis and the growth of soybean seedlings. It is one of the protective effect mechanisms of Ce(III) against the UV-B radiation-induced damage to plants.

Protective Effect of Garlic on Cellular Senescence in UVB-Exposed HaCaT Human Keratinocytes.

PubMed

Kim, Hye Kyung

2016-07-29

Ultraviolet (UV) irradiation generates reactive oxygen species (ROS) in the cells, which induces the cellular senescence and photoaging. The present study investigated the protective effects of garlic on photo-damage and cellular senescence in UVB-exposed human keratinocytes, HaCaT cells. An in vitro cell free system was used to examine the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and nitric oxide (NO). The effect of garlic extract on ROS formation, MMP-1 protein and mRNA expressions, cytokines such as interleukin (IL)-1β and IL-6, senescence associated-β-galactosidase (SA-β-gal) activity, and silent information regulator T1 (SIRT1) activity were determined in UVB-irradiated HaCaT cells. Garlic exhibited strong DPPH radical and NO scavenging activity in cell free system exhibiting IC50 values of 2.50 mg/mL and 4.38 mg/mL, respectively. Garlic pretreatment attenuated the production of UVB-induced intracellular ROS. MMP-1 level, which has been known to be induced by ROS, was dramatically elevated by UVB irradiation, and UVB-induced MMP-1 mRNA and protein expressions were significantly reduced by garlic treatment (50 µg/mL) comparable to those of UV-unexposed control cells. UV-induced pro-inflammatory cytokine productions (IL-6 and IL-1β) were significantly inhibited by pretreatment with garlic in a dose-dependent manner. SA-β-gal activity, a classical biomarker of cellular senescence, and SIRT1 activity, which has attracted attention as an anti-aging factor in recent years, were ameliorated by garlic treatment in UV-irradiated HaCaT cells. The present study provides the first evidence of garlic inhibiting UVB-induced photoaging as a result of augmentation of cellular senescence in HaCaT human keratinocytes.

Protective Effect of Garlic on Cellular Senescence in UVB-Exposed HaCaT Human Keratinocytes

PubMed Central

Kim, Hye Kyung

2016-01-01

Ultraviolet (UV) irradiation generates reactive oxygen species (ROS) in the cells, which induces the cellular senescence and photoaging. The present study investigated the protective effects of garlic on photo-damage and cellular senescence in UVB-exposed human keratinocytes, HaCaT cells. An in vitro cell free system was used to examine the scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and nitric oxide (NO). The effect of garlic extract on ROS formation, MMP-1 protein and mRNA expressions, cytokines such as interleukin (IL)-1β and IL-6, senescence associated-β-galactosidase (SA-β-gal) activity, and silent information regulator T1 (SIRT1) activity were determined in UVB-irradiated HaCaT cells. Garlic exhibited strong DPPH radical and NO scavenging activity in cell free system exhibiting IC50 values of 2.50 mg/mL and 4.38 mg/mL, respectively. Garlic pretreatment attenuated the production of UVB-induced intracellular ROS. MMP-1 level, which has been known to be induced by ROS, was dramatically elevated by UVB irradiation, and UVB-induced MMP-1 mRNA and protein expressions were significantly reduced by garlic treatment (50 µg/mL) comparable to those of UV-unexposed control cells. UV-induced pro-inflammatory cytokine productions (IL-6 and IL-1β) were significantly inhibited by pretreatment with garlic in a dose-dependent manner. SA-β-gal activity, a classical biomarker of cellular senescence, and SIRT1 activity, which has attracted attention as an anti-aging factor in recent years, were ameliorated by garlic treatment in UV-irradiated HaCaT cells. The present study provides the first evidence of garlic inhibiting UVB-induced photoaging as a result of augmentation of cellular senescence in HaCaT human keratinocytes. PMID:27483310

A Class I (Senofilcon A) Soft Contact Lens Prevents UVB-Induced Ocular Effects, Including Cataract, in the Rabbit In Vivo

PubMed Central

Lin, Li-Ren; Leverenz, Victor R.; Dang, Loan

2011-01-01

Purpose. UVB radiation from sunlight is known to be a risk factor for human cataract. The purpose in this study was to investigate the ability of a class I UV-blocking soft contact lens to protect against UVB-induced effects on the ocular tissues of the rabbit in vivo. Methods. Eyes of rabbits were exposed to UVB light for 30 minutes (270–360 nm, peak at 310 nm, 1.7 mW/cm2 on the cornea). Eyes were irradiated in the presence of either a UV-blocking senofilcon A contact lens, a minimally UV-blocking lotrafilcon A contact lens, or no contact lens at all. Effects on the cornea and lens were evaluated at various times after exposure. Results. Eyes irradiated with no contact lens protection showed corneal epithelial cell loss plus lens epithelial cell swelling, vacuole formation, and DNA single-strand breaks, as well as lens anterior subcapsular opacification. The senofilcon A lens protected nearly completely against the UVB-induced effects, whereas the lotrafilcon A lens showed no protection. Conclusions. The results indicate that use of a senofilcon A contact lens is beneficial in protecting ocular tissues of the rabbit against the harmful effects of UVB light, including photokeratitis and cataract. PMID:21421866

A class I (Senofilcon A) soft contact lens prevents UVB-induced ocular effects, including cataract, in the rabbit in vivo.

PubMed

Giblin, Frank J; Lin, Li-Ren; Leverenz, Victor R; Dang, Loan

2011-06-01

UVB radiation from sunlight is known to be a risk factor for human cataract. The purpose in this study was to investigate the ability of a class I UV-blocking soft contact lens to protect against UVB-induced effects on the ocular tissues of the rabbit in vivo. Eyes of rabbits were exposed to UVB light for 30 minutes (270-360 nm, peak at 310 nm, 1.7 mW/cm(2) on the cornea). Eyes were irradiated in the presence of either a UV-blocking senofilcon A contact lens, a minimally UV-blocking lotrafilcon A contact lens, or no contact lens at all. Effects on the cornea and lens were evaluated at various times after exposure. Eyes irradiated with no contact lens protection showed corneal epithelial cell loss plus lens epithelial cell swelling, vacuole formation, and DNA single-strand breaks, as well as lens anterior subcapsular opacification. The senofilcon A lens protected nearly completely against the UVB-induced effects, whereas the lotrafilcon A lens showed no protection. The results indicate that use of a senofilcon A contact lens is beneficial in protecting ocular tissues of the rabbit against the harmful effects of UVB light, including photokeratitis and cataract.

Oral administration of Lactobacillus plantarum HY7714 protects hairless mouse against ultraviolet B-induced photoaging.

PubMed

Kim, Hyun Mee; Lee, Dong Eun; Park, Soo Dong; Kim, Yong-Tae; Kim, Yu Jin; Jeong, Ji Woong; Jang, Sung Sik; Ahn, Young-Tae; Sim, Jae-Hun; Huh, Chul-Sung; Chung, Dae Kyun; Lee, Jung-Hee

2014-11-28

Ultraviolet (UV) irradiation alters multiple molecular pathways in the skin, thereby inducing skin damage, including photoaging. In recent years, probiotics have gained interest due to their beneficial effects on skin health, such as inhibiting atopic dermatitis and improving skin immunity or inflammation. However, little is known about the effects of probiotics on UVBinduced photoaging. In this study, we evaluated the effect of Lactobacillus plantarum HY7714 against UVB-induced photoaging in human dermal fibroblasts and hairless mice. The results showed that L. plantarum HY7714 treatment effectively rescued UVB-reduced procollagen expression through the inhibition of UVB-induced matrix metalloproteinase (MMP)-1 expression in human dermal fibroblasts. Data from a western blot showed that L. plantarum HY7714 inhibited the phosphorylation of Jun N-terminal kinase, thereby suppressing the UVB-induced phosphorylation and expression of c-Jun. Oral administration of L. plantarum HY7714 clearly inhibited the number, depth, and area of wrinkles in hairless mouse skin. Histological data showed that L. plantarum HY7714 significantly inhibited UVB-induced epidermal thickness in mice. Western blot and zymography data also revealed that L. plantarum HY7714 effectively inhibited MMP-13 expression as well as MMP-2 and -9 activities in dermal tissue. Collectively, these results provide further insight regarding the skin biological actions of L. plantarum HY7714, a potential skin anti-photoaging agent.

Epidermal PPARγ influences subcutaneous tumor growth and acts through TNF-α to regulate contact hypersensitivity and the acute photoresponse

PubMed Central

Konger, Raymond L.; Derr-Yellin, Ethel; Travers, Jeffrey B.; Ocana, Jesus A.; Sahu, Ravi P.

2017-01-01

It is known that ultraviolet B (UVB) induces PPARγ ligand formation while loss of murine epidermal PPARγ (Pparg-/-epi) promotes UVB-induced apoptosis, inflammation, and carcinogenesis. PPARγ is known to suppress tumor necrosis factor-α (TNF-α) production. TNF-α is also known to promote UVB-induced inflammation, apoptosis, and immunosuppression. We show that Pparg-/-epi mice exhibit increased baseline TNF-α expression. Neutralizing Abs to TNF-α block the increased photo-inflammation and photo-toxicity that is observed in Pparg-/-epi mouse skin. Interestingly, the increase in UVB-induced apoptosis in Pparg-/-epi mice is not accompanied by a change in cyclobutane pyrimidine dimer clearance or in mutation burden. This suggests that loss of epidermal PPARγ does not result in a significant alteration in DNA repair capacity. However, loss of epidermal PPARγ results in marked immunosuppression using a contact hypersensitivity (CHS) model. This impaired CHS response was significantly alleviated using neutralizing TNF-α antibodies or loss of germline Tnf. In addition, the PPARγ agonist rosiglitazone reversed UVB-induced systemic immunosuppression (UV-IS) as well as UV-induced growth of B16F10 melanoma tumor cells in syngeneic mice. Finally, increased B16F10 tumor growth was observed when injected subcutaneously into Pparg-/-epi mice. Thus, we provide novel evidence that epidermal PPARγ is important for cutaneous immune function and the acute photoresponse. PMID:29228682

Mitochondria-Targeted Vitamin E Protects Skin from UVB-Irradiation.

PubMed

Kim, Won-Serk; Kim, Ikyon; Kim, Wang-Kyun; Choi, Ju-Yeon; Kim, Doo Yeong; Moon, Sung-Guk; Min, Hyung-Keun; Song, Min-Kyu; Sung, Jong-Hyuk

2016-05-01

Mitochondria-targeted vitamin E (MVE) is designed to accumulate within mitochondria and is applied to decrease mitochondrial oxidative damage. However, the protective effects of MVE in skin cells have not been identified. We investigated the protective effect of MVE against UVB in dermal fibroblasts and immortalized human keratinocyte cell line (HaCaT). In addition, we studied the wound-healing effect of MVE in animal models. We found that MVE increased the proliferation and survival of fibroblasts at low concentration (i.e., nM ranges). In addition, MVE increased collagen production and downregulated matrix metalloproteinase1. MVE also increased the proliferation and survival of HaCaT cells. UVB increased reactive oxygen species (ROS) production in fibroblasts and HaCaT cells, while MVE decreased ROS production at low concentration. In an animal experiment, MVE accelerated wound healing from laser-induced skin damage. These results collectively suggest that low dose MVE protects skin from UVB irradiation. Therefore, MVE can be developed as a cosmetic raw material.

Induction and disappearance of thymine dimers in human skin exposed to UVB radiation: flow cytometric measurements in replicating and nonreplicating epidermal cells.

PubMed

Berg, R J; de Bueger, S C; Guikers, K; van Weelden, H; van Vloten, W A; van der Leun, J C; de Gruijl, F R

1995-12-01

We have earlier reported on determining UV-induced DNA damage in murine epidermal cell suspensions by flow cytometric analysis of the fluorescence from a fluorescein isothiocyanate-labeled antibody (H3) directed against thymine dimers (T < > T). Here we present an optimization of the technique for analysis of epidermal cell suspensions from 4 mm biopsies from human skin. Cells with different DNA contents can easily be distinguished in flow cytometry by the intensity of DNA-specific 7-amino-actinomycin D fluorescence. Genuine G2-M-phase cells can further be distinguished from cell doublets by pulse-shape discrimination. Thus, T < > T levels in individual cells with different DNA contents (i.e. G0-G1, S or G2-M phases) can be determined after in vivo exposure of human skin to environmentally relevant UVB (280-315 nm) doses. The method was applied to measure the decrease of T < > T in nonreplicating cells (G0-G1 phase) and replicating cells (S phase or G2-M phase) from seven volunteers exposed to twice their minimal erythema dose. The reduction in the average T < > T-specific fluorescence at 24 h after exposure was 46% (ranging between 16% and 66%) for the G0-G1 cells and 70% (ranging between 37% and 100%) for the S + G2-M cells. The difference was statistically highly significant. Determination of individual DNA repair capacities with this method can become a convenient diagnostic tool for patients with DNA repair disorders, or it may even be used to identify individuals with low repair proficiencies and increased risk of developing skin cancers.

A combination of He-Ne laser irradiation and exogenous NO application efficiently protect wheat seedling from oxidative stress caused by elevated UV-B stress.

PubMed

Li, Yongfeng; Gao, Limei; Han, Rong

2016-12-01

The elevated ultraviolet-B (UV-B) stress induces the accumulation of a variety of intracellular reactive oxygen species (ROS), which seems to cause oxidative stress for plants. To date, very little work has been done to evaluate the biological effects of a combined treatment with He-Ne laser irradiation and exogenous nitric oxide (NO) application on oxidative stress resulting from UV-B radiation. Thus, our study investigated the effects of a combination with He-Ne laser irradiation and exogenous NO treatment on oxidative damages in wheat seedlings under elevated UV-B stress. Our data showed that the reductions in ROS levels, membrane damage parameters, while the increments in antioxidant contents and antioxidant enzyme activity caused by a combination with He-Ne laser and exogenous NO treatment were greater than those of each individual treatment. Furthermore, these treatments had a similar effect on transcriptional activities of plant antioxidant enzymes. This implied that the protective effects of a combination with He-Ne laser irradiation and exogenous NO treatment on oxidative stress resulting from UV-B radiation was more efficient than each individual treatment with He-Ne laser or NO molecule. Our findings might provide beneficial theoretical references for identifying some effective new pathways for plant UV-B protection.

Enhanced UV-B radiation during pupal stage reduce body mass and fat content, while increasing deformities, mortality and cell death in female adults of solitary bee Osmia bicornis.

PubMed

Wasielewski, Oskar; Wojciechowicz, Tatiana; Giejdasz, Karol; Krishnan, Natraj

2015-08-01

The effects of enhanced UV-B radiation on the oogenesis and morpho-anatomical characteristics of the European solitary red mason bee Osmia bicornis L. (Hymenoptera: Megachilidae) were tested under laboratory conditions. Cocooned females in the pupal stage were exposed directly to different doses (0, 9.24, 12.32, and 24.64 kJ/m(2) /d) of artificial UV-B. Our experiments revealed that enhanced UV-B radiation can reduce body mass and fat body content, cause deformities and increase mortality. Following UV exposure at all 3 different doses, the body mass of bees was all significantly reduced compared to the control, with the highest UV dose causing the largest reduction. Similarly, following UV-B radiation, in treated groups the fat body index decreased and the fat body index was the lowest in the group receiving the highest dose of UV radiation. Mortality and morphological deformities, between untreated and exposed females varied considerably and increased with the dose of UV-B radiation. Morphological deformities were mainly manifested in the wings and mouthparts, and occurred more frequently with an increased dose of UV. Cell death was quantified by the Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay (DNA fragmentation) during early stages of oogenesis of O. bicornis females. The bees, after UV-B exposure exhibited more germarium cells with fragmented DNA. The TUNEL test indicated that in germarium, low doses of UV-B poorly induced the cell death during early development. However, exposure to moderate UV-B dose increased programmed cell death. In females treated with the highest dose of UV-B the vast majority of germarium cells were TUNEL-positive. © 2014 Institute of Zoology, Chinese Academy of Sciences.

Repair of UVB-damaged skin by the antioxidant sulphated flavone glycoside thalassiolin B isolated from the marine plant Thalassia testudinum Banks ex König.

PubMed

Regalado, Erik L; Rodríguez, María; Menéndez, Roberto; Concepción, Angel A; Nogueiras, Clara; Laguna, Abilio; Rodríguez, Armando A; Williams, David E; Lorenzo-Luaces, Patricia; Valdés, Olga; Hernandez, Yasnay

2009-01-01

Daily topical application of the aqueous ethanolic extract of the marine sea grass, Thalassia testudinum, on mice skin exposed to UVB radiation resulted in a dose-dependent recovery of the skin macroscopic alterations over a 6-day period. Maximal effect (90%) occurred at a dose of 240 microg/cm(2), with no additional effects at higher doses. Bioassay-guided fractionation of the plant extract resulted in the isolation of thalassiolin B (1). Topical application of 1 (240 microg/cm(2)) markedly reduces skin UVB-induced damage. In addition, thalassiolin B scavenged 2,2-diphenyl-2-picrylhydrazyl radical with an EC(50) = 100 microg/ml. These results suggest that thalassiolin B is responsible for the skin-regenerating effects of the crude extract of T. testudinum.

Piper retrofractum Vahl. Extract, as a PPARδ and AMPK Activator, Suppresses UVB-Induced Photoaging through Mitochondrial Biogenesis and MMPs Inhibition in Human Dermal Fibroblasts and Hairless Mice

PubMed Central

2018-01-01

Photoaging occurs by UVB-irradiation and involves production of reactive oxygen species (ROS) and overexpression of matrix metalloproteinases (MMPs), leading to extracellular matrix damage. Piper retrofractum Vahl. is used as a traditional medicine for antiflatulence, expectorant, sedative, and anti-irritant; however, its antiphotoaging effect has not yet been studied. The current study investigated the antiphotoaging effect of standardized Piper retrofractum extract (PRE) on UVB-damaged human dermal fibroblasts and hairless mouse skin. PRE treatment activated the peroxisome proliferator-activated receptor delta (PPARδ) and the adenosine monophosphate-activated protein kinase (AMPK), consequently upregulating mitochondrial synthesis and reducing ROS production. Additionally, PRE inhibited MMPs expression via suppressing mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1). PRE downregulated UVB-induced inflammatory reactions by inhibiting the nuclear factor-kappa B (NF-κB) activity. PRE also enhanced transforming growth factor-beta (TGF-β) and the Smad signaling pathway, thereby promoting procollagen gene transcription. Furthermore, oral administration of PRE (300 mg/kg/day) similarly regulated the signaling pathways and increased antioxidant enzyme expression, thus attenuating physiological deformations, such as wrinkle formation and erythema response. Collectively, these results suggest that PRE acts as a potent antiphotoaging agent via PPARδ and AMPK activation. PMID:29619069

Piper retrofractum Vahl. Extract, as a PPARδ and AMPK Activator, Suppresses UVB-Induced Photoaging through Mitochondrial Biogenesis and MMPs Inhibition in Human Dermal Fibroblasts and Hairless Mice.

PubMed

Yun, Jungon; Kim, Changhee; Kim, Mi-Bo; Hwang, Jae-Kwan

2018-01-01

Photoaging occurs by UVB-irradiation and involves production of reactive oxygen species (ROS) and overexpression of matrix metalloproteinases (MMPs), leading to extracellular matrix damage. Piper retrofractum Vahl. is used as a traditional medicine for antiflatulence, expectorant, sedative, and anti-irritant; however, its antiphotoaging effect has not yet been studied. The current study investigated the antiphotoaging effect of standardized Piper retrofractum extract (PRE) on UVB-damaged human dermal fibroblasts and hairless mouse skin. PRE treatment activated the peroxisome proliferator-activated receptor delta (PPAR δ ) and the adenosine monophosphate-activated protein kinase (AMPK), consequently upregulating mitochondrial synthesis and reducing ROS production. Additionally, PRE inhibited MMPs expression via suppressing mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1). PRE downregulated UVB-induced inflammatory reactions by inhibiting the nuclear factor-kappa B (NF- κ B) activity. PRE also enhanced transforming growth factor-beta (TGF- β ) and the Smad signaling pathway, thereby promoting procollagen gene transcription. Furthermore, oral administration of PRE (300 mg/kg/day) similarly regulated the signaling pathways and increased antioxidant enzyme expression, thus attenuating physiological deformations, such as wrinkle formation and erythema response. Collectively, these results suggest that PRE acts as a potent antiphotoaging agent via PPAR δ and AMPK activation.

UV-B-Responsive Association of the Arabidopsis bZIP Transcription Factor ELONGATED HYPOCOTYL5 with Target Genes, Including Its Own Promoter[W][OPEN

PubMed Central

Binkert, Melanie; Kozma-Bognár, László; Terecskei, Kata; De Veylder, Lieven; Nagy, Ferenc; Ulm, Roman

2014-01-01

In plants subjected to UV-B radiation, responses are activated that minimize damage caused by UV-B. The bZIP transcription factor ELONGATED HYPOCOTYL5 (HY5) acts downstream of the UV-B photoreceptor UV RESISTANCE LOCUS8 (UVR8) and promotes UV-B-induced photomorphogenesis and acclimation. Expression of HY5 is induced by UV-B; however, the transcription factor(s) that regulate HY5 transcription in response to UV-B and the impact of UV-B on the association of HY5 with its target promoters are currently unclear. Here, we show that HY5 binding to the promoters of UV-B-responsive genes is enhanced by UV-B in a UVR8-dependent manner in Arabidopsis thaliana. In agreement, overexpression of REPRESSOR OF UV-B PHOTOMORPHOGENESIS2, a negative regulator of UVR8 function, blocks UV-B-responsive HY5 enrichment at target promoters. Moreover, we have identified a T/G-box in the HY5 promoter that is required for its UV-B responsiveness. We show that HY5 and its homolog HYH bind to the T/GHY5-box cis-acting element and that they act redundantly in the induction of HY5 expression upon UV-B exposure. Therefore, HY5 is enriched at target promoters in response to UV-B in a UVR8 photoreceptor-dependent manner, and HY5 and HYH interact directly with a T/G-box cis-acting element of the HY5 promoter, mediating the transcriptional activation of HY5 in response to UV-B. PMID:25351492

MHY884, a newly synthesized tyrosinase inhibitor, suppresses UVB-induced activation of NF-κB signaling pathway through the downregulation of oxidative stress.

PubMed

Choi, Yeon Ja; Uehara, Yohei; Park, Ji Young; Kim, Seong Jin; Kim, So Ra; Lee, Hee Won; Moon, Hyung Ryong; Chung, Hae Young

2014-03-01

The skin is the primary target of prolonged and repeated ultraviolet (UVB) irradiation which induces cutaneous inflammation and pigmentation. Nuclear factor κB (NF-κB) is the major factor mediating UVB-induced inflammatory responses through the expression of various proinflammatory proteins such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). We have previously reported that the synthetic novel compound 4-(5-chloro-2,3-dihydrobenzo[d]thiazol-2-yl)-2,6-dimethoxyphenol (MHY884) strongly suppressed tyrosinase activity and melanin synthesis in B16F10 melanoma cells. In the present study, we investigated the effect of MHY884 on the inhibition of UVB-induced NF-κB activation and its proinflammatory downstream proteins through the suppression of oxidative stress in an in vivo model of photoaging. Generation of reactive oxygen species (ROS) and peroxynitrite was measured in vitro and in B16F10 melanoma cells to verify the scavenging activity of MHY884. MHY884 suppressed oxidative stress both in vitro and in the melanoma cells in a dose-dependent manner. Next, melanin-possessing hairless mice were pre-treated with MHY884 and then irradiated with UVB repeatedly. Topical application of MHY884 attenuated UVB-induced oxidative stress, resulting in reduced NF-κB activity. Pre-treatment with MHY884 inhibited Akt and IκB kinase α/β signaling pathways, leading to decreased translocation and phosphorylation of p65, a subunit of NF-κB. This result correlated with the expression levels of iNOS and COX-2 in the skin of MHY884-treated mice. Thus, the novel tyrosinase inhibitor MHY884 suppressed NF-κB activation signaling pathway by scavenging UVB-induced oxidative stress. The discovery of MHY884, a novel tyrosinase inhibitor that targets NF-κB signaling, is significant, because this compound is a promising protective agent against UVB-induced skin damage. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ultra-flexible nanocarriers for enhanced topical delivery of a highly lipophilic antioxidative molecule for skin cancer chemoprevention.

PubMed

Boakye, Cedar H A; Patel, Ketan; Doddapaneni, Ravi; Bagde, Arvind; Behl, Gautam; Chowdhury, Nusrat; Safe, Stephen; Singh, Mandip

2016-07-01

In this study, we developed cationic ultra-flexible nanocarriers (UltraFLEX-Nano) to surmount the skin barrier structure and to potentiate the topical delivery of a highly lipophilic antioxidative diindolylmethane derivative (DIM-D) for the inhibition of UV-induced DNA damage and skin carcinogenesis. UltraFLEX-Nano was prepared with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-3-trimethylammonium-propane, cholesterol and tween-80 by ethanolic injection method; was characterized by Differential Scanning Calorimetric (DSC), Fourier Transform Infrared (FT-IR) and Atomic Force Microscopic (phase-imaging) analyses and permeation studies were performed in dermatomed human skin. The efficacy of DIM-D-UltraFLEX-Nano for skin cancer chemoprevention was evaluated in UVB-induced skin cancer model in vivo. DIM-D-UltraFLEX-Nano formed a stable mono-dispersion (110.50±0.71nm) with >90% encapsulation of DIM-D that was supported by HPLC, DSC, FT-IR and AFM phase imaging. The blank formulation was non-toxic to human embryonic kidney cells. UltraFLEX-Nano was vastly deformable and highly permeable across the stratum corneum; there was significant (p<0.01) skin deposition of DIM-D for UltraFLEX-Nano that was superior to PEG solution (13.83-fold). DIM-D-UltraFLEX-Nano pretreatment delayed the onset of UVB-induced tumorigenesis (2 weeks) and reduced (p<0.05) the number of tumors observed in SKH-1 mice (3.33-fold), which was comparable to pretreatment with sunscreen (SPF30). Also, DIM-D-UltraFLEX-Nano caused decrease (p<0.05) in UV-induced DNA damage (8-hydroxydeoxyguanosine), skin inflammation (PCNA), epidermal hyperplasia (c-myc, CyclinD1), immunosuppression (IL10), cell survival (AKT), metastasis (Vimentin, MMP-9, TIMP1) but increase in apoptosis (p53 and p21). UltraFLEX-Nano was efficient in enhancing the topical delivery of DIM-D. DIM-D-UltraFLEX-Nano was efficacious in delaying skin tumor incidence and multiplicity in SKH mice comparable to sunscreen (SPF30). Copyright © 2016 Elsevier B.V. All rights reserved.

In vitro and in vivo photoprotective/photochemopreventive potential of Garcinia brasiliensis epicarp extract.

PubMed

Figueiredo, Sônia Aparecida; Vilela, Fernanda Maria Pinto; da Silva, Claudinei Alves; Cunha, Thiago Mattar; Dos Santos, Marcelo Henrique; Fonseca, Maria José Vieira

2014-02-05

The damaging effects of sunlight to the skin has triggered studies that involve the synthesis and extraction of organic compounds from natural sources that can absorb UV radiation, and studies on polyphenolic compounds with antioxidant and anti-inflammatory properties that can be used as photochemopreventive agents for reducing skin damage. We investigated the in vitro and in vivo photoprotective/photochemopreventive potential of Garcinia brasiliensis epicarp extract (GbEE). We evaluated the cell viability of L929 fibroblasts after UVB exposure using a quartz plate containing the extract solution or the GbEE formulation. The in vivo photoprotective effect of the GbEE formulation was evaluated by measuring the UVB damage-induced decrease in endogenous reduced glutathione (GSH), the increase in myeloperoxidase (MPO) activity and secretion of cytokines IL-1β and TNF-α. The in vitro methodology using fibroblasts showed that the photoprotective properties of the GbEE solutions and 10% GbEE formulation were similar to the commercial sunscreen (SPF-15). In vivo results demonstrated of the GbEE formulation in decreasing UVB induced-damage such as GSH depletion, an increased in MPO activity and secretion of cytokines IL-1β and TNF-α. The results showed that the extract has great potential for use as a sunscreen in topical formulations in addition to UV filters. Copyright © 2014 Elsevier B.V. All rights reserved.

Ferulic acid, a phenolic phytochemical, inhibits UVB-induced matrix metalloproteinases in mouse skin via posttranslational mechanisms.

PubMed

Staniforth, Vanisree; Huang, Wen-Ching; Aravindaram, Kandan; Yang, Ning-Sun

2012-05-01

Matrix metalloproteinases MMP-2 and -9 are known to be overexpressed in ultraviolet B (UVB)-irradiated skin tissues and contribute to the acceleration of photoaging and the development of skin cancer. But the specific molecular mechanisms that can control or interfere with the expression and regulation of these MMP-2 and -9 activities in skin are not clearly understood. The aim of the present study was to analyze the suppressive effects of ferulic acid (FA), an abundant phenolic compound present in various dietary and medicinal plants, on UVB radiation-induced MMP-2 and -9 activities in mouse skin. For attenuation of chronic UVB irradiation damage to skin, inhibition of MMP-2 and -9 protein expression was detected using immunohistochemistry analysis. However, the in situ suppressive effects of FA did not interfere with the transcription or translation of MMP-2 and -9, suggesting that its action could be mediated via the proteasome pathway. Histological analyses showed that FA attenuates the degradation of collagen fibers, abnormal accumulation of elastic fibers and epidermal hyperplasia induced by UVB, demonstrating the functional and physiological relevance of FA effects in UVB-irradiated skin tissues. Together, our findings provide a novel and increased insight into the in vivo action of FA and suggest a possible clinical application in skin pathophysiological conditions associated with overexpression of MMP-2 and -9. Copyright © 2012 Elsevier Inc. All rights reserved.

ALA-PDT elicits oxidative damage and apoptosis in UVB-induced premature senescence of human skin fibroblasts.

PubMed

Zhou, Bing-Rong; Zhang, Li-Chao; Permatasari, Felicia; Liu, Juan; Xu, Yang; Luo, Dan

2016-06-01

5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been used for the treatment of skin photoaging. It can significantly improve the appearance of fine lines, dotted pigmentation, and roughness of photoaged skin. However, the mechanisms by which ALA-PDT yields rejuvenating effects on photoaged skin have not been well elucidated. Thus, in this study we explored the effects of ALA-PDT in photoaged fibroblasts. We established a stress-induced premature senescence (SIPS) model by repeated exposures of human dermal fibroblasts (HDFs) to ultraviolet B (UVB) irradiation. Cells were irradiated by red light laser at 635nm wavelength (50mW/cm(2)). Intracellular protoporphyrin IX (PpIX) was detected by confocal microscopy. Intracellular reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) change were detected by fluorescence microscopy and flow cytometry. Morphological changes were observed by optical microscopy. Proliferative activity was measured by a cell counting kit-8 (CCK-8). Cell apoptosis was detected by fluorescence microscopy using Hoechst staining and flow cytometry using annexin V/propidium Iodide double staining. Intracellular PpIX fluorescence in UVB-induced premature senescent HDFs (UVB-SIPS-HDFs) reached the highest intensity after incubation with 1.00mmol/L ALA for 6h (P<0.05). Compared with control group, intracellular ROS level, MMP, and apoptotic rate were increased (P<0.05) and proliferative activity was decreased (P<0.05) in UVB-SIPS-HDFs treated with ALA-PDT, which were positively correlated to ALA incubation time and red light laser dose. Our study demonstrated that ALA-PDT elicits oxidative damage and apoptosis in photoaged fibroblasts in vitro, which may be the basis for the rejuvenating effects on photoaged skin. Copyright © 2016 Elsevier B.V. All rights reserved.

Inhibition of UV-B induced apoptosis in corneal epithelial cells by potassium channel modulators.

PubMed

Ubels, John L; Schotanus, Mark P; Bardolph, Susan L; Haarsma, Loren D; Koetje, Leah R; Louters, Julienne R

2010-02-01

The goal of this study was to determine whether prevention of K(+) loss can protect human corneal-limbal epithelial (HCLE) cells from UV-B induced apoptosis. Immunostaining for activated caspase-3 of HCLE cells exposed to 150-200 mJ/cm(2) UV-B demonstrated induction of apoptosis 6 h after exposure. The number of apoptotic cells was decreased by incubation in medium with 25 or 100 mM K(+). If this protection is due to a reduction of UV-induced K(+) loss then K(+) channel blockers should also protect HCLE cells from UV-B. Caspase-8 activity induced by exposure to UV-B at 150 mJ/cm(2) was significantly reduced when the cells were incubated in 0.3 microM BDS-I or 0.05-1 mM quinidine. Caspase-3 was also activated by UV-B and a reduction in activity was observed after incubation in 0.1-0.3 microM BDS-I and 0.1-1 mM quinidine. Induction of DNA fragmentation, as measured by the TUNEL assay, was decreased by treatment with 0.3 microM BDS-I and 0.01-0.05 mM quinidine. Patch-clamp recording showed activation of K(+) channels after exposure to UV-B and a decrease in outward K(+) current was observed following application of BDS-I. Quinidine did not block K(+) currents in HCLE cells, suggesting that the protective effect of quinidine occurs by a mechanism other than via K(+) channels. The effect of the K(+) channel blocker BDS-1 on HCLE cells exposed to UV-B confirms that preventing K(+) efflux protects corneal epithelial cells from apoptosis. This suggests the elevated [K(+)] in tears may protect the corneal epithelium from effects of ambient UV-B. Copyright 2009 Elsevier Ltd. All rights reserved.

Inhibition of UV-B Induced Apoptosis in Corneal Epithelial Cells by Potassium Channel Modulators

PubMed Central

Ubels, John L.; Schotanus, Mark P.; Bardolph, Susan L.; Haarsma, Loren D.; Koetje, Leah R.; Louters, Julienne R.

2009-01-01

The goal of this study was to determine whether prevention of K+ loss can protect human corneal-limbal epithelial (HCLE) cells from UV-B induced apoptosis. Immunostaining for activated caspase-3 of HCLE cells exposed to 150 – 200 mJ/cm2 UV-B demonstrated induction of apoptosis 6 hrs after exposure. The number of apoptotic cells was decreased by incubation in medium with 25 or 100 mM K+. If this protection is due to a reduction of UV induced K+ loss then K+ channel blockers should also protect HCLE cells from UV-B. Caspase-8 activity induced by exposure to UV-B at 150 mJ/cm2 was significantly reduced when the cells were incubated in 0.3 µM BDS-I or 0.05–1 mM quinidine. Caspase-3 was also activated by UV-B and a reduction in activity was observed after incubation in 0.1–0.3 µM BDS-I and 0.1–1mM quinidine. Induction of DNA fragmentation, as measured by the TUNEL assay, was decreased by treatment with 0.3 µM BDS-I and 0.01–0.05 mM quinidine. Patch-clamp recording showed activation of K+ channels after exposure to UV-B and a decrease in outward K+ current was observed following application of BDS-I. Quinidine did not block K+ currents in HCLE cells, suggesting that the protective effect of quinidine occurs by a mechanism other than via K+ channels. The effect of the K+ channel blocker BDS-1 on HCLE cells exposed to UV-B confirms that preventing K+ efflux protects corneal epithelial cells from apoptosis. This suggests the elevated [K+] in tears may protect the corneal epithelium from effects of ambient UV-B. PMID:19874821

QUANTIFICATION OF RECA GENE EXPRESSION AS AN INDICATOR OF REPAIR POTENTIAL IN MARINE BACTERIOPLANKTON COMMUNITIES OF ANTARCTICA.

EPA Science Inventory

Marine bacteria in surface waters must cope daily with the damaging effects of exposure to solar radiation (containing both UV-A and UV-B wavelengths), which produces lesions in their DNA. As the stratospheric ozone layer is depleted, these coping mechanisms are likely to play an...

Sulforaphane suppresses ultraviolet B-induced inflammation in HaCaT keratinocytes and HR-1 hairless mice.

PubMed

Shibata, Akira; Nakagawa, Kiyotaka; Yamanoi, Hiroko; Tsuduki, Tsuyoshi; Sookwong, Phumon; Higuchi, Ohki; Kimura, Fumiko; Miyazawa, Teruo

2010-08-01

Ultraviolet B (UVB) irradiation induces skin damage and inflammation. One way to reduce the inflammation is via the use of molecules termed photochemopreventive agents. Sulforaphane (4-methylsulfinylbutyl isothiocyanate, SF), which is found in cruciferous vegetables, is known for its potent physiological properties. This study was designed to evaluate the effect of SF on skin inflammation in vitro and in vivo. In in vitro study using immortalized human keratinocytes (HaCaT), UVB caused marked inflammatory responses [i.e., decrease of HaCaT viability and increase of production of an inflammatory marker interleukin-6 (IL-6)]. SF recovered the cell proliferation and suppressed the IL-6 production. These anti-inflammatory effects of SF were explained by its ability to reduce UVB-induced inflammatory gene expressions [IL-6, IL-1beta and cyclooxgenase-2 (COX-2)]. Because SF seems to have an impact on COX-2 expression, we focused on COX-2 and found that SF reduced UVB-induced COX-2 protein expression. In support of this, PGE(2) released from HaCaT was suppressed by SF. Western blot analysis revealed that SF inhibited p38, ERK and SAPK/JNK activation, indicating that the inhibition of mitogen-activated protein kinases (MAPK) by SF would attenuate the expression of inflammatory mediators (e.g., COX-2), thereby reducing inflammatory responses. Moreover, we conducted skin thickening assay using HR-1 hairless mice and found that UVB-induced skin thickness, COX-2 protein expression and hyperplasia were all suppressed by feeding SF to the mice. These results suggest that SF has a potential use as a compound for protection against UVB-induced skin inflammation. Copyright 2010 Elsevier Inc. All rights reserved.

Brown Pine Leaf Extract and Its Active Component Trans-Communic Acid Inhibit UVB-Induced MMP-1 Expression by Targeting PI3K

PubMed Central

Park, Gaeun; Lim, Tae-gyu; Kwon, Jung Yeon; Song, Da Som; Jeong, Eun Hee; Lee, Charles C.; Son, Joe Eun; Seo, Sang Gwon; Lee, Eunjung; Kim, Jong Rhan; Lee, Chang Yong; Park, Jun Seong; Lee, Ki Won

2015-01-01

Japanese red pine (Pinus densiflora) is widely present in China, Japan, and Korea. Its green pine leaves have traditionally been used as a food as well as a coloring agent. After being shed, pine leaves change their color from green to brown within two years, and although the brown pine leaves are abundantly available, their value has not been closely assessed. In this study, we investigated the potential anti-photoaging properties of brown pine leaves for skin. Brown pine leaf extract (BPLE) inhibited UVB-induced matrix metalloproteinase-1 (MMP-1) expression to a greater extent than pine leaf extract (PLE) in human keratinocytes and a human skin equivalent model. HPLC analysis revealed that the quantity of trans-communic acid (TCA) and dehydroabietic acid (DAA) significantly increases when the pine leaf color changes from green to brown. BPLE and TCA elicited reductions in UVB-induced MMP-1 mRNA expression and activator protein-1 (AP-1) transactivation by reducing DNA binding activity of phospho-c-Jun, c-fos and Fra-1. BPLE and TCA also inhibited UVB-induced Akt phosphorylation, but not mitogen activated protein kinase (MAPK), known regulators of AP-1 transactivation. We additionally found that BPLE and TCA inhibited phosphoinositide 3-kinase (PI3K), the upstream kinase of Akt, in vitro. In summary, both BPLE and its active component TCA exhibit protective effects against UVB-induced skin aging. Taken together, these findings underline the potential for BPLE and TCA to be utilized as anti-wrinkling agents and cosmetic ingredients, as they suppress UVB-induced MMP-1 expression. PMID:26066652

Exposure of vitamins to UVB and UVA radiation generates singlet oxygen.

PubMed

Knak, Alena; Regensburger, Johannes; Maisch, Tim; Bäumler, Wolfgang

2014-05-01

Deleterious effects of UV radiation in tissue are usually attributed to different mechanisms. Absorption of UVB radiation in cell constituents like DNA causes photochemical reactions. Absorption of UVA radiation in endogenous photosensitizers like vitamins generates singlet oxygen via photosensitized reactions. We investigated two further mechanisms that might be involved in UV mediated cell tissue damage. Firstly, UVB radiation and vitamins also generate singlet oxygen. Secondly, UVB radiation may change the chemical structure of vitamins that may change the role of such endogenous photosensitizers in UVA mediated mechanisms. Vitamins were irradiated in solution using monochromatic UVB (308 nm) or UVA (330, 355, or 370 nm) radiation. Singlet oxygen was directly detected and quantified by its luminescence at 1270 nm. All investigated molecules generated singlet oxygen with a quantum yield ranging from 0.007 (vitamin D3) to 0.64 (nicotinamide) independent of the excitation wavelength. Moreover, pre-irradiation of vitamins with UVB changed their absorption in the UVB and UVA spectral range. Subsequently, molecules such as vitamin E and vitamin K1, which normally exhibit no singlet oxygen generation in the UVA, now produce singlet oxygen when exposed to UVA at 355 nm. This interplay of different UV sources is inevitable when applying serial or parallel irradiation with UVA and UVB in experiments in vitro. These results should be of particular importance for parallel irradiation with UVA and UVB in vivo, e.g. when exposing the skin to solar radiation.

Protective effects of a new phloretin derivative against UVB-induced damage in skin cell model and human volunteers.

PubMed

Shin, Seoungwoo; Kum, Hyunwoo; Ryu, Dehun; Kim, Minkyung; Jung, Eunsun; Park, Deokhoon

2014-10-20

The phenolic compound phloretin is a prominent member of the chemical class of dihydrochalcones. Phloretin is specifically found in apple and apple juice and known for its biological properties. We were particularly interested in its potential dermo-cosmetic applications. However, practical limitations of phloretin do exist due to its poor water-solubility. Phloretin was sulfonated with sulfuric acid (98%, wt) and mixed with saturated salt water to produce phloretin 3',3-disulfonate in order to increase its water-solubility. Here we reported the photoprotective effect of phloretin 3',3-disulfonate (PS), a new semi-synthetic derivative of phloretin. Results showed that PS attenuated cyclobutane pyrimidine dimer (CPDs) formation, glutathione (GSH) depletion and apoptosis induced by ultraviolet B (UVB). The photoprotective effect of PS is tightly correlated to the enhancement of nucleotide excision repair (NER) gene expression. Furthemore, PS had inhibitory effects on UVB-induced release of the inflammatory mediators, such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of PS on human skin. Overall, the results demonstrated significant benefits of PS on the protection of keratinocytes against UVB-induced injuries and suggested its potential use in skin photoprotection.

Protective Effects of a New Phloretin Derivative against UVB-Induced Damage in Skin Cell Model and Human Volunteers

PubMed Central

Shin, Seoungwoo; Kum, Hyunwoo; Ryu, Dehun; Kim, Minkyung; Jung, Eunsun; Park, Deokhoon

2014-01-01

The phenolic compound phloretin is a prominent member of the chemical class of dihydrochalcones. Phloretin is specifically found in apple and apple juice and known for its biological properties. We were particularly interested in its potential dermo-cosmetic applications. However, practical limitations of phloretin do exist due to its poor water-solubility. Phloretin was sulfonated with sulfuric acid (98%, wt) and mixed with saturated salt water to produce phloretin 3',3-disulfonate in order to increase its water-solubility. Here we reported the photoprotective effect of phloretin 3',3-disulfonate (PS), a new semi-synthetic derivative of phloretin. Results showed that PS attenuated cyclobutane pyrimidine dimer (CPDs) formation, glutathione (GSH) depletion and apoptosis induced by ultraviolet B (UVB). The photoprotective effect of PS is tightly correlated to the enhancement of nucleotide excision repair (NER) gene expression. Furthemore, PS had inhibitory effects on UVB-induced release of the inflammatory mediators, such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of PS on human skin. Overall, the results demonstrated significant benefits of PS on the protection of keratinocytes against UVB-induced injuries and suggested its potential use in skin photoprotection. PMID:25334063

MRE11 and RAD50, but not NBS1, are essential for gene targeting in the moss Physcomitrella patens.

PubMed

Kamisugi, Yasuko; Schaefer, Didier G; Kozak, Jaroslav; Charlot, Florence; Vrielynck, Nathalie; Holá, Marcela; Angelis, Karel J; Cuming, Andrew C; Nogué, Fabien

2012-04-01

The moss Physcomitrella patens is unique among plant models for the high frequency with which targeted transgene insertion occurs via homologous recombination. Transgene integration is believed to utilize existing machinery for the detection and repair of DNA double-strand breaks (DSBs). We undertook targeted knockout of the Physcomitrella genes encoding components of the principal sensor of DNA DSBs, the MRN complex. Loss of function of PpMRE11 or PpRAD50 strongly and specifically inhibited gene targeting, whilst rates of untargeted transgene integration were relatively unaffected. In contrast, disruption of the PpNBS1 gene retained the wild-type capacity to integrate transforming DNA efficiently at homologous loci. Analysis of the kinetics of DNA-DSB repair in wild-type and mutant plants by single-nucleus agarose gel electrophoresis revealed that bleomycin-induced fragmentation of genomic DNA was repaired at approximately equal rates in each genotype, although both the Ppmre11 and Pprad50 mutants exhibited severely restricted growth and development and enhanced sensitivity to UV-B and bleomycin-induced DNA damage, compared with wild-type and Ppnbs1 plants. This implies that while extensive DNA repair can occur in the absence of a functional MRN complex; this is unsupervised in nature and results in the accumulation of deleterious mutations incompatible with normal growth and development.

MRE11 and RAD50, but not NBS1, are essential for gene targeting in the moss Physcomitrella patens

PubMed Central

Kamisugi, Yasuko; Schaefer, Didier G.; Kozak, Jaroslav; Charlot, Florence; Vrielynck, Nathalie; Holá, Marcela; Angelis, Karel J.; Cuming, Andrew C.; Nogué, Fabien

2012-01-01

The moss Physcomitrella patens is unique among plant models for the high frequency with which targeted transgene insertion occurs via homologous recombination. Transgene integration is believed to utilize existing machinery for the detection and repair of DNA double-strand breaks (DSBs). We undertook targeted knockout of the Physcomitrella genes encoding components of the principal sensor of DNA DSBs, the MRN complex. Loss of function of PpMRE11 or PpRAD50 strongly and specifically inhibited gene targeting, whilst rates of untargeted transgene integration were relatively unaffected. In contrast, disruption of the PpNBS1 gene retained the wild-type capacity to integrate transforming DNA efficiently at homologous loci. Analysis of the kinetics of DNA-DSB repair in wild-type and mutant plants by single-nucleus agarose gel electrophoresis revealed that bleomycin-induced fragmentation of genomic DNA was repaired at approximately equal rates in each genotype, although both the Ppmre11 and Pprad50 mutants exhibited severely restricted growth and development and enhanced sensitivity to UV-B and bleomycin-induced DNA damage, compared with wild-type and Ppnbs1 plants. This implies that while extensive DNA repair can occur in the absence of a functional MRN complex; this is unsupervised in nature and results in the accumulation of deleterious mutations incompatible with normal growth and development. PMID:22210882

Effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in mice.

PubMed

Satoh, T; Murata, M; Iwabuchi, N; Odamaki, T; Wakabayashi, H; Yamauchi, K; Abe, F; Xiao, J Z

2015-01-01

Probiotics have been shown to have a preventative effect on skin photoaging induced by short term UV irradiation, however, the underlying mechanisms and the effect of probiotics on skin photoaging induced by chronic UV irradiation remain unclear. In this study, we investigated the effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in hairless mice. Mice were irradiated with UVB three times weekly and orally administered B. breve B-3 (2×10(9) cfu/mouse /day) for 7 weeks. Nonirradiated mice and UVB-irradiated mice without probiotic treatment were used as controls. B. breve B-3 significantly suppressed the changes of transepidermal water loss, skin hydration, epidermal thickening and attenuated the damage to the tight junction structure and basement membrane induced by chronic UVB irradiation. Administration of B. breve B-3 tended to suppress the UV-induced interleukin-1β production in skin (P=0.09). These results suggest that B. breve B-3 could potentially be used to prevent photoaging induced by chronic UV irradiation.

Soybean resistance to stink bugs (Nezara viridula and Piezodorus guildinii) increases with exposure to solar UV-B radiation and correlates with isoflavonoid content in pods under field conditions.

PubMed

Zavala, Jorge A; Mazza, Carlos A; Dillon, Francisco M; Chludil, Hugo D; Ballaré, Carlos L

2015-05-01

Solar UV-B radiation (280-315 nm) has a significant influence on trophic relationships in natural and managed ecosystems, affecting plant-insect interactions. We explored the effects of ambient UV-B radiation on the levels of herbivory by stink bugs (Nezara viridula and Piezodorus guildinii) in field-grown soybean crops. The experiments included two levels of UV-B radiation (ambient and attenuated UV-B) and four soybean cultivars known to differ in their content of soluble leaf phenolics. Ambient UV-B radiation increased the accumulation of the isoflavonoids daidzin and genistin in the pods of all cultivars. Soybean crops grown under attenuated UV-B had higher numbers of unfilled pods and damaged seeds than crops grown under ambient UV-B radiation. Binary choice experiments with soybean branches demonstrated that stink bugs preferred branches of the attenuated UV-B treatment. We found a positive correlation between percentage of undamaged seeds and the contents of daidzin and genistin in pods. Our results suggest that constitutive and UV-B-induced isoflavonoids increase plant resistance to stink bugs under field conditions. © 2014 John Wiley & Sons Ltd.

Epigallocatechin-gallate (EGCG) regulates autophagy in human retinal pigment epithelial cells: a potential role for reducing UVB light-induced retinal damage.

PubMed

Li, Chao-Peng; Yao, Jin; Tao, Zhi-Fu; Li, Xiu-Miao; Jiang, Qin; Yan, Biao

2013-09-06

Autophagy is an intracellular catabolic process involved in protein and organelle degradation via the lysosomal pathway that has been linked in the pathogenesis of age-related macular degeneration (AMD). UVB irradiation-mediated degeneration of the macular retinal pigment epithelial (RPE) cells is an important hallmark of AMD, which is along with the change in RPE autophagy. Thus, pharmacological manipulation of RPE autophagy may offer an alternative therapeutic target in AMD. Here, we found that epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, plays a regulatory role in UVB irradiation-induced autophagy in RPE cells. UVB irradiation results in a marked increase in the amount of LC3-II protein in a dose-dependent manner. EGCG administration leads to a significant reduction in the formation of LC3-II and autophagosomes. mTOR signaling activation is required for EGCG-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation is significantly impaired by rapamycin administration. Moreover, EGCG significantly alleviates the toxic effects of UVB irradiation on RPE cells in an autophagy-dependent manner. Collectively, our study reveals a novel role of EGCG in RPE autophagy. EGCG may be exploited as a potential therapeutic reagent for the treatment of pathological conditions associated with abnormal autophagy. Published by Elsevier Inc.

Modeling photoionization of aqueous DNA and its components.

PubMed

Pluhařová, Eva; Slavíček, Petr; Jungwirth, Pavel

2015-05-19

Radiation damage to DNA is usually considered in terms of UVA and UVB radiation. These ultraviolet rays, which are part of the solar spectrum, can indeed cause chemical lesions in DNA, triggered by photoexcitation particularly in the UVB range. Damage can, however, be also caused by higher energy radiation, which can ionize directly the DNA or its immediate surroundings, leading to indirect damage. Thanks to absorption in the atmosphere, the intensity of such ionizing radiation is negligible in the solar spectrum at the surface of Earth. Nevertheless, such an ionizing scenario can become dangerously plausible for astronauts or flight personnel, as well as for persons present at nuclear power plant accidents. On the beneficial side, ionizing radiation is employed as means for destroying the DNA of cancer cells during radiation therapy. Quantitative information about ionization of DNA and its components is important not only for DNA radiation damage, but also for understanding redox properties of DNA in redox sensing or labeling, as well as charge migration along the double helix in nanoelectronics applications. Until recently, the vast majority of experimental and computational data on DNA ionization was pertinent to its components in the gas phase, which is far from its native aqueous environment. The situation has, however, changed for the better due to the advent of photoelectron spectroscopy in liquid microjets and its most recent application to photoionization of aqueous nucleosides, nucleotides, and larger DNA fragments. Here, we present a consistent and efficient computational methodology, which allows to accurately evaluate ionization energies and model photoelectron spectra of aqueous DNA and its individual components. After careful benchmarking, the method based on density functional theory and its time-dependent variant with properly chosen hybrid functionals and polarizable continuum solvent model provides ionization energies with accuracy of 0.2-0.3 eV, allowing for faithful modeling and interpretation of DNA photoionization. The key finding is that the aqueous medium is remarkably efficient in screening the interactions within DNA such that, unlike in the gas phase, ionization of a base, nucleoside, or nucleotide depends only very weakly on the particular DNA context. An exception is the electronic interaction between neighboring bases which can lead to sequence-specific effects, such as a partial delocalization of the cationic hole upon ionization enabled by presence of adjacent bases of the same type.

Wavelength-dependent ultraviolet induction of cyclobutane pyrimidine dimers in the human cornea.

PubMed

Mallet, Justin D; Rochette, Patrick J

2013-08-01

Exposition to ultraviolet (UV) light is involved in the initiation and the progression of skin cancer. The genotoxicity of UV light is mainly attributed to the induction of cyclobutane pyrimidine dimers (CPDs), the most abundant DNA damage generated by all UV types (UVA, B and C). The human cornea is also exposed to the harmful UV radiations, but no UV-related neoplasm has been reported in this ocular structure. The probability that a specific DNA damage leads to a mutation and eventually to cellular transformation is influenced by its formation frequency. To shed light on the genotoxic effect of sunlight in the human eye, we have analyzed CPD induction in the cornea and the iris following irradiation of ex vivo human eyes with UVA, B or C. The extent of CPD induction was used to establish the penetrance of the different UV types in the human cornea. We show that UVB- and UVC-induced CPDs are concentrated in the corneal epithelium and do not penetrate deeply beyond this corneal layer. On the other hand, UVA wavelengths penetrate deeper and induce CPDs in the entire cornea and in the first layers of the iris. Taken together, our results are undoubtedly an important step towards better understanding the consequences of UV exposure to the human eye.

An Evaluation of Root Phytochemicals Derived from Althea officinalis (Marshmallow) and Astragalus membranaceus as Potential Natural Components of UV Protecting Dermatological Formulations

PubMed Central

Curnow, Alison; Owen, Sara J.

2016-01-01

As lifetime exposure to ultraviolet (UV) radiation has risen, the deleterious effects have also become more apparent. Numerous sunscreen and skincare products have therefore been developed to help reduce the occurrence of sunburn, photoageing, and skin carcinogenesis. This has stimulated research into identifying new natural sources of effective skin protecting compounds. Alkaline single-cell gel electrophoresis (comet assay) was employed to assess aqueous extracts derived from soil or hydroponically glasshouse-grown roots of Althea officinalis (Marshmallow) and Astragalus membranaceus, compared with commercial, field-grown roots. Hydroponically grown root extracts from both plant species were found to significantly reduce UVA-induced DNA damage in cultured human lung and skin fibroblasts, although initial Astragalus experimentation detected some genotoxic effects, indicating that Althea root extracts may be better suited as potential constituents of dermatological formulations. Glasshouse-grown soil and hydroponic Althea root extracts afforded lung fibroblasts with statistically significant protection against UVA irradiation for a greater period of time than the commercial field-grown roots. No significant reduction in DNA damage was observed when total ultraviolet irradiation (including UVB) was employed (data not shown), indicating that the extracted phytochemicals predominantly protected against indirect UVA-induced oxidative stress. Althea phytochemical root extracts may therefore be useful components in dermatological formulations. PMID:26953144

An Evaluation of Root Phytochemicals Derived from Althea officinalis (Marshmallow) and Astragalus membranaceus as Potential Natural Components of UV Protecting Dermatological Formulations.

PubMed

Curnow, Alison; Owen, Sara J

2016-01-01

As lifetime exposure to ultraviolet (UV) radiation has risen, the deleterious effects have also become more apparent. Numerous sunscreen and skincare products have therefore been developed to help reduce the occurrence of sunburn, photoageing, and skin carcinogenesis. This has stimulated research into identifying new natural sources of effective skin protecting compounds. Alkaline single-cell gel electrophoresis (comet assay) was employed to assess aqueous extracts derived from soil or hydroponically glasshouse-grown roots of Althea officinalis (Marshmallow) and Astragalus membranaceus, compared with commercial, field-grown roots. Hydroponically grown root extracts from both plant species were found to significantly reduce UVA-induced DNA damage in cultured human lung and skin fibroblasts, although initial Astragalus experimentation detected some genotoxic effects, indicating that Althea root extracts may be better suited as potential constituents of dermatological formulations. Glasshouse-grown soil and hydroponic Althea root extracts afforded lung fibroblasts with statistically significant protection against UVA irradiation for a greater period of time than the commercial field-grown roots. No significant reduction in DNA damage was observed when total ultraviolet irradiation (including UVB) was employed (data not shown), indicating that the extracted phytochemicals predominantly protected against indirect UVA-induced oxidative stress. Althea phytochemical root extracts may therefore be useful components in dermatological formulations.

Evaluation of the UVB-screening capacity and restorative effects exerted by farnesol gel on UVB-caused sunburn.

PubMed

Wu, Guan Xuan; Huang, Han Hsiang; Chang, Huoy Rou; Kuo, Shyh Ming

2018-04-01

Farnesol, a natural 15-carbon organic compound, has various microbiological and cellular activities. It has been found to exert apoptosis-inducing effects against carcinoma cells as well as antiallergic and anti-inflammatory effects in vivo. In the current study, a series of formulations composed of various concentrations of hydroxypropyl methylcellulose (HPMC) with the addition of hyaluronan (HA) and xanthan gum (XG) was designed to evaluate the UVB-screening and H 2 O 2 -eliminating effects of farnesol in normal fibroblasts. Farnesol at 0.005, 0.0075, and 0.01% exhibited significant capacity for H 2 O 2 scavenging; at 0.0025%, it showed insignificant effects. Under 120-min UVB exposure, screening with plural gel composed of 0.0025% farnesol, 0.5% HA, and 0.5% XG containing 1.5% or 2% HPMC retained normal fibroblast viability. After 60-min exposure to UVB, screening with plural gel composed of farnesol, HA, XG, and 0.5%, 1.0%, 1.5%, or 2% HPMC decreased the ratio of the G1 phase and increased ratio of the S phase in comparison with the accumulated cell cycle of the normal fibroblasts without screening. The gel with 2% HPMC displayed the strongest cell cycle-reversal ability. In vivo histopathological results showed that the prepared plural gels with 0.5% or 2% HPMC and farnesol, HA, and XG had greater antiphotoaging and reparative effects against UVB-induced changes and damage in the skin. In conclusion, the current in vitro and in vivo results demonstrated that the prepared plural composed of 0.0025% farnesol, 0.5% HA, 0.5% XG, and 2% HPMC possessed the greatest UVB-screening capacity and the strongest restorative effects on UVB-induced sunburned skin. © 2018 Wiley Periodicals, Inc.

Light and the circadian clock mediate time-specific changes in sensitivity to UV-B stress under light/dark cycles

PubMed Central

Takeuchi, Tomomi; Newton, Linsey; Burkhardt, Alyssa; Mason, Saundra; Farré, Eva M.

2014-01-01

In Arabidopsis, the circadian clock regulates UV-B-mediated changes in gene expression. Here it is shown that circadian clock components are able to inhibit UV-B-induced gene expression in a gene-by-gene-specific manner and act downstream of the initial UV-B sensing by COP1 (CONSTITUTIVE PHOTOMORPHOGENIC 1) and UVR8 (UV RESISTANCE LOCUS 8). For example, the UV-B induction of ELIP1 (EARLY LIGHT INDUCIBLE PROTEIN 1) and PRR9 (PSEUDO-RESPONSE REGULATOR 9) is directly regulated by LUX (LUX ARRYTHMO), ELF4 (EARLY FLOWERING 4), and ELF3. Moreover, time-dependent changes in plant sensitivity to UV-B damage were observed. Wild-type Arabidopsis plants, but not circadian clock mutants, were more sensitive to UV-B treatment during the night periods than during the light periods under diel cycles. Experiments performed under short cycles of 6h light and 6h darkness showed that the increased stress sensitivity of plants to UV-B in the dark only occurred during the subjective night and not during the subjective day in wild-type seedlings. In contrast, the stress sensitivity of Arabidopsis mutants with a compromised circadian clock was still influenced by the light condition during the subjective day. Taken together, the results show that the clock and light modulate plant sensitivity to UV-B stress at different times of the day. PMID:25147271

Protective effect of mango (Mangifera indica L.) against UVB-induced skin aging in hairless mice.

PubMed

Song, Jae Hyoung; Bae, Eun Young; Choi, Goya; Hyun, Jin Won; Lee, Mi Young; Lee, Hye Won; Chae, Sungwook

2013-04-01

Mangifera indica L. (Anacardiaceae) is a medicinal plant whose extracts have been described as an antioxidant with anti-inflammatory and immunomodulatory activities. Skin aging is a consequence of chronic sun exposure to the sun and therefore ultraviolet (UV) radiation. Naturally occurring antioxidants are known to reduce skin aging. Therefore, the aim of the present study was to evaluate the protective role of mango extract against UVB-induced skin aging in hairless mice. HR-1 hairless male mice (6 weeks old) were divided into three groups: control (n = 5), UVB-treated vehicle (n = 5), and UVB-treated mango extract (n = 5) groups. UVB-irradiated mice from the mango extract group were orally administered 0.1 ml of water containing 100 mg of mango extract/kg body weight per day. The inhibitory activity of mango extract on wrinkle formation was determined by the analysis of the skin replica, epidermal thickness based on histological examination, and damage to collagen fiber. The mean length of wrinkles in UVB-treated vehicle group significantly improved after the oral administration of mango extract, which significantly inhibited the increase in epidermal thickness and epidermal hypertrophy (P < 0.05). Furthermore, a marked increase in collagen bundles was observed in the UVB-treated group after the administration of mango extract by Masson's trichrome staining. These results indicate that mango extract showed anti-photoaging activity in UVB-irradiated hairless mice. © 2013 John Wiley & Sons A/S.

Perception of solar UVB radiation by phytophagous insects: Behavioral responses and ecosystem implications

PubMed Central

Mazza, Carlos A.; Zavala, Jorge; Scopel, Ana L.; Ballaré, Carlos L.

1999-01-01

Most of our present knowledge about the impacts of solar UVB radiation on terrestrial ecosystems comes from studies with plants. Recently, the effects of UVB on the growth and survival of consumer species have begun to receive attention, but very little is known about UVB impacts on animal behavior. Here we report that manipulations of the flux of solar UVB received by field-grown soybean crops had large and consistent effects on the density of the thrips (Caliothrips phaseoli, Thysanoptera: Thripidae) populations that invaded the canopies, as well as on the amount of leaf damage caused by the insects. Solar UVB strongly reduced thrips herbivory. Thrips not only preferred leaves from plants that were not exposed to solar UVB over leaves from UVB-exposed plants in laboratory and field choice experiments, but they also appeared to directly sense and avoid exposure to solar UVB. Additional choice experiments showed that soybean leaf consumption by the late-season soybean worm Anticarsia gemmatalis (Lepidoptera: Noctuidae) was much less intense in leaves with even slight symptoms of an early thrips attack than in undamaged leaves. These experiments suggest that phytophagous insects can present direct and indirect behavioral responses to solar UVB. The indirect responses are mediated by changes in the plant host that are induced by UVB and, possibly, by other insects whose behavior is affected by UVB. PMID:9927679

Reproductive, morphological, and phytochemical responses of Arabidopsis thaliana ecotypes to enhanced UV-B radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trumbull, V.L.; McCloud, E.S.; Paige, K.N.

1994-06-01

Two ecotypes of Arabidopsis thaliana, collected from Libya and Norway, were grown in the greenhouse under. UV-B doses of 0 and 10.5 kJ m[sup [minus]2] UV-B[sub BE]. The high UV-B dose simulated midsummer ambient conditions over Libya and a 40% reduction in stratospheric ozone over Norway. The Libyan ectotype, which originated from latitudes where solar UV-B is high, showed no UV-B induced damage to plant growth. However the Norwegian ecotype, which originated from latitudes where solar UV-B is low, showed a significant reduction in plant height, inflorescence weight, and rosette weight in response to enhanced UV-B. Although fruit and seedmore » number for both ecotypes were unaffected by enhanced UV-B radiation the germination success of the seeds harvested from the irradiated Norwegian plants were significantly reduced. The two ecotypes also differed with respect to their accumulation of kaempferol, a putative UV-B protective filter. The Libyan ecotype increased kaempferol concentration by 38% over the 0 kJ treatment whereas the Norwegian ecotype increased by only 15%. These data suggest that, for these ecotypes, variation in UV-B sensitivity may be explained by the differential induction of UV-absorbing leaf pigments.« less

Protective activity of hamamelitannin on cell damage of murine skin fibroblasts induced by UVB irradiation.

PubMed

Masaki, H; Atsumi, T; Sakurai, H

1995-07-01

The protective activities of hamamelitannin (2',5-di-O-galloyl-hamamelose) in Hamamelis virginiana L. and its related compound, gallic acid, on damaged murine skin fibroblasts induced by UVB irradiation were investigated. In order to exclude the UV absorbing effect of the compounds, the protection study was performed such that the fibroblasts were pretreated with hamamelitannin or gallic acid for 24 h before UVB irradiation. At 200 microM concentration, hamamelitannin gave the higher survival of 72.6 +/- 0.4% in comparison with that of gallic acid (35.5 +/- 1.0%), while UVB absorbers such as 2-ethylhexyl p-methoxycinnamate and hexylbenzoate did not show such protection. The scavenging activities of hamamelitannin and gallic acid against active oxygens such as superoxide anion radicals, hydroxyl radicals and singlet oxygens were evaluated using electron spin resonance (ESR-spin trapping method). Hamamelitannin and gallic acid showed potent scavenging activities against all active oxygens tested. Furthermore, the association of hamamelitannin to fibroblasts was examined by comparing it with that of gallic acid, and the following results were obtained: (1) hamamelitannin reduces the reaction rate of liposome entrapped-nitroblue tetrazolium (NBT) with external superoxide anions, and (2) several glycosides associate with fibroblasts. From these results, it was concluded that hamamelitannin protects murine fibroblasts against external active oxygens by associating with the cell surface through its sugar moiety.

Hypersensitivity of skin fibroblasts from basal cell nevus syndrome patients to killing by ultraviolet B but not by ultraviolet C radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Applegate, L.A.; Goldberg, L.H.; Ley, R.D.

Basal cell nevus syndrome (BCNS) is an autosomal dominant genetic disorder in which the afflicted individuals are extremely susceptible to sunlight-induced skin cancers, particularly basal cell carcinomas. However, the cellular and molecular basis for BCNS is unknown. To ascertain whether there is any relationship between genetic predisposition to skin cancer and increased sensitivity of somatic cells from BCNS patients to killing by UV radiation, we exposed skin fibroblasts established from unexposed skin biopsies of several BCNS and age- and sex-matched normal individuals to either UV-B (280-320 nm) or UV-C (254 nm) radiation and determined their survival. The results indicated thatmore » skin fibroblasts from BCNS patients were hypersensitive to killing by UV-B but not UV-C radiation as compared to skin fibroblasts from normal individuals. DNA repair studies indicated that the increased sensitivity of BCNS skin fibroblasts to killing by UV-B radiation was not due to a defect in the excision repair of pyrimidine dimers. These results indicate that there is an association between hypersensitivity of somatic cells to killing by UV-B radiation and the genetic predisposition to skin cancer in BCNS patients. In addition, these results suggest that DNA lesions (and repair processes) other than the pyrimidine dimer are also involved in the pathogenesis of sunlight-induced skin cancers in BCNS patients. More important, the UV-B sensitivity assay described here may be used as a diagnostic tool to identify presymptomatic individuals with BCNS.« less

UV-B Inhibits Leaf Growth through Changes in Growth Regulating Factors and Gibberellin Levels1[OPEN

PubMed Central

Fina, Julieta; AbdElgawad, Hamada; Prinsen, Els

2017-01-01

Ultraviolet-B (UV-B) radiation affects leaf growth in a wide range of species. In this work, we demonstrate that UV-B levels present in solar radiation inhibit maize (Zea mays) leaf growth without causing any other visible stress symptoms, including the accumulation of DNA damage. We conducted kinematic analyses of cell division and expansion to understand the impact of UV-B radiation on these cellular processes. Our results demonstrate that the decrease in leaf growth in UV-B-irradiated leaves is a consequence of a reduction in cell production and a shortened growth zone (GZ). To determine the molecular pathways involved in UV-B inhibition of leaf growth, we performed RNA sequencing on isolated GZ tissues of control and UV-B-exposed plants. Our results show a link between the observed leaf growth inhibition and the expression of specific cell cycle and developmental genes, including growth-regulating factors (GRFs) and transcripts for proteins participating in different hormone pathways. Interestingly, the decrease in the GZ size correlates with a decrease in the concentration of GA19, the immediate precursor of the active gibberellin, GA1, by UV-B in this zone, which is regulated, at least in part, by the expression of GRF1 and possibly other transcription factors of the GRF family. PMID:28400494

Photoprotection against the UVB-induced oxidative stress and epidermal damage in mice using leaves of three different varieties of Lepidium meyenii (maca).

PubMed

Gonzales-Castañeda, Cynthia; Rivera, Valery; Chirinos, Ana Lucía; Evelson, Pablo; Gonzales, Gustavo Francisco

2011-08-01

Skin exposure to ultraviolet (UV) B radiation leads to epidermal damage and generation of reactive oxygen species. The photoprotective effect of extracts of three varieties of leaves (red, yellow, and black) from maca (Lepidium meyenii), a plant from the Peruvian highlands, was assessed in mouse skin exposed to UVB radiation. The hydroalcoholic extracts of three varieties of maca leaves were applied topically to the dorsal skin of young-adult male mice prior to exposition to UVB radiation. The three varieties had UVA/UVB absorptive properties and presented antioxidant activity, being highest with red maca, followed by black and yellow maca. The three varieties of maca leaves prevented the development of sunburn cells, epidermal hyperplasia, leukocytic infiltration, and other alterations produced by UVB radiation. Mice treated with black maca showed the highest superoxide dismutase levels, and mice treated with black and yellow maca showed higher catalase levels in skin, whereas red maca protected the skin and liver against significant increases in the lipid peroxidation activity observed in the unprotected animals. The presence of significant antioxidant activity and the inhibition of lipid peroxidation suggest that the observed protection could be partly attributable to this mechanism. © 2011 The International Society of Dermatology.

Djulis (Chenopodium formosanum Koidz.) Water Extract and Its Bioactive Components Ameliorate Dermal Damage in UVB-Irradiated Skin Models.

PubMed

Hong, Yong-Han; Huang, Ya-Ling; Liu, Yao-Cheng; Tsai, Pi-Jen

2016-01-01

Dermal photoaging is a condition of skin suffering inappropriate ultraviolet (UV) exposure and exerts inflammation, tissue alterations, redness, swelling, and uncomfortable feelings. Djulis ( Chenopodium formosanum Koidz.) is a cereal food and its antioxidant and pigment constituents may provide skin protection from photoaging, but it still lacks proved experiments. In this study, protective effects of djulis extract (CFE) on UVB-irradiated skin were explored. The results showed that HaCaT cells with 150  μ g/mL CFE treatment had higher survival and less production of interleukin- (IL-) 6, matrix metalloprotease- (MMP-) 1, and reactive oxygen species (ROS) in UVB-irradiated conditions. Subsequently, in animal studies, mice supplemented with CFE (100 mg/kg BW) were under UVB irradiation and had thinner epidermis and lower IL-6 levels in skin layer. These data demonstrate that bioactive compounds possessing the potency of antiphotoaging exist in CFE. Following that, we found rutin and chlorogenic acid (10-100  μ M) could significantly increase cell viability and decrease the production of IL-6 in UVB models. Additionally, djulis pigment-betanin has no effect of increasing cell viability in this study. Our findings suggest CFE can protect skin against UV-induced damage and this protection is mainly from contributions of rutin and chlorogenic acid.

Ginsenoside C-Mx Isolated from Notoginseng Stem-leaf Ginsenosides Attenuates Ultraviolet B-mediated Photoaging in Human Dermal Fibroblasts.

PubMed

Liu, Xiao-Yi; Hwang, Eunson; Park, Bom; Ngo, Hien T T; Xiao, Yong-Kun; Yi, Tae-Hoo

2018-05-20

Notoginseng is a traditional herbal medicine widely used for medicinal therapy in Asia, as it contains numerous ginsenosides with pharmacological effects. In this study, we submitted Notoginseng stem-leaf (NGL) ginsenosides to an enzyme to create reaction the monomer products of ginsenoside C-Mx and then investigated the ability of ginsenoside C-Mx to protect the skin against ultraviolet B-induced injury in normal human dermal fibroblasts (NHDFs). Ginsenoside C-Mx alleviated UVB-induced intracellular reactive oxygen species (ROS), MMP-1, and IL-6 expression while accelerating TGF-β and procollagen type I secretion. In addition, ginsenoside C-Mx reversed UVB-induced procollagen type I reduction by regulating the TGF-β/Smad signaling pathway. Moreover, ginsenoside C-Mx inhibited activation of AP-1 transcription factor, an inducer of MMPs. Ginsenoside C-Mx displayed an outstanding antioxidant capacity, increasing expression of cytoprotective antioxidants such as HO-1 and, NQO-1 expression by enhancing the nuclear accumulation of Nrf2. Interestingly, applied of ginsenoside C-Mx treatment (1, 10, 20μM) significantly diminished UVB-induced suppressed NF-κB expression, decreasing the over-released inflammatory cytokines. Taken together, our findings indicated that ginsenoside C-Mx may act as a promising natural cosmetic ingredient for prevention and treatment of UVB-induced skin damage. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Conditioned medium from human bone marrow-derived mesenchymal stem cells promotes skin moisturization and effacement of wrinkles in UVB-irradiated SKH-1 hairless mice.

PubMed

Kwon, Tae-Rin; Oh, Chang Taek; Choi, Eun Ja; Kim, Soon Re; Jang, Yu-Jin; Ko, Eun Jung; Yoo, Kwang Ho; Kim, Beom Joon

2016-05-01

Mesenchymal stem cells (MSCs) are promising therapeutic agents for various diseases. To investigate the effects of conditioned medium from human bone marrow-derived mesenchymal stem cells (MSC-CdM) on pro-collagen production and wrinkle formation, we performed in vitro and in vivo experiments. We assessed the effects of MSC-CdM on proliferation and photo-aging in human dermal fibroblasts after UVB exposure using enzyme activity assays for collagen type I secretion and MMP-1. To determine the effect of topically applied MSC-CdM on wrinkle formation, MSC-CdM (1% and 10%) and vehicle (propylene glycol: ethanol, 7 : 3) were applied to the dorsal skin of UVB-irradiated hairless mice for 8 weeks. We examined the effects on wrinkle formation by assessing visual skin grading, replica, tape stripping, transepidermal water loss (TEWL), and skin hydration measurement. We also examined histology of the lesions using hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining. MSC-CdM markedly reduced UV-induced matrix metalloproteinase-1 expression and increased pro-collagen synthesis in a dose-dependent manner. Our findings suggest that MSC-CdM induces repair of dermal damage and effacement of wrinkles on UVB-irradiated hairless mice through protective effect of hydration. These results support an anti-wrinkle effect of MSC-CdM that involves increased collagen synthesis and suggest that MSC-CdM might be a potential candidate for preventing UV-induced skin damage. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The protective effects of fucosterol against skin damage in UVB-irradiated human dermal fibroblasts.

PubMed

Hwang, Eunson; Park, Sang-Yong; Sun, Zheng-wang; Shin, Heon-Sub; Lee, Don-Gil; Yi, Tae Hoo

2014-06-01

Exposure to ultraviolet (UV) light causes matrix metalloproteinase (MMP) overexpression and extracellular matrix depletion, leading to skin photoaging. The activation of MMP is related to increased interlukin-6 (IL-6) and type I procollagen production, which is regulated by transforming growth factor-β1 (TGF-β1). Activator protein-1 (AP-1) activation induces MMP-1 production and reduces type I procollagen secretion. Fucosterol, which is extracted and purified from the brown algae Hizikia fusiformis, is a phytosterol. We assessed the effects of fucosterol on photodamage and investigated its molecular mechanism of action in UVB-irradiated normal human dermal fibroblasts by using enzyme-linked immunosorbent assay, Western blot analysis, and reverse transcription-polymerase chain reaction. Our results showed that fucosterol significantly decreased the UVB-induced expression of MMP-1, IL-6, p-c-Jun, and p-c-Fos. Additionally, fucosterol markedly increased the UVB-induced production of type I procollagen and TGF-β1. Our results indicate that fucosterol regulates MMP-1 and type I procollagen expression by modulating AP-1 and TGF-β1 signaling and that MMP-1 activation is correlated with IL-6. These data suggest that fucosterol is a promising botanical agent to protect against skin photodamage.

Effect of Microalgal Extracts of Tetraselmis suecica against UVB-Induced Photoaging in Human Skin Fibroblasts.

PubMed

Jo, Wol Soon; Yang, Kwang Mo; Park, Hee Sung; Kim, Gi Yong; Nam, Byung Hyouk; Jeong, Min Ho; Choi, Yoo Jin

2012-12-01

Exposure of cells to ultraviolet B (UVB) radiation can induce production of free radicals and reactive oxygen species (ROS), which damage cellular components. In addition, these agents can stimulate the expression of matrix metalloproteinase (MMP) and decrease collagen synthesis in human skin cells. In this study, we examined the anti-photoaging effects of extracts of Tetraselmis suecica (W-TS). W-TS showed the strongest scavenging activity against 2,2-difenyl-1-picrylhydrazyl (DPPH) and peroxyl radicals, followed by superoxide anions from the xanthine/xanthine oxidase system. We observed that the levels of both intracellular ROS and lipid peroxidation significantly increased in UVB-irradiated human skin fibroblast cells. Furthermore, the activities of enzymatic antioxidants (e.g., superoxide dismutase) and the levels of non-enzymatic antioxidants (e.g., glutathione) significantly decreased in cells. However, W-TS pretreatment, at the maximum tested concentration, significantly decreased intracellular ROS and malondialdehyde (MDA) levels, and increased superoxide dismutase and glutathione levels in the cells. At this same concentration, W-TS did not show cytotoxicity. Type 1 procollagen and MMP-1 released were quantified using RT-PCR techniques. The results showed that W-TS protected type 1 procollagen against UVBinduced depletion in fibroblast cells in a dose-dependent manner via inhibition of UVB-induced MMP-1. Taken together, the results of the study suggest that W-TS effectively inhibits UVB-induced photoaging in skin fibroblasts by its strong anti-oxidant ability.

Effect of Microalgal Extracts of Tetraselmis suecica against UVB-Induced Photoaging in Human Skin Fibroblasts

PubMed Central

Jo, Wol Soon; Yang, Kwang Mo; Park, Hee Sung; Kim, Gi Yong; Nam, Byung Hyouk

2012-01-01

Exposure of cells to ultraviolet B (UVB) radiation can induce production of free radicals and reactive oxygen species (ROS), which damage cellular components. In addition, these agents can stimulate the expression of matrix metalloproteinase (MMP) and decrease collagen synthesis in human skin cells. In this study, we examined the anti-photoaging effects of extracts of Tetraselmis suecica (W-TS). W-TS showed the strongest scavenging activity against 2,2-difenyl-1-picrylhydrazyl (DPPH) and peroxyl radicals, followed by superoxide anions from the xanthine/xanthine oxidase system. We observed that the levels of both intracellular ROS and lipid peroxidation significantly increased in UVB-irradiated human skin fibroblast cells. Furthermore, the activities of enzymatic antioxidants (e.g., superoxide dismutase) and the levels of non-enzymatic antioxidants (e.g., glutathione) significantly decreased in cells. However, W-TS pretreatment, at the maximum tested concentration, significantly decreased intracellular ROS and malondialdehyde (MDA) levels, and increased superoxide dismutase and glutathione levels in the cells. At this same concentration, W-TS did not show cytotoxicity. Type 1 procollagen and MMP-1 released were quantified using RT-PCR techniques. The results showed that W-TS protected type 1 procollagen against UVBinduced depletion in fibroblast cells in a dose-dependent manner via inhibition of UVB-induced MMP-1. Taken together, the results of the study suggest that W-TS effectively inhibits UVB-induced photoaging in skin fibroblasts by its strong anti-oxidant ability. PMID:24278616

Molecular response to phototoxic stress of UVB-irradiated ketoprofen through arresting cell cycle in G2/M phase and inducing apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu Shicheng; Mizu, Hideo; Yamauchi, Hitoshi

The phototoxicity of ketoprofen (KP), a non-steroidal anti-inflammatory drug, has recently attracted considerable attention, because it is photolabile and undergoes degradation when irradiated by sunlight to induce various skin diseases. The present study shows that combination of UVB irradiation with KP induced the cytotoxicity and suppressed DNA synthesis in HaCaT cells in a concentration-dependent manner. UVB-irradiated KP inhibited the cell growth and induced G2/M cell cycle arrest by modulating the levels of cdc2, cyclin B1, Chk1, Tyr15-phosphorylated cdc2 and p21. It also provoked a striking accumulation of cyclin B1-cdc2-p21 complexes, concomitantly with an increase in the levels of Tyr15-phosphorylated cdc2more » and p21 protein. The presence of KP accentuated the apoptotic response to UVB radiation in HaCaT cells as evidenced by DAPI staining. The apoptotic process was associated with activation of caspase-9, caspase-3 and cleavage of PARP, and this activation could be prevented by a specific caspase-3 inhibitor. Taken together, our results suggest that KP-photoinduced apoptosis may be a useful approach to reduce or prevent skin carcinogenesis.« less

The Role of AKT/mTOR Pathway in Stress Response to UV-Irradiation: Implication in Skin Carcinogenesis by Regulation of Apoptosis, Autophagy and Senescence

PubMed Central

Strozyk, Elwira; Kulms, Dagmar

2013-01-01

Induction of DNA damage by UVB and UVA radiation may generate mutations and genomic instability leading to carcinogenesis. Therefore, skin cells being repeatedly exposed to ultraviolet (UV) light have acquired multilayered protective mechanisms to avoid malignant transformation. Besides extensive DNA repair mechanisms, the damaged skin cells can be eliminated by induction of apoptosis, which is mediated through the action of tumor suppressor p53. In order to prevent the excessive loss of skin cells and to maintain the skin barrier function, apoptotic pathways are counteracted by anti-apoptotic signaling including the AKT/mTOR pathway. However, AKT/mTOR not only prevents cell death, but is also active in cell cycle transition and hyper-proliferation, thereby also counteracting p53. In turn, AKT/mTOR is tuned down by the negative regulators being controlled by the p53. This inhibition of AKT/mTOR, in combination with transactivation of damage-regulated autophagy modulators, guides the p53-mediated elimination of damaged cellular components by autophagic clearance. Alternatively, p53 irreversibly blocks cell cycle progression to prevent AKT/mTOR-driven proliferation, thereby inducing premature senescence. Conclusively, AKT/mTOR via an extensive cross talk with p53 influences the UV response in the skin with no black and white scenario deciding over death or survival. PMID:23887651

Enhancement of Protective Effects of Radix Scutellariae on UVB-induced Photo Damage in Human HaCaT Keratinocytes.

PubMed

Wang, Yu-Shuai; Cho, Jin-Gyeong; Hwang, Eun-Son; Yang, Jung-Eun; Gao, Wei; Fang, Min-Zhe; Zheng, Sheng-Dao; Yi, Tae-Hoo

2018-04-01

Radix Scutellariae (RS) has long been used in the treatment of inflammatory and allergic diseases. Its main flavonoids, baicalin (BG) and wogonoside (WG), can be hydrolyzed into their corresponding aglycones, baicalein (B) and wogonin (W). In this study, we developed a safe and effective method of transforming these glycosides using Peclyve PR. The transformation rate of BG and WG reached 98.5 and 98.1%, respectively, with 10% enzyme at 40 °C for 60 h. Furthermore, we compared the anti-photoaging activity of RS before and after enzyme treatment, as well as their respective main components, in UVB-irradiated HaCaT cells. Results found that enzyme-treated RS (ERS) appeared to be much better at preventing UVB-induced photoaging than RS. ERS significantly inhibited the upregulation of matrix metalloproteinase-1 and IL-6 caused by UVB radiation by inactivating the MAPK/AP-1 and NF-κB/IκB-α signaling pathways. ERS treatment also recovered UVB-induced reduction of procollagen type I by activating the TGF-β/Smad pathway. In addition, ERS exhibited an excellent antioxidant activity, which could increase the expression of cytoprotective antioxidants such as HO-1 and NQ-O1, by facilitating Nrf2 nuclear transfer. These findings demonstrated that the photoprotective effects of RS were significantly improved by enzyme-modified biotransformation.

Understanding the Physical and Molecular Basis of Stability of Arabidopsis DNA Pol λ under UV-B and High NaCl Stress.

PubMed

Roy, Sujit; Banerjee, Victor; Das, Kali Pada

2015-01-01

Here, we have investigated the physical and molecular basis of stability of Arabidopsis DNA Pol λ, the sole X family DNA polymerase member in plant genome, under UV-B and salinity stress in connection with the function of the N-terminal BRCT (breast cancer-associated C terminus) domain and Ser-Pro rich region in the regulation of the overall structure of this protein. Tryptophan fluorescence studies, fluorescence quenching and Bis-ANS binding experiments using purified recombinant full length Pol λ and its N-terminal deletion forms have revealed UV-B induced conformational change in BRCT domain deficient Pol λ. On the other hand, the highly conserved C-terminal catalytic core PolX domain maintained its tertiary folds under similar condition. Circular dichroism (CD) and fourier transform infrared (FT-IR) spectral studies have indicated appreciable change in the secondary structural elements in UV-B exposed BRCT domain deficient Pol λ. Increased thermodynamic stability of the C-terminal catalytic core domain suggested destabilizing effect of the N-terminal Ser-Pro rich region on the protein structure. Urea-induced equilibrium unfolding studies have revealed increased stability of Pol λ and its N-terminal deletion mutants at high NaCl concentration. In vivo aggregation studies using transient expression systems in Arabidopsis and tobacco indicated possible aggregation of Pol λ lacking the BRCT domain. Immunoprecipitation assays revealed interaction of Pol λ with the eukaryotic molecular chaperone HSP90, suggesting the possibility of regulation of Pol λ stability by HSP90 in plant cell. Overall, our results have provided one of the first comprehensive information on the biophysical characteristics of Pol λ and indicated the importance of both BRCT and Ser-Pro rich modules in regulating the stability of this protein under genotoxic stress in plants.

Heme oxygenase up-regulation under ultraviolet-B radiation is not epigenetically restricted and involves specific stress-related transcriptions factors.

PubMed

Santa-Cruz, Diego; Pacienza, Natalia; Zilli, Carla; Pagano, Eduardo; Balestrasse, Karina; Yannarelli, Gustavo

2017-08-01

Heme oxygenase-1 (HO-1) plays a protective role against oxidative stress in plants. The mechanisms regulating its expression, however, remain unclear. Here we studied the methylation state of a GC rich HO-1 promoter region and the expression of several stress-related transcription factors (TFs) in soybean plants subjected to ultraviolet-B (UV-B) radiation. Genomic DNA and total RNA were isolated from leaves of plants irradiated with 7.5 and 15kJm-2 UV-B. A 304bp HO-1 promoter region was amplified by PCR from sodium bisulfite-treated DNA, cloned into pGEMT plasmid vector and evaluated by DNA sequencing. Bisulfite sequencing analysis showed similar HO-1 promoter methylation levels in control and UV-B-treated plants (C: 3.4±1.3%; 7.5: 2.6±0.5%; 15: 3.1±1.1%). Interestingly, HO-1 promoter was strongly unmethylated in control plants. Quantitative RT-PCR analysis of TFs showed that GmMYB177, GmMYBJ6, GmWRKY21, GmNAC11, GmNAC20 and GmGT2A but not GmWRK13 and GmDREB were induced by UV-B radiation. The expression of several TFs was also enhanced by hemin, a potent and specific HO inducer, inferring that they may mediate HO-1 up-regulation. These results suggest that soybean HO-1 gene expression is not epigenetically regulated. Moreover, the low level of HO-1 promoter methylation suggests that this antioxidant enzyme can rapidly respond to environmental stress. Finally, this study has identified some stress-related TFs involved in HO-1 up-regulation under UV-B radiation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

A C. elegans homolog for the UV-hypersensitivity syndrome disease gene UVSSA.

PubMed

Babu, Vipin; Schumacher, Björn

2016-05-01

The transcription-coupled repair pathway (TC-NER) plays a vital role in removing transcription-blocking DNA lesions, particularly UV-induced damage. Clinical symptoms of the two TC-NER-deficiency syndromes, Cockayne syndrome (CS) and UV-hypersensitivity syndrome (UVSS) are dissimilar and the underlying molecular mechanism causing this difference in disease pathology is not yet clearly understood. UV-stimulated scaffold protein A (UVSSA) has been identified recently as a new causal gene for UVSS. Here we describe a functional homolog of the human UVSSA gene in the nematode Caenorhabditis elegans, uvs-1 (UVSSA-like-1). Mutations in uvs-1 render the animals hypersensitive to UV-B irradiation and transcription-blocking lesion-inducing illudin-M, similar to mutations in TC-NER deficient mutants. Moreover, we demonstrate that TC-NER factors including UVS-1 are required for the survival of the adult animals after UV-treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Recombinant Human Acidic Fibroblast Growth Factor (aFGF) Expressed in Nicotiana benthamiana Potentially Inhibits Skin Photoaging.

PubMed

Ha, Jang-Ho; Kim, Ha-Neul; Moon, Ki-Beom; Jeon, Jae-Heung; Jung, Dai-Hyun; Kim, Su-Jung; Mason, Hugh S; Shin, Seo-Yeon; Kim, Hyun-Soon; Park, Kyung-Mok

2017-07-01

Responding to the need for recombinant acidic fibroblast growth factor in the pharmaceutical and cosmetic industries, we established a scalable expression system for recombinant human aFGF using transient and a DNA replicon vector expression in Nicotiana benthamiana . Recombinant human-acidic fibroblast growth factor was recovered following Agrobacterium infiltration of N. benthamiana . The optimal time point at which to harvest recombinant human acidic fibroblast growth factor expressing leaves was found to be 4 days post-infiltration, before necrosis was evident. Commassie-stained SDS-PAGE gels of His-tag column eluates, concentrated using a 10 000 molecular weight cut-off column, showed an intense band at the expected molecular weight for recombinant human acidic fibroblast growth factor. An immunoblot confirmed that this band was recombinant human acidic fibroblast growth factor. Up to 10 µg recombinant human-acidic fibroblast growth factor/g of fresh leaves were achieved by a simple affinity purification protocol using protein extract from the leaves of agroinfiltrated N. benthamiana . The purified recombinant human acidic fibroblast growth factor improved the survival rate of UVB-irradiated HaCaT and CCD-986sk cells approximately 89 and 81 %, respectively. N. benthamiana -derived recombinant human acidic fibroblast growth factor showed similar effects on skin cell proliferation and UVB protection compared to those of Escherichia coli -derived recombinant human acidic fibroblast growth factor. Additionally, N. benthamiana- derived recombinant human acidic fibroblast growth factor increased type 1 procollagen synthesis up to 30 % as well as reduced UVB-induced intracellular reactive oxygen species generation in fibroblast (CCD-986sk) cells.UVB is a well-known factor that causes various types of skin damage and premature aging. Therefore, the present study demonstrated that N. benthamiana -derived recombinant human acidic fibroblast growth factor effectively protects skin cell from UVB, suggesting its potential use as a cosmetic or therapeutic agent against skin photoaging. Georg Thieme Verlag KG Stuttgart · New York.

Effects of UV-B irradiation on isoforms of antioxidant enzymes and their activities in red alga Grateloupia filicina (Rhodophyta)

NASA Astrophysics Data System (ADS)

Zhao, Jiqiang; Li, Lixia

2014-11-01

Macroalgae in a littoral zone are inevitably exposed to UV-B irradiance. We analyzed the effects of UV-B on isoenzyme patterns and activities of superoxide dismutase (SOD), peroxidase (POX), catalase (CAT), and ascorbate peroxidase (APX) of red algae Grateloupia filicina (Lamour.) C. Agardh. The activities of SOD, CAT, and APX changed in response to UV-B in a time- and dose-dependent manner. POX activity increased significantly under all three UV-B treatments. The enzymatic assay showed three distinct bands of SODI (Mn-SOD), SODII (Fe-SOD), and SODIII (CuZn-SOD) under a low (Luv) and medium (Muv) dose of UV-B irradiation, while SODI and SODIII activities decreased significantly when exposed to a high dose of UV-B irradiation (Huv). The activity of POX isoenzymes increased significantly after exposure to UV-B, which is consistent with the total activity. In addition, a clear decrease in activity of CATIV was detected in response to all the three doses of UV treatments. Some bands of APX isoenzyme were also clearly influenced by UV-B irradiation. Correspondingly, the daily growth rate declined under all the three exposure doses, and was especially significant under Muv and Huv treatments. These data suggest that, although the protection mechanisms of antioxidant defense system are partly inducible by UV-B to prevent the damage, G. filicina has incomplete tolerance to higher UV-B irradiation stress.

Micro-Raman spectroscopy study of the effect of Mid-Ultraviolet radiation on erythrocyte membrane.

PubMed

Li, N; Li, S X; Guo, Z Y; Zhuang, Z F; Li, R; Xiong, K; Chen, S J; Liu, S H

2012-07-02

Mid-Ultraviolet (UVB) has a significant influence on human health. In this study, human erythrocytes were exposed to UVB to investigate the effects of UVB radiation on erythrocytes membrane. And Micro-Raman spectroscopy was employed to detect the damage. Principal component analysis (PCA) was used to classify the control erythrocytes and the irradiated erythrocytes. Results showed that the erythrocytes membrane was damaged by Mid-Ultraviolet (UVB) radiation. The intensity of the Raman peaks at 1126 cm(-1) and 1082 cm(-1) were used to calculate the Longitudinal Order-Parameters in Chains (S(trans)) which can present the liquidity and ionic permeability of erythrocyte membrane. After UVB radiation for 30 min, both the liquidity and ionic permeability decreased. At the same time, the intensity of the peaks at 1302 cm(-1) (α-helix), 1254 cm(-1) (random coil), 1452 cm(-1) and 1430 cm(-1) (CH(2)/CH(3) stretch) have also changed which indicated the membrane protein also been damaged by UVB. In the whole process of radiation, the more UVB radiation dose the more damage on the erythrocyte membrane. Copyright © 2012 Elsevier B.V. All rights reserved.

Djulis (Chenopodium formosanum Koidz.) Water Extract and Its Bioactive Components Ameliorate Dermal Damage in UVB-Irradiated Skin Models

PubMed Central

Huang, Ya-Ling; Liu, Yao-Cheng; Tsai, Pi-Jen

2016-01-01

Dermal photoaging is a condition of skin suffering inappropriate ultraviolet (UV) exposure and exerts inflammation, tissue alterations, redness, swelling, and uncomfortable feelings. Djulis (Chenopodium formosanum Koidz.) is a cereal food and its antioxidant and pigment constituents may provide skin protection from photoaging, but it still lacks proved experiments. In this study, protective effects of djulis extract (CFE) on UVB-irradiated skin were explored. The results showed that HaCaT cells with 150 μg/mL CFE treatment had higher survival and less production of interleukin- (IL-) 6, matrix metalloprotease- (MMP-) 1, and reactive oxygen species (ROS) in UVB-irradiated conditions. Subsequently, in animal studies, mice supplemented with CFE (100 mg/kg BW) were under UVB irradiation and had thinner epidermis and lower IL-6 levels in skin layer. These data demonstrate that bioactive compounds possessing the potency of antiphotoaging exist in CFE. Following that, we found rutin and chlorogenic acid (10–100 μM) could significantly increase cell viability and decrease the production of IL-6 in UVB models. Additionally, djulis pigment-betanin has no effect of increasing cell viability in this study. Our findings suggest CFE can protect skin against UV-induced damage and this protection is mainly from contributions of rutin and chlorogenic acid. PMID:27847821

Mechanistic considerations on the wavelength-dependent variations of UVR genotoxicity and mutagenesis in skin: the discrimination of UVA-signature from UV-signature mutation.

PubMed

Ikehata, Hironobu

2018-05-31

Ultraviolet radiation (UVR) predominantly induces UV-signature mutations, C → T and CC → TT base substitutions at dipyrimidine sites, in the cellular and skin genome. I observed in our in vivo mutation studies of mouse skin that these UVR-specific mutations show a wavelength-dependent variation in their sequence-context preference. The C → T mutation occurs most frequently in the 5'-TCG-3' sequence regardless of the UVR wavelength, but is recovered more preferentially there as the wavelength increases, resulting in prominent occurrences exclusively in the TCG sequence in the UVA wavelength range, which I will designate as a "UVA signature" in this review. The preference of the UVB-induced C → T mutation for the sequence contexts shows a mixed pattern of UVC- and UVA-induced mutations, and a similar pattern is also observed for natural sunlight, in which UVB is the most genotoxic component. In addition, the CC → TT mutation hardly occurs at UVA1 wavelengths, although it is detected rarely but constantly in the UVC and UVB ranges. This wavelength-dependent variation in the sequence-context preference of the UVR-specific mutations could be explained by two different photochemical mechanisms of cyclobutane pyrimidine dimer (CPD) formation. The UV-signature mutations observed in the UVC and UVB ranges are known to be caused mainly by CPDs produced through the conventional singlet/triplet excitation of pyrimidine bases after the direct absorption of the UVC/UVB photon energy in those bases. On the other hand, a novel photochemical mechanism through the direct absorption of the UVR energy to double-stranded DNA, which is called "collective excitation", has been proposed for the UVA-induced CPD formation. The UVA photons directly absorbed by DNA produce CPDs with a sequence context preference different from that observed for CPDs caused by the UVC/UVB-mediated singlet/triplet excitation, causing CPD formation preferentially at thymine-containing dipyrimidine sites and probably also preferably at methyl CpG-associated dipyrimidine sites, which include the TCG sequence. In this review, I present a mechanistic consideration on the wavelength-dependent variation of the sequence context preference of the UVR-specific mutations and rationalize the proposition of the UVA-signature mutation, in addition to the UV-signature mutation.

Keratin-6 driven ODC expression to hair follicle keratinocytes enhances stemness and tumorigenesis by negatively regulating Notch

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arumugam, Aadithya; Weng, Zhiping; Chaudhary, Sandeep C.

Highlights: • Targeting ODC to hair follicle augments skin carcinogenesis and invasive SCCs. • Hair follicle ODC expands stem cell compartment carrying CD34{sup +}/K15{sup +}/p63{sup +} keratinocytes. • Negatively regulated Notch1 is associated with expansion of stem cell compartment. - Abstract: Over-expression of ornithine decarboxylase (ODC) is known to be involved in the epidermal carcinogenesis. However, the mechanism by which it enhances skin carcinogenesis remains undefined. Recently, role of stem cells localized in various epidermal compartments has been shown in the pathogenesis of skin cancer. To direct ODC expression in distinct epidermal compartments, we have developed keratin 6 (K6)-ODC/SKH-1 andmore » keratin 14 (K14)-ODC/SKH-1 mice and employed them to investigate the role of ODC directed to these epidermal compartments on UVB-induced carcinogenesis. K6-driven ODC over-expression directed to outer root sheath (ORS) of hair follicle was more effective in augmenting tumorigenesis as compared to mice where K14-driven ODC expression was directed to inter-follicular epidermal keratinocytes. Chronically UVB-irradiated K6-ODC/SKH-1 developed 15 ± 2.5 tumors/mouse whereas K14-ODC/SKH-1 developed only 6.8 ± 1.5 tumors/mouse. K6-ODC/SKH-1 showed augmented UVB-induced proliferation and much higher pro-inflammatory responses than K14-ODC/SKH-1 mice. Tumors induced in K6-ODC/SKH-1 were rapidly growing, invasive and ulcerative squamous cell carcinoma (SCC) showing decreased expression of epidermal polarity marker E-cadherin and enhanced mesenchymal marker, fibronectin. Interestingly, the number of CD34/CK15/p63 positive stem-like cells was significantly higher in chronically UVB-irradiated K6-ODC/SKH-1 as compared to K14-ODC/SKH-1 mice. Reduced Notch1 expression was correlated with the expansion of stem cell compartment in these animals. However, other signaling pathways such as DNA damage response or mTOR signaling pathways were not significantly different in tumors induced in these two murine models suggesting the specificity of Notch pathway in this regard. These data provide a novel role of ODC in augmenting tumorigenesis via negatively regulated Notch-mediated expansion of stem cell compartment.« less

UVA-UVB photoprotective activity of topical formulations containing Morinda citrifolia extract.

PubMed

Serafini, Mairim Russo; Detoni, Cassia Britto; Menezes, Paula dos Passos; Pereira Filho, Rose Nely; Fortes, Vanessa Silveira; Vieira, Maria José Fonseca; Guterres, Sílvia Stanisçuaski; Cavalcanti de Albuquerque Junior, Ricardo Luiz; Araújo, Adriano Antunes de Souza

2014-01-01

Exposure to solar radiation, particularly its ultraviolet (UV) component, has a variety of harmful effects on human health. Some of these effects include sunburn cell formations, basal and squamous cell cancers, melanoma, cataracts, photoaging of the skin, and immune suppression. The beneficial photoprotective effects of topical formulations with the extract, Morinda citrifolia, have not been investigated. This present study aims to investigate the potential benefits of M. citrifolia topical application on the dorsal skin of mice, exposed to UVA-UVB light. Using 7 days of treatment, [before (baseline values) and 20 h after UV exposure], the thickness, skin barrier damage (TEWL), erythema, and histological alterations were evaluated. The results showed that the formulations containing the extract protected the skin against UV-induced damage.

Protective effect of silk lutein on ultraviolet B-irradiated human keratinocytes.

PubMed

Pongcharoen, Sutatip; Warnnissorn, Prateep; Leŗtkajornsin, Ongart; Limpeanchob, Nanteetip; Sutheerawattananonda, Manote

2013-01-01

Carotenoids are efficient antioxidants that are of great importance for human health. Lutein and zeaxanthin are carotinoids present in high concentrations in the human retina which are involved in the photoprotection of the human eye. Lutein may also protect the skin from ultraviolet (UV)-induced damage. The present study investigated the protective effect of lutein extracted from yellow silk cocoons of Bombyx mori on human keratinocytes against UVB irradiation. A human keratinocyte cell line and primary human keratinocytes were used to investigate the UVB protection effects of silk lutein and plant lutein. Silk lutein showed no cytotoxicity to keratinocytes. Treatment with silk lutein prior to UVB irradiation enhanced cell viability and cell proliferation, and reduced cell apoptosis. The protective effects of silk lutein may be superior to those of plant lutein. Silk lutein may have a benefit for protection of keratinocytes against UVB-irradiation.

Tryptophan-to-Tryptophan Energy Transfer in UV-B photoreceptor UVR8

NASA Astrophysics Data System (ADS)

Li, Xiankun; Zhong, Dongping

UVR8 (UV RESISTANCE LOCUS 8) protein is a UV-B photoreceptor in high plants. UVR8 is a homodimer that dissociates into monomers upon UV-B irradiation (280 nm to 315 nm), which triggers various protective mechanisms against UV damages. Uniquely, UVR8 does not contain any external chromophores and utilizes the UV-absorbing natural amino acid tryptophan (Trp) to perceive UV-B. Each UVR8 monomer has 14 tryptophan residues. However, only 2 epicenter Trp (W285 W233) are critical to the light induced dimer-to-monomer transformation. Here, we revealed, using site-directed mutagenesis and spectroscopy, a striking energy flow network, in which other tryptophan chromophores serve as antenna to transfer excitation energy to epicenter Trp, greatly enhancing UVR8 light-harvesting efficiency. Furthermore, Trp-to-Trp energy transfer rates were measured and agree well with theoretical values.

Measuring sunscreen protection against solar-simulated radiation-induced structural radical damage to skin using ESR/spin trapping: development of an ex vivo test method.

PubMed

Haywood, Rachel; Volkov, Arsen; Andrady, Carima; Sayer, Robert

2012-03-01

The in vitro star system used for sunscreen UVA-testing is not an absolute measure of skin protection being a ratio of the total integrated UVA/UVB absorption. The in vivo persistent-pigment-darkening method requires human volunteers. We investigated the use of the ESR-detectable DMPO protein radical-adduct in solar-simulator-irradiated skin substitutes for sunscreen testing. Sunscreens SPF rated 20+ with UVA protection, reduced this adduct by 40-65% when applied at 2 mg/cm(2). SPF 15 Organic UVA-UVB (BMDBM-OMC) and TiO(2)-UVB filters and a novel UVA-TiO(2) filter reduced it by 21, 31 and 70% respectively. Conventional broad-spectrum sunscreens do not fully protect against protein radical-damage in skin due to possible visible-light contributions to damage or UVA-filter degradation. Anisotropic spectra of DMPO-trapped oxygen-centred radicals, proposed intermediates of lipid-oxidation, were detected in irradiated sunscreen and DMPO. Sunscreen protection might be improved by the consideration of visible-light protection and the design of filters to minimise radical leakage and lipid-oxidation.

The relationship between UV-irradiance, photoprotective compounds and DNA damage in two intertidal invertebrates with contrasting mobility characteristics.

PubMed

Cubillos, Victor Mauricio; Burritt, David J; Lamare, Miles D; Peake, Barrie M

2015-08-01

The photoprotective role of mycosporine-like amino acids (MAA) against the generation of DNA cyclobutane pyrimidine dimers (CPD) was studied in the sessile intertidal anemone Actinia tenebrosa and the mobile intertidal gastropod Diloma aethiops through 27months at a mid-latitude New Zealand location. MAA were sequestered by A. tenebrosa and D. aethiops from their diet, although maximum total MAA levels in both species were not correlated with seasonal variation in maximum ambient UV-B levels recorded at the collection site. Temporal changes in total MAA in A. tenebrosa showed a six months lag-time in their concentration regarding to the environmental UV-B levels. This lag period corresponded to an observed increase in CPD production from spring to summer; suggesting that MAA do not completely protect the anemone from UV-B during summer. For D. aethiops, total MAA concentrations did not change significantly during the study, although qualitative changes in MAA were apparent. A month lag-time in MAA concentration in D. aethiops and possibly the physical barrier that the shell confers to the animal, can explain reduced CPD levels in comparative terms with A. tenebrosa. Although MAA are used by invertebrates for photoprotection, contrasting mobility characteristics and the presence of physical adaptations can confer them important protection levels during temporal changes of UV-B at mid-latitude places of the Southern Hemisphere. Copyright © 2015 Elsevier B.V. All rights reserved.

Anti-Photoaging Effect of Jeju Putgyul (Unripe Citrus) Extracts on Human Dermal Fibroblasts and Ultraviolet B-induced Hairless Mouse Skin.

PubMed

Choi, Seung-Hyun; Choi, Sun-Il; Jung, Tae-Dong; Cho, Bong-Yeon; Lee, Jin-Ha; Kim, Seung-Hyung; Yoon, Seon-A; Ham, Young-Min; Yoon, Weon-Jong; Cho, Ju-Hyun; Lee, Ok-Hawn

2017-09-25

Ultraviolet (UV) radiation stimulates the expression of matrix metalloproteinases (MMPs) and inflammatory cytokines. These signaling pathways participate in the degradation of the extracellular matrix and induce inflammatory responses that lead to photoaging. This study evaluated the antioxidant activity and the effect on MMPs and procollagen of putgyul extract in vitro. The anti-photoaging activity of putgyul extracts was estimated in vivo using hairless mice (HR-1). The putgyul extracts reduced MMP-1 production and increased the content of procollagen type I carboxy-terminal peptide in human dermal fibroblasts. Ultravilot-B (UVB)-induced expression of inflammatory cytokines and MMPs was detected in mice, and putgyul extracts suppressed the expression. These results suggest that putgyul extract inhibits photoaging by inhibiting the expression of MMPs that degrade collagen and inhibiting cytokines that induce inflammatory responses. The mouse model also demonstrated that oral administration of putgyul extracts decreased wrinkle depth, epidermal thickness, collagen degradation, and trans-epidermal water loss, and increased β-glucosidase activity on UVB exposed skin. Putgyul extract protects against UVB-induced damage of skin and could be valuable in the prevention of photoaging.

Protective effect of crocin on ultraviolet B‑induced dermal fibroblast photoaging.

PubMed

Deng, Mingwu; Li, Dong; Zhang, Yichen; Zhou, Guangdong; Liu, Wei; Cao, Yilin; Zhang, Wenjie

2018-06-11

Ultraviolet B (UVB) radiation induces the production of reactive oxygen species (ROS), resulting in the aging of dermal fibroblasts. Crocin, a bioactive constituent of Crocus sativus, possesses anti‑oxidation effects. The purpose of the present study was to evaluate the protective effect of crocin on UVB‑induced dermal fibroblast photoaging. Human dermal fibroblasts were isolated and cultured with different concentrations of crocin prior to and following exposure to UVB irradiation. The senescent phenotypes of cells were evaluated, including cell proliferation, cell cycle, senescence‑associated β‑galactosidase (SA‑β‑gal) expression, intracellular ROS, expression of antioxidant protein glutathione peroxidase 1 (GPX‑1) and extracellular matrix protein collagen type 1 (Col‑1). Crocin rescued the cell proliferation inhibited by UVB irradiation, prevented cell cycle arrest and markedly decreased the number of SA‑β‑gal‑positive cells. In addition, crocin reduced UVB‑induced ROS by increasing GPX‑1 expression and other direct neutralization effects. Furthermore, crocin promoted the expression of the extracellular matrix protein Col‑1. Crocin could effectively prevent UVB‑induced cell damage via the reduction of intracellular ROS; thus, it could potentially be used in the prevention of skin photoaging.

A Combination of Soybean and Haematococcus Extract Alleviates Ultraviolet B-Induced Photoaging

PubMed Central

Shin, Jieun; Kim, Jong-Eun; Pak, Kum-Ju; Kang, Jung Il; Kim, Tae-Seok; Lee, Sang-Yoon; Yeo, Ik-Hyun; Park, Jung Han Yoon; Kim, Jong Hun; Kang, Nam Joo; Lee, Ki Won

2017-01-01

Soybean-derived isoflavones have been investigated for their preventative effects against UV-induced symptoms of skin damage including wrinkle formation and inflammation. Haematococcus pluvialis is a freshwater species of Chlorophyta that contains high concentrations of the natural carotenoid pigment astaxanthin. Astaxanthin is known to be involved in retinoic acid receptor (RAR) signaling and previously been associated with the inhibition of activator protein (AP)-1 dependent transcription. Based on previous studies, we hypothesized that a combination of soy extract (SE) and Haematococcus extract (HE) may prevent UVB-induced photoaging through specific signaling pathways, as measured by UVB-induced wrinkling on hairless mice skin and expression changes in human dermal fibroblasts (HDFs). The 1:2 ratio of SE and HE mixture (SHM) showed the optimal benefit in vivo. SHM was found to inhibit wrinkle formation via the downregulation of matrix metalloproteinase (MMP)-1 mRNA and protein expression. SHM also inhibited mitogen-activated protein kinase (MAPK) phosphorylation and the transactivation of AP-1 which plays an important role in regulating MMP expression. These results highlight the potential for SHM to be developed as a therapeutic agent to prevent UVB-induced skin wrinkling. PMID:28327532

Anti-Photoaging Effect of Jeju Putgyul (Unripe Citrus) Extracts on Human Dermal Fibroblasts and Ultraviolet B-induced Hairless Mouse Skin

PubMed Central

Choi, Seung-Hyun; Choi, Sun-Il; Jung, Tae-Dong; Cho, Bong-Yeon; Lee, Jin-Ha; Kim, Seung-Hyung; Yoon, Seon-A; Ham, Young-Min; Yoon, Weon-Jong; Cho, Ju-Hyun; Lee, Ok-Hawn

2017-01-01

Ultraviolet (UV) radiation stimulates the expression of matrix metalloproteinases (MMPs) and inflammatory cytokines. These signaling pathways participate in the degradation of the extracellular matrix and induce inflammatory responses that lead to photoaging. This study evaluated the antioxidant activity and the effect on MMPs and procollagen of putgyul extract in vitro. The anti-photoaging activity of putgyul extracts was estimated in vivo using hairless mice (HR-1). The putgyul extracts reduced MMP-1 production and increased the content of procollagen type I carboxy-terminal peptide in human dermal fibroblasts. Ultravilot-B (UVB)-induced expression of inflammatory cytokines and MMPs was detected in mice, and putgyul extracts suppressed the expression. These results suggest that putgyul extract inhibits photoaging by inhibiting the expression of MMPs that degrade collagen and inhibiting cytokines that induce inflammatory responses. The mouse model also demonstrated that oral administration of putgyul extracts decreased wrinkle depth, epidermal thickness, collagen degradation, and trans-epidermal water loss, and increased β-glucosidase activity on UVB exposed skin. Putgyul extract protects against UVB-induced damage of skin and could be valuable in the prevention of photoaging. PMID:28946661

A Combination of Soybean and Haematococcus Extract Alleviates Ultraviolet B-Induced Photoaging.

PubMed

Shin, Jieun; Kim, Jong-Eun; Pak, Kum-Ju; Kang, Jung Il; Kim, Tae-Seok; Lee, Sang-Yoon; Yeo, Ik-Hyun; Park, Jung Han Yoon; Kim, Jong Hun; Kang, Nam Joo; Lee, Ki Won

2017-03-22

Soybean-derived isoflavones have been investigated for their preventative effects against UV-induced symptoms of skin damage including wrinkle formation and inflammation. Haematococcus pluvialis is a freshwater species of Chlorophyta that contains high concentrations of the natural carotenoid pigment astaxanthin. Astaxanthin is known to be involved in retinoic acid receptor (RAR) signaling and previously been associated with the inhibition of activator protein (AP)-1 dependent transcription. Based on previous studies, we hypothesized that a combination of soy extract (SE) and Haematococcus extract (HE) may prevent UVB-induced photoaging through specific signaling pathways, as measured by UVB-induced wrinkling on hairless mice skin and expression changes in human dermal fibroblasts (HDFs). The 1:2 ratio of SE and HE mixture (SHM) showed the optimal benefit in vivo. SHM was found to inhibit wrinkle formation via the downregulation of matrix metalloproteinase (MMP)-1 mRNA and protein expression. SHM also inhibited mitogen-activated protein kinase (MAPK) phosphorylation and the transactivation of AP-1 which plays an important role in regulating MMP expression. These results highlight the potential for SHM to be developed as a therapeutic agent to prevent UVB-induced skin wrinkling.

UV-B-induced cutaneous inflammation and prospects for antioxidant treatment in Kindler syndrome.

PubMed

Maier, Kristin; He, Yinghong; Wölfle, Ute; Esser, Philipp R; Brummer, Tilman; Schempp, Christoph; Bruckner-Tuderman, Leena; Has, Cristina

2016-12-15

Kindler syndrome (KS), a rare, autosomal recessive disorder comprises mechanical skin fragility and photosensitivity, which manifest early in life. The progression of the disorder is irreversible and results in tissue damage in form of cutaneous and mucosal atrophy and scarring and epithelial cancers. Here, we unravel molecular mechanisms of increased UV-B sensitivity of keratinocytes derived from KS patients. We show that the pro-inflammatory cytokines, IL-1ß, IL-6 and TNF-α, are upregulated in KS skin and in UV-B irradiated KS keratinocytes. These cytokines are dependent on p38 activation, which is increased in the absence of kindlin-1 and induced by higher ROS levels. Other dysregulated cytokines and growth factors were identified in this study and might be involved in paracrine interactions contributing to KS pathology. We show a direct relationship between kindlin-1 abundance and UV-B induced apoptosis in keratinocytes, whereas kindlin-2 overexpression has no compensatory effect. Importantly, low levels of kindlin-1 are sufficient to relieve or rescue this feature. Reduction of pro-inflammatory cytokines and of UV-B induced apoptosis is a valid therapeutic goal to influence long term complications of KS. Here, we demonstrate that antioxidants and the plant flavonoid luteolin represent feasible topical therapeutic approaches decreasing UV-B induced apoptosis in two-dimensional and organotypic KS cultures. We provide evidence for potential new therapeutic approaches to mitigate the progressive course of KS, for which no cure is available to date. Furthermore, we established organotypic KS models, a valuable in vitro tool for research with a morphology similar to the skin of patients in situ. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Extremophilic Acinetobacter strains from high-altitude lakes in Argentinean Puna: remarkable UV-B resistance and efficient DNA damage repair.

PubMed

Albarracín, Virginia Helena; Pathak, Gopal P; Douki, Thierry; Cadet, Jean; Borsarelli, Claudio Darío; Gärtner, Wolfgang; Farias, María Eugenia

2012-06-01

High-Altitude Andean Lakes (HAAL) of the South American Andes are almost unexplored ecosystems of shallow lakes. The HAAL are recognized by a remarkably high UV exposure, strong changes in temperature and salinity, and a high content of toxic elements, especially arsenic. Being exposed to remarkably extreme conditions, they have been classified as model systems for the study of life on other planets. Particularly, Acinetobacter strains isolated from the HAAL were studied for their survival competence under strong UV-B irradiation. Clinical isolates, Acinetobacter baumannii and Acinetobacter johnsonii, served as reference material. Whereas the reference strains rapidly lost viability under UV-B irradiation, most HAAL-derived strains readily survived this exposure and showed less change in cell number after the treatment. Controls for DNA repair activity, comparing dark repair (DR) or photo repair (PR), gave evidence for the involvement of photolyases in the DNA repair. Comparative measurements by HPLC-mass spectrometry detected the number of photoproducts: bipyrimidine dimers under both PR and DR treatments were more efficiently repaired in the HAAL strains (up to 85 % PR and 38 % DR) than in the controls (31 % PR and zero DR ability). Analysis of cosmid-cloned total genomic DNA from the most effective DNA-photorepair strain (Ver3) yielded a gene (HQ443199) encoding a protein with clear photolyase signatures belonging to class I CPD-photolyases. Despite the relatively low sequence similarity of 41 % between the enzymes from Ver3 and from E. coli (PDB 1DNPA), a model-building approach revealed a high structural homology to the CPD-photolyase of E. coli.

Caffeine and caffeine sodium benzoate have a sunscreen effect, enhance UVB-induced apoptosis, and inhibit UVB-induced skin carcinogenesis in SKH-1 mice.

PubMed

Lu, Yao-Ping; Lou, You-Rong; Xie, Jian-Guo; Peng, Qing-Yun; Zhou, Sherry; Lin, Yong; Shih, Weichung Joe; Conney, Allan H

2007-01-01

Topical application of caffeine sodium benzoate (caffeine-SB) immediately after UVB irradiation of SKH-1 mice enhanced UVB-induced apoptosis by a 2- to 3-fold greater extent than occurred after the topical application of an equimolar amount of caffeine. Although topical application of caffeine-SB or caffeine enhanced UVB-induced apoptosis, both substances were inactive on non-UVB-treated normal skin. Topical application of caffeine-SB or caffeine (each has UVB absorption properties) 0.5 h before irradiation with a high dose of UVB decreased UVB-induced thymine dimer formation and sunburn lesions (sunscreen effect). Caffeine-SB was more active than an equimolar amount of caffeine in exerting a sunscreen effect. In additional studies, caffeine-SB strongly inhibited the formation of tumors in UVB-pretreated 'high-risk mice' and in tumor-bearing mice, and the growth of UVB-induced tumors was also inhibited. Caffeine-SB and caffeine are the first examples of compounds that have both a sunscreen effect and enhance UVB-induced apoptosis. Our studies suggest that caffeine-SB and caffeine may be good agents for inhibiting the formation of sunlight-induced skin cancer.

Response of antioxidant defense system to laser radiation apical meristem of Isatis indigotica seedlings exposed to UV-B.

PubMed

Chen, Yi-Ping

2009-07-01

To determine the response of antioxidant defense system to laser radiation apical meristem of Isatis indigotica seedlings, Isatis indigotica seedlings were subjected to UV-B radiation (10.08 kJ m(-2)) for 8 h day(-1) for 8 days (PAR, 220 micromol m(-2) s(-1)) and then exposed to He-Ne laser radiation (633 nm; 5.23 mW mm(-2); beam diameter: 1.5 mm) for 5 min each day without ambient light radiation. Changes in free radical elimination systems were measured, the results indicate that: (1) UV-B radiation enhanced the concentration of Malondialdahyde (MDA) and decreased the activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) in seedlings compared with the control. The concentration of MDA was decreased and the activities of SOD, CAT and POD were increased when seedlings were subjected to elevated UV-B damage followed by laser; (2) the concentration of UV absorbing compounds and proline were increased progressively with UV-B irradiation, laser irradiation and He-Ne laser irradiation plus UV-B irradiation compared with the control. These results suggest that laser radiation has an active function in repairing UV-B-induced lesions in seedlings.

Recruitment of TRF2 to laser-induced DNA damage sites.

PubMed

Huda, Nazmul; Abe, Satoshi; Gu, Ling; Mendonca, Marc S; Mohanty, Samarendra; Gilley, David

2012-09-01

Several lines of evidence suggest that the telomere-associated protein TRF2 plays critical roles in the DNA damage response. TRF2 is rapidly and transiently phosphorylated by an ATM-dependent pathway in response to DNA damage and this DNA damage-induced phosphoryation is essential for the DNA-PK-dependent pathway of DNA double-strand break repair (DSB). However, the type of DNA damage that induces TRF2 localization to the damage sites, the requirement for DNA damage-induced phosphorylation of TRF2 for its recruitment, as well as the detailed kinetics of TRF2 accumulation at DNA damage sites have not been fully investigated. In order to address these questions, we used an ultrafast femtosecond multiphoton laser and a continuous wave 405-nm single photon laser to induce DNA damage at defined nuclear locations. Our results showed that DNA damage produced by a femtosecond multiphoton laser was sufficient for localization of TRF2 to these DNA damage sites. We also demonstrate that ectopically expressed TRF2 was recruited to DNA lesions created by a 405-nm laser. Our data suggest that ATM and DNA-PKcs kinases are not required for TRF2 localization to DNA damage sites. Furthermore, we found that phosphorylation of TRF2 at residue T188 was not essential for its recruitment to laser-induced DNA damage sites. Thus, we provide further evidence that a protein known to function in telomere maintenance, TRF2, is recruited to sites of DNA damage and plays critical roles in the DNA damage response. Copyright © 2012 Elsevier Inc. All rights reserved.

Both Complexity and Location of DNA Damage Contribute to Cellular Senescence Induced by Ionizing Radiation

PubMed Central

Zhang, Xurui; Ye, Caiyong; Sun, Fang; Wei, Wenjun; Hu, Burong; Wang, Jufang

2016-01-01

Persistent DNA damage is considered as a main cause of cellular senescence induced by ionizing radiation. However, the molecular bases of the DNA damage and their contribution to cellular senescence are not completely clear. In this study, we found that both heavy ions and X-rays induced senescence in human uveal melanoma 92–1 cells. By measuring senescence associated-β-galactosidase and cell proliferation, we identified that heavy ions were more effective at inducing senescence than X-rays. We observed less efficient repair when DNA damage was induced by heavy ions compared with X-rays and most of the irreparable damage was complex of single strand breaks and double strand breaks, while DNA damage induced by X-rays was mostly repaired in 24 hours and the remained damage was preferentially associated with telomeric DNA. Our results suggest that DNA damage induced by heavy ion is often complex and difficult to repair, thus presents as persistent DNA damage and pushes the cell into senescence. In contrast, persistent DNA damage induced by X-rays is preferentially associated with telomeric DNA and the telomere-favored persistent DNA damage contributes to X-rays induced cellular senescence. These findings provide new insight into the understanding of high relative biological effectiveness of heavy ions relevant to cancer therapy and space radiation research. PMID:27187621

Lack of photoprotection against UVB-induced erythema by immediate pigmentation induced by 382 nm radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Black, G.; Matzinger, E.; Gange, R.W.

Immediate pigment darkening (IPD) was induced on the backs of 11 human volunteers of skin types III and IV by exposing the skin to UVA radiation (382 nm). The minimum erythema dose (MED) of UVB radiation was also determined by exposing sites to graduated doses of 304 nm radiation. The order of exposure of distinct anatomic areas was as follow: UVB followed by IPD induction; IPD induction followed by UVB; IPD induction followed 3 h later by UVB; and UVB only. Erythema responses induced by UVB were graded by inspection 24 h later and the MEDs in the 4 areasmore » were compared. The induction of IPD before UVB exposure caused no significant change in the MED compared to sites receiving UVB only, or receiving UVA radiation after UVB, confirming that the IPD reaction does not protect against UVB-induced erythema. There was also no evidence of photorecovery, i.e., an increase in the MED of UVB resulting from exposure to longer wavelength, UV or visible radiation following UVB exposure.« less

UVA-potentiated damage to calf thymus DNA by Fenton reaction system and protection by para-aminobenzoic acid.

PubMed

Shih, M K; Hu, M L

1996-03-01

Calf thymus DNA was irradiated with low-intensity UVA (main output at 365 nm, 2 mW cm-2 or 36 kJ m-2 for 30 min), and the role of metal ions, hydrogen peroxide and reactive oxygen species (ROS) was examined. DNA damage was measured as thiobarbituric acid-reactive substances (possibly from degradation of deoxyribose) and as changes in ethidium bromide-DNA fluorescence due to unwinding from strand breaks. Under the present experimental conditions, UVA alone or in the presence of H2O2 had no effect on DNA but slightly enhanced the damage by iron/EDTA. Ultraviolet A strongly enhanced DNA damage (ca four- to five-fold) by the Fenton reaction system (50 microM Fe2+/100 microM EDTA + 0.5 mM H2O2). The results suggest that the Fenton reaction system was "photosensitized" to damage DNA by low-intensity UVA radiation. The enhanced damage by UVA was attributed in part to the reduction of Fe3+ to Fe2+. Ultraviolet A had no effect when iron (ferric or ferrous) ions were replaced by Cu2+, Zn2+, Mn2+ or Cd2+. The ROS involved in the UVA-enhanced damage to DNA by the Fenton reagents were OH and, to a lesser extent, superoxide anions. The UVA-potentiated DNA damage by the Fenton reaction system was then used to examine the protective effect of para-aminobenzoate (PABA), a UVB-absorbing sunscreen that protects against photocarcinogenesis in hairless mice. The results show that PABA and mannitol dose-dependently inhibited the damage with concentrations required for 50% inhibition at 0.1 mM and 3 mM, respectively. The protection by PABA was attributed to its radical-scavenging ability because PABA does not absorb light in the UVA region. These findings may be relevant to the biological damage by UVA and suggest that PABA is useful in protection against photocarcinogenesis by wide-range UV radiation.

Ultraviolet-B radiation and the immune response of rainbow trout: Chapter 18

USGS Publications Warehouse

Fabacher, David L.; Little, Edward E.; Jones, S.B.; DeFabo, E.C.; Webber, L.J.; Stolen, Joanne S.; Fletcher, Thelma C.

1994-01-01

As part of a larger study on global climate change and ozone depletion we are investigating the effects of ultraviolet-B (UVB) radiation on fishes. We conducted a number of experiments to explore the possible effects of UVB radiation on the immune response of juvenile rainbow trout Oncorhynchus mykiss. In one study, the fish developed sunburn and fungal infection on the dorsal skin after exposure to levels of UVB that simulated ambient solar UVB levels observed at mid-latitudes. In a separate study, UVB-exposed rainbow trout with surgically administered dorsal lesions developed fungal infection on the lesions and surrounding skin. Many of these fish subsequently died within a 9 day exposure period. Fish with surgical lesions, but not exposed to UVB radiation, did not develop fungal infection and did not die. In mammals, UVB-induced immunosuppression is thought to occur through the isomerization of urocanic acid or the formation of DNA pyrimidine dimers, or through some interaction between the two. We found a substance that appeared, upon HPLC detection, to be trans-urocanic acid in the skin of UVB-exposed and unexposed rainbow trout. Neurotransmitter stimulation of adrenoceptors may be involved in changes in pigmentation observed in UVB-exposed fishes. We measured adrenoceptors in skin membranes from rainbow trout exposed to UVB and found a decrease in cz2-adrenoceptors compared with fish not exposed to UVB. Results of our study indicate that prolonged exposure of juvenile rainbow trout to mid-latitude levels of solar UVB may play an important role in the initiation of certain disease outbreaks and may decrease survival of fish that have lesions on the dorsal skin.

UVA-UVB Photoprotective Activity of Topical Formulations Containing Morinda citrifolia Extract

PubMed Central

Serafini, Mairim Russo; Detoni, Cassia Britto; Menezes, Paula dos Passos; Pereira Filho, Rose Nely; Fortes, Vanessa Silveira; Vieira, Maria José Fonseca; Guterres, Sílvia Stanisçuaski; de Albuquerque Junior, Ricardo Luiz Cavalcanti; Araújo, Adriano Antunes de Souza

2014-01-01

Exposure to solar radiation, particularly its ultraviolet (UV) component, has a variety of harmful effects on human health. Some of these effects include sunburn cell formations, basal and squamous cell cancers, melanoma, cataracts, photoaging of the skin, and immune suppression. The beneficial photoprotective effects of topical formulations with the extract, Morinda citrifolia, have not been investigated. This present study aims to investigate the potential benefits of M. citrifolia topical application on the dorsal skin of mice, exposed to UVA-UVB light. Using 7 days of treatment, [before (baseline values) and 20 h after UV exposure], the thickness, skin barrier damage (TEWL), erythema, and histological alterations were evaluated. The results showed that the formulations containing the extract protected the skin against UV-induced damage. PMID:25133171

RNF168 forms a functional complex with RAD6 during the DNA damage response

PubMed Central

Liu, Chao; Wang, Degui; Wu, Jiaxue; Keller, Jennifer; Ma, Teng; Yu, Xiaochun

2013-01-01

Summary Protein ubiquitination plays an important role in initiating the DNA damage response. Following DNA damage, E2 ubiquitin conjugating enzymes are crucial for catalyzing substrate ubiquitination that recruits downstream DNA repair factors to DNA lesions. To identify novel E2 conjugating enzymes important for initiating the DNA-damage-induced ubiquitination cascade, we screened most of the known E2 enzymes and found that RAD6A and RAD6B function together with RNF168 in the ionizing radiation (IR)-induced DNA damage response. Similarly to RNF168-deficient cells, RAD6A- or RAD6B-deficient cells exhibit a reduction in DNA-damage-induced protein ubiquitination. Correspondingly, DNA-damage-induced foci formation of DNA damage repair proteins, such as BRCA1 and 53BP1, is impaired in the absence of RAD6A or RAD6B. Moreover, the RNF168–RAD6 complex targeted histone H1.2 for ubiquitination in vitro and regulated DNA-damage-induced histone H1.2 ubiquitination in vivo. Collectively, these data demonstrate that RNF168, in complex with RAD6A or RAD6B, is activated in the DNA-damage-induced protein ubiquitination cascade. PMID:23525009

Evaluating the combined effects of pretilachlor and UV-B on two Azolla species.

PubMed

Prasad, Sheo Mohan; Kumar, Sushil; Parihar, Parul; Singh, Anita; Singh, Rachana

2016-03-01

The present study assessed the comparative responses of two agronomic species of Azolla (A.microphylla and A. pinnata) exposed to man-made and natural stressors by evaluating biomass accumulation, pigments (chlorophyll a and b and carotenoid contents), photosynthetic activity and nitrogen metabolism. The study was carried out in field where two species of Azolla were cultured and treated with various concentrations (5, 10 and 20 μg ml(-1)) of herbicide; pretilachlor [2-chloro-2,6-diethyl-N-(2-propoxyethyl) acetanilide] and enhanced levels (UV-B1: ambient +2.2 kJ m(-2) day(-1) and UV-B2: ambient +4.4 kJ m(-2) day(-1)) of UV-B, alone as well as in combination. Biomass accumulation, photosynthetic pigments; chlorophyll a, b and carotenoids, photosynthetic oxygen yield and photosynthetic electron transport activities i.e. photosystem II (PS II) and photosystem I (PS I) in both the species declined with the increasing doses of pretilachlor and UV-B radiation, which further declined when applied in combination. The lower doses (5 and 10 μg ml(-1)) of pretilachlor and UV-B (UV-B1 and UV-B2) alone, damaged mainly the oxidation side of PS II, whereas higher dose (20 μg ml(-1)) of pretilachlor alone and in combination with UV-B1 and UV-B2 caused damage to PS II reaction centre and beyond this towards the reduction side. A significant enhancement in respiration was also noticed in fronds of both the Azolla species following pretilachlor and UV-B treatment, hence indicating strong damaging effect. The nitrate assimilating enzymes - nitrate reductase and nitrite reductase and ammonium assimilating enzymes - glutamine synthetase and glutamate synthase were also severely affected when treated either with pretilachlor and/or UV-B while glutamate dehydrogenase exhibited a stimulatory response. The study suggests that both the species of Azolla showed considerable damage under pretilachlor and UV-B treatments alone, however, in combination the effect was more intense. Further, in comparison to A. pinnata, A. microphylla exhibited greater resistance against tested doses of both the stresses, either alone or in combination. Copyright © 2015 Elsevier Inc. All rights reserved.

The impact of solar UV radiation on the early biosphere

NASA Astrophysics Data System (ADS)

Horneck, G.

2007-08-01

Stratospheric ozone, photochemically produced from atmospheric oxygen, is a protective filter of the Earth's atmosphere by absorbing most of the biologically harmful UV radiation of our sun in the UV-C (190-280 nm) and short wavelength-region of the UV-B (280-315 nm). Numerous lines of isotopic and geologic evidence suggest that the Archean atmosphere was essentially anoxic. As a result the column abundance of ozone would have been insufficient to affect the surface UV radiation environment. Thus, as well as UV-B radiation, UV-C radiation would have penetrated to the Earth's surface with its associated biological consequences. The history of this ultraviolet stress for the early Earth has been determined from theoretical data and data obtained in Earth orbit on the inactivation of Bacillus subtilis spores under a simulated ozone layer of different thicknesses. Although the UV-C and UV-B regions contribute only 2 % of the entire solar extraterrestrial irradiance, photobiological experiments in space have demonstrated a high mutagenicity and lethality of this UV range to living organisms. The reason for these severe effects of extraterrestrial solar UV radiation - compared to conditions on present-day Earth - lies in the absorption characteristics of the DNA, which is the decisive target for inactivation and mutation induction at this UV range. Being a strong mutagen, UV-radiation is considered as a powerful promoter of biological evolution on the one hand, one the other hand, it may have deleterious consequences to individual cells and organisms, e.g. by causing inactivation, mutations or cancer induction. In response to potential harmful effects of environmental UV radiation, life on Earth has developed several strategies of survival, either avoiding exposure to UV radiation or restoring UV damage. Mechanisms of avoidance of exposure to UV radiation include (i) moving away from the UV radiation into shadowed areas, which requires the development of UV radiation sensing mechanisms; (ii) application of external shielding, such as covering by mud, sand or rock material; (iii) development of intrinsic UV screening pigments, such as tanning, inductive flavonoid production of plants, intracellular mycosporin production in cyanobacteria, (iv) accumulation of antioxidants and quenching substances. However, if UV damage has been induced - in spite of all avoidance efforts, organisms may restore their functionality by numerous repair processes. Repair pathways of a rich diversity and functional universality include (i) direct repair with the reversal of photochemical abnormalities, e.g. in the DNA; (ii) recombination repair removing the UV-induced abnormality by homologous recombination; and (iii) excision repair, where the section of the DNA strand containing the abnormality is removed and a repair patch is synthesized using the intact strand as a template. In addition to efficient repair systems for radiation-induced DNA injury, life has developed a variety of defense mechanisms, such as the increase in the production of stress proteins and the activation of the immune defence system. Some of these capacities have certainly already been evolved in the early biosphere, when it was exposed to the extended UV-spectrum of the sun. Only since the early Proterozoic, due to a rapid rise in the atmospheric oxygen concentration and consequently a photochemical built up of the stratospheric ozone layer, a more moderate UV radiation climate prevailed with wavelengths shorter than 295 nm being effectively cut off.

Passiflora tarminiana fruits reduce UVB-induced photoaging in human skin fibroblasts.

PubMed

Bravo, Karent; Duque, Luisa; Ferreres, Federico; Moreno, Diego A; Osorio, Edison

2017-03-01

Skin aging is a complex process that is strongly affected by UV radiation, which stimulates the production of reactive oxygen species (ROS) in the epidermis and dermis and subsequently causes skin damage. Among the major consequences are increased collagen degradation and reduced collagen synthesis. Previous reports have demonstrated the beneficial effects of polyphenols for healthy skin. Passiflora tarminiana Coppens & V.E. Barney, a species of the Passifloraceae family, is widely distributed in South America and is rich in flavonoids. We show that UVB radiation increases metalloproteinase 1 (MMP-1) and reduces procollagen production in human dermal fibroblast (HDF) cells in a dose- and time-dependent manner. We examined the antioxidant and antiaging effects of the extract and fractions of P. tarminiana fruits. The fractions showed high polyphenol content (620mg EAG/g) and antioxidant activity, as measured by ORAC (4097μmol ET/g) and ABTS (2992μmol ET/g) assays. The aqueous fraction drastically inhibited the collagenase enzyme (IC 50 0.43μg/mL). The extract and fractions presented photoprotective effects by reducing UVB-induced MMP-1 production, increasing UVB-inhibited procollagen production, and decreasing ROS production after UVB irradiation in HDF. Finally, the polyphenol contents of the extracts and fractions from P. tarminiana were analyzed by HPLC-DAD-ESI-MS n , and procyanidins and glycosylated flavonoids were identified. Copyright © 2017 Elsevier B.V. All rights reserved.

Repeated exposure of mouse dermal fibroblasts at a sub-cytotoxic dose of UVB leads to premature senescence: a robust model of cellular photoaging.

PubMed

Zeng, Ji-ping; Bi, Bo; Chen, Liang; Yang, Ping; Guo, Yu; Zhou, Yi-qun; Liu, Tian-yi

2014-01-01

Photoaging skin is due to accumulative effect of UV irradiation that mainly imposes its damage on dermal fibroblasts. To mimic the specific cellular responses invoked by long term effect of UVB, it is preferable to develop a photo-damaged model in vitro based on repeated UVB exposure instead of a single exposure. To develop a photo-damaged model of fibroblasts by repeated UVB exposure allowing for investigation of molecular mechanism underlying premature senescence and testing of potential anti-photoaging compounds. Mouse dermal fibroblasts (MDFs) at early passages (passages 1-3) were exposed to a series of 4 sub-cytotoxic dose of UVB. The senescent phenotypes were detected at 24 or 48h after the last irradiation including cell viability, ROS generation, mitochondrial membrane potential, cell cycle, production and degradation of extracellular matrix. Repeated exposure of UVB resulted in remarkable features of senescence. It effectively avoided the disadvantages of single dose such as induction of cell death rather than senescence, inadequate stress resulting in cellular self-rehabilitation. Our work confirms the possibility of detecting cellular machinery that mediates UVB damage to fibroblasts in vitro by repeated exposure, while the potential molecular mechanisms including cell surface receptors, protein kinase signal transduction pathways, and transcription factors remain to be further evaluated. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Escin-induced DNA damage promotes escin-induced apoptosis in human colorectal cancer cells via p62 regulation of the ATM/γH2AX pathway.

PubMed

Wang, Zhong; Chen, Qiang; Li, Bin; Xie, Jia-Ming; Yang, Xiao-Dong; Zhao, Kui; Wu, Yong; Ye, Zhen-Yu; Chen, Zheng-Rong; Qin, Zheng-Hong; Xing, Chun-Gen

2018-05-31

Escin, a triterpene saponin isolated from horse chestnut seed, has been used to treat encephaledema, tissue swelling and chronic venous insufficiency. Recent studies show that escin induces cell cycle arrest, tumor proliferation inhibition and tumor cell apoptosis. But the relationship between escin-induced DNA damage and cell apoptosis in tumor cells remains unclear. In this study, we investigated whether and how escin-induced DNA damage contributed to escin-induced apoptosis in human colorectal cancer cells. Escin (5-80 μg/mL) dose-dependently inhibited the cell viability and colony formation in HCT116 and HCT8 cells. Escin treatment induced DNA damage, leading to p-ATM and γH2AX upregulation. Meanwhile, escin treatment increased the expression of p62, an adaptor protein, which played a crucial role in controlling cell survival and tumorigenesis, and had a protective effect against escin-induced DNA damage: knockdown of p62 apparently enhanced escin-induced DNA damage, whereas overexpression of p62 reduced escin-induced DNA damage. In addition, escin treatment induced concentration- and time-dependent apoptosis. Similarly, knockdown of p62 significantly increased escin-induced apoptosis in vitro and produced en escin-like antitumor effect in vivo. Overexpression of p62 decreased the rate of apoptosis. Further studies revealed that the functions of p62 in escin-induced DNA damage were associated with escin-induced apoptosis, and p62 knockdown combined with the ATM inhibitor KU55933 augmented escin-induced DNA damage and further increased escin-induced apoptosis. In conclusion, our results demonstrate that p62 regulates ATM/γH2AX pathway-mediated escin-induced DNA damage and apoptosis.

Understanding the Physical and Molecular Basis of Stability of Arabidopsis DNA Pol λ under UV-B and High NaCl Stress

PubMed Central

Das, Kali Pada

2015-01-01

Here, we have investigated the physical and molecular basis of stability of Arabidopsis DNA Pol λ, the sole X family DNA polymerase member in plant genome, under UV-B and salinity stress in connection with the function of the N-terminal BRCT (breast cancer-associated C terminus) domain and Ser-Pro rich region in the regulation of the overall structure of this protein. Tryptophan fluorescence studies, fluorescence quenching and Bis-ANS binding experiments using purified recombinant full length Pol λ and its N-terminal deletion forms have revealed UV-B induced conformational change in BRCT domain deficient Pol λ. On the other hand, the highly conserved C-terminal catalytic core PolX domain maintained its tertiary folds under similar condition. Circular dichroism (CD) and fourier transform infrared (FT-IR) spectral studies have indicated appreciable change in the secondary structural elements in UV-B exposed BRCT domain deficient Pol λ. Increased thermodynamic stability of the C-terminal catalytic core domain suggested destabilizing effect of the N-terminal Ser-Pro rich region on the protein structure. Urea-induced equilibrium unfolding studies have revealed increased stability of Pol λ and its N-terminal deletion mutants at high NaCl concentration. In vivo aggregation studies using transient expression systems in Arabidopsis and tobacco indicated possible aggregation of Pol λ lacking the BRCT domain. Immunoprecipitation assays revealed interaction of Pol λ with the eukaryotic molecular chaperone HSP90, suggesting the possibility of regulation of Pol λ stability by HSP90 in plant cell. Overall, our results have provided one of the first comprehensive information on the biophysical characteristics of Pol λ and indicated the importance of both BRCT and Ser-Pro rich modules in regulating the stability of this protein under genotoxic stress in plants. PMID:26230318

TELOMERE AND TELOMERASE MODULATION BY BERGAMOT POLYPHENOLIC FRACTION IN EXPERIMENTAL PHOTOAGEING IN HUMAN KERATINOCYTES.

PubMed

Nisticò, S; Ehrlich, J; Gliozzi, M; Maiuolo, J; Del Duca, E; Muscoli, C; Mollace, V

2015-01-01

Photoageing represents the addition of extrinsic chronic ultraviolet radiation-induced damage on intrinsic ageing and accounts for most age-associated changes in skin appearance. In this study, we evaluated the effect of 38% BPF, a highly concentrated extract of the bergamot fruit (Citrus bergamia) on UVB-induced photoageing by examining inflammatory cytokine expression, telomere length/telomerase alterations and cellular viability in human immortalized HaCaT keratinocytes. Our results suggest that 38% BPF protects HaCaT cells against UVB-induced oxidative stress and markers of photoageing in a dose-dependent manner and could be a useful supplement in skin care products. Together with antioxidant properties, BPF, a highly concentrated extract of the bergamot fruit, appears to modulate basic cellular signal transduction pathways leading to anti-proliferative, anti-aging and immune modulating responses.

The effects of metal ions on the DNA damage induced by hydrogen peroxide.

PubMed

Kobayashi, S; Ueda, K; Komano, T

1990-01-01

The effects of metal ions on DNA damage induced by hydrogen peroxide were investigated using two methods, agarose-gel electrophoretic analysis of supercoiled DNA and sequencing-gel analysis of single end-labeled DNA fragments of defined sequences. Hydrogen peroxide induced DNA damage when iron or copper ion was present. At least two classes of DNA damage were induced, one being direct DNA-strand cleavage, and the other being base modification labile to hot piperidine. The investigation of the damaged sites and the inhibitory effects of radical scavengers revealed that hydroxyl radical was the species which attacked DNA in the reaction of H2O2/Fe(II). On the other hand, two types of DNA damage were induced by H2O2/Cu(II). Type I damage was predominant and inhibited by potassium iodide, but type II was not. The sites of the base-modification induced by type I damage were similar to those by lipid peroxidation products and by ascorbate in the presence of Cu(II), suggesting the involvement of radical species other than free hydroxyl radical in the damaging reactions.

Life and the solar uv environment on the early Earth

NASA Astrophysics Data System (ADS)

Bérces, A.; Kovács, G.; Rontó, G.; Lammer, H.; Kargl, G.; Kömle, N.; Bauer, S.

2003-04-01

The solar UV radiation environment on planetary surfaces and within their atmospheres is of importance in a wide range of scientific disciplines. Solar UV radiation is the driving force of chemical and organic evolution and serves also as a constraint in biological evolution. Studies of the solar UV environment of the early Earth 2.0 Gyr to 3.8 Gyr ago suggest that the terrestrial atmosphere was essentially anoxic, resulting in an ozone column abundance insufficient for protecting the planetary surface in the UV-B and the UV-C ranges. Since, short wavelength solar UV radiation in the UV-B ind UV-C range penetrated through the unprotected atmosphere to the surface on early Earth, associated biological consequences may be expected. For DNA-based terrestrial solar UV dosimetry, bacteriophage T7, isolated phage-DNA ind polycrystalline Uracil samples have been used. The effect of solar UV radiation can be measured by detecting the biological-structural consequences of the damage induced by UV photons. We show model calculations for the Biological Effective Dose (BED) rate of Uracil and bacteriophage T7, for various ozone concentrations representing early atmospheric conditions on Earth up to a UV protecting ozone layer comparable to present times. Further, we discuss experimental data which show the photo-reverse effect of Uracil molecules caused by short UV wavelengths. These photoreversion effect highly depend on the wavelength of the radiation. Shorter wavelength UV radiation of about 200 nm is strongly effective in monomerisation, while the longer wavelengths prefer the production of dimerisation. We could demonstrate experimentally, for the case of an Uracil thin-layer that the photo-reaction process of the nucleotides can be both, dimerization and the reverse process: monomerization. These results are important for the study of solar UV exposure on organisms in the terrestrial environment more than 2 Gyr ago where Earth had no UV protecting ozone layer as well as for the search for life on Mars since we can show that biological harmful effects can also be reduced by shorter wavelength UV radiation, which is of importance in reducing DNA damages provoked by wavelengths longer than about 240 nm.

Dietary Foeniculum vulgare Mill extract attenuated UVB irradiation-induced skin photoaging by activating of Nrf2 and inhibiting MAPK pathways.

PubMed

Sun, Zhengwang; Park, Sang Yong; Hwang, Eunson; Park, Bom; Seo, Seul A; Cho, Jin-Gyeong; Zhang, Mengyang; Yi, Tae-Hoo

2016-11-15

Foeniculum vulgare Mill (FV) has long been prescribed in traditional medicine due to its antioxidant anti-inflammatory properties. However, little research has been done on the use of FV to alleviate changes in UVB-induced photoaging PURPOSE: This study was to investigate the photoprotective effects and mechanism of FV in vitro and in vivo. The anti-photoaging effect of FV was assessed in normal human dermal fibroblasts (NHDFs) in vitro. The secretion of reactive oxygen species (ROS), lactate dehydrogenase (LDH), GSH, matrix metalloproteinases (MMPs), procollagen type I, IL-6 and transforming growth factor-β1 (TGF-β1) were measured by kits. Additionally, the level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), p-ERK and p38 were evaluated by western blotting. In vivo, H&E and Masson's trichrome staining were employed. The expression of MMP-1, procollagen type I, TGF-β1 and elastin were measured by western blot. FV significantly increased the production of collagen, elastin and TGF-β1 levels, while blocked matrix metalloproteinases (MMPs) production in UVB irradiation induced hairless mice, which were consistent with the result in NHDFs. Furthermore, FV dose-dependently decreased the production of ROS and LDH by promoting the nuclear amount of Nrf2 and enhancing the expression of cytoprotective antioxidants such as GSH. FV also significantly quenched UVB-induced phosphorylation of ERK and p38 in NHDFs. Our results indicate that FV is a potential botanical agent for the treatment of skin damage induced by UV irradiation. Copyright © 2016 Elsevier GmbH. All rights reserved.

UV-B Perception and Acclimation in Chlamydomonas reinhardtii[OPEN

PubMed Central

Chappuis, Richard; Allorent, Guillaume

2016-01-01

Plants perceive UV-B, an intrinsic component of sunlight, via a signaling pathway that is mediated by the photoreceptor UV RESISTANCE LOCUS8 (UVR8) and induces UV-B acclimation. To test whether similar UV-B perception mechanisms exist in the evolutionarily distant green alga Chlamydomonas reinhardtii, we identified Chlamydomonas orthologs of UVR8 and the key signaling factor CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1). Cr-UVR8 shares sequence and structural similarity to Arabidopsis thaliana UVR8, has conserved tryptophan residues for UV-B photoreception, monomerizes upon UV-B exposure, and interacts with Cr-COP1 in a UV-B-dependent manner. Moreover, Cr-UVR8 can interact with At-COP1 and complement the Arabidopsis uvr8 mutant, demonstrating that it is a functional UV-B photoreceptor. Chlamydomonas shows apparent UV-B acclimation in colony survival and photosynthetic efficiency assays. UV-B exposure, at low levels that induce acclimation, led to broad changes in the Chlamydomonas transcriptome, including in genes related to photosynthesis. Impaired UV-B-induced activation in the Cr-COP1 mutant hit1 indicates that UVR8-COP1 signaling induces transcriptome changes in response to UV-B. Also, hit1 mutants are impaired in UV-B acclimation. Chlamydomonas UV-B acclimation preserved the photosystem II core proteins D1 and D2 under UV-B stress, which mitigated UV-B-induced photoinhibition. These findings highlight the early evolution of UVR8 photoreceptor signaling in the green lineage to induce UV-B acclimation and protection. PMID:27020958

Early induced protein 1 (PrELIP1) and other photosynthetic, stress and epigenetic regulation genes are involved in Pinus radiata D. don UV-B radiation response.

PubMed

Valledor, Luis; Cañal, María Jesús; Pascual, Jesús; Rodríguez, Roberto; Meijón, Mónica

2012-11-01

The continuous atmospheric and environmental deterioration is likely to increase, among others, the influx of ultraviolet B (UV-B) radiation. The plants have photoprotective responses, which are complex mechanisms involving different physiological responses, to avoid the damages caused by this radiation that may lead to plant death. We have studied the adaptive responses to UV-B in Pinus radiata, given the importance of this species in conifer forests and reforestation programs. We analyzed the photosynthetic activity, pigments content, and gene expression of candidate genes related to photosynthesis, stress and gene regulation in needles exposed to UV-B during a 96 h time course. The results reveal a clear increase of pigments under UV-B stress while photosynthetic activity decreased. The expression levels of the studied genes drastically changed after UV-B exposure, were stress related genes were upregulated while photosynthesis (RBCA and RBCS) and epigenetic regulation were downregulated (MSI1, CSDP2, SHM4). The novel gene PrELIP1, fully sequenced for this work, was upregulated and expressed mainly in the palisade parenchyma of needles. This gene has conserved domains related to the dissipation of the UV-B radiation that give to this protein a key role during photoprotection response of the needles in Pinus radiata. Copyright © Physiologia Plantarum 2012.

Climate change conditions (elevated CO2 and temperature) and UV-B radiation affect grapevine (Vitis vinifera cv. Tempranillo) leaf carbon assimilation, altering fruit ripening rates.

PubMed

Martínez-Lüscher, J; Morales, F; Sánchez-Díaz, M; Delrot, S; Aguirreolea, J; Gomès, E; Pascual, I

2015-07-01

The increase in grape berry ripening rates associated to climate change is a growing concern for wine makers as it rises the alcohol content of the wine. The present work studied the combined effects of elevated CO2, temperature and UV-B radiation on leaf physiology and berry ripening rates. Three doses of UV-B: 0, 5.98, 9.66 kJm(-2)d(-1), and two CO2-temperature regimes: ambient CO2-24/14 °C (day/night) (current situation) and 700 ppm CO2-28/18 °C (climate change) were imposed to grapevine fruit-bearing cuttings from fruit set to maturity under greenhouse-controlled conditions. Photosynthetic performance was always higher under climate change conditions. High levels of UV-B radiation down regulated carbon fixation rates. A transient recovery took place at veraison, through the accumulation of flavonols and the increase of antioxidant enzyme activities. Interacting effects between UV-B and CO2-temperature regimes were observed for the lipid peroxidation, which suggests that UV-B may contribute to palliate the signs of oxidative damage induced under elevated CO2-temperature. Photosynthetic and ripening rates were correlated. Thereby, the hastening effect of climate change conditions on ripening, associated to higher rates of carbon fixation, was attenuated by UV-B radiation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Impact of ambient and supplemental ultraviolet-B stress on kidney bean plants: an insight into oxidative stress management.

PubMed

Singh, Suruchi; Sarkar, Abhijit; Agrawal, S B; Agrawal, Madhoolika

2014-11-01

In the present study, the response of kidney bean (Phaseolus vulgaris L. cv. Pusa Komal) plants was evaluated under three different levels of ultraviolet-B (UV-B), i.e., excluded UV-B (eUV-B), ambient UV-B (aUV-B; 5.8 kJ m(-2) day(-1)), and supplemental UV-B (sUV-B; 280-315 nm; ambient + 7.2 kJ m(-2) day(-1)), under near-natural conditions. eUV-B treatment clearly demonstrated that both aUV-B and sUV-B are capable of causing significant changes in the plant's growth, metabolism, economic yield, genome template stability, total protein, and antioxidative enzyme profiles. The experimental findings showed maximum plant height at eUV-B, but biomass accumulation was minimum. Significant reductions in quantum yield (Fv/Fm) were observed under both aUV-B and sUV-B, as compared to eUV-B. UV-B-absorbing flavonoids increased under higher UV-B exposures with consequent increments in phenylalanine ammonia lyase (PAL) activities. The final yield was significantly higher in plants grown under eUV-B, compared to those under aUV-B and sUV-B. Total protein profile through sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and analysis of isoenzymes, like superoxide dismutase (SOD), peroxidase (POX), catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), and glutathione reductase (GR), through native PAGE revealed major changes in the leaf proteome under aUV-B and sUV-B, depicting induction of some major stress-related proteins. The random amplified polymorphic DNA (RAPD) profile of genomic DNA also indicated a significant reduction of genome template stability under UV-B exposure. Thus, it can be inferred that more energy is diverted for inducing protection mechanisms rather than utilizing it for growth under high UV-B level.

DNA damage induced by ascorbate in the presence of Cu2+.

PubMed

Kobayashi, S; Ueda, K; Morita, J; Sakai, H; Komano, T

1988-01-25

DNA damage induced by ascorbate in the presence of Cu2+ was investigated by use of bacteriophage phi X174 double-stranded supercoiled DNA and linear restriction fragments as substrates. Single-strand cleavage was induced when supercoiled DNA was incubated with 5 microM-10 mM ascorbate and 50 microM Cu2+ at 37 degrees C for 10 min. The induced DNA damage was analyzed by sequencing of fragments singly labeled at their 5'- or 3'-end. DNA was cleaved directly and almost uniformly at every nucleotide by ascorbate and Cu2+. Piperidine treatment after the reaction showed that ascorbate and Cu2+ induced another kind of DNA damage different from the direct cleavage. The damage proceeded to DNA cleavage by piperidine treatment and was sequence-specific rather than random. These results indicate that ascorbate induces two classes of DNA damage in the presence of Cu2+, one being direct strand cleavage, probably via damage to the DNA backbone, and the other being a base modification labile to alkali treatment. These two classes of DNA damage were inhibited by potassium iodide, catalase and metal chelaters, suggesting the involvement of radicals generated from ascorbate hydroperoxide.

Curcumin-Mediated HDAC Inhibition Suppresses the DNA Damage Response and Contributes to Increased DNA Damage Sensitivity

PubMed Central

Wang, Shu-Huei; Lin, Pei-Ya; Chiu, Ya-Chen; Huang, Ju-Sui; Kuo, Yi-Tsen; Wu, Jen-Chine; Chen, Chin-Chuan

2015-01-01

Chemo- and radiotherapy cause multiple forms of DNA damage and lead to the death of cancer cells. Inhibitors of the DNA damage response are candidate drugs for use in combination therapies to increase the efficacy of such treatments. In this study, we show that curcumin, a plant polyphenol, sensitizes budding yeast to DNA damage by counteracting the DNA damage response. Following DNA damage, the Mec1-dependent DNA damage checkpoint is inactivated and Rad52 recombinase is degraded by curcumin, which results in deficiencies in double-stand break repair. Additive effects on damage-induced apoptosis and the inhibition of damage-induced autophagy by curcumin were observed. Moreover, rpd3 mutants were found to mimic the curcumin-induced suppression of the DNA damage response. In contrast, hat1 mutants were resistant to DNA damage, and Rad52 degradation was impaired following curcumin treatment. These results indicate that the histone deacetylase inhibitor activity of curcumin is critical to DSB repair and DNA damage sensitivity. PMID:26218133

Silicon nanoparticles more effectively alleviated UV-B stress than silicon in wheat (Triticum aestivum) seedlings.

PubMed

Tripathi, Durgesh Kumar; Singh, Swati; Singh, Vijay Pratap; Prasad, Sheo Mohan; Dubey, Nawal Kishore; Chauhan, Devendra Kumar

2017-01-01

The role of silicon (Si) in alleviating biotic as well as abiotic stresses is well known. However, the potential of silicon nanoparticle (SiNP) in regulating abiotic stress and associated mechanisms have not yet been explored. Therefore, in the present study hydroponic experiments were conducted to investigate whether Si or SiNp are more effective in the regulation of UV-B stress. UV-B (ambient and enhanced) radiation caused adverse effect on growth of wheat (Triticum aestivum) seedlings, which was accompanied by declined photosynthetic performance and altered vital leaf structures. Levels of superoxide radical and H 2 O 2 were enhanced by UV-B as also evident from their histochemical stainings, which was accompanied by increased lipid peroxidation (LPO) and electrolyte leakage. Activities of superoxide dismutase and ascorbate peroxidase were inhibited by UV-B while catalase and guaiacol peroxidase, and all non-enzymatic antioxidants were stimulated by UV-B. Although, nitric oxide (NO) content was increased at all tested combinations, but its maximum content was observed under SiNps together with UV-B enhanced treatment. Pre-additions of SiNp as well as Si protected wheat seedlings against UV-B by regulating oxidative stress through enhanced antioxidants. Data indicate that SiNp might have protected wheat seedlings through NO-mediated triggering of antioxidant defense system, which subsequently counterbalance reactive oxygen species-induced damage to photosynthesis. Further, SiNp appear to be more effective in reducing UV-B stress than Si, which is related to its greater availability to wheat seedlings. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Unrepaired DNA damage in macrophages causes elevation of particulate matter- induced airway inflammatory response.

PubMed

Luo, Man; Bao, Zhengqiang; Xu, Feng; Wang, Xiaohui; Li, Fei; Li, Wen; Chen, Zhihua; Ying, Songmin; Shen, Huahao

2018-04-14

The inflammatory cascade can be initiated with the recognition of damaged DNA. Macrophages play an essential role in particulate matter (PM)-induced airway inflammation. In this study, we aim to explore the PM induced DNA damage response of macrophages and its function in airway inflammation. The DNA damage response and inflammatory response were assessed using bone marrow-derived macrophages following PM treatment and mouse model instilled intratracheally with PM. We found that PM induced significant DNA damage both in vitro and in vivo and simultaneously triggered a rapid DNA damage response, represented by nuclear RPA, 53BP1 and γH2AX foci formation. Genetic ablation or chemical inhibition of the DNA damage response sensor amplified the production of cytokines including Cxcl1, Cxcl2 and Ifn-γ after PM stimulation in bone marrow-derived macrophages. Similar to that seen in vitro , mice with myeloid-specific deletion of RAD50 showed higher levels of airway inflammation in response to the PM challenge, suggesting a protective role of DNA damage sensor during inflammation. These data demonstrate that PM exposure induces DNA damage and activation of DNA damage response sensor MRN complex in macrophages. Disruption of MRN complex lead to persistent, unrepaired DNA damage that causes elevated inflammatory response.

Protective effect of the standardized green tea seed extract on UVB-induced skin photoaging in hairless mice

PubMed Central

Lim, Jae-Youn; Kim, Ok-Kyung; Lee, Jeongmin; Lee, Min-Jae; Kang, Namgil

2014-01-01

BACKGROUND/OBJECTIVES Ultraviolet B (UVB) irradiation on skin can induce production of reactive oxygen species (ROS), which cause expression of matrix metalloproteinases (MMPs) and collagen degradation. Thus, chronic exposure of skin to UVB irradiation leads to histological changes consistent with aging, such as wrinkling, abnormal pigmentation, and loss of elasticity. We investigated the protective effect of the standardized green tea seed extract (GSE) on UVB-induced skin photoaging in hairless mice. MATERIALS/METHODS Skin photoaging was induced by UVB irradiation on the back of Skh-1 hairless mice three times per week and UVB irradiation was performed for 10 weeks. Mice were divided into six groups; normal control, UVB irradiated control group, positive control (UVB + dietary supplement of vitamin C 100 mg/kg), GSE 10 mg/kg (UVB + dietary supplement of GSE 10 mg/kg), GSE 100 mg/kg (UVB + dietary supplement of GSE 100 mg/kg), and GSE 200 mg/kg (UVB + dietary supplement of GSE 200 mg/kg). RESULTS The dietary supplement GSE attenuated UVB irradiation-induced wrinkle formation and the decrease in density of dermal collagen fiber. In addition, results of the antioxidant analysis showed that GSE induced a significant increase in antioxidant enzyme activity compared with the UVB irradiation control group. Dietary supplementation with GSE 200 mg/kg resulted in a significant decrease in expression of MMP-1, MMP-3, and MMP-9 and an increase in expression of TIMP and type-1 collagen. CONCLUSIONS Findings of this study suggest that dietary supplement GSE could be useful in attenuation of UVB irradiation-induced skin photoaging and wrinkle formation due to regulation of antioxidant defense systems and MMPs expression. PMID:25110559

Protective effect of the standardized green tea seed extract on UVB-induced skin photoaging in hairless mice.

PubMed

Lim, Jae-Youn; Kim, Ok-Kyung; Lee, Jeongmin; Lee, Min-Jae; Kang, Namgil; Hwang, Jae-Kwan

2014-08-01

Ultraviolet B (UVB) irradiation on skin can induce production of reactive oxygen species (ROS), which cause expression of matrix metalloproteinases (MMPs) and collagen degradation. Thus, chronic exposure of skin to UVB irradiation leads to histological changes consistent with aging, such as wrinkling, abnormal pigmentation, and loss of elasticity. We investigated the protective effect of the standardized green tea seed extract (GSE) on UVB-induced skin photoaging in hairless mice. Skin photoaging was induced by UVB irradiation on the back of Skh-1 hairless mice three times per week and UVB irradiation was performed for 10 weeks. Mice were divided into six groups; normal control, UVB irradiated control group, positive control (UVB + dietary supplement of vitamin C 100 mg/kg), GSE 10 mg/kg (UVB + dietary supplement of GSE 10 mg/kg), GSE 100 mg/kg (UVB + dietary supplement of GSE 100 mg/kg), and GSE 200 mg/kg (UVB + dietary supplement of GSE 200 mg/kg). The dietary supplement GSE attenuated UVB irradiation-induced wrinkle formation and the decrease in density of dermal collagen fiber. In addition, results of the antioxidant analysis showed that GSE induced a significant increase in antioxidant enzyme activity compared with the UVB irradiation control group. Dietary supplementation with GSE 200 mg/kg resulted in a significant decrease in expression of MMP-1, MMP-3, and MMP-9 and an increase in expression of TIMP and type-1 collagen. Findings of this study suggest that dietary supplement GSE could be useful in attenuation of UVB irradiation-induced skin photoaging and wrinkle formation due to regulation of antioxidant defense systems and MMPs expression.

UV-B Radiation Induces Root Bending Through the Flavonoid-Mediated Auxin Pathway in Arabidopsis.

PubMed

Wan, Jinpeng; Zhang, Ping; Wang, Ruling; Sun, Liangliang; Wang, Wenying; Zhou, Huakun; Xu, Jin

2018-01-01

Ultraviolet (UV)-B radiation-induced root bending has been reported; however, the underlying mechanisms largely remain unclear. Here, we investigate whether and how auxin and flavonoids are involved in UV-B radiation-induced root bending in Arabidopsis using physiological, pharmacological, and genetic approaches. UV-B radiation modulated the direction of root growth by decreasing IAA biosynthesis and affecting auxin distribution in the root tips, where reduced auxin accumulation and asymmetric auxin distribution were observed. UV-B radiation increased the distribution of auxin on the nonradiated side of the root tips, promoting growth and causing root bending. Further analysis indicated that UV-B induced an asymmetric accumulation of flavonoids; this pathway is involved in modulating the accumulation and asymmetric distribution of auxin in root tips and the subsequent redirection of root growth by altering the distribution of auxin carriers in response to UV-B radiation. Taken together, our results indicate that UV-B radiation-induced root bending occurred through a flavonoid-mediated phototropic response to UV-B radiation.

UV-B Radiation Induces Root Bending Through the Flavonoid-Mediated Auxin Pathway in Arabidopsis

PubMed Central

Wan, Jinpeng; Zhang, Ping; Wang, Ruling; Sun, Liangliang; Wang, Wenying; Zhou, Huakun; Xu, Jin

2018-01-01

Ultraviolet (UV)-B radiation-induced root bending has been reported; however, the underlying mechanisms largely remain unclear. Here, we investigate whether and how auxin and flavonoids are involved in UV-B radiation-induced root bending in Arabidopsis using physiological, pharmacological, and genetic approaches. UV-B radiation modulated the direction of root growth by decreasing IAA biosynthesis and affecting auxin distribution in the root tips, where reduced auxin accumulation and asymmetric auxin distribution were observed. UV-B radiation increased the distribution of auxin on the nonradiated side of the root tips, promoting growth and causing root bending. Further analysis indicated that UV-B induced an asymmetric accumulation of flavonoids; this pathway is involved in modulating the accumulation and asymmetric distribution of auxin in root tips and the subsequent redirection of root growth by altering the distribution of auxin carriers in response to UV-B radiation. Taken together, our results indicate that UV-B radiation-induced root bending occurred through a flavonoid-mediated phototropic response to UV-B radiation. PMID:29868074

Chemical peeling by SA-PEG remodels photo-damaged skin: suppressing p53 expression and normalizing keratinocyte differentiation.

PubMed

Dainichi, Teruki; Amano, Satoshi; Matsunaga, Yukiko; Iriyama, Shunsuke; Hirao, Tetsuji; Hariya, Takeshi; Hibino, Toshihiko; Katagiri, Chika; Takahashi, Motoji; Ueda, Setsuko; Furue, Masutaka

2006-02-01

Chemical peeling with salicylic acid in polyethylene glycol vehicle (SA-PEG), which specifically acts on the stratum corneum, suppresses the development of skin tumors in UVB-irradiated hairless mice. To elucidate the mechanism through which chemical peeling with SA-PEG suppresses skin tumor development, the effects of chemical peeling on photodamaged keratinocytes and cornified envelopes (CEs) were evaluated in vivo. Among UVB-irradiated hairless mice, the structural atypia and expression of p53 protein in keratinocytes induced by UVB irradiation were intensely suppressed in the SA-PEG-treated mice 28 days after the start of weekly SA-PEG treatments when compared to that in the control UVB-irradiated mice. Incomplete expression of filaggrin and loricrin in keratinocytes from the control mice was also improved in keratinocytes from the SA-PEG-treated mice. In photo-exposed human facial skin, immature CEs were replaced with mature CEs 4 weeks after treatment with SA-PEG. Restoration of photodamaged stratum corneum by treatment with SA-PEG, which may affect remodeling of the structural environment of the keratinocytes, involved the normalization of keratinocyte differentiation and suppression of skin tumor development. These results suggest that the stratum corneum plays a protective role against carcinogenesis, and provide a novel strategy for the prevention of photo-induced skin tumors.

Solar Irradiance Changes And Photobiological Effects At Earth's Surface Following Astrophysical Ionizing Radiation Events

NASA Astrophysics Data System (ADS)

Thomas, Brian; Neale, Patrick

2016-01-01

Astrophysical ionizing radiation events have been recognized as a potential threat to life on Earth for decades. Although there is some direct biological damage on the surface from redistributed radiation several studies have indicated that the greatest long term threat is from ozone depletion and subsequent heightened solar ultraviolet (UV) radiation. It is known that organisms exposed to this irradiation experience harmful effects such as sunburn and even direct damage to DNA, proteins, or other cellular structures. Simulations of the atmospheric effects of a variety of events (such as supernovae, gamma-ray bursts, and solar proton events) have been previously published, along with estimates of biological damage at Earth's surface. In the present work, we employed a radiative transfer model to expand and improve calculations of surface-level irradiance and biological impacts following an ionizing radiation event. We considered changes in surface-level UVB, UVA, and photosynthetically active radiation (visible light). Using biological weighting functions we have considered a wide range of effects, including: erythema and skin cancer in humans; inhibition of photosynthesis in the diatom Phaeodactylum sp. and dinoflagellate Prorocentrum micans inhibition of carbon fixation in Antarctic phytoplankton; inhibition of growth of oat (Avena sativa L. cv. Otana) seedlings; and cataracts. We found that past work overestimated UVB irradiance, but that relative estimates for increase in exposure to DNA damaging radiation are still similar to our improved calculations. We also found that the intensity of biologically damaging radiation varies widely with organism and specific impact considered; these results have implications for biosphere-level damage following astrophysical ionizing radiation events. When considering changes in surface-level visible light irradiance, we found that, contrary to previous assumptions, a decrease in irradiance is only present for a short time in very limited geographical areas; instead we found a net increase for most of the modeled time-space region. This result has implications for proposed climate changes associated with ionizing radiation events.

Comparative Transcriptome Profiling of an SV40-Transformed Human Fibroblast (MRC5CVI) and Its Untransformed Counterpart (MRC-5) in Response to UVB Irradiation

PubMed Central

Chang, Cheng-Wei; Chen, Chaang-Ray; Huang, Chao-Ying; Shu, Wun-Yi; Chiang, Chi-Shiun; Hong, Ji-Hong; Hsu, Ian C.

2013-01-01

Simian virus 40 (SV40) transforms cells through the suppression of tumor-suppressive responses by large T and small t antigens; studies on the effects of these two oncoproteins have greatly improved our knowledge of tumorigenesis. Large T antigen promotes cellular transformation by binding and inactivating p53 and pRb tumor suppressor proteins. Previous studies have shown that not all of the tumor-suppressive responses were inactivated in SV40-transformed cells; however, the underlying cause is not fully studied. In this study, we investigated the UVB-responsive transcriptome of an SV40-transformed fibroblast (MRC5CVI) and that of its untransformed counterpart (MRC-5). We found that, in response to UVB irradiation, MRC-5 and MRC5CVI commonly up-regulated the expression of oxidative phosphorylation genes. MRC-5 up-regulated the expressions of chromosome condensation, DNA repair, cell cycle arrest, and apoptotic genes, but MRC5CVI did not. Further cell death assays indicated that MRC5CVI was more sensitive than MRC-5 to UVB-induced cell death with increased caspase-3 activation; combining with the transcriptomic results suggested that MRC5CVI may undergo UVB-induced cell death through mechanisms other than transcriptional regulation. Our study provides a further understanding of the effects of SV40 transformation on cellular stress responses, and emphasizes the value of SV40-transformed cells in the researches of sensitizing neoplastic cells to radiations. PMID:24019915

UVA phototransduction drives early melanin synthesis in human melanocytes.

PubMed

Wicks, Nadine L; Chan, Jason W; Najera, Julia A; Ciriello, Jonathan M; Oancea, Elena

2011-11-22

Exposure of human skin to solar ultraviolet radiation (UVR), a powerful carcinogen [1] comprising ~95% ultraviolet A (UVA) and ~5% ultraviolet B (UVB) at the Earth's surface, promotes melanin synthesis in epidermal melanocytes [2, 3], which protects skin from DNA damage [4, 5]. UVB causes DNA lesions [6] that lead to transcriptional activation of melanin-producing enzymes, resulting in delayed skin pigmentation within days [7]. In contrast, UVA causes primarily oxidative damage [8] and leads to immediate pigment darkening (IPD) within minutes, via an unknown mechanism [9, 10]. No receptor protein directly mediating phototransduction in skin has been identified. Here we demonstrate that exposure of primary human epidermal melanocytes (HEMs) to UVA causes calcium mobilization and early melanin synthesis. Calcium responses were abolished by treatment with G protein or phospholipase C (PLC) inhibitors or by depletion of intracellular calcium stores. We show that the visual photopigment rhodopsin [11] is expressed in HEMs and contributes to UVR phototransduction. Upon UVR exposure, significant melanin production was measured within one hour; cellular melanin continued to increase in a retinal- and calcium-dependent manner up to 5-fold after 24 hr. Our findings identify a novel UVA-sensitive signaling pathway in melanocytes that leads to calcium mobilization and melanin synthesis and may underlie the mechanism of IPD in human skin. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ultraviolet absorbing compounds provide a rapid response mechanism for UV protection in some reef fish.

PubMed

Braun, C; Reef, R; Siebeck, U E

2016-07-01

The external mucus surface of reef fish contains ultraviolet absorbing compounds (UVAC), most prominently Mycosporine-like Amino Acids (MAAs). MAAs in the external mucus of reef fish are thought to act as sunscreens by preventing the damaging effects of ultraviolet radiation (UVR), however, direct evidence for their protective role has been missing. We tested the protective function of UVAC's by exposing fish with naturally low, Pomacentrus amboinensis, and high, Thalassoma lunare, mucus absorption properties to a high dose of UVR (UVB: 13.4W∗m(-2), UVA: 6.1W∗m(-2)) and measuring the resulting DNA damage in the form of cyclobutane pyrimidine dimers (CPDs). For both species, the amount of UV induced DNA damage sustained following the exposure to a 1h pulse of high UVR was negatively correlated with mucus absorbance, a proxy for MAA concentration. Furthermore, a rapid and significant increase in UVAC concentration was observed in P. amboinensis following UV exposure, directly after capture and after ten days in captivity. No such increase was observed in T. lunare, which maintained relatively high levels of UV absorbance at all times. P. amboinensis, in contrast to T. lunare, uses UV communication and thus must maintain UV transparent mucus to be able to display its UV patterns. The ability to rapidly alter the transparency of mucus could be an important adaptation in the trade off between protection from harmful UVR and UV communication. Copyright © 2016 Elsevier B.V. All rights reserved.

The polypeptide in Chlamys farreri can protect human dermal fibroblasts from ultraviolet B damage

NASA Astrophysics Data System (ADS)

Zhang, Yujiang; Zhan, Songmei; Cao, Pengli; Liu, Ning; Chen, Xuehong; Wang, Yuejun; Wang, Chunbo

2005-09-01

To investigate the effect of polypeptide from Chlamys farreri (PCF) on NHDF in vitro, we modeled oxidative damage on normal human dermal fibroblasts (NHDF) exposed to ultraviolet B (UVB). In this study, 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) were tested to measure cell viability. Enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) and xanthine oxidase (XOD) were determined biochemically. Total antioxidative capacity (T-AOC) and anti-superoxide anion capacity (A-SAC) were also determined. Ultrastructure of fibroblasts was observed under transmission electron microscope. The results showed that: UVB (1.176×10-4 J/cm2) suppressed the growth of fibroblasts and the introduction of PCF (0.25% 1%) before UVB reduced the suppression in a concentration-dependent manner. PCF could enhance the activities of SOD, GSH-PX and T-AOC as well as A-SAC. Also PCF could inhibit XOD activity, while it did not affect CAT activity. Ultrastructure of fibroblasts were damaged after UVB irradiation, concentration-dependent PCF reduced the destructive effect of UVB on cells. These results indicated that PCF can protect human dermal fibroblasts from being harmed by UVB irradiation via its antioxidant proerty.

TNF-R1 and FADD mediate UVB-Induced activation of K+ channels in corneal epithelial cells

PubMed Central

Boersma, Peter M.; Haarsma, Loren D.; Schotanus, Mark P.; Ubels, John L.

2017-01-01

The goal of this study was to elucidate the role of Fas, TNF-R1, FADD and cytochrome c in UVB-induced K+ channel activation, an early step in UVB-induced apoptosis, in human corneal limbal epithelial (HCLE) cells. HCLE cells were treated with Fas, TNF-R1 or FADD siRNA and exposed to 80 or 150 mJ/cm2 UVB. K+ channel activation and loss of intracellular K+ were measured using whole-cell patch-clamp recording and ion chromatography, respectively. Cytochrome c was measured with an ELISA kit. Cells in which Fas was knocked down exhibited identical UVB-induced K+ channel activation and loss of intracellular K+ to control cells. Cells in which TNF-R1 or FADD were knocked down demonstrated reduced K+ channel activation and decreased loss of intracellular K+ following UVB, relative to control cells. Application of TNF-α, the natural ligand of TNF-R1, to HCLE cells induced K+ channel activation and loss of intracellular K+. Cytochrome c was translocated to the cytosol by 2 h after exposure to 150 mJ/cm2 UVB. However, there was no release by 10 min post-UVB. The data suggest that UVB activates TNF-R1, which in turn may activate K+ channels via FADD. This conclusion is supported by the observation that TNF-α also causes loss of intracellular K+. This signaling pathway appears to be integral to UVB-induced K+ efflux, since knockdown of TNF-R1 or FADD inhibits the UVB-induced K+ efflux. The lack of rapid cytochrome c translocation indicates cytochrome c does not play a role in UVB-induced K+ channel activation. PMID:27818316

Temporal variations in sirtuin expression under normal and ultraviolet B-induced conditions and their correlation to energy levels in normal human epidermal keratinocytes.

PubMed

Pelle, Edward; Dong, Kelly; Pernodet, Nadine

2015-01-01

Sirtuins are post-translational modifiers that affect transcriptional signaling, metabolism, and DNA repair. Although originally identified as gene silencers capable of extending cell lifespan, the involvement of sirtuins in many different areas of cell biology has now become widespread. Our approach has been to study the temporal variation and also the effect of environmental stressors, such as ultraviolet B (UVB) and ozone, on sirtuin expression in human epidermal keratinocytes. In this report, we measured the variation in expression of several sirtuins over time and also show how a low dose of UVB can affect this pattern of expression. Moreover, we correlated these changes to variations in hydrogen peroxide (H2O2) and ATP levels. Our data show significant variations in normal sirtuin expression, which may indicate a generalized response by sirtuins to cell cycle kinetics. These results also demonstrate that sirtuins as a family of molecules are sensitive to UVB-induced disruption and may suggest a new paradigm for determining environmental stress on aging and provide direction for the development of new cosmetic products.

The ovarian DNA damage repair response is induced prior to phosphoramide mustard-induced follicle depletion, and ataxia telangiectasia mutated inhibition prevents PM-induced follicle depletion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide and destroys primordial and primary follicles potentially by DNA damage induction. The temporal pattern by which PM induces DNA damage and initiation of the ovarian response to DNA damage has not yet been well characterized. This study investigated DNA damage initiation, the DNA repair response, as well as induction of follicular demise using a neonatal rat ovarian culture system. Additionally, to delineate specific mechanisms involved in the ovarian response to PM exposure, utility was made of PKC delta (PKCδ) deficient mice as well as an ATM inhibitor (KU 55933; AI). Fishermore » 344 PND4 rat ovaries were cultured for 12, 24, 48 or 96 h in medium containing DMSO ± 60 μM PM or KU 55933 (48 h; 10 nM). PM-induced activation of DNA damage repair genes was observed as early as 12 h post-exposure. ATM, PARP1, E2F7, P73 and CASP3 abundance were increased but RAD51 and BCL2 protein decreased after 96 h of PM exposure. PKCδ deficiency reduced numbers of all follicular stages, but did not have an additive impact on PM-induced ovotoxicity. ATM inhibition protected all follicle stages from PM-induced depletion. In conclusion, the ovarian DNA damage repair response is active post-PM exposure, supporting that DNA damage contributes to PM-induced ovotoxicity. - Highlights: • PM exposure induces DNA damage repair gene expression. • Inhibition of ATM prevented PM-induced follicle depletion. • PKCδ deficiency did not impact PM-induced ovotoxicity.« less

Terrestrial ozone depletion due to a Milky Way gamma-ray burst

NASA Astrophysics Data System (ADS)

Thomas, Brian C.

Gamma-Ray Bursts (GRBs) are short, incredibly powerful astrophysical events which produce a flux of radiation detectable across the observable universe. A GRB within our own galaxy could cause major damage to the Earth's biosphere. Rate estimates suggest that at least one GRB has occurred within a dangerous range (about 2 kpc) in the last billion years. The gamma radiation from such a burst would quickly deplete much of the Earth's protective ozone layer, allowing an increase in solar UVB radiation reaching the surface. This radiation is harmful to life, causing sunburn and damaging DNA. In addition, NO 2 produced in the atmosphere would cause a decrease in visible sunlight reaching the surface and could cause global cooling. Nitric acid rain could stress portions of the biosphere, but the increased nitrate deposition could be helpful to land plants. We have used a two-dimensional atmospheric model to investigate the effects on the Earth's atmosphere of a GRB. We have simulated bursts delivering a range of fluences, at various latitudes, at the equinoxes and solstices, and at different times of day. We have computed DNA damage caused by increased solar UVB radiation, reduction in solar visible light due to NO 2 opacity; and deposition of nitrates through rainout of HNO 3 . For a "typical" burst in the last billion years, we find globally averaged ozone depletion up to 38%. Localized depletion reaches as much as 74%. Significant global depletion (at least 10%) persists up to about 7 years after the burst. Our results depend strongly on time of year and latitude over which the burst occurs. We find DNA damage of up to 16 times the normal annual global average, with greatest damage occurring at low to mid latitudes. We find reductions in visible sunlight of a few percent, primarily in the polar regions. Nitrate deposition similar to or slightly greater than that currently caused by lightning is also observed. We find support in our results for the hypothesis that the Late Ordovician mass extinction may have been initiated by a GRB and this connection is briefly discussed.

Irradiation of skin with visible light induces reactive oxygen species and matrix-degrading enzymes.

PubMed

Liebel, Frank; Kaur, Simarna; Ruvolo, Eduardo; Kollias, Nikiforos; Southall, Michael D

2012-07-01

Daily skin exposure to solar radiation causes cells to produce reactive oxygen species (ROS), which are a primary factor in skin damage. Although the contribution of the UV component to skin damage has been established, few studies have examined the effects of non-UV solar radiation on skin physiology. Solar radiation comprises <10% of UV, and thus the purpose of this study was to examine the physiological response of skin to visible light (400-700 nm). Irradiation of human skin equivalents with visible light induced production of ROS, proinflammatory cytokines, and matrix metalloproteinase (MMP)-1 expression. Commercially available sunscreens were found to have minimal effects on reducing visible light-induced ROS, suggesting that UVA/UVB sunscreens do not protect the skin from visible light-induced responses. Using clinical models to assess the generation of free radicals from oxidative stress, higher levels of free radical activity were found after visible light exposure. Pretreatment with a photostable UVA/UVB sunscreen containing an antioxidant combination significantly reduced the production of ROS, cytokines, and MMP expression in vitro, and decreased oxidative stress in human subjects after visible light irradiation. Taken together, these findings suggest that other portions of the solar spectrum aside from UV, particularly visible light, may also contribute to signs of premature photoaging in skin.

Noise Induced DNA Damage Within the Auditory Nerve.

PubMed

Guthrie, O'neil W

2017-03-01

An understanding of the molecular pathology that underlies noise induced neurotoxicity is a prerequisite to the design of targeted therapies. The objective of the current experiment was to determine whether or not DNA damage is part of the pathophysiologic sequela of noise induced neurotoxicity. The experiment consisted of 41 hooded Long-Evans rats (2 month old males) that were randomized into control and noise exposed groups. Both the control and the noise group followed the same time schedule and therefore started and ended the experiment together. The noise dose consisted of a 6000 Hz noise band at 105 dB SPL. Temporal bones from both groups were harvested, and immunohistochemistry was used to identify neurons with DNA damage. Quantitative morphometric analyses was then employed to determine the level of DNA damage. Neural action potentials were recorded to assess the functional impact of noise induced DNA damage. Immunohistochemical reactions revealed that the noise exposure precipitated DNA damage within the nucleus of auditory neurons. Quantitative morphometry confirmed the noise induced increase in DNA damage levels and the precipitation of DNA damage was associated with a significant loss of nerve sensitivity. Therefore, DNA damage is part of the molecular pathology that drives noise induced neurotoxicity. Anat Rec, 300:520-526, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The effects of phototherapy and melanocytes on keratinocytes

PubMed Central

Tang, Luyan; Wu, Wenyu; Fu, Wenwen; Hu, Yao

2018-01-01

Phototherapy is widely used in the treatment of vitiligo. Previous studies have focused on the effects of ultraviolet (UV) radiation on melanocytes; however, the biological effects of phototherapy and melanocytes on keratinocytes remain to be elucidated. To investigate and assess the effects of clinically doses of broad band (BB)-UVA, narrow band (NB)-UVB and melanocytes on human keratinocytes in vitro, clinical doses of BB-UVA or NB-UVB radiation and human melanoma cell A375 co-culture were performed as stress divisors to HaCaT cells. Cell proliferation, expression of protease-activated receptor-2 (PAR-2) and nuclear factor E2-related factor 2 mRNA, lipid peroxidation and intracellular antioxidant level of keratinocytes were analyzed. It was demonstrated that UV radiation inhibited the proliferation of cells apart from following exposure to low dose (1 J/cm2) UVA. Medium dose (5 J/cm2) UVA radiation had no adverse effects on lipid peroxidation and increased antioxidant levels in HaCaT cells. Medium (200 mJ/cm2) and high (400 mJ/cm2) doses of UVB radiation induced cellular damage due to increased lipid peroxidation as indicated by levels of malondialdehyde. Furthermore, A375 co-culture treatment induced a similar effect on the lipid peroxidation of HaCaT as with low dose UVB radiation. Therefore, the results of the present study determined that clinical doses of BB-UVA and NB-UVB radiation had varying effects on proliferation and related protein levels in HaCaT cells. Co-culture with A375 had similar effects as those of low dose UVA and UVB radiation, in which the PAR-2 expression was significantly upregulated. PMID:29545869

Protective effect of Disporum sessile D.Don extract against UVB-induced photoaging via suppressing MMP-1 expression and collagen degradation in human skin cells.

PubMed

Mohamed, Mohamed Antar Aziz; Jung, Mira; Lee, Sang Min; Lee, Tae Hoon; Kim, Jiyoung

2014-04-05

In the present study, we report that Disporum sessile D.Don herbal extract (DDE) possesses anti-skin photoaging effect through inhibition of MMP-1 mRNA and protein expression levels and increase collagen production in UVB-irradiated human dermal fibroblast cells (NHDF). To delineate the molecular mechanism by which DDE inhibited MMP-1 expression, immortal human keratinocytes cells (HaCaT) have been used. We have found that DDE inhibited UVB-induced MMP-1 mRNA and protein expression levels in HaCaT cells through inhibition of UVB-induced activation of NF-κB in HaCaT cells. Inhibitors of NF-κB (Bay11-7082), and mitogen-activated protein kinases such as extracellular regulated kinase (PD98059), c-Jun N-terminal kinase (SP600125), and p38 (SB203580) suppressed expression of MMP-1, and phosphorylation of these signaling molecules were attenuated by DDE. DDE also inhibited phosphorylation of IKKα and IκBα, and reduced nuclear translocation of NF-κB. Our results also demonstrated that DDE inhibited NF-κB driven expression of luciferase reporter gene and the DNA binding of NF-κB to its cognate binding site in UV-irradiated cells. Therefore, these results strongly suggest that DDE can be utilized as a potential agent for prevention and treatment of skin photoaging. Copyright © 2014 Elsevier B.V. All rights reserved.

Prior Corneal Scarification and Injection of Immune Serum are Not Required Before Ocular HSV-1 Infection for UV-B-Induced Virus Reactivation and Recurrent Herpetic Corneal Disease in Latently Infected Mice

PubMed Central

BenMohamed, Lbachir; Osorio, Nelson; Khan, Arif A.; Srivastava, Ruchi; Huang, Lei; Krochmal, John J.; Garcia, Jairo M.; Simpson, Jennifer L.; Wechsler, Steven L.

2017-01-01

Purpose Blinding ocular herpetic disease in humans is due to spontaneous reactivation of herpes simplex virus type 1 (HSV-1) from latency, rather than to primary acute infection. Mice latently infected with HSV-1 undergo little or no in vivo spontaneous reactivation with accompanying virus shedding in tears. HSV-1 reactivation can be induced in latently infected mice by several in vivo procedures, with UV-B-induced reactivation being one commonly used method. In the UV-B model, corneas are scarified (lightly scratched) just prior to ocular infection to increase efficiency of the primary infection and immune serum containing HSV-1 neutralizing antibodies is injected intraperitoneally (i.p.) to increase survival and decrease acute corneal damage. Since scarification can significantly alter host gene transcription in the cornea and in the trigeminal ganglia (TG; the site of HSV-1 latency) and since injection of immune serum likely modulates innate and adaptive herpes immunity, we investigated eliminating both treatments. Material and Methods Mice were infected with HSV-1 with or without corneal scarification and immune serum. HSV-1 reactivation and recurrent disease were induced by UV-B irradiation. Results When corneal scarification and immune serum were both eliminated, UV-B irradiation still induced both HSV-1 reactivation, as measured by shedding of reactivated virus in tears and herpetic eye disease, albeit at reduced levels compared to the original procedure. Conclusion Despite the reduced reactivation and disease, avoidance of both corneal scarification and immune serum should improve the clinical relevance of the UV-B mouse model. PMID:26398722

Solar Ultraviolet-B Radiation Affects Seedling Emergence, DNA Integrity, Plant Morphology, Growth Rate, and Attractiveness to Herbivore Insects in Datura ferox.

PubMed Central

Ballare, C. L.; Scopel, A. L.; Stapleton, A. E.; Yanovsky, M. J.

1996-01-01

To study functional relationships between the effects of solar ultraviolet-B radiation (UV-B) on different aspects of the physiology of a wild plant, we carried out exclusion experiments in the field with the summer annual Datura ferox L. Solar UV-B incident over Buenos Aires reduced daytime seedling emergence, inhibited stem elongation and leaf expansion, and tended to reduce biomass accumulation during early growth. However, UV-B had no effect on calculated net assimilation rate. Using a monoclonal antibody specific to the cyclobutane-pyrimidine dimer (CPD), we found that plants receiving full sunlight had more CPDs per unit of DNA than plants shielded from solar UV-B, but the positive correlation between UV-B and CPD burden tended to level off at high (near solar) UV-B levels. At our field site, Datura plants were consumed by leaf beetles (Coleoptera), and the proportion of plants attacked by insects declined with the amount of UV-B received during growth. Field experiments showed that plant exposure to solar UV-B reduced the likelihood of leaf beetle attack by one-half. Our results highlight the complexities associated with scaling plant responses to solar UV-B, because they show: (a) a lack of correspondence between UV-B effects on net assimilation rate and whole-plant growth rate, (b) nonlinear UV-B dose-response curves, and (c) UV-B effects of plant attractiveness to natural herbivores. PMID:12226382

Alpha-phellandrene-induced DNA damage and affect DNA repair protein expression in WEHI-3 murine leukemia cells in vitro.

PubMed

Lin, Jen-Jyh; Wu, Chih-Chung; Hsu, Shu-Chun; Weng, Shu-Wen; Ma, Yi-Shih; Huang, Yi-Ping; Lin, Jaung-Geng; Chung, Jing-Gung

2015-11-01

Although there are few reports regarding α-phellandrene (α-PA), a natural compound from Schinus molle L. essential oil, there is no report to show that α-PA induced DNA damage and affected DNA repair associated protein expression. Herein, we investigated the effects of α-PA on DNA damage and repair associated protein expression in murine leukemia cells. Flow cytometric assay was used to measure the effects of α-PA on total cell viability and the results indicated that α-PA induced cell death. Comet assay and 4,6-diamidino-2-phenylindole dihydrochloride staining were used for measuring DNA damage and condensation, respectively, and the results indicated that α-PA induced DNA damage and condensation in a concentration-dependent manner. DNA gel electrophoresis was used to examine the DNA damage and the results showed that α-PA induced DNA damage in WEHI-3 cells. Western blotting assay was used to measure the changes of DNA damage and repair associated protein expression and the results indicated that α-PA increased p-p53, p-H2A.X, 14-3-3-σ, and MDC1 protein expression but inhibited the protein of p53, MGMT, DNA-PK, and BRCA-1. © 2014 Wiley Periodicals, Inc.

Ultraviolet-B phototoxicity and hypothetical photomelanomagenesis: intraocular and crystalline lens photoprotection.

PubMed

Mainster, Martin A; Turner, Patricia L

2010-04-01

Ultraviolet-B (UV-B) radiation can cause phototoxic macular injuries in young people who have been sunbathing but not sungazing and in welders. Welders have a reportedly increased risk of uveal melanoma. We analyze phakic and pseudophakic risks for solar and welding arc UV-B exposure. Optical radiation measurement, analysis, and perspective. Spectral transmittances were measured for UV-transmitting, UV-blocking, and blue-blocking intraocular lenses (IOLs). The photoprotective performances of crystalline and intraocular lenses were analyzed using relevant epidemiologic and laboratory data and action spectra for acute retinal phototoxicity and melanoma photocarcinogenesis. Crystalline lens UV-B retinal protection is deficient in children and young adults, increasing their potential susceptibility to acute retinal phototoxicity and hypothetical photomelanomagenesis. UV-B radiation has sufficient energy/photon to induce primary melanomagenic DNA lesions, unlike blue light or UV-A radiation. UV-blocking and blue-blocking IOLs have negligible UV-B transmittance. UV-transmitting IOL transmittance of UV-B radiation is equivalent to that of a 15-year-old crystalline lens. If optical radiation exposure is responsible for welders' increased risk of uveal melanoma, then UV-B radiation is the most probable causative agent and spectacle wear is a potential confounding factor in epidemiologic studies of ocular melanoma. Welders under 30 years of age are at greater risk for welding maculopathy than older welders. Children, adults under 30 years of age, and pseudophakic individuals with UV-transmitting IOLs should wear sunglasses in bright environments because of the UV-B window in their crystalline lenses or IOLs. Copyright 2010 Elsevier Inc. All rights reserved.

Entire Photodamaged Chloroplasts Are Transported to the Central Vacuole by Autophagy[OPEN

PubMed Central

2017-01-01

Turnover of dysfunctional organelles is vital to maintain homeostasis in eukaryotic cells. As photosynthetic organelles, plant chloroplasts can suffer sunlight-induced damage. However, the process for turnover of entire damaged chloroplasts remains unclear. Here, we demonstrate that autophagy is responsible for the elimination of sunlight-damaged, collapsed chloroplasts in Arabidopsis thaliana. We found that vacuolar transport of entire chloroplasts, termed chlorophagy, was induced by UV-B damage to the chloroplast apparatus. This transport did not occur in autophagy-defective atg mutants, which exhibited UV-B-sensitive phenotypes and accumulated collapsed chloroplasts. Use of a fluorescent protein marker of the autophagosomal membrane allowed us to image autophagosome-mediated transport of entire chloroplasts to the central vacuole. In contrast to sugar starvation, which preferentially induced distinct type of chloroplast-targeted autophagy that transports a part of stroma via the Rubisco-containing body (RCB) pathway, photooxidative damage induced chlorophagy without prior activation of RCB production. We further showed that chlorophagy is induced by chloroplast damage caused by either artificial visible light or natural sunlight. Thus, this report establishes that an autophagic process eliminates entire chloroplasts in response to light-induced damage. PMID:28123106

Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation

NASA Technical Reports Server (NTRS)

Sutherland, B. M.; Bennett, P. V.; Sidorkina, O.; Laval, J.; Lowenstein, D. I. (Principal Investigator)

2000-01-01

Clustered DNA damages-two or more closely spaced damages (strand breaks, abasic sites, or oxidized bases) on opposing strands-are suspects as critical lesions producing lethal and mutagenic effects of ionizing radiation. However, as a result of the lack of methods for measuring damage clusters induced by ionizing radiation in genomic DNA, neither the frequencies of their production by physiological doses of radiation, nor their repairability, nor their biological effects are known. On the basis of methods that we developed for quantitating damages in large DNAs, we have devised and validated a way of measuring ionizing radiation-induced clustered lesions in genomic DNA, including DNA from human cells. DNA is treated with an endonuclease that induces a single-strand cleavage at an oxidized base or abasic site. If there are two closely spaced damages on opposing strands, such cleavage will reduce the size of the DNA on a nondenaturing gel. We show that ionizing radiation does induce clustered DNA damages containing abasic sites, oxidized purines, or oxidized pyrimidines. Further, the frequency of each of these cluster classes is comparable to that of frank double-strand breaks; among all complex damages induced by ionizing radiation, double-strand breaks are only about 20%, with other clustered damage constituting some 80%. We also show that even low doses (0.1-1 Gy) of high linear energy transfer ionizing radiation induce clustered damages in human cells.

Repair of DNA Damage Induced by the Cytidine Analog Zebularine Requires ATR and ATM in Arabidopsis[OPEN

PubMed Central

Liu, Chun-Hsin; Finke, Andreas; Díaz, Mariana; Rozhon, Wilfried; Poppenberger, Brigitte; Baubec, Tuncay; Pecinka, Ales

2015-01-01

DNA damage repair is an essential cellular mechanism that maintains genome stability. Here, we show that the nonmethylable cytidine analog zebularine induces a DNA damage response in Arabidopsis thaliana, independent of changes in DNA methylation. In contrast to genotoxic agents that induce damage in a cell cycle stage-independent manner, zebularine induces damage specifically during strand synthesis in DNA replication. The signaling of this damage is mediated by additive activity of ATAXIA TELANGIECTASIA MUTATED AND RAD3-RELATED and ATAXIA TELANGIECTASIA MUTATED kinases, which cause postreplicative cell cycle arrest and increased endoreplication. The repair requires a functional STRUCTURAL MAINTENANCE OF CHROMOSOMES5 (SMC5)-SMC6 complex and is accomplished predominantly by synthesis-dependent strand-annealing homologous recombination. Here, we provide insight into the response mechanism for coping with the genotoxic effects of zebularine and identify several components of the zebularine-induced DNA damage repair pathway. PMID:26023162

An Overview of Ultraviolet B Radiation-Induced Skin Cancer Chemoprevention by Silibinin.

PubMed

Kumar, Rahul; Deep, Gagan; Agarwal, Rajesh

2015-06-01

Skin cancer incidences are rising worldwide, and one of the major causative factors is excessive exposure to solar ultraviolet radiation (UVR). Annually, ~5 million skin cancer patients are treated in United States, mostly with nonmelanoma skin cancer (NMSC), which is also frequent in other Western countries. As sunscreens do not provide adequate protection against deleterious effects of UVR, additional and alternative chemoprevention strategies are urgently needed to reduce skin cancer burden. Over the last couple of decades, extensive research has been conducted to understand the molecular basis of skin carcinogenesis, and to identifying novel agents which could be useful in the chemoprevention of skin cancer. In this regard, several natural non-toxic compounds have shown promising efficacy in preventing skin carcinogenesis at initiation, promotion and progression stages, and are considered important in better management of skin cancer. Consistent with this, we and others have studied and established the notable efficacy of natural flavonolignan silibinin against UVB-induced skin carcinogenesis. Extensive pre-clinical animal and cell culture studies report strong anti-inflammatory, anti-oxidant, DNA damage repair, immune-modulatory and anti-proliferative properties of silibinin. Molecular studies have identified that silibinin targets pleotropic signaling pathways including mitogenic, cell cycle, apoptosis, autophagy, p53, NF-κB, etc. Overall, the skin cancer chemopreventive potential of silibinin is well supported by comprehensive mechanistic studies, suggesting its greater use against UV-induced cellular damages and photocarcinogenesis.

An Overview of Ultraviolet B Radiation-Induced Skin Cancer Chemoprevention by Silibinin

PubMed Central

Kumar, Rahul; Deep, Gagan; Agarwal, Rajesh

2015-01-01

Skin cancer incidences are rising worldwide, and one of the major causative factors is excessive exposure to solar ultraviolet radiation (UVR). Annually, ~5 million skin cancer patients are treated in United States, mostly with nonmelanoma skin cancer (NMSC), which is also frequent in other Western countries. As sunscreens do not provide adequate protection against deleterious effects of UVR, additional and alternative chemoprevention strategies are urgently needed to reduce skin cancer burden. Over the last couple of decades, extensive research has been conducted to understand the molecular basis of skin carcinogenesis, and to identifying novel agents which could be useful in the chemoprevention of skin cancer. In this regard, several natural non-toxic compounds have shown promising efficacy in preventing skin carcinogenesis at initiation, promotion and progression stages, and are considered important in better management of skin cancer. Consistent with this, we and others have studied and established the notable efficacy of natural flavonolignan silibinin against UVB-induced skin carcinogenesis. Extensive pre-clinical animal and cell culture studies report strong anti-inflammatory, anti-oxidant, DNA damage repair, immune-modulatory and anti-proliferative properties of silibinin. Molecular studies have identified that silibinin targets pleotropic signaling pathways including mitogenic, cell cycle, apoptosis, autophagy, p53, NF-κB, etc. Overall, the skin cancer chemopreventive potential of silibinin is well supported by comprehensive mechanistic studies, suggesting its greater use against UV-induced cellular damages and photocarcinogenesis. PMID:26097804

House dust mite-induced asthma causes oxidative damage and DNA double-strand breaks in the lungs.

PubMed

Chan, Tze Khee; Loh, Xin Yi; Peh, Hong Yong; Tan, W N Felicia; Tan, W S Daniel; Li, Na; Tay, Ian J J; Wong, W S Fred; Engelward, Bevin P

2016-07-01

Asthma is related to airway inflammation and oxidative stress. High levels of reactive oxygen and nitrogen species can induce cytotoxic DNA damage. Nevertheless, little is known about the possible role of allergen-induced DNA damage and DNA repair as modulators of asthma-associated pathology. We sought to study DNA damage and DNA damage responses induced by house dust mite (HDM) in vivo and in vitro. We measured DNA double-strand breaks (DSBs), DNA repair proteins, and apoptosis in an HDM-induced allergic asthma model and in lung samples from asthmatic patients. To study DNA repair, we treated mice with the DSB repair inhibitor NU7441. To study the direct DNA-damaging effect of HDM on human bronchial epithelial cells, we exposed BEAS-2B cells to HDM and measured DNA damage and reactive oxygen species levels. HDM challenge increased lung levels of oxidative damage to proteins (3-nitrotyrosine), lipids (8-isoprostane), and nucleic acid (8-oxoguanine). Immunohistochemical evidence for HDM-induced DNA DSBs was revealed by increased levels of the DSB marker γ Histone 2AX (H2AX) foci in bronchial epithelium. BEAS-2B cells exposed to HDM showed enhanced DNA damage, as measured by using the comet assay and γH2AX staining. In lung tissue from human patients with asthma, we observed increased levels of DNA repair proteins and apoptosis, as shown by caspase-3 cleavage, caspase-activated DNase levels, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining. Notably, NU7441 augmented DNA damage and cytokine production in the bronchial epithelium and apoptosis in the allergic airway, implicating DSBs as an underlying driver of asthma pathophysiology. This work calls attention to reactive oxygen and nitrogen species and HDM-induced cytotoxicity and to a potential role for DNA repair as a modulator of asthma-associated pathophysiology. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

TDP1 repairs nuclear and mitochondrial DNA damage induced by chain-terminating anticancer and antiviral nucleoside analogs

PubMed Central

Huang, Shar-yin N.; Murai, Junko; Dalla Rosa, Ilaria; Dexheimer, Thomas S.; Naumova, Alena; Gmeiner, William H.; Pommier, Yves

2013-01-01

Chain-terminating nucleoside analogs (CTNAs) that cause stalling or premature termination of DNA replication forks are widely used as anticancer and antiviral drugs. However, it is not well understood how cells repair the DNA damage induced by these drugs. Here, we reveal the importance of tyrosyl–DNA phosphodiesterase 1 (TDP1) in the repair of nuclear and mitochondrial DNA damage induced by CTNAs. On investigating the effects of four CTNAs—acyclovir (ACV), cytarabine (Ara-C), zidovudine (AZT) and zalcitabine (ddC)—we show that TDP1 is capable of removing the covalently linked corresponding CTNAs from DNA 3′-ends. We also show that Tdp1−/− cells are hypersensitive and accumulate more DNA damage when treated with ACV and Ara-C, implicating TDP1 in repairing CTNA-induced DNA damage. As AZT and ddC are known to cause mitochondrial dysfunction, we examined whether TDP1 repairs the mitochondrial DNA damage they induced. We find that AZT and ddC treatment leads to greater depletion of mitochondrial DNA in Tdp1−/− cells. Thus, TDP1 seems to be critical for repairing nuclear and mitochondrial DNA damage caused by CTNAs. PMID:23775789

Myricetin inhibits UVB-induced angiogenesis by regulating PI-3 kinase in vivo

PubMed Central

Jung, Sung Keun; Lee, Ki Won; Byun, Sanguine; Lee, Eun Jung; Kim, Jong-Eun; Bode, Ann M.; Dong, Zigang

2010-01-01

Myricetin is one of the principal phytochemicals in onions, berries and red wine. Previous studies showed that myricetin exhibits potent anticancer and chemopreventive effects. The present study examined the effect of myricetin on ultraviolet (UV) B-induced angiogenesis in an SKH-1 hairless mouse skin tumorigenesis model. Topical treatment with myricetin inhibited repetitive UVB-induced neovascularization in SKH-1 hairless mouse skin. The induction of vascular endothelial growth factor, matrix metalloproteinase (MMP)-9 and MMP-13 expression by chronic UVB irradiation was significantly suppressed by myricetin treatment. Immunohistochemical and western blot analyses revealed that myricetin inhibited UVB-induced hypoxia inducible factor-1α expression in mouse skin. Western blot analysis and kinase assay data revealed that myricetin suppressed UVB-induced phosphatidylinositol-3 (PI-3) kinase activity and subsequently attenuated the UVB-induced phosphorylation of Akt/p70S6K in mouse skin lysates. A pull-down assay revealed the direct binding of PI-3 kinase and myricetin in mouse skin lysates. Our results indicate that myricetin suppresses UVB-induced angiogenesis by regulating PI-3 kinase activity in vivo in mouse skin. PMID:20008033

The green tea modulates large intestinal microbiome and exo/endogenous metabolome altered through chronic UVB-exposure.

PubMed

Jung, Eun Sung; Park, Hye Min; Hyun, Seung Min; Shon, Jong Cheol; Singh, Digar; Liu, Kwang-Hyeon; Whon, Tae Woong; Bae, Jin-Woo; Hwang, Jae Sung; Lee, Choong Hwan

2017-01-01

The attenuating effects of green tea supplements (GTS) against the ultraviolet (UV) radiation induced skin damages are distinguished. However, the concomitant effects of GTS on the large intestinal microbiomes and associated metabolomes are largely unclear. Herein, we performed an integrated microbiome-metabolome analysis to uncover the esoteric links between gut microbiome and exo/endogenous metabolome maneuvered in the large intestine of UVB-exposed mice subjected to dietary GTS. In UVB-exposed mice groups (UVB), class Bacilli and order Bifidobacteriales were observed as discriminant taxa with decreased lysophospholipid levels compared to the unexposed mice groups subjected to normal diet (NOR). Conversely, in GTS fed UVB-exposed mice (U+GTS), the gut-microbiome diversity was greatly enhanced with enrichment in the classes, Clostridia and Erysipelotrichia, as well as genera, Allobaculum and Lachnoclostridium. Additionally, the gut endogenous metabolomes changed with an increase in amino acids, fatty acids, lipids, and bile acids contents coupled with a decrease in nucleobases and carbohydrate levels. The altered metabolomes exhibited high correlations with GTS enriched intestinal microflora. Intriguingly, the various conjugates of green tea catechins viz., sulfated, glucuronided, and methylated ones including their exogenous derivatives were detected from large intestinal contents and liver samples. Hence, we conjecture that the metabolic conversions for the molecular components in GTS strongly influenced the gut micro-environment in UVB-exposed mice groups, ergo modulate their gut-microbiome as well as exo/endogenous metabolomes.

Efficacy of Pre- and Post-Treatment by Topical Formulations Containing Dissolved and Suspended Silybum marianum against UVB-Induced Oxidative Stress in Guinea Pig and on HaCaT Keratinocytes.

PubMed

Fehér, Pálma; Ujhelyi, Zoltán; Váradi, Judit; Fenyvesi, Ferenc; Róka, Eszter; Juhász, Béla; Varga, Balázs; Bombicz, Mariann; Priksz, Dániel; Bácskay, Ildikó; Vecsernyés, Miklós

2016-09-22

Plants with high amounts of antioxidants may be a promising therapy for preventing and curing UV-induced oxidative skin damage. The objective of this study was to verify the efficacy of topical formulations containing dissolved and suspended Silybum marianum extract against UVB-induced oxidative stress in guinea pig and HaCaT keratinocytes. Herbal extract was dissolved in Transcutol HP (TC) and sucrose-esters were incorporated as penetration enhancers in creams. Biocompatibility of compositions was tested on HeLa cells and HaCaT keratinocytes as in vitro models. Transepidermal water loss (TEWL) tests were performed to prove the safety of formulations in vivo. Drug release of different compositions was assessed by Franz diffusion methods. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and lipid peroxidation (MDA) activities were evaluated before and after UVB irradiation in a guinea pig model and HaCaT cells. Heme oxygenase-1 (HO-1) enzyme activity was measured in the epidermis of guinea pigs treated by different creams before and after UVB irradiation. Treatment with compositions containing silymarin powder (SM) dissolved in TC and sucrose stearate SP 50 or SP 70 resulted in increased activities of all reactive oxygen species (ROS) eliminating enzymes in the case of pre- and post-treatment as well. Reduction in the levels of lipid peroxidation end products was also detected after treatment with these two compositions. Post-treatment was more effective as the increase of the activity of antioxidants was higher. Lower HO-1 enzyme levels were measured in the case of pre- and post-treatment groups compared to control groups. Therefore, this study demonstrates the effectiveness of topical formulations containing silymarin in inhibiting UVB irradiation induced oxidative stress of the skin.

DNA-damage response during mitosis induces whole-chromosome missegregation.

PubMed

Bakhoum, Samuel F; Kabeche, Lilian; Murnane, John P; Zaki, Bassem I; Compton, Duane A

2014-11-01

Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here, we show that activation of the DNA-damage response (DDR) during mitosis selectively stabilizes kinetochore-microtubule (k-MT) attachments to chromosomes through Aurora-A and PLK1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or CHK2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, the DDR during mitosis inappropriately stabilizes k-MTs, creating a link between s-CIN and w-CIN. The genome-protective role of the DDR depends on its ability to delay cell division until damaged DNA can be fully repaired. Here, we show that when DNA damage is induced during mitosis, the DDR unexpectedly induces errors in the segregation of entire chromosomes, thus linking structural and numerical chromosomal instabilities. ©2014 American Association for Cancer Research.

Molecular Insights into SIRT1 Protection Against UVB-Induced Skin Fibroblast Senescence by Suppression of Oxidative Stress and p53 Acetylation.

PubMed

Chung, Ki Wung; Choi, Yeon Ja; Park, Min Hi; Jang, Eun Ji; Kim, Dae Hyun; Park, Byung Hyun; Yu, Byung Pal; Chung, Hae Young

2015-08-01

Stresses, such as exposure to ultraviolet radiation and those associated with aging, are known to cause premature cellular senescence that is characterized by growth arrest and morphological and gene expression changes. This study was designed to investigate the protective effect of Sirtuin1 (SIRT1) on the UVB-induced premature senescence. Under in vitro experimental conditions, exposure to a subcytotoxic dose of UVB enhanced human skin fibroblasts senescence, as characterized by increased β-galactosidase activity and increased levels of senescence-associated proteins. However, adenovirus-mediated SIRT1 overexpression significantly protected fibroblasts from UVB-induced cellular deterioration. Exposure to UVB-induced cell senescence was associated with oxidative stress and p38 mitogen-activated protein kinase activation. Molecular analysis demonstrated that deacetylation of Forkhead box O3α (FOXO3α) by SIRT1 changed the transcriptional activity of FOXO3α and increased resistance to the oxidative stress. In addition, SIRT1 suppressed UVB-induced p53 acetylation and its transcriptional activity, which directly affected the cell cycle arrest induced by UVB. Further study demonstrated that SIRT1 activation inhibited cell senescence in the skin of the HR1 hairless mouse exposed to UVB. The study identifies a new role for SIRT1 in the UVB-induced senescence of skin fibroblats and provides a potential target for skin protection through molecuar insights into the mechanisms responsible for UVB-induced photoaging. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Naked eye detection of mutagenic DNA photodimers using gold nanoparticles.

PubMed

Kim, Joong Hyun; Chung, Bong Hyun

2011-01-15

We developed a method to detect mutagenic DNA photodimers by the naked eye using gold nanoparticles. The stability of gold nanoparticles in a high ionic strength solution is maintained by straight ssDNA adsorbed physically on the AuNPs. However, we found that UV-irradiated DNA was less adsorptive onto gold nanoparticles because of a conformational change of UV-irradiated DNA. The accumulated deformation of the DNA structure by multiple-dimer formation triggered aggregation of the gold nanoparticles mixed with the UV-irradiated DNA and thus red to purple color changes of the mixture, which allowed colorimetric detection of the DNA photodimers by the naked eye. No fragmented mass and reactive oxygen species production under the UVB irradiation confirmed that the aggregation of gold nanoparticles was solely attributed to the accumulated deformation of the UV irradiated DNA. The degree of gold nanoparticles-aggregation was dependent on the UVB irradiated time and base compositions of the UV-irradiated oligonucleotides. In addition, we successfully demonstrated how to visually qualify the photosensitizing effect of chemical compounds in parallel within only 10 min by applying this new method. Since our method does not require any chemical or biochemical treatments or special instruments for purifying and qualifying the DNA photolesions, it should provide a feasible tool for the studies of the UV-induced mutagenic or carcinogenic DNA dimers and accelerate screening of a large number of drug candidates. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Characterization of a Human Skin Equivalent Model to Study the Effects of Ultraviolet B Radiation on Keratinocytes

PubMed Central

Van Lonkhuyzen, Derek R.; Dawson, Rebecca A.; Kimlin, Michael G.; Upton, Zee

2014-01-01

The incidences of skin cancers resulting from chronic ultraviolet radiation (UVR) exposure are on the incline in both Australia and globally. Hence, the cellular and molecular pathways that are associated with UVR-induced photocarcinogenesis need to be urgently elucidated, in order to develop more robust preventative and treatment strategies against skin cancers. In vitro investigations into the effects of UVR (in particular, the highly mutagenic UVB wavelength) have, to date, mainly involved the use of cell culture and animal models. However, these models possess biological disparities to native skin, which, to some extent, have limited their relevance to the in vivo situation. To address this, we characterized a three-dimensional, tissue-engineered human skin equivalent (HSE) model (consisting of primary human keratinocytes cultured on a dermal-derived scaffold) as a representation of a more physiologically relevant platform to study keratinocyte responses to UVB. Significantly, we demonstrate that this model retains several important epidermal properties of native skin. Moreover, UVB irradiation of the HSE constructs was shown to induce key markers of photodamage in the HSE keratinocytes, including the formation of cyclobutane pyrimidine dimers, the activation of apoptotic pathways, the accumulation of p53, and the secretion of inflammatory cytokines. Importantly, we also demonstrate that the UVB-exposed HSE constructs retain the capacity for epidermal repair and regeneration after photodamage. Together, our results demonstrate the potential of this skin equivalent model as a tool to study various aspects of the acute responses of human keratinocytes to UVB radiation damage. PMID:24219750

Oral nanotherapeutics: Redox nanoparticles attenuate ultraviolet B radiation-induced skin inflammatory disorders in Kud:Hr- hairless mice.

PubMed

Feliciano, Chitho P; Nagasaki, Yukio

2017-10-01

The active participation of an anti-inflammatory drug in the biological pathways of inflammation is crucial for the achievement of beneficial and therapeutic effects. This study demonstrated the development of redox nanoparticles that can circulate in the blood at significantly high levels, thus increasing their efficacy as an oral treatment against the deleterious effects of reactive oxygen species (ROS) in an in vivo inflammatory skin model. To confirm the blood bioavailability of the nanoparticles, mice were injected with the nanoparticles solution (RNP N ) via oral gavage. Using electron spin resonance and radioactive labeling techniques, the blood circulation of the redox polymer that forms the nanoparticles was confirmed 24 h after oral administration. This contrasted with its low molecular weight counterpart (NH 2 -TEMPO), which peaked 15 min post injection and was found to be cleared rapidly within minutes after the peak. We then tested its efficacy in the inflammatory skin model. Kud:Hr-hairless mice were irradiated with UVB (302 nm) to induce skin damage and inflammation. Throughout the entire period of UVB irradiation, RNP N was administered to mice by free drinking. NH 2 -TEMPO was used as the control. The results showed that oral supplementation of RNP N significantly improved the therapeutic effects of the core nitroxide radical compared with its low molecular weight counterpart. Furthermore, RNP N significantly reduced UVB-induced skin aging, epidermal thickening, edema, erythema, skin lesions, and various pathological skin inflammatory disorders in vivo. From the obtained data, we concluded that the use of long-circulating redox nanoparticles (RNP N ) provided an effective treatment against the damaging effects of excessive ROS in the body. Copyright © 2017 Elsevier Ltd. All rights reserved.

Extract from Periostracum cicadae Inhibits Oxidative Stress and Inflammation Induced by Ultraviolet B Irradiation on HaCaT Keratinocytes

PubMed Central

Tsen, Jen-Horng; Yen, Hsuan; Yang, Ting-Ya

2017-01-01

Periostracum cicadae is widely used for the treatment of skin diseases such as eczema, pruritus, and itching. The current study sought to evaluate the effect of P. cicadae extract on ultraviolet B (UVB) irradiation and identify the mechanisms involved. Photodamage-protective activity of P. cicadae extracts against oxidative challenge was screened using HaCaT keratinocytes. P. cicadae extracts did not affect cell viability but decreased reactive oxygen species (ROS) production. The extract attenuates the expression of interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2), and MMP-9 in UVB-treated HaCaT cells. Also, P. cicadae abrogated UVB-induced activation of NF-κB, p53, and activator protein-1 (AP-1). The downmodulation of IL-6 by P. cicadae was inhibited by the p38 inhibitor (SB203580) or JNK inhibitor (SP600125). Moreover, the extract attenuated the expression of NF-κB and induced thrombomodulin in keratinocytes and thereby effectively downregulated inflammatory responses in the skin. The nuclear accumulation and expression of NF-E2-related factor (Nrf2) were increased by P. cicadae treatment. Furthermore, treatment with P. cicadae remarkably ameliorated the skin's structural damage induced by irradiation. This study demonstrates that P. cicadae may protect skin cells against oxidative insult by modulating ROS concentration, IL-6, MMPs generation, antioxidant enzymes activity, and cell signaling pathways. PMID:28465707

Detection of in vivo DNA damage induced by ethanol in multiple organs of pregnant mice using the alkaline single cell gel electrophoresis (Comet) assay.

PubMed

Kido, Ryoko; Sato, Itaru; Tsuda, Shuji

2006-01-01

Ethanol is principal ingredient of alcohol beverage, but considered as human carcinogen, and has neurotoxicity. Alcohol consumption during pregnancy often causes fetal alcohol syndrome. The DNA damage is one of the important factors in carcinogenicity or teratogenicity. To detect the DNA damage induced by ethanol, we used an in vivo alkaline single cell gel electrophoresis (Comet) assay in pregnant mice organs and embryos. Pregnant ICR mice on Day 7 of gestation were treated with 2, 4 or 8 g/kg ethanol, and maternal organs/tissues and embryos were subjected to the Comet assay at 4, 8, 12 and 24 hr after ethanol treatment. Four and 8 g/kg ethanol induced DNA damage in brain, lung and embryos at 4 or 8 hr after the treatment. Two g/kg ethanol did not cause any DNA damage, and 8 g/kg ethanol only increased the duration of DNA damage without distinct increase in the degree of the damage. No significant DNA damage was observed in the liver. To detect the effect of acetaldehyde, disulfiram, acetaldehyde dehydrogenase inhibitor, was administered before 4 g/kg ethanol treatment. No significant increase of DNA damage was observed in the disulfiram pre-treated group. These data indicate that ethanol induces DNA damage, which might be related to ethanol toxicity. Since pre-treatment of disulfiram did not increase DNA damage, DNA damage observed in this study might not be the effect of acetaldehyde.

Protective mechanisms and acclimation to solar ultraviolet-B radiation in Oenothera stricta

NASA Technical Reports Server (NTRS)

Robberecht, R.; Caldwell, M. M.

1981-01-01

Plant adaptations ameliorating or repairing the damaging effects of ultraviolet-B (UV-B) radiation on plant tissue were investigated. The degree of phenotype plasticity in UV protective mechanisms and acclimation in relation to the natural solar UV-B radiation flux and in an enhanced UV-B irradiance environment was also examined. Mechanisms by which plants avoid radiation, adaptations altering the path of radiation incident on the leaf, and repair processes were considered. Attenuation of UV-B by tissues, UV-B irradiation into the leaf, and the effects of UV-B on photosynthesis were investigated.

Ultraviolet B preconditioning enhances the hair growth-promoting effects of adipose-derived stem cells via generation of reactive oxygen species.

PubMed

Jeong, Yun-Mi; Sung, Young Kwan; Kim, Wang-Kyun; Kim, Ji Hye; Kwack, Mi Hee; Yoon, Insoo; Kim, Dae-Duk; Sung, Jong-Hyuk

2013-01-01

Hypoxia induces the survival and regenerative potential of adipose-derived stem cells (ASCs), but there are tremendous needs to find alternative methods for ASC preconditioning. Therefore, this work investigated: (1) the ability of low-dose ultraviolet B (UVB) radiation to stimulate the survival, migration, and tube-forming activity of ASCs in vitro; (2) the ability of UVB preconditioning to enhance the hair growth-promoting capacity of ASCs in vivo; and (3) the mechanism of action for ASC stimulation by UVB. Although high-dose UVB decreased the proliferation of ASCs, low-dose (10 or 20 mJ/cm(2)) treatment increased their survival, migration, and tube-forming activity. In addition, low-dose UVB upregulated the expression of ASC-derived growth factors, and a culture medium conditioned by UVB-irradiated ASCs increased the proliferation of dermal papilla and outer root sheet cells. Notably, injection of UVB-preconditioned ASCs into C(3)H/HeN mice significantly induced the telogen-to-anagen transition and increased new hair weight in vivo. UVB treatment significantly increased the generation of reactive oxygen species (ROS) in cultured ASCs, and inhibition of ROS generation by diphenyleneiodonium chloride (DPI) significantly attenuated UVB-induced ASC stimulation. Furthermore, NADPH oxidase 4 (Nox4) expression was induced in ASCs by UVB irradiation, and Nox4 silencing by small interfering RNA, like DPI, significantly reduced UVB-induced ROS generation. These results suggest that the primary involvement of ROS generation in UVB-mediated ASC stimulation occurs via the Nox4 enzyme. This is the first indication that a low dose of UVB radiation and/or the control of ROS generation could potentially be incorporated into a novel ASC preconditioning method for hair regeneration.

Protective effect of Fucoxanthin against UVB-induced skin photoaging in hairless mice.

PubMed

Urikura, Itaru; Sugawara, Tatsuya; Hirata, Takashi

2011-01-01

Fucoxanthin, a major carotenoid in brown algae, has various beneficial effects. In this study, we evaluated the effect of topical fucoxanthin on UVB-induced skin photoaging in hairless mice. The dorsal skins were treated topically with a 0.001% fucoxanthin solution 2 h each time before UVB irradiation (5 times a week) for 10 weeks. The formation of wrinkles in UVB-irradiated skin treated with vehicle alone significantly increased, as compared with the non-irradiated control. Treatment with fucoxanthin tended to suppress UVB-induced wrinkle formation, but there was no significant difference between wrinkle formation in the control group and the fucoxanthin treatment group. However, topical treatment with fucoxanthin significantly lessened UVB-induced epidermal hypertrophy, VEGF, and MMP-13 expression in the epidermis and thiobarbituric acid reactive substances (TBARS) in the skin. These results indicate that topical treatment with fucoxanthin prevents skin photoaging in UVB-irradiated hairless mice, possibly via antioxidant and antiangiogenic effects.

Identification of microRNA-mRNA functional interactions in UVB-induced senescence of human diploid fibroblasts

PubMed Central

2013-01-01

Background Cellular senescence can be induced by a variety of extrinsic stimuli, and sustained exposure to sunlight is a key factor in photoaging of the skin. Accordingly, irradiation of skin fibroblasts by UVB light triggers cellular senescence, which is thought to contribute to extrinsic skin aging, although molecular mechanisms are incompletely understood. Here, we addressed molecular mechanisms underlying UVB induced senescence of human diploid fibroblasts. Results We observed a parallel activation of the p53/p21WAF1 and p16INK4a/pRb pathways. Using genome-wide transcriptome analysis, we identified a transcriptional signature of UVB-induced senescence that was conserved in three independent strains of human diploid fibroblasts (HDF) from skin. In parallel, a comprehensive screen for microRNAs regulated during UVB-induced senescence was performed which identified five microRNAs that are significantly regulated during the process. Bioinformatic analysis of miRNA-mRNA networks was performed to identify new functional mRNA targets with high confidence for miR-15a, miR-20a, miR-20b, miR-93, and miR-101. Already known targets of these miRNAs were identified in each case, validating the approach. Several new targets were identified for all of these miRNAs, with the potential to provide new insight in the process of UVB-induced senescence at a genome-wide level. Subsequent analysis was focused on miR-101 and its putative target gene Ezh2. We confirmed that Ezh2 is regulated by miR-101 in human fibroblasts, and found that both overexpression of miR-101 and downregulation of Ezh2 independently induce senescence in the absence of UVB irradiation. However, the downregulation of miR-101 was not sufficient to block the phenotype of UVB-induced senescence, suggesting that other UVB-induced processes induce the senescence response in a pathway redundant with upregulation of miR-101. Conclusion We performed a comprehensive screen for UVB-regulated microRNAs in human diploid fibroblasts, and identified a network of miRNA-mRNA interactions mediating UVB-induced senescence. In addition, miR-101 and Ezh2 were identified as key players in UVB-induced senescence of HDF. PMID:23557329

The imprints of the high light and UV-B stresses in Oryza sativa L. 'Kanchana' seedlings are differentially modulated.

PubMed

Faseela, Parammal; Puthur, Jos T

2018-01-01

High light and ultraviolet-B radiation (UV-B) are generally considered to have negative impact on photosynthesis and plant growth. The present study evaluates the tolerance potential of three cultivars of Oryza sativa L. (Kanchana, Mattatriveni and Harsha) seedlings towards high light and UV-B stress on the basis of photosynthetic pigment degradation, chlorophyll a fluorescence parameters and rate of lipid peroxidation, expressed by malondialdehyde content. Surprisingly, it was revealed that Kanchana was the most sensitive cultivar towards high light and at the same time it was the most tolerant cultivar towards UV-B stress. This contrasting feature of Kanchana towards high light and UV-B tolerance was further studied by analyzing photosystem (PS) I and II activity, mitochondrial activity, chlorophyll a fluorescence transient, enzymatic and non-enzymatic antioxidant defense system. Due to the occurrence of more PS I and PSII damages, the inhibition of photochemical efficiency and emission of dissipated energy as heat or fluorescence per PSII reaction center was higher upon high light exposure than UV-B treatments in rice seedlings of Kanchana. The mitochondrial activity was also found to be drastically altered upon high light as compared to UV-B treatments. The UV-B induced accumulation of non-enzymatic antioxidants (proline, total phenolics, sugar and ascorbate) and enzymatic antioxidants (ascorbate peroxidase, guaiacol peroxidase, superoxide dismutase and glutathione reductase) in rice seedlings than those subjected to high light exposure afforded more efficient protection against UV-B radiation in rice seedlings. Our results proved that high tolerance of Kanchana towards UV-B than high light treatments, correlated linearly with the protected photosynthetic and mitochondrial machinery which was provided by upregulation of antioxidants particularly by total phenolics, ascorbate and ascorbate peroxidase in rice seedlings. Data presented in this study conclusively proved that rice cultivar Kanchana respond to different environmental signals independently and tolerance mechanisms to individual stress factors was also varied. Copyright © 2017 Elsevier B.V. All rights reserved.

Impacts of long-term enhanced UV-B radiation on bryophytes in two sub-Arctic heathland sites of contrasting water availability.

PubMed

Arróniz-Crespo, M; Gwynn-Jones, D; Callaghan, T V; Núñez-Olivera, E; Martínez-Abaigar, J; Horton, P; Phoenix, G K

2011-09-01

Anthropogenic depletion of stratospheric ozone in Arctic latitudes has resulted in an increase of ultraviolet-B radiation (UV-B) reaching the biosphere. UV-B exposure is known to reduce above-ground biomass and plant height, to increase DNA damage and cause accumulation of UV-absorbing compounds in polar plants. However, many studies on Arctic mosses tended to be inconclusive. The importance of different water availability in influencing UV-B impacts on lower plants in the Arctic has been poorly explored and might partially explain the observed wide variation of responses, given the importance of water in controlling bryophyte physiology. This study aimed to assess the long-term responses of three common sub-Arctic bryophytes to enhanced UV-B radiation (+UV-B) and to elucidate the influence of water supply on those responses. Responses of three sub-Arctic bryophytes (the mosses Hylocomium splendens and Polytrichum commune and the liverwort Barbilophozia lycopodioides) to +UV-B for 15 and 13 years were studied in two field experiments using lamps for UV-B enhancement with identical design and located in neighbouring areas with contrasting water availability (naturally mesic and drier sites). Responses evaluated included bryophyte abundance, growth, sporophyte production and sclerophylly; cellular protection by accumulation of UV-absorbing compounds, β-carotene, xanthophylls and development of non-photochemical quenching (NPQ); and impacts on photosynthesis performance by maximum quantum yield (F(v) /F(m)) and electron transport rate (ETR) through photosystem II (PSII) and chlorophyll concentrations. Responses were species specific: H. splendens responded most to +UV-B, with reduction in both annual growth (-22 %) and sporophyte production (-44 %), together with increased β-carotene, violaxanthin, total chlorophyll and NPQ, and decreased zeaxanthin and de-epoxidation of the xanthophyll cycle pool (DES). Barbilophozia lycopodioides responded less to +UV-B, showing increased β-carotene and sclerophylly and decreased UV-absorbing compounds. Polytrichum commune only showed small morphogenetic changes. No effect of UV-B on bryophyte cover was observed. Water availability had profound effects on bryophyte ecophysiology, and plants showed, in general, lower growth and ETR, together with a higher photoprotection in the drier site. Water availability also influenced bryophyte responses to +UV-B and, in particular, responses were less detectable in the drier site. Impacts of UV-B exposure on Arctic bryophytes were significant, in contrast to modest or absent UV-B effects measured in previous studies. The impacts were more easily detectable in species with high plasticity such as H. splendens and less obvious, or more subtle, under drier conditions. Species biology and water supply greatly influences the impact of UV-B on at least some Arctic bryophytes and could contribute to the wide variation of responses observed previously.

Mechanisms of free radical-induced damage to DNA.

PubMed

Dizdaroglu, Miral; Jaruga, Pawel

2012-04-01

Endogenous and exogenous sources cause free radical-induced DNA damage in living organisms by a variety of mechanisms. The highly reactive hydroxyl radical reacts with the heterocyclic DNA bases and the sugar moiety near or at diffusion-controlled rates. Hydrated electron and H atom also add to the heterocyclic bases. These reactions lead to adduct radicals, further reactions of which yield numerous products. These include DNA base and sugar products, single- and double-strand breaks, 8,5'-cyclopurine-2'-deoxynucleosides, tandem lesions, clustered sites and DNA-protein cross-links. Reaction conditions and the presence or absence of oxygen profoundly affect the types and yields of the products. There is mounting evidence for an important role of free radical-induced DNA damage in the etiology of numerous diseases including cancer. Further understanding of mechanisms of free radical-induced DNA damage, and cellular repair and biological consequences of DNA damage products will be of outmost importance for disease prevention and treatment.

Attenuation of UV-B exposure-induced inflammation by abalone hypobranchial gland and gill extracts.

PubMed

Kuanpradit, Chitraporn; Jaisin, Yamaratee; Jungudomjaroen, Sumon; Akter Mitu, Shahida; Puttikamonkul, Srisombat; Sobhon, Prasert; Cummins, Scott F

2017-05-01

Exposure to solar ultraviolet B (UV-B) is a known causative factor for many skin complications such as wrinkles, black spots, shedding and inflammation. Within the wavelengths 280‑320 nm, UV-B can penetrate to the epidermal level. This investigation aimed to test whether extracts from the tropical abalone [Haliotis asinina (H. asinina)] mucus-secreting tissues, the hypobranchial gland (HBG) and gills, were able to attenuate the inflammatory process, using the human keratinocyte HaCaT cell line. Cytotoxicity of abalone tissue extracts was determined using an AlamarBlue viability assay. Results showed that HaCaT cells could survive when incubated in crude HBG and gill extracts at concentrations between <11.8 and <16.9 µg/ml, respectively. Subsequently, cell viability was compared between cultured HaCaT cells exposed to serial doses of UV-B from 1 to 11 (x10) mJ/cm2 and containing 4 different concentrations of abalone extract from both the HBG and gill (0, 0.1, 2.5, 5 µg/ml). A significant increase in cell viability was observed (P<0.001) following treatment with 2.5 and 5 µg/ml extract. Without extract, cell viability was significantly reduced upon exposure to UV-B at 4 mJ/cm2. Three morphological changes were observed in HaCaT cells following UV-B exposure, including i) condensation of cytoplasm; ii) shrunken cells and plasma membrane bubbling; and iii) condensation of chromatin material. A calcein AM‑propidium iodide live‑dead assay showed that cells could survive cytoplasmic condensation, yet cell death occurred when damage also included membrane bubbling and chromatin changes. Western blot analysis of HaCaT cell COX‑2, p38, phospho‑p38, SPK/JNK and phospho‑SPK/JNK following exposure to >2.5 µg/ml extract showed a significant decrease in intensity for COX‑2, phospho‑p38 and phospho‑SPK/JNK. The present study demonstrated that abalone extracts from the HGB and gill can attenuate inflammatory proteins triggered by UV-B. Hence, the contents of abalone extract, including cellmetabolites and peptides, may provide new agents for skin anti‑inflammation, preventing damage due to UV-B.

Attenuation of UV-B exposure-induced inflammation by abalone hypobranchial gland and gill extracts

PubMed Central

Kuanpradit, Chitraporn; Jaisin, Yamaratee; Jungudomjaroen, Sumon; Mitu, Shahida Akter; Puttikamonkul, Srisombat; Sobhon, Prasert; Cummins, Scott F.

2017-01-01

Exposure to solar ultraviolet B (UV-B) is a known causative factor for many skin complications such as wrinkles, black spots, shedding and inflammation. Within the wavelengths 280–320 nm, UV-B can penetrate to the epidermal level. This investigation aimed to test whether extracts from the tropical abalone [Haliotis asinina (H. asinina)] mucus-secreting tissues, the hypobranchial gland (HBG) and gills, were able to attenuate the inflammatory process, using the human keratinocyte HaCaT cell line. Cytotoxicity of abalone tissue extracts was determined using an AlamarBlue viability assay. Results showed that HaCaT cells could survive when incubated in crude HBG and gill extracts at concentrations between <11.8 and <16.9 μg/ml, respectively. Subsequently, cell viability was compared between cultured HaCaT cells exposed to serial doses of UV-B from 1 to 11 (x10) mJ/cm2 and containing 4 different concentrations of abalone extract from both the HBG and gill (0, 0.1, 2.5, 5 μg/ml). A significant increase in cell viability was observed (P<0.001) following treatment with 2.5 and 5 μg/ml extract. Without extract, cell viability was significantly reduced upon exposure to UV-B at 4 mJ/cm2. Three morphological changes were observed in HaCaT cells following UV-B exposure, including i) condensation of cytoplasm; ii) shrunken cells and plasma membrane bubbling; and iii) condensation of chromatin material. A calcein AM-propidium iodide live-dead assay showed that cells could survive cytoplasmic condensation, yet cell death occurred when damage also included membrane bubbling and chromatin changes. Western blot analysis of HaCaT cell COX-2, p38, phospho-p38, SPK/JNK and phospho-SPK/JNK following exposure to >2.5 μg/ml extract showed a significant decrease in intensity for COX-2, phospho-p38 and phospho-SPK/JNK. The present study demonstrated that abalone extracts from the HGB and gill can attenuate inflammatory proteins triggered by UV-B. Hence, the contents of abalone extract, including cellmetabolites and peptides, may provide new agents for skin anti-inflammation, preventing damage due to UV-B. PMID:28358420

DNA Replication Arrest and DNA Damage Responses Induced by Alkylating Minor Groove Binders

DTIC Science & Technology

2001-05-01

We are interested in the molecular mechanisms involved in DNA replication arrest by the S phase DNA damage checkpoints. Using in vitro simian virus...40 DNA replication assays, we have found three factors that directly contribute to DNA damage-induced DNA replication arrest: Replication Protein A...trans-acting inhibitors. RPA is the major eukaryotic single-stranded DNA binding protein required for DNA replication , repair and recombination. Upon DNA

Current knowledge in Polypodium leucotomos effect on skin protection.

PubMed

Palomino, Olga María

2015-04-01

This article provides an overview of pharmacology, toxicity, pharmacokinetics and clinical data of Polypodium leucotomos L. (PL). PL aerial part has proven to exert antioxidant, photoprotective and immunomodulatory activities; its mechanism of action is complex and includes several activities: (1) PL diminishes the production of reactive oxygen and nitrogen species (ROS, RNS); (2) PL inhibits the photoisomerization of trans-urocanic acid (t-UCA); (3) PL inhibits apoptosis induced by ultraviolet radiation; (4) PL prevents damage to genetic material and (5) PL enhances DNA repair. PL is not mutagenic and does not induce acute or chronic toxicity. Its biological effects have been proved in cell cultures, animal models, murine models and in human beings. Photoprotective activity has been assessed in healthy volunteers as well as in patients suffering from several cutaneous diseases such as vitiligo, psoriasis, idiopathic photodermatosis or melasma. PL results to be an efficient treatment especially for sensitive cutaneous phototypes and adds extra protection when ultraviolet radiation (UVR) exposure cannot be avoided, such as wide or narrow band UVB phototherapy or treatment with psoralens plus UVA exposure radiation.

Induction and prevention of micronuclei and chromosomal aberrations in cultured human lymphocytes exposed to the light of halogen tungsten lamps.

PubMed

D'Agostini, F; Caimo, A; De Filippi, S; De Flora, S

1999-07-01

Previous studies have shown that the light emitted by halogen tungsten lamps contains UV radiation in the UV-A, UV-B and UV-C regions, induces mutations and irreparable DNA damage in bacteria, enhances the frequency of micronuclei in cultured human lymphocytes and is potently carcinogenic to the skin of hairless mice. The present study showed that the light emitted by an uncovered, traditional halogen lamp induces a significant, dose-related and time-related increase not only in micronuclei but also in chromosome-type aberrations, such as breaks, and even more in chromatid-type aberrations, such as isochromatid breaks, exchanges and isochromatid/chromatid interchanges, all including gaps or not, in cultured human lymphocytes. All these genotoxic effects were completely prevented by shielding the same lamp with a silica glass cover, blocking UV radiation. A new model of halogen lamp, having the quartz bulb treated in order to reduce the output of UV radiation, was considerably less genotoxic than the uncovered halogen lamp, yet induction of chromosomal alterations was observed at high illuminance levels.

Gamma-Ray Bursts and the Earth: Exploration of Atmospheric, Biological, Climatic, and Biogeochemical Effects

NASA Astrophysics Data System (ADS)

Thomas, Brian C.; Melott, Adrian L.; Jackman, Charles H.; Laird, Claude M.; Medvedev, Mikhail V.; Stolarski, Richard S.; Gehrels, Neil; Cannizzo, John K.; Hogan, Daniel P.; Ejzak, Larissa M.

2005-11-01

Gamma-ray bursts (GRBs) are likely to have made a number of significant impacts on the Earth during the last billion years. The gamma radiation from a burst within a few kiloparsecs would quickly deplete much of the Earth's protective ozone layer, allowing an increase in solar UVB radiation reaching the surface. This radiation is harmful to life, damaging DNA and causing sunburn. In addition, NO2 produced in the atmosphere would cause a decrease in visible sunlight reaching the surface and could cause global cooling. Nitric acid rain could stress portions of the biosphere, but the increased nitrate deposition could be helpful to land plants. We have used a two-dimensional atmospheric model to investigate the effects on the Earth's atmosphere of GRBs delivering a range of fluences, at various latitudes, at the equinoxes and solstices, and at different times of day. We have estimated DNA damage levels caused by increased solar UVB radiation, reduction in solar visible light due to NO2 opacity, and deposition of nitrates through rainout of HNO3. For the ``typical'' nearest burst in the last billion years, we find globally averaged ozone depletion up to 38%. Localized depletion reaches as much as 74%. Significant global depletion (at least 10%) persists up to about 7 yr after the burst. Our results depend strongly on time of year and latitude over which the burst occurs. The impact scales with the total fluence of the GRB at the Earth but is insensitive to the time of day of the burst and its duration (1-1000 s). We find DNA damage of up to 16 times the normal annual global average, well above lethal levels for simple life forms such as phytoplankton. The greatest damage occurs at mid- to low latitudes. We find reductions in visible sunlight of a few percent, primarily in the polar regions. Nitrate deposition similar to or slightly greater than that currently caused by lightning is also observed, lasting several years. We discuss how these results support the hypothesis that the Late Ordovician mass extinction may have been initiated by a GRB.

Photo-damage protective effect of two facial products, containing a unique complex of Dead Sea minerals and Himalayan actives.

PubMed

Wineman, Eitan; Portugal-Cohen, Meital; Soroka, Yoram; Cohen, Dror; Schlippe, Gerrit; Voss, Werner; Brenner, Sarah; Milner, Yoram; Hai, Noam; Ma'or, Zeevi

2012-09-01

Skin appearance is badly affected when exposed to solar UV rays, which encourage physiological and structural cutaneous alterations that eventually lead to skin photo-damage. To test the capability of two facial preparations, extreme day cream (EXD) and extreme night treatment (EXN), containing a unique complex of Dead Sea water and three Himalayan extracts, to antagonize biological effects induced by photo-damage. Pieces of organ cultures of human skin were used as a model to assess the biological effects of UVB irradiation and the protective effect of topical application of two Extreme preparations. Skin pieces were analyzed for mitochondrial activity by MTT assay, for apoptosis by caspase 3 assay, and for cytokine secretion by solid phase ELISA. Human subjects were tested to evaluate the effect of Extreme preparations on skin wrinkle depth using PRIMOS and skin hydration by a corneometer. UVB irradiation induced cell apoptosis in the epidermis of skin organ cultures and increased their pro-inflammatory cytokine, tumor necrosis α (TNFα) secretion. Topical applications of both preparations significantly attenuated all these effects. Furthermore, in human subjects, a reduction in wrinkle depth and an elevation in the intense skin moisture were observed. The observations clearly show that EXD and EXN preparations have protective anti-apoptotic and anti-inflammatory properties that can attenuate biological effects of skin photo-damage. Topical application of the preparations improves skin appearance by reducing its wrinkles depth and increasing its moisturizing impact. © 2012 Wiley Periodicals, Inc.

Accumulation of flavonoids and related compounds in birch induced by UV-B irradiance.

PubMed

Lavola, Anu

1998-01-01

A growth chamber experiment was conducted to examine the effects of UV-B exposure (4.9 kJ m(-2) day(-1) of biologically effective UV-B, 280-320 nm) on shoot growth and secondary metabolite production in Betula pendula (Roth) and B. resinifera (Britt.) seedlings originating from environments in Finland, Germany and Alaska differing in solar UV-B radiation and climate. Neither shoot growth nor the composition of secondary metabolites was affected by UV-B irradiance, but the treatment induced significant changes in the amounts of individual secondary metabolites in leaves. Leaves of seedlings exposed to UV-B radiation contained higher concentrations of several flavonoids, condensed tannins and some hydroxycinnamic acids than leaves of control seedlings that received no UV-B radiation. At the population level, there was considerable variation in secondary metabolite responses to UV-B radiation: among populations, the induced response was most prominent in Alaskan populations, which were adapted to the lowest ambient UV-B radiation environment. I conclude that solar UV-B radiation plays an important role in the formation of secondary chemical characteristics in birch trees.

Chemical determination of free radical-induced damage to DNA.

PubMed

Dizdaroglu, M

1991-01-01

Free radical-induced damage to DNA in vivo can result in deleterious biological consequences such as the initiation and promotion of cancer. Chemical characterization and quantitation of such DNA damage is essential for an understanding of its biological consequences and cellular repair. Methodologies incorporating the technique of gas chromatography/mass spectrometry (GC/MS) have been developed in recent years for measurement of free radical-induced DNA damage. The use of GC/MS with selected-ion monitoring (SIM) facilitates unequivocal identification and quantitation of a large number of products of all four DNA bases produced in DNA by reactions with hydroxyl radical, hydrated electron, and H atom. Hydroxyl radical-induced DNA-protein cross-links in mammalian chromatin, and products of the sugar moiety in DNA are also unequivocally identified and quantitated. The sensitivity and selectivity of the GC/MS-SIM technique enables the measurement of DNA base products even in isolated mammalian chromatin without the necessity of first isolating DNA, and despite the presence of histones. Recent results reviewed in this article demonstrate the usefulness of the GC/MS technique for chemical determination of free radical-induced DNA damage in DNA as well as in mammalian chromatin under a vast variety of conditions of free radical production.

Non-homologous end joining pathway is the major route of protection against 4β-hydroxywithanolide E-induced DNA damage in MCF-7 cells.

PubMed

You, B-J; Wu, Y-C; Lee, C-L; Lee, H-Z

2014-03-01

4β-Hydroxywithanolide E is a bioactive withanolide extracted from Physalis peruviana. 4β-Hydroxywithanolide E caused reactive oxygen species production and cell apoptosis in human breast cancer MCF-7 cells. We further found that 4β-hydroxywithanolide E induced DNA damage and regulated the DNA damage signaling in MCF-7 cells. The DNA damage sensors and repair proteins act promptly to remove DNA lesions by 4β-hydroxywithanolide E. The ataxia-telangiectasia mutated protein (ATM)-dependent DNA damage signaling pathway is involved in 4β-hydroxywithanolide E-induced apoptosis of MCF-7 cells. Non-homologous end joining pathway, but not homologous recombination, is the major route of protection of MCF-7 cells against 4β-hydroxywithanolide E-induced DNA damage. 4β-Hydroxywithanolide E had no significant impact on the base excision repair pathway. In this study, we examined the 4β-hydroxywithanolide E-induced DNA damage as a research tool in project investigating the DNA repair signaling in breast cancer cells. We also suggest that 4β-hydroxywithanolide E assert its anti-tumor activity in carcinogenic progression and develop into a dietary chemopreventive agent. Copyright © 2014 Elsevier Ltd. All rights reserved.

Organic honey supplementation reverses pesticide-induced genotoxicity by modulating DNA damage response.

PubMed

Alleva, Renata; Manzella, Nicola; Gaetani, Simona; Ciarapica, Veronica; Bracci, Massimo; Caboni, Maria Fiorenza; Pasini, Federica; Monaco, Federica; Amati, Monica; Borghi, Battista; Tomasetti, Marco

2016-10-01

Glyphosate (GLY) and organophosphorus insecticides such as chlorpyrifos (CPF) may cause DNA damage and cancer in exposed individuals through mitochondrial dysfunction. Polyphenols ubiquitously present in fruits and vegetables, have been viewed as antioxidant molecules, but also influence mitochondrial homeostasis. Here, honey containing polyphenol compounds was evaluated for its potential protective effect on pesticide-induced genotoxicity. Honey extracts from four floral organic sources were evaluated for their polyphenol content, antioxidant activity, and potential protective effects on pesticide-related mitochondrial destabilization, reactive oxygen and nitrogen species formation, and DNA damage response in human bronchial epithelial and neuronal cells. The protective effect of honey was, then evaluated in a residential population chronically exposed to pesticides. The four honey types showed a different polyphenol profile associated with a different antioxidant power. The pesticide-induced mitochondrial dysfunction parallels ROS formation from mitochondria (mtROS) and consequent DNA damage. Honey extracts efficiently inhibited pesticide-induced mtROS formation, and reduced DNA damage by upregulation of DNA repair through NFR2. Honey supplementation enhanced DNA repair activity in a residential population chronically exposed to pesticides, which resulted in a marked reduction of pesticide-induced DNA lesions. These results provide new insight regarding the effect of honey containing polyphenols on pesticide-induced DNA damage response. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microbial pathogens trigger host DNA double-strand breaks whose abundance is reduced by plant defense responses.

PubMed

Song, Junqi; Bent, Andrew F

2014-04-01

Immune responses and DNA damage repair are two fundamental processes that have been characterized extensively, but the links between them remain largely unknown. We report that multiple bacterial, fungal and oomycete plant pathogen species induce double-strand breaks (DSBs) in host plant DNA. DNA damage detected by histone γ-H2AX abundance or DNA comet assays arose hours before the disease-associated necrosis caused by virulent Pseudomonas syringae pv. tomato. Necrosis-inducing paraquat did not cause detectable DSBs at similar stages after application. Non-pathogenic E. coli and Pseudomonas fluorescens bacteria also did not induce DSBs. Elevation of reactive oxygen species (ROS) is common during plant immune responses, ROS are known DNA damaging agents, and the infection-induced host ROS burst has been implicated as a cause of host DNA damage in animal studies. However, we found that DSB formation in Arabidopsis in response to P. syringae infection still occurs in the absence of the infection-associated oxidative burst mediated by AtrbohD and AtrbohF. Plant MAMP receptor stimulation or application of defense-activating salicylic acid or jasmonic acid failed to induce a detectable level of DSBs in the absence of introduced pathogens, further suggesting that pathogen activities beyond host defense activation cause infection-induced DNA damage. The abundance of infection-induced DSBs was reduced by salicylic acid and NPR1-mediated defenses, and by certain R gene-mediated defenses. Infection-induced formation of γ-H2AX still occurred in Arabidopsis atr/atm double mutants, suggesting the presence of an alternative mediator of pathogen-induced H2AX phosphorylation. In summary, pathogenic microorganisms can induce plant DNA damage. Plant defense mechanisms help to suppress rather than promote this damage, thereby contributing to the maintenance of genome integrity in somatic tissues.

Myricetin suppresses UVB-induced wrinkle formation and MMP-9 expression by inhibiting Raf

PubMed Central

Jung, Sung Keun; Lee, Ki Won; Kim, Ho Young; Oh, Mi Hyun; Byun, Sanguine; Lim, Sung Hwan; Heo, Yong-Seok; Kang, Nam Joo; Bode, Ann M.; Dong, Zigang; Lee, Hyong Joo

2010-01-01

Chronic exposure to solar ultraviolet (UV) light causes skin photoaging. Many studies have shown that naturally occurring phytochemicals have anti-photoaging effects, but their direct target molecule(s) and mechanism(s) remain unclear. We found that myricetin, a major flavonoid in berries and red wine, inhibited wrinkle formation in mouse skin induced by chronic UVB irradiation (0.18 J/cm2, 3 days/wk for 15 wk). Myricetin treatment reduced UVB-induced epidermal thickening of mouse skin and also suppressed UVB-induced matrix metalloproteinase-9 (MMP-9) protein expression and enzyme activity. Myricetin appeared to exert its anti-aging effects by suppressing UVB-induced Raf kinase activity and subsequent attenuation of UVB-induced phosphorylation of MEK and ERK in mouse skin. In vitro and in vivo pull-down assays revealed that myricetin bound with Raf in an ATP-noncompetitive manner. Overall, these results indicate that myricetin exerts potent anti-photoaging activity by regulating MMP-9 expression through the suppression of Raf kinase activity. PMID:20093107

Metabolic responses induced by DNA damage and poly (ADP-ribose) polymerase (PARP) inhibition in MCF-7 cells

PubMed Central

Bhute, Vijesh J.; Palecek, Sean P.

2015-01-01

Genomic instability is one of the hallmarks of cancer. Several chemotherapeutic drugs and radiotherapy induce DNA damage to prevent cancer cell replication. Cells in turn activate different DNA damage response (DDR) pathways to either repair the damage or induce cell death. These DDR pathways also elicit metabolic alterations which can play a significant role in the proper functioning of the cells. The understanding of these metabolic effects resulting from different types of DNA damage and repair mechanisms is currently lacking. In this study, we used NMR metabolomics to identify metabolic pathways which are altered in response to different DNA damaging agents. By comparing the metabolic responses in MCF-7 cells, we identified the activation of poly (ADP-ribose) polymerase (PARP) in methyl methanesulfonate (MMS)-induced DNA damage. PARP activation led to a significant depletion of NAD+. PARP inhibition using veliparib (ABT-888) was able to successfully restore the NAD+ levels in MMS-treated cells. In addition, double strand break induction by MMS and veliparib exhibited similar metabolic responses as zeocin, suggesting an application of metabolomics to classify the types of DNA damage responses. This prediction was validated by studying the metabolic responses elicited by radiation. Our findings indicate that cancer cell metabolic responses depend on the type of DNA damage responses and can also be used to classify the type of DNA damage. PMID:26478723

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srinivas, L.; Shalini, V.K.

Twigs-dry leaves smoke condensate (TDS), as a source of clastogenic ROS and carcinogenic PAH, was investigated for its in vitro DNA-damaging effect in calf thymus DNA and human peripheral lymphocytes. An aqueous turmeric component--Aq.T--with an established antioxidant activity, was tested as a DNA protectant. TDS induced 13-fold damage to calf thymus DNA as judged by the emergence of a DNA damage specific, fluorescent product (em: 405 nm). Aq.T at 800 ng/microL extended 69% protection to calf thymus DNA and was comparable to the other protectants such as curcumin, BHA, vitamin E, SOD, and CAT. In human peripheral lymphocytes, TDS inducedmore » extensive DNA damage in comparison with the tumor promoter TPA, as judged by FADU. Aq.T at 300 ng/microL extended 90% protection to human lymphocyte DNA against TDS-induced damage, and was more effective than the other protectants--DABCO, D-mannitol, sodium benzoate, vitamin E (ROS quenchers), SOD, CAT (antioxidant enzymes), tannic acid, flufenamic acid, BHA, BHT, n-PG, curcumin and quercetin (antioxidants). Aq.T offered 65% protection to human lymphocyte DNA against TPA-induced damage and was comparable to SOD. The above results indicate that TDS induces substantial DNA damage in calf thymus DNA and human lymphocytes and Aq.T is an efficient protectant.« less

Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

Phosphoramide mustard (PM), the ovotoxic metabolite of the anti-cancer agent cyclophosphamide (CPA), destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage. A previous study demonstrated that PM induces ovarian DNA damage in rat ovaries. To investigate whether PM induces DNA adduct formation, DNA damage and induction of the DNA repair response, rat spontaneously immortalized granulosa cells (SIGCs) were treated with vehicle control (1% DMSO) or PM (3 or 6 μM) for 24 or 48 h. Cell viability was reduced (P < 0.05) after 48 h of exposure to 3 or 6more » μM PM. The NOR-G-OH DNA adduct was detected after 24 h of 6 μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48 h by exposure to both PM concentrations. Phosphorylated H2AX (γH2AX), a marker of DNA double stranded break occurrence, was also increased by PM exposure, coincident with DNA adduct formation. Additionally, induction of genes (Atm, Parp1, Prkdc, Xrcc6, and Brca1) and proteins (ATM, γH2AX, PARP-1, PRKDC, XRCC6, and BRCA1) involved in DNA repair were observed in both a time- and dose-dependent manner. These data support that PM induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response. - Highlights: • PM forms ovarian DNA adducts. • DNA damage marker γH2AX increased by PM exposure. • PM induces ovarian DNA double strand break repair.« less

Oral administration of Aloe vera gel powder prevents UVB-induced decrease in skin elasticity via suppression of overexpression of MMPs in hairless mice.

PubMed

Saito, Marie; Tanaka, Miyuki; Misawa, Eriko; Yao, Ruiquing; Nabeshima, Kazumi; Yamauchi, Kouji; Abe, Fumiaki; Yamamoto, Yuki; Furukawa, Fukumi

2016-07-01

This study reports the effects of oral Aloe vera gel powder (AVGP) containing Aloe sterols on skin elasticity and the extracellular matrix in ultraviolet B (UVB)-irradiated hairless mice. Ten-week-old hairless mice were fed diets containing 0.3% AVGP for 8 weeks and irradiated UVB for 6 weeks. Mice treated with AVGP showed significant prevention of the UVB-induced decrease in skin elasticity. To investigate the mechanism underlying this suppression of skin elasticity loss, we measured the expression of matrix metalloproteinase (MMP)-2, -9, and -13. AVGP prevented both the UVB-induced increases in MMPs expressions. Moreover, we investigated hyaluronic acid (HA) content of mice dorsal skin and gene expression of HA synthase-2 (Has2). In the results, AVGP oral administration prevented UVB-induced decreasing in skin HA content and Has2 expression and attenuates the UVB-induced decrease in serum adiponectin, which promotes Has2 expression. These results suggested that AVGP has the ability to prevent the skin photoaging.

Genoprotective effect of hyaluronic acid against benzalkonium chloride-induced DNA damage in human corneal epithelial cells

PubMed Central

Wu, Han; Zhang, Huina; Wang, Changjun; Wu, Yihua; Xie, Jiajun; Jin, Xiuming; Yang, Jun

2011-01-01

Purpose The aim of this study was to investigate hyaluronic acid (HA) protection on cultured human corneal epithelial cells (HCEs) against benzalkonium chloride (BAC)-induced DNA damage and intracellular reactive oxygen species (ROS) increase. Methods Cells were incubated with different concentrations of BAC with or without the presence of 0.2% HA for 30 min. DNA damage to HCEs was examined by alkaline comet assay and by immunofluorescence microscopic detection of the phosphorylated form of histone variant H2AX (γH2AX) foci. ROS production was assessed by the fluorescent probe, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Cell apoptosis was determined with annexin V staining by flow cytometry. Results HA significantly reduced BAC-induced DNA damage as indicated by the tail length (TL) and tail moment (TM) of alkaline comet assay and by γH2AX foci formation, respectively. Moreover, HA significantly decreased BAC-induced ROS increase and cell apoptosis. However, exposure to HA alone did not produce any significant change in DNA damage, ROS generation, or cell apoptosis. Conclusions BAC could induce DNA damage and cell apoptosis in HCEs, probably through increasing oxidative stress. Furthermore, HA was an effective protective agent that had antioxidant properties and could decrease DNA damage and cell apoptosis induced by BAC. PMID:22219631

Different mechanisms for the photoinduced production of oxidative DNA damage by fluoroquinolones differing in photostability.

PubMed

Spratt, T E; Schultz, S S; Levy, D E; Chen, D; Schlüter, G; Williams, G M

1999-09-01

Several fluoroquinolone antibacterial agents exhibit an adverse phototoxic effect in humans and are photo-cocarcinogenic in mice. The UV-induced production of reactive oxygen species plays a role in the toxicity and may be involved in carcinogenicity. Four fluoroquinolones were examined for the ability to photochemically produce oxidative damage in naked DNA. The major structural difference in the fluoroquinolones that would have an effect on their photostability is the functionality at the 8-position. At this position, 1-cyclopropyl-7-(2,8-diazbicyclo[4.3.0]non-8-yl)-6, 8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (BAY y3118) contains a chlorine atom, lomefloxacin a fluorine atom, ciprofloxacin a proton, and moxifloxacin a methoxy group. The formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in calf thymus DNA was assessed by HPLC with electrochemical detection, and strand breaks were measured in pBR322 with agarose gel electrophoresis. The relative photolability of the fluoroquinolones correlated to the extent of production of 8-oxodGuo and strand breaks, with both UVA and UVB irradiation, in the following order: BAY y3118 approximately lomefloxacin > ciprofloxacin > moxifloxacin. Experiments were performed to determine whether the mechanism of damage was due to a type I (radical) or type II (singlet oxygen) pathway. Nitrogen depletion of oxygen resulted in a decrease in the extent of formation of 8-oxodGuo, suggesting that oxygen was involved. The use of selective radical or singlet oxygen inhibitors was inconclusive with respect to which pathway was involved. The use of D(2)O as a solvent, which would extend the lifetime of singlet oxygen, suggested that this species is involved in the formation of 8-oxodGuo by moxifloxacin and ciprofloxacin, but not by lomefloxacin and BAY y3118. Similarly, it was found that singlet oxygen was not involved in strand break formation. Thus, the evidence suggests that fluoroquinolones can photochemically produce DNA damage by both type I and type II mechanisms.

Caffeic Acid Inhibits Chronic UVB-Induced Cellular Proliferation Through JAK-STAT3 Signaling in Mouse Skin.

PubMed

Agilan, Balupillai; Rajendra Prasad, N; Kanimozhi, Govindasamy; Karthikeyan, Ramasamy; Ganesan, Muthusamy; Mohana, Shanmugam; Velmurugan, Devadasan; Ananthakrishnan, Dhanapalan

2016-05-01

Signal transducers and activators of transcription 3 (STAT3) play a critical role in inflammation, proliferation and carcinogenesis. Inhibition of JAK-STAT3 signaling is proved to be a novel target for prevention of UVB-induced skin carcinogenesis. In this study, chronic UVB irradiation (180 mJ cm(-2) ; weekly thrice for 30 weeks) induces the expression of IL-10 and JAK1 that eventually activates the STAT3 which leads to the transcription of proliferative and antiapoptotic markers such as PCNA, Cyclin-D1, Bcl2 and Bcl-xl, respectively. Caffeic acid (CA) inhibits JAK-STAT3 signaling, thereby induces apoptotic cell death by upregulating Bax, Cytochrome-C, Caspase-9 and Caspase-3 expression in mouse skin. Furthermore, TSP-1 is an antiangiogeneic protein, which is involved in the inhibition of angiogenesis and proliferation. Chronic UVB exposure decreased the expression of TSP-1 and pretreatment with CA prevented the UVB-induced loss of TSP-1 in UVB-irradiated mouse skin. Thus, CA offers protection against UVB-induced photocarcinogenesis probably through modulating the JAK-STAT3 in the mouse skin. © 2016 The American Society of Photobiology.

The gender differences in the inhibitory action of UVB-induced melanocyte activation by the administration of tranexamic acid.

PubMed

Hiramoto, Keiichi; Yamate, Yurika; Sugiyama, Daijiro; Takahashi, Yumi; Mafune, Eiichi

2016-05-01

Tranexamic acid has an inhibitory action on ultraviolet (UV) B-induced melanocyte activation. This study examined the sex differences in the inhibitory action of tranexamic acid on UVB-induced melanocyte activation. We irradiated the eye and ear of male and female mice with UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp. We orally administered tranexamic acid (750 mg/kg/day) at 30 min before UVB exposure. Tranexamic acid inhibited the UVB-induced epidermal melanocyte activation, and the effect was more remarkable under UVB eye irradiation than under UVB ear irradiation. Furthermore, the melanocyte activity suppression effect was stronger in female mice than in male mice. Following the administration of tranexamic acid, the female displayed increased blood levels of β-endorphin and μ-opioid receptor and estradiol receptor β expression in comparison with the male. Furthermore, the effect of melanocyte activity suppression in the female mice was decreased by the administration of tamoxifen (antagonist of estrogen receptor) or naltrexone (antagonist of μ-opioid receptor). These results suggest that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inflammation-Induced Cell Proliferation Potentiates DNA Damage-Induced Mutations In Vivo

PubMed Central

Kiraly, Orsolya; Gong, Guanyu; Olipitz, Werner; Muthupalani, Sureshkumar; Engelward, Bevin P.

2015-01-01

Mutations are a critical driver of cancer initiation. While extensive studies have focused on exposure-induced mutations, few studies have explored the importance of tissue physiology as a modulator of mutation susceptibility in vivo. Of particular interest is inflammation, a known cancer risk factor relevant to chronic inflammatory diseases and pathogen-induced inflammation. Here, we used the fluorescent yellow direct repeat (FYDR) mice that harbor a reporter to detect misalignments during homologous recombination (HR), an important class of mutations. FYDR mice were exposed to cerulein, a potent inducer of pancreatic inflammation. We show that inflammation induces DSBs (γH2AX foci) and that several days later there is an increase in cell proliferation. While isolated bouts of inflammation did not induce HR, overlap between inflammation-induced DNA damage and inflammation-induced cell proliferation induced HR significantly. To study exogenously-induced DNA damage, animals were exposed to methylnitrosourea, a model alkylating agent that creates DNA lesions relevant to both environmental exposures and cancer chemotherapy. We found that exposure to alkylation damage induces HR, and importantly, that inflammation-induced cell proliferation and alkylation induce HR in a synergistic fashion. Taken together, these results show that, during an acute bout of inflammation, there is a kinetic barrier separating DNA damage from cell proliferation that protects against mutations, and that inflammation-induced cell proliferation greatly potentiates exposure-induced mutations. These studies demonstrate a fundamental mechanism by which inflammation can act synergistically with DNA damage to induce mutations that drive cancer and cancer recurrence. PMID:25647331

Effects of enhanced ultraviolet-B radiation, water deficit, and their combination on UV-absorbing compounds and osmotic adjustment substances in two different moss species.

PubMed

Hui, Rong; Zhao, Ruiming; Song, Guang; Li, Yixuan; Zhao, Yang; Wang, Yanli

2018-05-01

A simulation experiment was conducted to explore the influence of enhanced ultraviolet-B (UV-B) radiation, water deficit, and their combination on UV-absorbing compounds and osmotic adjustment substances of mosses Bryum argenteum and Didymodon vinealis isolated from biological soil crusts (BSCs) growing in a revegetated area of the Tengger Desert, China. Four levels of UV-B radiation and two gradients of water regime were employed. Compared with their controls, amounts of total flavonoids, chlorophyll, carotenoids, soluble sugars, and soluble proteins significantly decreased (p < 0.05), but proline content significantly increased (p < 0.05), when exposed to either enhanced UV-B or water deficit. The negative effects of enhanced UV-B were alleviated when water deficit was applied. There were increases in UV-absorbing compounds and osmotic adjustment substances when exposed to a combination of enhanced UV-B and water deficit compared with single stresses, except for the proline content in D. vinealis. In addition, our results also indicated interspecific differences in response to enhanced UV-B, water deficit, and their combination. Compared with B. argenteum, D. vinealis was more resistant to enhanced UV-B and water deficit singly and in combination. These results suggest that the damage of enhanced UV-B on both species might be alleviated by water deficit. This alleviation is important for understanding the response of BSCs to UV-B radiation in future global climate change. This also provides novel insights into assessment damages of UV-B to BSC stability in arid and semiarid regions.

Curcumin causes DNA damage and affects associated protein expression in HeLa human cervical cancer cells.

PubMed

Shang, Hung-Sheng; Chang, Chuan-Hsun; Chou, Yu-Ru; Yeh, Ming-Yang; Au, Man-Kuan; Lu, Hsu-Feng; Chu, Yung-Lin; Chou, Hsiao-Min; Chou, Hsiu-Chen; Shih, Yung-Luen; Chung, Jing-Gung

2016-10-01

Cervical cancer is one of the most common cancers in women worldwide and it is a prominent cause of cancer mortality. Curcumin is one of the major compounds from Turmeric and has been shown to induce cytotoxic cell death in human cervical cancer cells. However, there is no study to show curcumin induced DNA damage action via the effect on the DNA damage and repair protein in cervical cancer cells in detail. In this study, we investigated whether or not curcumin induced cell death via DNA damage, chromatin condensation in human cervical cancer HeLa cells by using comet assay and DAPI staining, respectively, we found that curcumin induced cell death through the induction of DNA damage, and chromatin condensation. Western blotting and confocal laser microscopy examination were used to examine the effects of curcumin on protein expression associated with DNA damage, repair and translocation of proteins. We found that curcumin at 13 µM increased the protein levels associated with DNA damage and repair, such as O6-methylguanine-DNA methyltransferase, early-onset breast cancer 1 (BRCA1), mediator of DNA damage checkpoint 1, p-p53 and p-H2A.XSer140 in HeLa cells. Results from confocal laser systems microscopy indicated that curcumin increased the translocation of p-p53 and p-H2A.XSer140 from cytosol to nuclei in HeLa cells. In conclusion, curcumin induced cell death in HeLa cells via induction of DNA damage, and chromatin condensation in vitro.

Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Juanjuan; Zhang, Yu; Xu, Wentao, E-mail: xuwentaoboy@sina.com

Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did notmore » affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by OTA in vitro.« less

The human intra-S checkpoint response to UVC-induced DNA damage.

PubMed

Kaufmann, William K

2010-05-01

The intra-S checkpoint response to 254 nm light (UVC)-induced DNA damage appears to have dual functions to slow the rate of DNA synthesis and stabilize replication forks that become stalled at sites of UVC-induced photoproducts in DNA. These functions should provide more time for repair of damaged DNA before its replication and thereby reduce the frequencies of mutations and chromosomal aberrations in surviving cells. This review tries to summarize the history of discovery of the checkpoint, the current state of understanding of the biological features of intra-S checkpoint signaling and its mechanisms of action with a focus primarily on intra-S checkpoint responses in human cells. The differences in the intra-S checkpoint responses to UVC and ionizing radiation-induced DNA damage are emphasized. Evidence that [6-4]pyrimidine-pyrimidone photoproducts in DNA trigger the response is discussed and the relationships between cellular responses to UVC and the molecular dose of UVC-induced DNA damage are briefly summarized. The role of the intra-S checkpoint response in protecting against solar radiation carcinogenesis remains to be determined.

Binding of antibodies to the extractable nuclear antigens SS-A/Ro and SS-B/La is induced on the surface of human keratinocytes by ultraviolet light (UVL): Implications for the pathogenesis of photosensitive cutaneous lupus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furukawa, F.; Kashihara-Sawami, M.; Lyons, M.B.

1990-01-01

Autoantibodies to the non-histone nucleoprotein antigens SS-A/Ro, SS-B/La, and RNP are highly associated with photosensitive cutaneous lupus erythematosus (LE). In order to better understand the potential mechanisms of ultraviolet (UV) light on photosensitivity in patients with cutaneous LE, we designed immunopathologic in vitro and in vivo experiments to evaluate the effects of UV on the binding of such autoantibodies to the surface of human keratinocytes, one major target of immunologic damage in photosensitive LE. Short-term 2% paraformaldehyde fixation of suspensions of cultured human keratinocytes previously incubated with monospecific antiserum probes enabled the detection of ENA expression on the cell surfacemore » by flow-cytometry analysis. UVB light (280-320 nm) induced the binding of monospecific antibody probes for SS-A/Ro and SS-B/La on keratinocytes in a dose-dependent pattern with maximal induction observed at the dose of 200 mJ/cm2 UVB. Binding of SS-A/Ro, SS-B/La, and RNP antibody was augmented strongly, but binding of anti-Sm was very weak. In contrast, UVA (320-400 nm) light had no effect on the induction of binding of these antibody probes. Identical results were seen by standard immunofluorescence techniques. Hydroxyurea-treated keratinocytes showed similar induction of those antigens by UVB irradiation, which suggested that ENA expression on cultured keratinocytes by UVB were cell-cycle independent. Tunicamycin, an inhibitor of glycosylation of proteins, reduced UVB light effect on the SS-A/Ro and SS-B/La antigen's expression. These in vitro FACS analyses revealed that ENA augmentation on the keratinocyte cell surface was dose dependent, UVB dependent, glycosylation dependent, and cell-cycle independent. In vivo ENA augmentation on the keratinocyte surface was examined in suction blister epidermal roofs.« less

Expression Profile of DNA Damage Signaling Genes in Proton Exposed Mouse Brain

NASA Astrophysics Data System (ADS)

Ramesh, Govindarajan; Wu, Honglu

Exposure of living systems to radiation results in a wide assortment of lesions, the most signif-icant of is damage to genomic DNA which induce several cellular functions such as cell cycle arrest, repair, apoptosis etc. The radiation induced DNA damage investigation is one of the im-portant area in biology, but still the information available regarding the effects of proton is very limited. In this report, we investigated the differential gene expression pattern of DNA damage signaling genes particularly, damaged DNA binding, repair, cell cycle arrest, checkpoints and apoptosis using quantitative real-time RT-PCR array in proton exposed mouse brain tissues. The expression profiles showed significant changes in DNA damage related genes in 2Gy proton exposed mouse brain tissues as compared with control brain tissues. Furthermore, we also show that significantly increased levels of apoptotic related genes, caspase-3 and 8 activities in these cells, suggesting that in addition to differential expression of DNA damage genes, the alteration of apoptosis related genes may also contribute to the radiation induced DNA damage followed by programmed cell death. In summary, our findings suggest that proton exposed brain tissue undergo severe DNA damage which in turn destabilize the chromatin stability.

DNA damage in cells exhibiting radiation-induced genomic instability

DOE PAGES

Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

2015-02-22

Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesismore » that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.« less

DNA damage induced by the direct effect of radiation

NASA Astrophysics Data System (ADS)

Yokoya, A.; Shikazono, N.; Fujii, K.; Urushibara, A.; Akamatsu, K.; Watanabe, R.

2008-10-01

We have studied the nature of DNA damage induced by the direct effect of radiation. The yields of single- (SSB) and double-strand breaks (DSB), base lesions and clustered damage were measured using the agarose gel electrophoresis method after exposing to various kinds of radiations to a simple model DNA molecule, fully hydrated closed-circular plasmid DNA (pUC18). The yield of SSB does not show significant dependence on linear energy transfer (LET) values. On the other hand, the yields of base lesions revealed by enzymatic probes, endonuclease III (Nth) and formamidopyrimidine DNA glycosylase (Fpg), which excise base lesions and leave a nick at the damage site, strongly depend on LET values. Soft X-ray photon (150 kVp) irradiation gives a maximum yield of the base lesions detected by the enzymatic probes as SSB and clustered damage, which is composed of one base lesion and proximate other base lesions or SSBs. The clustered damage is visualized as an enzymatically induced DSB. The yields of the enzymatically additional damages strikingly decrease with increasing levels of LET. These results suggest that in higher LET regions, the repair enzymes used as probes are compromised because of the dense damage clustering. The studies using simple plasmid DNA as a irradiation sample, however, have a technical difficulty to detect multiple SSBs in a plasmid DNA. To detect the additional SSBs induced in opposite strand of the first SSB, we have also developed a novel technique of DNA-denaturation assay. This allows us to detect multiply induced SSBs in both strand of DNA, but not induced DSB.

An improved method for the isolation of rat alveolar type II lung cells: Use in the Comet assay to determine DNA damage induced by cigarette smoke.

PubMed

Dalrymple, Annette; Ordoñez, Patricia; Thorne, David; Dillon, Debbie; Meredith, Clive

2015-06-01

Smoking is a cause of serious diseases, including lung cancer, emphysema, chronic bronchitis and heart disease. DNA damage is thought to be one of the mechanisms by which cigarette smoke (CS) initiates disease in the lung. Indeed, CS induced DNA damage can be measured in vitro and in vivo. The potential of the Comet assay to measure DNA damage in isolated rat lung alveolar type II epithelial cells (AEC II) was explored as a means to include a genotoxicity end-point in rodent sub-chronic inhalation studies. In this study, published AEC II isolation methods were improved to yield viable cells suitable for use in the Comet assay. The improved method reduced the level of basal DNA damage and DNA repair in isolated AEC II. CS induced DNA damage could also be quantified in isolated cells following a single or 5 days CS exposure. In conclusion, the Comet assay has the potential to determine CS or other aerosol induced DNA damage in AEC II isolated from rodents used in sub-chronic inhalation studies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAY

EPA Science Inventory

A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposur...

DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENNTIAL FLUORESENCE ASSAY

EPA Science Inventory

A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposures...

Electrochemical detection of DNA damage induced by acrylamide and its metabolite at the graphene-ionic liquid-Nafion modified pyrolytic graphite electrode.

PubMed

Qiu, Yanyan; Qu, Xiangjin; Dong, Jing; Ai, Shiyun; Han, Ruixia

2011-06-15

A new electrochemical biosensor for directly detecting DNA damage induced by acrylamide (AA) and its metabolite was presented in this work. The graphene-ionic liquid-Nafion modified pyrolytic graphite electrode (PGE) was prepared, and then horseradish peroxidase (HRP) and natural double-stranded DNA were alternately assembled on the modified electrode by the layer-by-layer method. The PGE/graphene-ionic liquid-Nafion and the construction of the (HRP/DNA)(n) film were characterized by electrochemical impedance spectroscopy. With the guanine signal in DNA as an indicator, the damage of DNA was detected by differential pulse voltammetry after PGE/graphene-ionic liquid-Nafion/(HRP/DNA)(n) was incubated in AA solution or AA+H(2)O(2) solution at 37°C. This method provides a new model to mimic and directly detect DNA damage induced by chemical pollutants and their metabolites in vitro. The results indicated that, in the presence of H(2)O(2), HRP was activated and catalyzed the transformation of AA to glycidamide, which could form DNA adducts and induce more serious damage of DNA than AA. In order to further verify these results, UV-vis spectrophotometry was also used to investigate DNA damage induced by AA and its metabolites in solution and the similar results were obtained. Copyright © 2011 Elsevier B.V. All rights reserved.

Alkaline ceramidase 2 and its bioactive product sphingosine are novel regulators of the DNA damage response

PubMed Central

Xu, Ruijuan; Wang, Kai; Mileva, Izolda; Hannun, Yusuf A.; Obeid, Lina M.; Mao, Cungui

2016-01-01

Human cells respond to DNA damage by elevating sphingosine, a bioactive sphingolipid that induces programmed cell death (PCD) in response to various forms of stress, but its regulation and role in the DNA damage response remain obscure. Herein we demonstrate that DNA damage increases sphingosine levels in tumor cells by upregulating alkaline ceramidase 2 (ACER2) and that the upregulation of the ACER2/sphingosine pathway induces PCD in response to DNA damage by increasing the production of reactive oxygen species (ROS). Treatment with the DNA damaging agent doxorubicin increased both ACER2 expression and sphingosine levels in HCT116 cells in a dose-dependent manner. ACER2 overexpression increased sphingosine in HeLa cells whereas knocking down ACER2 inhibited the doxorubicin-induced increase in sphingosine in HCT116 cells, suggesting that DNA damage elevates sphingosine by upregulating ACER2. Knocking down ACER2 inhibited an increase in the apoptotic and necrotic cell population and the cleavage of poly ADP ribose polymerase (PARP) in HCT116 cells in response to doxorubicin as well as doxorubicin-induced release of lactate dehydrogenase (LDH) from these cells. Similar to treatment with doxorubicin, ACER2 overexpression induced an increase in the apoptotic and necrotic cell population and PARP cleavage in HeLa cells and LDH release from cells, suggesting that ACER2 upregulation mediates PCD in response to DNA damage through sphingosine. Mechanistic studies demonstrated that the upregulation of the ACER2/sphingosine pathway induces PCD by increasing ROS levels. Taken together, these results suggest that the ACER2/sphingosine pathway mediates PCD in response to DNA damage through ROS production. PMID:26943039

p53-Regulated Apoptosis Is Differentiation Dependent in Ultraviolet B-Irradiated Mouse Keratinocytes

PubMed Central

Tron, Victor A.; Trotter, Martin J.; Tang, Liren; Krajewska, Maryla; Reed, John C.; Ho, Vincent C.; Li, Gang

1998-01-01

Previous studies from our laboratory, using p53 transgenic mice, have suggested that ultraviolet (UV) light-induced keratinocyte apoptosis in the skin is not affected by overexpression of mutant p53 protein. To further elucidate a possible role for p53 in UV-induced keratinocyte cell death, we now examine apoptosis in skin and isolated keratinocytes from p53 null (−/−) mice and assess the influence of cell differentiation on this process. In vivo, using this knockout model, epidermal keratinocytes in p53−/− mice exhibited only a 5.2-fold increase in apoptosis after 2000 J/m2 UVB irradiation compared with a 26.3-fold increase in normal control animals. If this p53-dependent apoptosis is important in elimination of precancerous, UV-damaged keratinocytes, then it should be active in the undifferentiated cells of the epidermal basal layer. To test this hypothesis, we examined the effect of differentiation on UV-induced apoptosis in primary cultures of murine and human keratinocytes. Apoptosis was p53-independent in undifferentiated murine keratinocytes, which exhibited relative resistance to UVB-induced killing with only a 1.5-fold increase in apoptosis in p53+/+ cells and a 1.4-fold increase in p53−/− cells. Differentiated keratinocytes, in contrast, showed a 9.4-fold UVB induction of apoptosis in p53+/+ cells, almost three times the induction observed in p53−/− cells. This UV-induced difference in apoptosis was observed when keratinocytes were cultured on type IV collagen substrate, but not on plastic alone. Western blotting of UV-irradiated, differentiated keratinocytes did not support a role for either Bax or Bcl-2 in this process. In support of these findings in mice, cell death in human cultured keratinocytes also occurred in a differentiation-associated fashion. We conclude that p53-induced apoptosis eliminates damaged keratinocytes in the differentiated cell compartment, but this mechanism is not active in the basal, undifferentiated cells and is therefore of questionable significance in protection against skin cancer induction. PMID:9708817

[Blocking 1800 MHz mobile phone radiation-induced reactive oxygen species production and DNA damage in lens epithelial cells by noise magnetic fields].

PubMed

Wu, Wei; Yao, Ke; Wang, Kai-jun; Lu, De-qiang; He, Ji-liang; Xu, Li-hong; Sun, Wen-jun

2008-01-01

To investigate whether the exposure to the electromagnetic noise can block reactive oxygen species (ROS) production and DNA damage of lens epithelial cells induced by 1800 MHz mobile phone radiation. The DCFH-DA method and comet assay were used respectively to detect the intracellular ROS and DNA damage of cultured human lens epithelial cells induced by 4 W/kg 1800 MHz mobile phone radiation or/and 2 muT electromagnetic noise for 24 h intermittently. 1800 MHz mobile phone radiation at 4 W/kg for 24 h increased intracellular ROS and DNA damage significantly (P<0.05). However, the ROS level and DNA damage of mobile phone radiation plus noise group were not significant enhanced (P>0.05) as compared to sham exposure group. Electromagnetic noise can block intracellular ROS production and DNA damage of human lens epithelial cells induced by 1800 MHz mobile phone radiation.

UV-Induced cell death in plants.

PubMed

Nawkar, Ganesh M; Maibam, Punyakishore; Park, Jung Hoon; Sahi, Vaidurya Pratap; Lee, Sang Yeol; Kang, Chang Ho

2013-01-14

Plants are photosynthetic organisms that depend on sunlight for energy. Plants respond to light through different photoreceptors and show photomorphogenic development. Apart from Photosynthetically Active Radiation (PAR; 400-700 nm), plants are exposed to UV light, which is comprised of UV-C (below 280 nm), UV-B (280-320 nm) and UV-A (320-390 nm). The atmospheric ozone layer protects UV-C radiation from reaching earth while the UVR8 protein acts as a receptor for UV-B radiation. Low levels of UV-B exposure initiate signaling through UVR8 and induce secondary metabolite genes involved in protection against UV while higher dosages are very detrimental to plants. It has also been reported that genes involved in MAPK cascade help the plant in providing tolerance against UV radiation. The important targets of UV radiation in plant cells are DNA, lipids and proteins and also vital processes such as photosynthesis. Recent studies showed that, in response to UV radiation, mitochondria and chloroplasts produce a reactive oxygen species (ROS). Arabidopsis metacaspase-8 (AtMC8) is induced in response to oxidative stress caused by ROS, which acts downstream of the radical induced cell death (AtRCD1) gene making plants vulnerable to cell death. The studies on salicylic and jasmonic acid signaling mutants revealed that SA and JA regulate the ROS level and antagonize ROS mediated cell death. Recently, molecular studies have revealed genes involved in response to UV exposure, with respect to programmed cell death (PCD).

UV-Induced Cell Death in Plants

PubMed Central

Nawkar, Ganesh M.; Maibam, Punyakishore; Park, Jung Hoon; Sahi, Vaidurya Pratap; Lee, Sang Yeol; Kang, Chang Ho

2013-01-01

Plants are photosynthetic organisms that depend on sunlight for energy. Plants respond to light through different photoreceptors and show photomorphogenic development. Apart from Photosynthetically Active Radiation (PAR; 400–700 nm), plants are exposed to UV light, which is comprised of UV-C (below 280 nm), UV-B (280–320 nm) and UV-A (320–390 nm). The atmospheric ozone layer protects UV-C radiation from reaching earth while the UVR8 protein acts as a receptor for UV-B radiation. Low levels of UV-B exposure initiate signaling through UVR8 and induce secondary metabolite genes involved in protection against UV while higher dosages are very detrimental to plants. It has also been reported that genes involved in MAPK cascade help the plant in providing tolerance against UV radiation. The important targets of UV radiation in plant cells are DNA, lipids and proteins and also vital processes such as photosynthesis. Recent studies showed that, in response to UV radiation, mitochondria and chloroplasts produce a reactive oxygen species (ROS). Arabidopsis metacaspase-8 (AtMC8) is induced in response to oxidative stress caused by ROS, which acts downstream of the radical induced cell death (AtRCD1) gene making plants vulnerable to cell death. The studies on salicylic and jasmonic acid signaling mutants revealed that SA and JA regulate the ROS level and antagonize ROS mediated cell death. Recently, molecular studies have revealed genes involved in response to UV exposure, with respect to programmed cell death (PCD). PMID:23344059

Determining the Location of DNA Modification and Mutation Caused by UVB Light in Skin Cancer

DTIC Science & Technology

2015-09-01

Award Number: W81XWH-12-1-0333 TITLE: Determining the Location of DNA Modification and Mutation Caused by UVB Light in Skin Cancer PRINCIPAL...COVERED 15 Aug 2012 – 14 Aug 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-12-1-0333 Determining the Location of DNA Modification and Mutation ...sequencing libraries generated for both yeast and human cells show pyrimidine bias on the 5’ end, indicating that we are sequencing the dimers

Amelioration of ultraviolet-induced photokeratitis in mice treated with astaxanthin eye drops.

PubMed

Lennikov, Anton; Kitaichi, Nobuyoshi; Fukase, Risa; Murata, Miyuki; Noda, Kousuke; Ando, Ryo; Ohguchi, Takeshi; Kawakita, Tetsuya; Ohno, Shigeaki; Ishida, Susumu

2012-01-01

Ultraviolet (UV) acts as low-dose ionizing radiation. Acute UVB exposure causes photokeratitis and induces apoptosis in corneal cells. Astaxanthin (AST) is a carotenoid, present in seafood, that has potential clinical applications due to its high antioxidant activity. In the present study, we examined whether topical administration of AST has preventive and therapeutic effects on UV-photokeratitis in mice. C57BL/6 mice were administered with AST diluted in polyethylene glycol (PEG) in instillation form (15 μl) to the right eye. Left eyes were given vehicle alone as controls. Immediately after the instillation, the mice, under anesthesia, were irradiated with UVB at a dose of 400 mJ/cm². Eyeballs were collected 24 h after irradiation and stained with H&E and TUNEL. In an in vitro study, mouse corneal epithelial (TKE2) cells were cultured with AST before UV exposure to quantify the UV-derived cytotoxicity. UVB exposure induced cell death and thinning of the corneal epithelium. However, the epithelium was morphologically well preserved after irradiation in AST-treated corneas. Irradiated corneal epithelium was significantly thicker in eyes treated with AST eye drops, compared to those treated with vehicles (p<0.01), in a doses dependent manner. Significantly fewer apoptotic cells were observed in AST-treated eyes than controls after irradiation (p<0.01). AST also reduced oxidative stress in irradiated corneas. The in vitro study showed less cytotoxicity of TKE2 cells in AST-treated cultures after UVB-irradiation (p<0.01). The cytoprotective effect increased with the dose of AST. Topical AST administration may be a candidate treatment to limit the damages by UV irradiation with wide clinical applications.

An ultraviolet simulator for the incident Martian surface radiation and its applications

NASA Astrophysics Data System (ADS)

Kolb, C.; Abart, R.; Bérces, A.; Garry, J. R. C.; Hansen, A. A.; Hohenau, W.; Kargl, G.; Lammer, H.; Patel, M. R.; Rettberg, P.; Stan-Lotter, H.

2005-10-01

Ultraviolet (UV) radiation can act on putative organic/biological matter at the Martian surface in several ways. Only absorbed, but not transmitted or reflected, radiation energy can be photo-chemically effective. The most important biological UV effects are due to photochemical reactions in nucleic acids, DNA or RNA, which constitute the genetic material of all cellular organisms and viruses. Protein or lipid effects generally play a minor role, but they are also relevant in some cases. UV radiation can induce wavelengths-specific types of DNA damage. At the same time it can also induce the photo-reversion reaction of a UV induced DNA photoproduct of nucleic acid bases, the pyrimidine dimers. Intense UVB and UVC radiation, experienced on early Earth and present-day Mars, has been revealed to be harmful to all organisms, including extremophile bacteria and spores. Moreover, the formation of oxidants, catalytically produced in the Martian environment through UV irradiation, may be responsible for the destruction of organic matter on Mars. Following this, more laboratory simulations are vital in order to investigate and understand UV effects on organic matter in the case of Mars. We have designed a radiation apparatus that simulates the anticipated Martian UV surface spectrum between 200 and 400 nm (UVC UVA). The system comprises a UV enhanced xenon arc lamp, special filter-sets and mirrors to simulate the effects of the Martian atmospheric column and dust loading. We describe the technical setup and performance of the system and discuss its uses for different applications. The design is focused on portability, therefore, the Mars-UV simulator represents a device for several different Mars simulation facilities with specific emphasis on Mars research topics.

Poly-l-cysteine/electrospun copper oxide nanofibers-zinc oxide nanoparticles nanocomposite as sensing element of an electrochemical sensor for simultaneous determination of adenine and guanine in biological samples and evaluation of damage to dsDNA and DNA purine bases by UV radiation.

PubMed

Arvand, Majid; Sayyar Ardaki, Masoomeh

2017-09-15

A new nanocomposite film constructed of poly-l-cysteine/zinc oxide nanoparticles-electrospun copper oxide nanofibers (PLC/ZnO-NPs-CuO-NFs) was prepared on the surface of the graphite electrode (GE). The novel electrode was successfully applied for the simultaneous determination of guanine (G) and adenine (A), two of the most important components of DNA and RNA. The PLC/ZnO-NPs-CuO-NFs/GE enhanced the anodic peak currents of the purine bases conspicuously and could determine them sensitively and separately in 0.1 M phosphate buffer solution at the physiological pH (7.0). The synthesized nanofibers, nanoparticles and nanocomposite were characterized by different methods such as Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and energy dispersive X-ray analysis (EDS). Under the optimum operating conditions, linear calibration curves were obtained in the range of 0.05-6.78 and 0.01-3.87 μM with a detection limit of 12.48 and 1.25 nM for G and A, respectively. The proposed method was applied to quantify A and G in three different DNA samples with satisfactory results. In addition, damage to human blood double-stranded DNA (dsDNA) and DNA purine bases (liberated in previously hydrolyzed human blood dsDNA) caused by UV-C and UV-B were evaluated. The results demonstrated that the proposed biosensing platform not only provides a novel and sensitive approach to detecting DNA damage, but also can be used for simultaneous determination of purine bases and major products of DNA oxidative damage. Copyright © 2017 Elsevier B.V. All rights reserved.

Bioenergetic metabolites regulate base excision repair dependent cell death in response to DNA damage

PubMed Central

Tang, Jiang-bo; Goellner, Eva M.; Wang, Xiao-hong; Trivedi, Ram N.; Croix, Claudette M. St; Jelezcova, Elena; Svilar, David; Brown, Ashley R.; Sobol, Robert W.

2009-01-01

Base excision repair (BER) protein expression is important for resistance to DNA damage-induced cytotoxicity. Conversely, BER imbalance (Polß deficiency or repair inhibition) enhances cytotoxicity of radiation and chemotherapeutic DNA-damaging agents. Whereas inhibition of critical steps in the BER pathway result in the accumulation of cytotoxic DNA double-strand breaks, we report that DNA damage-induced cytotoxicity due to deficiency in the BER protein Polß triggers cell death dependent on PARP activation yet independent of poly(ADP-ribose) (PAR)-mediated AIF nuclear translocation or PARG, suggesting that cytotoxicity is not from PAR or PAR-catabolite signaling. Cell death is rescued by the NAD+ metabolite NMN and is synergistic with inhibition of NAD+ biosynthesis, demonstrating that DNA damage-induced cytotoxicity mediated via BER inhibition is primarily dependent on cellular metabolite bioavailability. We offer a mechanistic justification for the elevated alkylation-induced cytotoxicity of Polß deficient cells, suggesting a linkage between DNA repair, cell survival and cellular bioenergetics. PMID:20068071

Diverse Responses to UV-B Radiation and Repair Mechanisms of Bacteria Isolated from High-Altitude Aquatic Environments▿

PubMed Central

Fernández Zenoff, V.; Siñeriz, F.; Farías, M. E.

2006-01-01

Acinetobacter johnsonii A2 isolated from the natural community of Laguna Azul (Andean Mountains at 4,560 m above sea level), Serratia marcescens MF42, Pseudomonas sp. strain MF8 isolated from the planktonic community, and Cytophaga sp. strain MF7 isolated from the benthic community from Laguna Pozuelos (Andean Puna at 3,600 m above sea level) were subjected to UV-B (3,931 J m−2) irradiation. In addition, a marine Pseudomonas putida strain, 2IDINH, and a second Acinetobacter johnsonii strain, ATCC 17909, were used as external controls. Resistance to UV-B and kinetic rates of light-dependent (UV-A [315 to 400 nm] and cool white light [400 to 700 nm]) and -independent reactivation following exposure were determined by measuring the survival (expressed as CFU) and accumulation of cyclobutane pyrimidine dimers (CPD). Significant differences in survival after UV-B irradiation were observed: Acinetobacter johnsonii A2, 48%; Acinetobacter johnsonii ATCC 17909, 20%; Pseudomonas sp. strain MF8, 40%; marine Pseudomonas putida strain 2IDINH, 12%; Cytophaga sp. strain MF7, 20%; and Serratia marcescens, 21%. Most bacteria exhibited little DNA damage (between 40 and 80 CPD/Mb), except for the benthic isolate Cytophaga sp. strain MF7 (400 CPD/Mb) and Acinetobacter johnsonii ATCC 17909 (160 CPD/Mb). The recovery strategies through dark and light repair were different in all strains. The most efficient in recovering were both Acinetobacter johnsonii A2 and Cytophaga sp. strain MF7; Serratia marcescens MF42 showed intermediate recovery, and in both Pseudomonas strains, recovery was essentially zero. The UV-B responses and recovery abilities of the different bacteria were consistent with the irradiation levels in their native environment. PMID:17056692

[Effect of long-wave ultraviolet light (UV-A) and medium-wave ultraviolet rays (UV-B) on human skin. Critical comparison].

PubMed

Raab, W

1980-04-15

When discussing the effects of ultraviolet radiation on human skin, one should carefully distinguish between the long wave ultraviolet light (UV-A) and the short wave radiations (UV-B and UV-C). Ultraviolet A induces immediate pigmentation but, if high energies are applied, a permanent pigmentation is elicited. This type of ultraviolet A-induced pigmentation has been called "spontaneous" pigmentation as no erythematous reaction is necessary to induce or accelerate melanine formation. Ultraviolet B provokes erythema and consecutive pigmentation. Upon chronic exposure, ultraviolet B causes the wellknown actinic damage of the skin and even provokes carcinoma. With exposures to the sunlight (global radiation), one should be most careful. The public must be informed extensively about the dangers of excessive sunbaths. The use of artificial "suns" with spectra between 260 and 400 nm is limited as it may cause the same type of damage as the global radiation. An exact schedule for use of artificial lamps is strongly recommended. After one cycle of exposures, an interruption is necessary until the next cycle of irradiations may start. Upon continual use for tanning of the skin, artificial lamps may provoke irreversible damage of the skin. Radiation sources with emission spectra of wavelengths between 315 and 400 nm exclusively are well suited for the induction of skin pigmentation (cosmetic use). Potent radiation such as UVASUN systems provoke a "pleasant" permanent pigmentation after exposures for less than one hour. The use of ultraviolet A (UV-A) does not carry any risk for the human skin.

Naringenin targets ERK2 and suppresses UVB-induced photoaging.

PubMed

Jung, Sung Keun; Ha, Su Jeong; Jung, Chang Hwa; Kim, Yun Tai; Lee, Hoo-Keun; Kim, Myoung Ok; Lee, Mee-Hyun; Mottamal, Madhusoodanan; Bode, Ann M; Lee, Ki Won; Dong, Zigang

2016-05-01

A number of natural phytochemicals have anti-photoaging properties that appear to be mediated through the inhibition of matrix metalloproteinase-1 (MMP-1) expression, but their direct target molecule(s) and mechanism(s) remain unclear. We investigated the effect of naringenin, a major flavonoid found in citrus, on UVB-induced MMP-1 expression and identified its direct target. The HaCaT human skin keratinocyte cell line and 3-dimensional (3-D) human skin equivalent cultures were treated or not treated with naringenin for 1 hr before exposure to UVB. The mechanism and target(s) of naringenin were analysed by kinase assay and multiplex molecular assays. Dorsal skins of hairless mice were exposed to UVB 3 times per week, with a dose of irradiation that was increased weekly by 1 minimal erythema dose (MED; 45 mJ/cm(2)) to 4 MED over 15 weeks. Wrinkle formation, water loss and water content were then assessed. Naringenin suppressed UVB-induced MMP-1 expression and AP-1 activity, and strongly suppressed UVB-induced phosphorylation of Fos-related antigen (FRA)-1 at Ser265. Importantly, UVB irradiation-induced FRA1 protein stability was reduced by treatment with naringenin, as well as with a mitogen-activated protein kinase (MEK) inhibitor. Naringenin significantly suppressed UVB-induced extracellular signal-regulated kinase 2 (ERK2) activity and subsequently attenuated UVB-induced phosphorylation of p90(RSK) by competitively binding with ATP. Constitutively active MEK (CA-MEK) increased FRA1 phosphorylation and expression and also induced MMP-1 expression, whereas dominant-negative ERK2 (DN-ERK2) had opposite effects. U0126, a MEK inhibitor, also decreased FRA1 phosphorylation and expression as well as MMP-1 expression. The photoaging data obtained from mice clearly demonstrated that naringenin significantly inhibited UVB-induced wrinkle formation, trans-epidermal water loss and MMP-13 expression. Naringenin exerts potent anti-photoaging effects by suppressing ERK2 activity and decreasing FRA1 stability, followed by down-regulation of AP-1 transactivation and MMP-1 expression. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Effect of complex polyphenols and tannins from red wine (WCPT) on chemically induced oxidative DNA damage in the rat.

PubMed

Casalini, C; Lodovici, M; Briani, C; Paganelli, G; Remy, S; Cheynier, V; Dolara, P

1999-08-01

Flavonoids are polyphenolic antioxidants occurring in vegetables and fruits as well as beverages such as tea and wine which have been thought to influence oxidative damage. We wanted to verify whether a complex mixture of wine tannins (wine complex polyphenols and tannins, WCPT) prevent chemically-induced oxidative DNA damage in vivo. Oxidative DNA damage was evaluated by measuring the ratio of 8-hydroxy-2'-deoxyguanosine (80HdG)/ 2-deoxyguanosine (2dG) x 10(-6) in hydrolyzed DNA using HPLC coupled with electrochemical and UV detectors. We treated rats with WCPT (57 mg/kg p.o.) for 14 d, a dose 10-fold higher than what a moderate wine drinker would be exposed to. WCPT administration significantly reduced the ratio of 80HdG/2dG x 10(-6) in liver DNA obtained from rats treated with 2-nitropropane (2NP) relative to controls administered 2NP only (33. 3 +/- 2.5 vs. 44.9 +/- 3.2 x 10(-6) 2dG; micro +/- SE; p<0.05). On the contrary, pretreatment with WCPT for 10 d did not protect the colon mucosa from oxidative DNA damage induced by 1, 2-dimethylhydrazine (DMH). 2NP and DMH are hepatic and colon carcinogens, respectively, capable of inducing oxidative DNA damage. WCPT have protective action against some types of chemically-induced oxidative DNA damage in vivo.

Doxorubicin-induced necrosis is mediated by poly-(ADP-ribose) polymerase 1 (PARP1) but is independent of p53.

PubMed

Shin, Hyeon-Jun; Kwon, Hyuk-Kwon; Lee, Jae-Hyeok; Gui, Xiangai; Achek, Asma; Kim, Jae-Ho; Choi, Sangdun

2015-11-02

Necrosis, unregulated cell death, is characterized by plasma membrane rupture as well as nuclear and cellular swelling. However, it has recently been reported that necrosis is a regulated form of cell death mediated by poly-(ADP-ribose) polymerase 1 (PARP1). PARP1 is thought to mediate necrosis by inducing DNA damage, although this remains unconfirmed. In this study, we examined the mechanisms of PARP1-mediated necrosis following doxorubicin (DOX)-induced DNA damage in human kidney proximal tubular (HK-2) cells. DOX initiated DNA damage response (DDR) and upregulated PARP1 and p53 expression, resulting in morphological changes similar to those observed during necrosis. Additionally, DOX induced mitochondrial hyper-activation, as evidenced by increased mitochondrial respiration and cytosolic ATP (cATP) production. However, DOX affected mitochondrial mass. DOX-induced DNA damage, cytosolic reactive oxygen species (cROS) generation, and mitochondrial hyper-activation decreased in cells with inhibited PARP1 expression, while generation of nitric oxide (NO) and mitochondrial ROS (mROS) remained unaffected. Moreover, DOX-induced DNA damage, cell cycle changes, and oxidative stress were not affected by p53 inhibition. These findings suggest that DNA damage induced necrosis through a PARP1-dependent and p53-independent pathway.

Doxorubicin-induced necrosis is mediated by poly-(ADP-ribose) polymerase 1 (PARP1) but is independent of p53

PubMed Central

Shin, Hyeon-Jun; Kwon, Hyuk-Kwon; Lee, Jae-Hyeok; Gui, Xiangai; Achek, Asma; Kim, Jae-Ho; Choi, Sangdun

2015-01-01

Necrosis, unregulated cell death, is characterized by plasma membrane rupture as well as nuclear and cellular swelling. However, it has recently been reported that necrosis is a regulated form of cell death mediated by poly-(ADP-ribose) polymerase 1 (PARP1). PARP1 is thought to mediate necrosis by inducing DNA damage, although this remains unconfirmed. In this study, we examined the mechanisms of PARP1-mediated necrosis following doxorubicin (DOX)-induced DNA damage in human kidney proximal tubular (HK-2) cells. DOX initiated DNA damage response (DDR) and upregulated PARP1 and p53 expression, resulting in morphological changes similar to those observed during necrosis. Additionally, DOX induced mitochondrial hyper-activation, as evidenced by increased mitochondrial respiration and cytosolic ATP (cATP) production. However, DOX affected mitochondrial mass. DOX-induced DNA damage, cytosolic reactive oxygen species (cROS) generation, and mitochondrial hyper-activation decreased in cells with inhibited PARP1 expression, while generation of nitric oxide (NO) and mitochondrial ROS (mROS) remained unaffected. Moreover, DOX-induced DNA damage, cell cycle changes, and oxidative stress were not affected by p53 inhibition. These findings suggest that DNA damage induced necrosis through a PARP1-dependent and p53-independent pathway. PMID:26522181

Enhanced susceptibility of ovaries from obese mice to 7,12-dimethylbenz[a]anthracene-induced DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Nteeba, Jackson, E-mail: nteeba@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

7,12-Dimethylbenz[a]anthracene (DMBA) depletes ovarian follicles and induces DNA damage in extra-ovarian tissues, thus, we investigated ovarian DMBA-induced DNA damage. Additionally, since obesity is associated with increased offspring birth defect incidence, we hypothesized that a DMBA-induced DNA damage response (DDR) is compromised in ovaries from obese females. Wild type (lean) non agouti (a/a) and KK.Cg-Ay/J heterozygote (obese) mice were dosed with sesame oil or DMBA (1 mg/kg; intraperitoneal injection) at 18 weeks of age, for 14 days. Total ovarian RNA and protein were isolated and abundance of Ataxia telangiectasia mutated (Atm), X-ray repair complementing defective repair in Chinese hamster cells 6more » (Xrcc6), breast cancer type 1 (Brca1), Rad 51 homolog (Rad51), poly [ADP-ribose] polymerase 1 (Parp1) and protein kinase, DNA-activated, catalytic polypeptide (Prkdc) were quantified by RT-PCR or Western blot. Phosphorylated histone H2AX (γH2AX) level was determined by Western blotting. Obesity decreased (P < 0.05) basal protein abundance of PRKDC and BRCA1 proteins but increased (P < 0.05) γH2AX and PARP1 proteins. Ovarian ATM, XRCC6, PRKDC, RAD51 and PARP1 proteins were increased (P < 0.05) by DMBA exposure in lean mice. A blunted DMBA-induced increase (P < 0.05) in XRCC6, PRKDC, RAD51 and BRCA1 was observed in ovaries from obese mice, relative to lean counterparts. Taken together, DMBA exposure induced γH2AX as well as the ovarian DDR, supporting that DMBA causes ovarian DNA damage. Additionally, ovarian DDR was partially attenuated in obese females raising concern that obesity may be an additive factor during chemical-induced ovotoxicity. - Highlights: • DMBA induces markers of ovarian DNA damage. • Obesity induces low level ovarian DNA damage. • DMBA-induced DNA repair response is altered by obesity.« less

The sequence specificity of UV-induced DNA damage in a systematically altered DNA sequence.

PubMed

Khoe, Clairine V; Chung, Long H; Murray, Vincent

2018-06-01

The sequence specificity of UV-induced DNA damage was investigated in a specifically designed DNA plasmid using two procedures: end-labelling and linear amplification. Absorption of UV photons by DNA leads to dimerisation of pyrimidine bases and produces two major photoproducts, cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). A previous study had determined that two hexanucleotide sequences, 5'-GCTC*AC and 5'-TATT*AA, were high intensity UV-induced DNA damage sites. The UV clone plasmid was constructed by systematically altering each nucleotide of these two hexanucleotide sequences. One of the main goals of this study was to determine the influence of single nucleotide alterations on the intensity of UV-induced DNA damage. The sequence 5'-GCTC*AC was designed to examine the sequence specificity of 6-4PPs and the highest intensity 6-4PP damage sites were found at 5'-GTTC*CC nucleotides. The sequence 5'-TATT*AA was devised to investigate the sequence specificity of CPDs and the highest intensity CPD damage sites were found at 5'-TTTT*CG nucleotides. It was proposed that the tetranucleotide DNA sequence, 5'-YTC*Y (where Y is T or C), was the consensus sequence for the highest intensity UV-induced 6-4PP adduct sites; while it was 5'-YTT*C for the highest intensity UV-induced CPD damage sites. These consensus tetranucleotides are composed entirely of consecutive pyrimidines and must have a DNA conformation that is highly productive for the absorption of UV photons. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Hui; Shi, Qiong; Song, Xiufang

2015-07-01

Our previous studies demonstrated that polychlorinated biphenyl (PCB) quinone induced oxidative DNA damage in HepG2 cells. To promote genomic integrity, DNA damage response (DDR) coordinates cell-cycle transitions, DNA repair and apoptosis. PCB quinone-induced cell cycle arrest and apoptosis have been documented, however, whether PCB quinone insult induce DNA repair signaling is still unknown. In this study, we identified the activation of DDR and corresponding signaling events in HepG2 cells upon the exposure to a synthetic PCB quinone, PCB29-pQ. Our data illustrated that PCB29-pQ induces the phosphorylation of p53, which was mediated by ataxia telangiectasia mutated (ATM) protein kinase. The observedmore » phosphorylated histone H2AX (γ-H2AX) foci and the elevation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) indicated that DDR was stimulated by PCB29-pQ treatment. Additionally, we found PCB29-pQ activates non-homologous end joining (NHEJ), base excision repair (BER) and nucleotide excision repair (NER) signalings. However, these repair pathways are not error-free processes and aberrant repair of DNA damage may cause the potential risk of carcinogenesis and mutagenesis. - Highlights: • Polychlorinated biphenyl quinone induces oxidative DNA damage in HepG2 cells. • The elevation of γ-H2AX and 8-OHdG indicates the activation of DNA damage response. • ATM-p53 signaling acts as the DNA damage sensor and effector. • Polychlorinated biphenyl quinone activates NHEJ, BER and NER signalings.« less

Photoprotection of human skin beyond ultraviolet radiation.

PubMed

Grether-Beck, Susanne; Marini, Alessandra; Jaenicke, Thomas; Krutmann, Jean

2014-01-01

Photoprotection of human skin by means of sunscreens or daily skin-care products is traditionally centered around the prevention of acute (e.g. sunburn) and chronic (e.g. skin cancer and photoaging) skin damage that may result from exposure to ultraviolet rays (UVB and UVA). Within the last decade, however, it has been appreciated that wavelengths beyond the ultraviolet spectrum, in particular visible light and infrared radiation, contribute to skin damage in general and photoaging of human skin in particular. As a consequence, attempts have been made to develop skin care/sunscreen products that not only protect against UVB or UVA radiation but provide photoprotection against visible light and infrared radiation as well. In this article, we will briefly review the current knowledge about the mechanisms responsible for visible light/infrared radiation-induced skin damage and then, based on this information, discuss strategies that have been successfully used or may be employed in the future to achieve photoprotection of human skin beyond ultraviolet radiation. In this regard we will particularly focus on the use of topical antioxidants and the challenges that result from the task of showing their efficacy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Amphetamines promote mitochondrial dysfunction and DNA damage in pulmonary hypertension

PubMed Central

Chen, Pin-I; Cao, Aiqin; Miyagawa, Kazuya; Tojais, Nancy F.; Hennigs, Jan K.; Li, Caiyun G.; Sweeney, Nathaly M.; Inglis, Audrey S.; Wang, Lingli; Li, Dan; Ye, Matthew; Feldman, Brian J.

2017-01-01

Amphetamine (AMPH) or methamphetamine (METH) abuse can cause oxidative damage and is a risk factor for diseases including pulmonary arterial hypertension (PAH). Pulmonary artery endothelial cells (PAECs) from AMPH-associated-PAH patients show DNA damage as judged by γH2AX foci and DNA comet tails. We therefore hypothesized that AMPH induces DNA damage and vascular pathology by interfering with normal adaptation to an environmental perturbation causing oxidative stress. Consistent with this, we found that AMPH alone does not cause DNA damage in normoxic PAECs, but greatly amplifies DNA damage in hypoxic PAECs. The mechanism involves AMPH activation of protein phosphatase 2A, which potentiates inhibition of Akt. This increases sirtuin 1, causing deacetylation and degradation of HIF1α, thereby impairing its transcriptional activity, resulting in a reduction in pyruvate dehydrogenase kinase 1 and impaired cytochrome c oxidase 4 isoform switch. Mitochondrial oxidative phosphorylation is inappropriately enhanced and, as a result of impaired electron transport and mitochondrial ROS increase, caspase-3 is activated and DNA damage is induced. In mice given binge doses of METH followed by hypoxia, HIF1α is suppressed and pulmonary artery DNA damage foci are associated with worse pulmonary vascular remodeling. Thus, chronic AMPH/METH can induce DNA damage associated with vascular disease by subverting the adaptive responses to oxidative stress. PMID:28138562

p-Coumaric Acid Attenuates UVB-Induced Release of Stratifin from Keratinocytes and Indirectly Regulates Matrix Metalloproteinase 1 Release from Fibroblasts

PubMed Central

Seok, Jin Kyung

2015-01-01

Ultraviolet (UV) radiation-induced loss of dermal extracellular matrix is associated with skin photoaging. Recent studies demonstrated that keratinocyte-releasable stratifin (SFN) plays a critical role in skin collagen metabolism by inducing matrix metalloproteinase 1 (MMP1) expression in target fibroblasts. In the present study, we examined whether SFN released from UVB-irradiated epidermal keratinocytes increases MMP1 release from dermal fibroblasts, and whether these events are affected by p-coumaric acid (p-CA), a natural phenolic compound with UVB-shielding and antioxidant properties. HaCaT cells were exposed to UVB in the absence and presence of p-CA, and the conditioned medium was used to stimulate fibroblasts in medium transfer experiments. The cells and media were analyzed to determine the expressions/releases of SFN and MMP1. UVB exposure increased SFN release from keratinocytes into the medium. The conditioned medium of UVB-irradiated keratinocytes increased MMP1 release from fibroblasts. The depletion of SFN using a siRNA rendered the conditioned medium of UVB-irradiated keratinocytes ineffective at stimulating fibroblasts to release MMP1. p-CA mitigated UVB-induced SFN expression in keratinocytes, and attenuated the MMP1 release by fibroblasts in medium transfer experiments. In conclusion, the present study demonstrated that the use of UV absorbers such as p-CA would reduce UV-induced SFN-centered signaling events involved in skin photoaging. PMID:25954129

p-Coumaric Acid Attenuates UVB-Induced Release of Stratifin from Keratinocytes and Indirectly Regulates Matrix Metalloproteinase 1 Release from Fibroblasts.

PubMed

Seok, Jin Kyung; Boo, Yong Chool

2015-05-01

Ultraviolet (UV) radiation-induced loss of dermal extracellular matrix is associated with skin photoaging. Recent studies demonstrated that keratinocyte-releasable stratifin (SFN) plays a critical role in skin collagen metabolism by inducing matrix metalloproteinase 1 (MMP1) expression in target fibroblasts. In the present study, we examined whether SFN released from UVB-irradiated epidermal keratinocytes increases MMP1 release from dermal fibroblasts, and whether these events are affected by p-coumaric acid (p-CA), a natural phenolic compound with UVB-shielding and antioxidant properties. HaCaT cells were exposed to UVB in the absence and presence of p-CA, and the conditioned medium was used to stimulate fibroblasts in medium transfer experiments. The cells and media were analyzed to determine the expressions/releases of SFN and MMP1. UVB exposure increased SFN release from keratinocytes into the medium. The conditioned medium of UVB-irradiated keratinocytes increased MMP1 release from fibroblasts. The depletion of SFN using a siRNA rendered the conditioned medium of UVB-irradiated keratinocytes ineffective at stimulating fibroblasts to release MMP1. p-CA mitigated UVB-induced SFN expression in keratinocytes, and attenuated the MMP1 release by fibroblasts in medium transfer experiments. In conclusion, the present study demonstrated that the use of UV absorbers such as p-CA would reduce UV-induced SFN-centered signaling events involved in skin photoaging.

IKKα contributes to UVB-induced VEGF expression by regulating AP-1 transactivation

PubMed Central

Dong, Wen; Li, Yi; Gao, Ming; Hu, Meiru; Li, Xiaoguang; Mai, Sanyue; Guo, Ning; Yuan, Shengtao; Song, Lun

2012-01-01

Exposure to ultraviolet B (UVB) irradiation from sunlight induces the upregulation of VEGF, a potent angiogenic factor that is critical for mediating angiogenesis-associated photodamage. However, the molecular mechanisms related to UVB-induced VEGF expression have not been fully defined. Here, we demonstrate that one of the catalytic subunits of the IκB kinase complex (IKK), IKKα, plays a critical role in mediating UVB-induced VEGF expression in mouse embryonic fibroblasts (MEFs), which requires IKKα kinase activity but is independent of IKKβ, IKKγ and the transactivation of NF-κB. We further show that the transcriptional factor AP-1 functions as the downstream target of IKKα that is responsible for VEGF induction under UVB exposure. Both the accumulation of AP-1 component, c-Fos and the transactivation of AP-1 by UVB require the activated IKKα located within the nucleus. Moreover, nuclear IKKα can associate with c-Fos and recruit to the vegf promoter regions containing AP-1-responsive element and then trigger phosphorylation of the promoter-bound histone H3. Thus, our results have revealed a novel independent role for IKKα in controlling VEGF expression during the cellular UVB response by regulating the induction of the AP-1 component and phosphorylating histone H3 to facilitate AP-1 transactivation. Targeting IKKα shows promise for the prevention of UVB-induced angiogenesis and the associated photodamage. PMID:22169952

An extended sequence specificity for UV-induced DNA damage.

PubMed

Chung, Long H; Murray, Vincent

2018-01-01

The sequence specificity of UV-induced DNA damage was determined with a higher precision and accuracy than previously reported. UV light induces two major damage adducts: cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). Employing capillary electrophoresis with laser-induced fluorescence and taking advantages of the distinct properties of the CPDs and 6-4PPs, we studied the sequence specificity of UV-induced DNA damage in a purified DNA sequence using two approaches: end-labelling and a polymerase stop/linear amplification assay. A mitochondrial DNA sequence that contained a random nucleotide composition was employed as the target DNA sequence. With previous methodology, the UV sequence specificity was determined at a dinucleotide or trinucleotide level; however, in this paper, we have extended the UV sequence specificity to a hexanucleotide level. With the end-labelling technique (for 6-4PPs), the consensus sequence was found to be 5'-GCTC*AC (where C* is the breakage site); while with the linear amplification procedure, it was 5'-TCTT*AC. With end-labelling, the dinucleotide frequency of occurrence was highest for 5'-TC*, 5'-TT* and 5'-CC*; whereas it was 5'-TT* for linear amplification. The influence of neighbouring nucleotides on the degree of UV-induced DNA damage was also examined. The core sequences consisted of pyrimidine nucleotides 5'-CTC* and 5'-CTT* while an A at position "1" and C at position "2" enhanced UV-induced DNA damage. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Calculation on spectrum of direct DNA damage induced by low-energy electrons including dissociative electron attachment.

PubMed

Liu, Wei; Tan, Zhenyu; Zhang, Liming; Champion, Christophe

2017-03-01

In this work, direct DNA damage induced by low-energy electrons (sub-keV) is simulated using a Monte Carlo method. The characteristics of the present simulation are to consider the new mechanism of DNA damage due to dissociative electron attachment (DEA) and to allow determining damage to specific bases (i.e., adenine, thymine, guanine, or cytosine). The electron track structure in liquid water is generated, based on the dielectric response model for describing electron inelastic scattering and on a free-parameter theoretical model and the NIST database for calculating electron elastic scattering. Ionization cross sections of DNA bases are used to generate base radicals, and available DEA cross sections of DNA components are applied for determining DNA-strand breaks and base damage induced by sub-ionization electrons. The electron elastic scattering from DNA components is simulated using cross sections from different theoretical calculations. The resulting yields of various strand breaks and base damage in cellular environment are given. Especially, the contributions of sub-ionization electrons to various strand breaks and base damage are quantitatively presented, and the correlation between complex clustered DNA damage and the corresponding damaged bases is explored. This work shows that the contribution of sub-ionization electrons to strand breaks is substantial, up to about 40-70%, and this contribution is mainly focused on single-strand break. In addition, the base damage induced by sub-ionization electrons contributes to about 20-40% of the total base damage, and there is an evident correlation between single-strand break and damaged base pair A-T.

Chemopreventive apigenin controls UVB-induced cutaneous proliferation and angiogenesis through HuR and thrombospondin-1

PubMed Central

Veliceasa, Dorina; Bridgeman, Bryan B.; Fitchev, Philip; Cornwell, Mona L.; Crawford, Susan E.; Pelling, Jill C.; Volpert, Olga V.

2014-01-01

Plant flavonoid apigenin prevents and inhibits UVB-induced carcinogenesis in the skin and has strong anti-proliferative and anti-angiogenic properties. Here we identify mechanisms, by which apigenin controls these oncogenic events. We show that apigenin acts, at least in part, via endogenous angiogenesis inhibitor, thrombospondin-1 (TSP1). TSP1 expression by the epidermal keratinocytes is potently inhibited by UVB. It inhibits cutaneous angiogenesis and UVB-induced carcinogenesis. We show that apigenin restores TSP1 in epidermal keratinocytes subjected to UVB and normalizes proliferation and angiogenesis in UVB-exposed skin. Importantly, reconstituting TSP1 anti-angiogenic function in UVB-irradiated skin with a short bioactive peptide mimetic representing exclusively its anti-angiogenic domain reproduced the anti-proliferative and anti-angiogenic effects of apigenin. Cox-2 and HIF-1α are important mediators of angiogenesis. Both apigenin and TSP1 peptide mimetic attenuated their induction by UVB. Finally we identified the molecular mechanism, whereby apigenin did not affect TSP1 mRNA, but increased de novo protein synthesis. Knockdown studies implicated the RNA-binding protein HuR, which controls mRNA stability and translation. Apigenin increased HuR cytoplasmic localization and physical association with TSP1 mRNA causing de novo TSP1 synthesis. HuR cytoplasmic localization was, in turn, dependent on CHK2 kinase. Together, our data provide a new mechanism, by which apigenin controls UVB-induced carcinogenesis. PMID:25526033

Oxidative damage in response to natural levels of UV-B radiation in larvae of the tropical sea urchin Tripneustes gratilla.

PubMed

Lister, Kathryn Naomi; Lamare, Miles D; Burritt, David J

2010-01-01

To assess the effects of UV radiation (280-400nm) on development, oxidative damage and antioxidant defence in larvae of the tropical sea urchin Tripneustes gratilla, a field experiment was conducted at two depths in Aitutaki, Cook Islands (18.85°S, 159.75°E) in May 2008. Compared with field controls (larvae shielded from UV-R but exposed to VIS-radiation), UV-B exposure resulted in developmental abnormality and increases in oxidative damage to proteins (but not lipids) in embryos of T. gratilla held at 1m depth. Results also indicated that larvae had the capacity to increase the activities of protective antioxidant enzymes when exposed to UV-B. The same trends in oxidative damage and antioxidant defence were observed for embryos held at 4m, although the differences were smaller and more variable. In contrast to UV-B exposure, larvae exposed to UV-A only showed no significant increases in abnormality or oxidative damage to lipids and proteins compared with field controls. This was true at both experimental depths. Furthermore, exposure to UV-A did not cause a significant increase in the activities of antioxidants. This study indicates that oxidative stress is an important response of tropical sea urchin larvae to exposure to UV radiation. © 2010 The Authors. Journal Compilation. The American Society of Photobiology.

Overlapping Leaves Covering Flowers in the Alpine Species Eriophyton wallichii (Lamiaceae): Key Driving Factors and Their Potential Impact on Pollination.

PubMed

Peng, De-Li; Song, Bo; Yang, Yang; Niu, Yang; Sun, Hang

2016-01-01

Extrafloral structures are supposed to have evolved to protect flowers from harsh physical environments but might have effects on pollination. Overlapping leaves cover flowers in Eriophyton wallichii, an alpine perennial endemic to the Himalaya-Hengduan Mountains. In previous study, it has showed that these extrafloral leaves can protect interior flowers from temperature fluctuations caused by drastic solar radiation fluctuations, but these leaves may also protect interior flowers from rain wash and UVB damage, and we do not know which one is the main function. In this study, we investigated whether rain and UVB protection are the main functions of overlapping leaves covering flowers and their potential impact on pollination. We first measured the intensities of UVB radiation in open air, beneath leaves and corollas, and then examined pollen susceptibility to different intensities of UVB and rain in the laboratory to estimate whether corollas per se protect interior pollen from UVB and rain damage. We also carried out pollination treatments and observed pollinator visitation of flowers with and without leaves in the field to assess whether the overlapping leaves covering flowers impair pollinator attraction. Our results showed that (1) water and strong UVB significantly decreased pollen germinability, but corollas per se could protect pollen from UVB and rain damage; (2) no autonomous self-pollination and apomixis occurred, and pollinators were essential for the reproduction of E. wallichii; however, flower coverage by overlapping leaves did not limit pollination. We suggested that rain and UVB protection was not the main function of overlapping leaves covered flowers, given that this protection can be provided by corollas per se. Alternatively, this extrafloral structure in E. wallichii may have evolved in response to extreme high temperatures associated with the strong solar radiation fluctuations. This indicates that, even in alpine plants, extreme high temperature may affect the evolution of plant extrafloral structures.

Overlapping Leaves Covering Flowers in the Alpine Species Eriophyton wallichii (Lamiaceae): Key Driving Factors and Their Potential Impact on Pollination

PubMed Central

Peng, De-Li; Song, Bo; Yang, Yang; Niu, Yang; Sun, Hang

2016-01-01

Extrafloral structures are supposed to have evolved to protect flowers from harsh physical environments but might have effects on pollination. Overlapping leaves cover flowers in Eriophyton wallichii, an alpine perennial endemic to the Himalaya-Hengduan Mountains. In previous study, it has showed that these extrafloral leaves can protect interior flowers from temperature fluctuations caused by drastic solar radiation fluctuations, but these leaves may also protect interior flowers from rain wash and UVB damage, and we do not know which one is the main function. In this study, we investigated whether rain and UVB protection are the main functions of overlapping leaves covering flowers and their potential impact on pollination. We first measured the intensities of UVB radiation in open air, beneath leaves and corollas, and then examined pollen susceptibility to different intensities of UVB and rain in the laboratory to estimate whether corollas per se protect interior pollen from UVB and rain damage. We also carried out pollination treatments and observed pollinator visitation of flowers with and without leaves in the field to assess whether the overlapping leaves covering flowers impair pollinator attraction. Our results showed that (1) water and strong UVB significantly decreased pollen germinability, but corollas per se could protect pollen from UVB and rain damage; (2) no autonomous self-pollination and apomixis occurred, and pollinators were essential for the reproduction of E. wallichii; however, flower coverage by overlapping leaves did not limit pollination. We suggested that rain and UVB protection was not the main function of overlapping leaves covered flowers, given that this protection can be provided by corollas per se. Alternatively, this extrafloral structure in E. wallichii may have evolved in response to extreme high temperatures associated with the strong solar radiation fluctuations. This indicates that, even in alpine plants, extreme high temperature may affect the evolution of plant extrafloral structures. PMID:27716786

Flow cytometric detection of micronuclei by combined staining of DNA and membranes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wessels, J.M.; Nuesse, M.

1995-03-01

A new staining method is presented for flow cytometric measurement of micronuclei (MN) in cell cultures and human lymphocytes using membrane-specific fluorescent dyes in addition to DNA staining. Several combinations of fluorescent membrane and DNA dyes were studied for a better discrimination of MN from debris in a suspension of nuclei and micronuclei. For staining of membranes, the lipophilic dyes 2-hydroxyethyl-7,12,17-tris(methoxyethyl)porphycene (HEPn) and 1,6-diphenyl-1,3,5-hexatriene (DPH) were used in combination with ethidium bromide (EB), proflavine (PF), and Hoechst 33258 (HO). Due to their spectral properties, HO or EB combined with HEPn were not as suitable for the discrimination of MN frommore » debris as was HEPn in combination with PF. With HEPn in combination with PF, however, additional noise was found at low fluorescence intensities, probably due to free fluorescent dye molecules in the solution. The optimal simultaneous staining of membranes and DNA was obtained using a combination of DPH and EB. The induction of MN in Chinese hamster and mouse NIH-3T3 cells by UV-B illumination was studied with this new staining technique. UV-B illumination (280-360 nm) induced MN in both cell lines. Chinese hamster cells were found to be more sensitive to these wavelengths. Illumination with wavelengths above 360 nm did not induce MN in either cell line. The results obtained from human lymphocytes using the combination of EB or DPH were comparable to the results obtained with the combination of EB and HO. 23 refs., 7 figs.« less

Simulation study of natural UV-B radiation on Catla catla and its impact on physiology, oxidative stress, Hsp 70 and DNA fragmentation.

PubMed

Singh, Moirangthem Kameshwor; Sharma, Jai Gopal; Chakrabarti, Rina

2015-08-01

UV-B radiation is a potential stressor to the aquacultural species. Catla catla, catla larvae (1.08±0.065g) were exposed to different doses of UV-B radiation, 0 (control), 504, 1008, 1512 and 2016mJ/cm(2) at a mean radiant energy of 80μW/cm(2) for 21days. The dose of UV-B radiation was selected on the basis of the field study conducted in Lake Naini, Delhi, India (Latitude: 28°41'26″N and Longitude: 77°12″37″E). Significantly (P<0.05) lower survival, average weight and specific growth rate were found in UV-B irradiated larvae compared to the control one. Food conversion ratio was 1.5-4-fold higher in UV-B treated larvae compared to the control one. The carbonyl protein (CP), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) levels were significantly (P <0.05) higher in UV-B irradiated larvae compared to the control group. Among the treated larvae, CP and SOD were significantly (P <0.05) higher in larvae exposed at 1512mJ/cm(2) UV-B. A correlation was found between the CP and SOD (R(2)=0.834). Highest TBARS level was found in 2016mJ/cm(2) UV-B exposed catla. Nitric oxide synthase level was significantly (P <0.05) lower in UV-B exposed larvae compared to the control one. A 3-fold increased Hsp 70 level was recorded in UV-B irradiated catla compared to the control larvae. Comet assay analysis indicated that UV-B irradiation enhanced DNA fragmentation. Tail extent moment and the olive tail moment were significantly (P <0.05) higher in 2016mJ/cm(2) UV-B exposed catla compared to others. The tail length was significantly (P <0.05) higher in 1512 and 2016mJ/cm(2) UV-B exposed larvae compared to the other doses. The present study suggests that the catla is a useful species for the biomonitoring of stress in the aquatic environment. Copyright © 2015 Elsevier B.V. All rights reserved.

Time and dose-response effects of honokiol on UVB-induced skin cancer development.

PubMed

Guillermo, Ruth F; Chilampalli, Chandeshwari; Zhang, Xiaoying; Zeman, David; Fahmy, Hesham; Dwivedi, Chandradhar

2012-06-01

Honokiol has shown chemopreventive effects in chemically-induced and UVB-induced skin cancer in mice. In this investigation, we assessed the time-effects of a topical low dose of honokiol (30 μg), and then the effects of different honokiol doses (30, 45, and 60 μg) on a UVB-induced skin cancer model to find an optimal dose and time for desirable chemopreventive effects. UVB radiation (30 mJ/cm(2), 5 days/week for 25 or 27 weeks) was used to induce skin carcinogenesis in SKH-1 mice. For the time-response experiment 30 μg honokiol in acetone was applied topically to the animals before the UVB exposure (30 min, 1 h, and 2 h) and after the UVB exposure (immediately, 30 min, and 1 h). Control groups were treated with acetone. For the dose-response study, animals were treated topically with acetone or honokiol (30, 45, and 60 μg) one hour before the UVB exposure. In the time-response experiment, honokiol inhibited skin tumor multiplicity by 49-58% while reducing tumor volumes by 70-89%. In the dose-response study, honokiol (30, 45, and 60 μg) significantly decreased skin tumor multiplicity by 36-78% in a dose-dependent manner, while tumor area was reduced by 76-94%. Honokiol (60 μg) significantly reduced tumor incidence by 40% as compared to control group. Honokiol applied in very low doses (30 μg) either before or after UVB radiation shows chemopreventive effects. Honokiol (30, 45, and 60 μg) prevents UVB-induced skin cancer in a dose-dependent manner. Honokiol can be an effective chemopreventive agent against skin cancer.

DNA damage, DNA susceptibility to oxidation and glutathione redox status in patients with Alzheimer's disease treated with and without memantine.

PubMed

Akkaya, Çağlayan; Yavuzer, Serap Sahin; Yavuzer, Hakan; Erkol, Gökhan; Bozluolcay, Melda; Dinçer, Yıldız

2017-07-15

The aim of the current study was to compare oxidative DNA damage, DNA susceptibility to oxidation, and ratio of GSH/GSSG in patients with Alzheimer's disease (AD) treated with acetylcholinesterase inhibitor (AChEI) and combined AChEI+memantine. The study included 67 patients with AD and 42 volunteers as control. DNA damage parameters (strand breaks, oxidized purines, H 2 O 2 -induced DNA damage) in lymphocyte DNA and GSH/GSSG ratio in erythrocytes were determined by the comet assay and spectrophotometric assay, respectively. DNA damage was found to be higher, GSH/GSSG ratio was found to be lower in the AD group than those in the control group. DNA strand breaks and H 2 O 2 -induced DNA damage were lower in the patients taking AChEI+memantine than those in the patients taking AChEI but no significant difference was determined between the groups for oxidized purines and GSH/GSSG ratio. In conclusion, increased systemic oxidative DNA damage and DNA susceptibility to oxidation may be resulted from diminished GSH/GSSG ratio in AD patients. Although DNA strand breaks and H 2 O 2 -induced DNA damage are lower in the AD patients treated with combined AChEI and memantine, this may not indicate protective effect of memantine against DNA oxidation due to similar levels of oxidized purines in the patients treated with AChEI and AChEI+memantine. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanisms of sulfur mustard analog 2-chloroethyl ethyl sulfide-induced DNA damage in skin epidermal cells and fibroblasts.

PubMed

Inturi, Swetha; Tewari-Singh, Neera; Gu, Mallikarjuna; Shrotriya, Sangeeta; Gomez, Joe; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

2011-12-15

Employing mouse skin epidermal JB6 cells and dermal fibroblasts, here we examined the mechanisms of DNA damage by 2-chloroethyl ethyl sulfide (CEES), a monofunctional analog of sulfur mustard (SM). CEES exposure caused H2A.X and p53 phosphorylation as well as p53 accumulation in both cell types, starting at 1h, that was sustained for 24h, indicating a DNA-damaging effect of CEES, which was also confirmed and quantified by alkaline comet assay. CEES exposure also induced oxidative stress and oxidative DNA damage in both cell types, measured by an increase in mitochondrial and cellular reactive oxygen species and 8-hydroxydeoxyguanosine levels, respectively. In the studies distinguishing between oxidative and direct DNA damage, 1h pretreatment with glutathione (GSH) or the antioxidant Trolox showed a decrease in CEES-induced oxidative stress and oxidative DNA damage. However, only GSH pretreatment decreased CEES-induced total DNA damage measured by comet assay, H2A.X and p53 phosphorylation, and total p53 levels. This was possibly due to the formation of GSH-CEES conjugates detected by LC-MS analysis. Together, our results show that CEES causes both direct and oxidative DNA damage, suggesting that to rescue SM-caused skin injuries, pleiotropic agents (or cocktails) are needed that could target multiple pathways of mustard skin toxicities. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of climate change and UV-B on materials.

PubMed

Andrady, Anthony L; Hamid, Halim S; Torikai, Ayako

2003-01-01

The outdoor service life of common plastic materials is limited by their susceptibility to solar ultraviolet radiation. Of the solar wavelengths the UV-B component is particularly efficient in bringing about photodamage in synthetic and naturally occurring materials. This is particularly true of plastics, rubber and wood used in the building and agricultural industries. Any depletion in the stratospheric ozone layer and resulting increase in the UV-B component of terrestrial sunlight will therefore tend to decrease the service life of these materials. The extent to which the service life is reduced is, however, difficult to estimate as it depends on several factors. These include the chemical nature of the material, the additives it contains, the type and the amount of light-stabilizers (or protective coatings) used, and the amount of solar exposure it receives. Concomitant climate change is likely to increase the ambient temperature and humidity in some of the same regions likely to receive increased UV-B radiation. These factors, particularly higher temperatures, are also well known to accelerate the rate of photodegradation of materials, and may therefore further limit the service life of materials in these regions. To reliably assess the damage to materials as a consequence of ozone layer depletion, the wavelength sensitivity of the degradation process, dose-response relationships for the material and the effectiveness of available stabilizers need to be quantified. The data needed for the purpose are not readily available at this time for most of the commonly used plastics or wood materials. Wavelength sensitivity of a number of common plastic materials and natural biopolymers are available and generally show the damage (per photon) to decrease exponentially with the wavelength. Despite the relatively higher fraction of UV-A in sunlight, the UV-B content is responsible for a significant part of light-induced damage of materials. The primary approach to mitigation relies on the effectiveness of the existing light stabilizers (such as hindered amine light stabilizers, HALS) used in plastics exposed to harsh solar UV conditions coupled with climate change factors. In developing advanced light-stabilizer technologies, more light-resistant grades of common plastics, or surface protection technologies for wood, the harsh weathering environment created by the simultaneous action of increased UV-B levels due to ozone depletion as well as the relevant climate change factors need to be taken into consideration. Recent literature includes several studies on synergism of HALS-based stabilizers, stabilizer effectiveness in the new m-polyolefins and elucidation of the mechanism of stabilization afforded by titania pigment in vinyl plastics.

Interactive Effects of UV-B Light with Abiotic Factors on Plant Growth and Chemistry, and Their Consequences for Defense against Arthropod Herbivores

PubMed Central

Escobar-Bravo, Rocio; Klinkhamer, Peter G. L.; Leiss, Kirsten A.

2017-01-01

Ultraviolet-B (UV-B) light plays a crucial role in plant–herbivorous arthropods interactions by inducing changes in constitutive and inducible plant defenses. In particular, constitutive defenses can be modulated by UV-B-induced photomorphogenic responses and changes in the plant metabolome. In accordance, the prospective use of UV-B light as a tool to increase plant protection in agricultural practice has gained increasing interest. Changes in the environmental conditions might, however, modulate the UV-B -induced plant responses. While in some cases plant responses to UV-B can increase adaptation to changes in certain abiotic factors, UV-B-induced responses might be also antagonized by the changing environment. The outcome of these interactions might have a great influence on how plants interact with their enemies, e.g., herbivorous arthropods. Here, we provide a review on the interactive effects of UV-B and light quantity and quality, increased temperature and drought stress on plant biochemistry, and we discuss the implications of the outcome of these interactions for plant resistance to arthropod pests. PMID:28303147

The role of lipid raft translocation of prohibitin in regulation of Akt and Raf-protected apoptosis of HaCaT cells upon ultraviolet B irradiation.

PubMed

Wu, Qiong; Wu, Shiyong

2017-07-01

Prohibitin (PHB) plays a role in regulation of ultraviolet B light (UVB)-induced apoptosis of human keratinocytes, HaCaT cells. The regulatory function of PHB appears to be associated with its lipid raft translocation. However, the detailed mechanism for PHB-mediated apoptosis of these keratinocytes upon UVB irradiation is not clear. In this report, we determined the role of lipid raft translocation of PHB in regulation of UVB-induced apoptosis. Our data show that upon UVB irradiation PHB is translocated from the non-raft membrane to the lipid rafts, which is correlated with a release of both Akt and Raf from membrane. Overexpression of Akt and/or Raf impedes UVB-induced lipid raft translocation of PHB. Immunoprecipitation analysis indicates that UVB alters the interactions among PHB, Akt, and Raf. Reduced expression of PHB leads to a decreased phosphorylation of Akt and ERK, as well as a decreased activity of Akt, and increased apoptosis of the cells upon UVB irradiation. These results suggest that PHB regulates UVB-induced apoptosis of keratinocytes via a mechanism that involves detachment from Akt and Raf on the plasma membrane, and sequential lipid raft translocation. © 2017 Wiley Periodicals, Inc.

DETECTION OF LOW DOSE RADIATION-AND CHEMICALLY-INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAYS

EPA Science Inventory

Rapid, sensitive and simple assays for radiation- and chemically-induced DNA damage can be of significant benefit to a number of fields including radiation biology, clinical research, and environmental monitoring. Although temperature-induced DNA strand separation has been use...

Glucose transporter member 1 is involved in UVB-induced epidermal hyperplasia by enhancing proliferation in epidermal keratinocytes.

PubMed

Tochio, Takumi; Tanaka, Hiroshi; Nakata, Satoru

2013-03-01

Glucose transporter member 1 (GLUT-1) is one of the major facilitated glucose transporters and contributes to the promotion of keratinocyte proliferation in psoriasis and carcinogenic lesions. In this study, we postulate that GLUT-1 is involved in ultraviolet B (UVB)-induced epidermal hyperplasia. The purpose of this study is to investigate the possible role of GLUT-1 in UVB-induced hyperplasia. The effects of UVB on GLUT-1 expression levels were investigated in in vitro and in vivo studies. In addition, the involvement of epidermal growth factor (EGF) and hypoxia inducible factor-1 alpha (HIF-1α), transcriptional factors for GLUT-1, in GLUT-1-related events were investigated. GLUT-1 mRNA and its protein levels were markedly increased by UVB irradiation in HaCaT cells. In in vivo studies, a strong immunofluorescence signal of GLUT-1 was clearly observed around the basal layer of the epidermis, which proliferated excessively by UVB irradiation. In HaCaT cells, EGF mRNA and its protein levels were markedly increased by UVB irradiation, and then the GLUT-1 mRNA level was significantly increased by treatment with EGF. Additionally, the upregulation of GLUT-1 by both UVB irradiation and treatment with EGF was significantly suppressed by transfection with HIF-1α siRNA. We conclude that GLUT-1 is involved in UVB-induced epidermal hyperplasia by enhancing proliferation of epidermal basal cells, and the GLUT-1-related event might be regulated by an increase in HIF-1α stimulated by EGF. © 2013 The International Society of Dermatology.

Cold atmospheric-pressure plasma induces DNA-protein crosslinks through protein oxidation.

PubMed

Guo, Li; Zhao, Yiming; Liu, Dingxin; Liu, Zhichao; Chen, Chen; Xu, Ruobing; Tian, Miao; Wang, Xiaohua; Chen, Hailan; Kong, Michael G

2018-05-03

Reactive oxygen and nitrogen species (ROS and RNS) generated by cold atmospheric-pressure plasma could damage genomic DNA, although the precise type of these DNA damage induced by plasma are poorly characterized. Understanding plasma-induced DNA damage will help to elucidate the biological effect of plasma and guide the application of plasma in ROS-based therapy. In this study, it was shown that ROS and RNS generated by physical plasma could efficiently induce DNA-protein crosslinks (DPCs) in bacteria, yeast, and human cells. An in vitro assay showed that plasma treatment resulted in the formation of covalent DPCs by activating proteins to crosslink with DNA. Mass spectrometry and hydroperoxide analysis detected oxidation products induced by plasma. DPC formation were alleviated by singlet oxygen scavenger, demonstrating the importance of singlet oxygen in this process. These results suggested the roles of DPC formation in DNA damage induced by plasma, which could improve the understanding of the biological effect of plasma and help to develop a new strategy in plasma-based therapy including infection and cancer therapy.

Direct observation of ultrafast-electron-transfer reactions unravels high effectiveness of reductive DNA damage

PubMed Central

Nguyen, Jenny; Ma, Yuhan; Luo, Ting; Bristow, Robert G.; Jaffray, David A.; Lu, Qing-Bin

2011-01-01

Both water and electron-transfer reactions play important roles in chemistry, physics, biology, and the environment. Oxidative DNA damage is a well-known mechanism, whereas the relative role of reductive DNA damage is unknown. The prehydrated electron (), a novel species of electrons in water, is a fascinating species due to its fundamental importance in chemistry, biology, and the environment. is an ideal agent to observe reductive DNA damage. Here, we report both the first in situ femtosecond time-resolved laser spectroscopy measurements of ultrafast-electron-transfer (UET) reactions of with various scavengers (KNO3, isopropanol, and dimethyl sulfoxide) and the first gel electrophoresis measurements of DNA strand breaks induced by and OH• radicals co-produced by two-UV-photon photolysis of water. We strikingly found that the yield of reductive DNA strand breaks induced by each is twice the yield of oxidative DNA strand breaks induced by each OH• radical. Our results not only unravel the long-standing mystery about the relative role of radicals in inducing DNA damage under ionizing radiation, but also challenge the conventional notion that oxidative damage is the main pathway for DNA damage. The results also show the potential of femtomedicine as a new transdisciplinary frontier and the broad significance of UET reactions of in many processes in chemistry, physics, biology, and the environment. PMID:21730183

Intake of high-fat diet stimulates the risk of ultraviolet radiation-induced skin tumors and malignant progression of papillomas to carcinoma in SKH-1 hairless mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaid, Mudit; Singh, Tripti; Prasad, Ram

Previously, we showed that administration of a high-fat diet (HF-diet) to C57BL/6 mice exacerbates their response to short-term UVB radiation-induced inflammation in the skin. To explore the effects of an HF-diet on UVB-induced tumorigenesis, we have used the SKH-1 hairless mouse model in which the mice are exposed to UVB radiation (180 mJ/cm{sup 2}) three times a week for 24 weeks. The development of UVB-induced skin tumors was rapid and the tumor multiplicity and tumor size were significantly higher (P < 0.01–0.005) in the mice fed an HF-diet than the mice fed a control-diet (C-diet). Moreover, the malignant progression ofmore » UVB-induced papillomas to carcinomas was higher in HF-diet-fed mice. On analysis of tumors and tumor-uninvolved skin samples from the tumor-bearing mice, we found that administration of an HF-diet significantly enhanced the levels of UVB-induced expression of cyclooxygenase-2 (COX-2), prostaglandin E{sub 2} (P < 0.01), and PGE{sub 2} receptors, and activation of NF-κB in the UVB-exposed skin as well as in tumors. In addition the HF-diet enhanced the expression of proinflammatory cytokines, including tumor necrosis factor-α (P < 0.01), interleukin (IL)-1β (P < 0.01) and IL-6 (P < 0.05) in the UVB-exposed skin as well as in tumors. Western blot analysis revealed that HF-diet enhanced the levels of epidermal cell proliferation, phosphatidylinositol 3-kinase and phosphorylation of Akt at Ser{sup 473} in UVB-exposed skin and skin tumors. Collectively, these data demonstrate that the regular consumption of an HF-diet increases the risk of photocarcinogenesis in mice and that this is associated with enhanced expression of inflammatory mediators in the UVB-exposed skin and tumors. - Highlights: • Consumption of high-fat diet increases UVB-induced skin tumor development in mice. • Intake of high-fat diet stimulates progression of UV-induced papilloma to carcinoma. • Intake of high-fat diet enhances inflammation in UV-exposed skin • Regular consumption of low-fat diet may inhibit the risk of photocarcinogenesis.« less

UV-B Induced Generation of Reactive Oxygen Species Promotes Formation of BFA-Induced Compartments in Cells of Arabidopsis Root Apices

PubMed Central

Yokawa, Ken; Kagenishi, Tomoko; Baluška, František

2016-01-01

UV-B radiation is an important part of the electromagnetic spectrum emitted by the sun. For much of the period of biological evolution organisms have been exposed to UV radiation, and have developed diverse mechanisms to cope with this potential stress factor. Roots are usually shielded from exposure to UV by the surrounding soil, but may nevertheless be exposed to high energy radiation on the soil surface. Due to their high sensitivity to UV-B radiation, plant roots need to respond rapidly in order to minimize exposure on the surface. In addition to root gravitropism, effective light perception by roots has recently been discovered to be essential for triggering negative root phototropism in Arabidopsis. However, it is not fully understood how UV-B affects root growth and phototropism. Here, we report that UV-B induces rapid generation of reactive oxygen species which in turn promotes the formation of BFA-induced compartments in the Arabidopsis root apex. During unilateral UV-B irradiation of roots changes in auxin concentration on the illuminated side have been recorded. In conclusion, UV-B-induced and ROS-mediated stimulation of vesicle recycling promotes root growth and induces negative phototropism. PMID:26793199

Interplay between DNA repair and inflammation, and the link to cancer

PubMed Central

Kidane, Dawit; Chae, Wook Jin; Czochor, Jennifer; Eckert, Kristin A.; Glazer, Peter M.; Bothwell, Alfred L. M.; Sweasy, Joann B.

2015-01-01

DNA damage and repair are linked to cancer. DNA damage that is induced endogenously or from exogenous sources has the potential to result in mutations and genomic instability if not properly repaired, eventually leading to cancer. Inflammation is also linked to cancer. Reactive oxygen and nitrogen species (RONs) produced by inflammatory cells at sites of infection can induce DNA damage. RONs can also amplify inflammatory responses, leading to increased DNA damage. Here, we focus on the links between DNA damage, repair, and inflammation, as they relate to cancer. We examine the interplay between chronic inflammation, DNA damage and repair and review recent findings in this rapidly emerging field, including the links between DNA damage and the innate immune system, and the roles of inflammation in altering the microbiome, which subsequently leads to the induction of DNA damage in the colon. Mouse models of defective DNA repair and inflammatory control are extensively reviewed, including treatment of mouse models with pathogens, which leads to DNA damage. The roles of microRNAs in regulating inflammation and DNA repair are discussed. Importantly, DNA repair and inflammation are linked in many important ways, and in some cases balance each other to maintain homeostasis. The failure to repair DNA damage or to control inflammatory responses has the potential to lead to cancer. PMID:24410153

Inhibition of mTOR by apigenin in UVB-irradiated keratinocytes: A new implication of skin cancer prevention.

PubMed

Bridgeman, Bryan B; Wang, Pu; Ye, Boping; Pelling, Jill C; Volpert, Olga V; Tong, Xin

2016-05-01

Ultraviolet B (UVB) radiation is the major environmental risk factor for developing skin cancer, the most common cancer worldwide, which is characterized by aberrant activation of Akt/mTOR (mammalian target of rapamycin). Importantly, the link between UV irradiation and mTOR signaling has not been fully established. Apigenin is a naturally occurring flavonoid that has been shown to inhibit UV-induced skin cancer. Previously, we have demonstrated that apigenin activates AMP-activated protein kinase (AMPK), which leads to suppression of basal mTOR activity in cultured keratinocytes. Here, we demonstrated that apigenin inhibited UVB-induced mTOR activation, cell proliferation and cell cycle progression in mouse skin and in mouse epidermal keratinocytes. Interestingly, UVB induced mTOR signaling via PI3K/Akt pathway, however, the inhibition of UVB-induced mTOR signaling by apigenin was not Akt-dependent. Instead, it was driven by AMPK activation. In addition, mTOR inhibition by apigenin in keratinocytes enhanced autophagy, which was responsible, at least in part, for the decreased proliferation in keratinocytes. In contrast, apigenin did not alter UVB-induced apoptosis. Taken together, our results indicate the important role of mTOR inhibition in UVB protection by apigenin, and provide a new target and strategy for better prevention of UV-induced skin cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Inactivation of NADPH oxidases NOX4 and NOX5 protects human primary fibroblasts from ionizing radiation-induced DNA damage.

PubMed

Weyemi, Urbain; Redon, Christophe E; Aziz, Towqir; Choudhuri, Rohini; Maeda, Daisuke; Parekh, Palak R; Bonner, Michael Y; Arbiser, Jack L; Bonner, William M

2015-03-01

Human exposure to ionizing radiation from medical procedures has increased sharply in the last three decades. Recent epidemiological studies suggest a direct relationship between exposure to ionizing radiation and health problems, including cancer incidence. Therefore, minimizing the impact of radiation exposure in patients has become a priority in the development of future clinical practices. Crucial players in radiation-induced DNA damage include reactive oxygen species (ROS), but the sources of these have remained elusive. To the best of our knowledge, we show here for the first time that two members of the ROS-generating NADPH oxidase family (NOXs), NOX4 and NOX5, are involved in radiation-induced DNA damage. Depleting these two NOXs in human primary fibroblasts resulted in reduced levels of DNA damage as measured by levels of radiation-induced foci, a marker of DNA double-strand breaks (DSBs) and the comet assay coupled with increased cell survival. NOX involvement was substantiated with fulvene-5, a NOXs-specific inhibitor. Moreover, fulvene-5 mitigated radiation-induced DNA damage in human peripheral blood mononuclear cells ex vivo. Our results provide evidence that the inactivation of NOXs protects cells from radiation-induced DNA damage and cell death. These findings suggest that NOXs inhibition may be considered as a future pharmacological target to help minimize the negative effects of radiation exposure for millions of patients each year.

Inactivation of NADPH Oxidases NOX4 and NOX5 Protects Human Primary Fibroblasts from Ionizing Radiation-Induced DNA Damage

PubMed Central

Weyemi, Urbain; Redon, Christophe E.; Aziz, Towqir; Choudhuri, Rohini; Maeda, Daisuke; Parekh, Palak R.; Bonner, Michael Y.; Arbiser, Jack L.; Bonner, William M.

2015-01-01

Human exposure to ionizing radiation from medical procedures has increased sharply in the last three decades. Recent epidemiological studies suggest a direct relationship between exposure to ionizing radiation and health problems, including cancer incidence. Therefore, minimizing the impact of radiation exposure in patients has become a priority in the development of future clinical practices. Crucial players in radiation-induced DNA damage include reactive oxygen species (ROS), but the sources of these have remained elusive. To the best of our knowledge, we show here for the first time that two members of the ROS-generating NADPH oxidase family (NOXs), NOX4 and NOX5, are involved in radiation-induced DNA damage. Depleting these two NOXs in human primary fibroblasts resulted in reduced levels of DNA damage as measured by levels of radiation-induced foci, a marker of DNA double-strand breaks (DSBs) and the comet assay coupled with increased cell survival. NOX involvement was substantiated with fulvene-5, a NOXs-specific inhibitor. Moreover, fulvene-5 mitigated radiation-induced DNA damage in human peripheral blood mononuclear cells ex vivo. Our results provide evidence that the inactivation of NOXs protects cells from radiation-induced DNA damage and cell death. These findings suggest that NOXs inhibition may be considered as a future pharmacological target to help minimize the negative effects of radiation exposure for millions of patients each year. PMID:25706776

Ultraviolet Radiations: Skin Defense-Damage Mechanism.

PubMed

Mohania, Dheeraj; Chandel, Shikha; Kumar, Parveen; Verma, Vivek; Digvijay, Kumar; Tripathi, Deepika; Choudhury, Khushboo; Mitten, Sandeep Kumar; Shah, Dilip

2017-01-01

UV-radiations are the invisible part of light spectra having a wavelength between visible rays and X-rays. Based on wavelength, UV rays are subdivided into UV-A (320-400 nm), UV-B (280-320 nm) and UV-C (200-280 nm). Ultraviolet rays can have both harmful and beneficial effects. UV-C has the property of ionization thus acting as a strong mutagen, which can cause immune-mediated disease and cancer in adverse cases. Numbers of genetic factors have been identified in human involved in inducing skin cancer from UV-radiations. Certain heredity diseases have been found susceptible to UV-induced skin cancer. UV radiations activate the cutaneous immune system, which led to an inflammatory response by different mechanisms. The first line of defense mechanism against UV radiation is melanin (an epidermal pigment), and UV absorbing pigment of skin, which dissipate UV radiation as heat. Cell surface death receptor (e.g. Fas) of keratinocytes responds to UV-induced injury and elicits apoptosis to avoid malignant transformation. In addition to the formation of photo-dimers in the genome, UV also can induce mutation by generating ROS and nucleotides are highly susceptible to these free radical injuries. Melanocortin 1 receptor (MC1R) has been known to be implicated in different UV-induced damages such as pigmentation, adaptive tanning, and skin cancer. UV-B induces the formation of pre-vitamin D3 in the epidermal layer of skin. UV-induced tans act as a photoprotection by providing a sun protection factor (SPF) of 3-4 and epidermal hyperplasia. There is a need to prevent the harmful effects and harness the useful effects of UV radiations.

EPA attenuates ultraviolet radiation-induced downregulation of aquaporin-3 in human keratinocytes.

PubMed

Jeon, Byoung-Kook; Kang, Moon-Kyung; Lee, Ghang-Tai; Lee, Kun-Kuk; Lee, Ho-Sub; Woo, Won-Hong; Mun, Yeun-Ja

2015-08-01

Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid (ω-3 PUFA) that protects against photodamage and photocarcinogenesis in mammals. Aquaporin-3 (AQP3) is a water/glycerol transport protein that is found in basal layer keratinocytes. In this study, we have investigated the protective effect of EPA against ultraviolet B (UVB)-induced AQP3 downregulation in human keratinocytes. EPA treatment was found to increase AQP3 gene and protein expression in human epidermal keratinocytes (HaCaT). Using a specific inhibitor, we observed that the effect of EPA on AQP3 expression was mediated by extracellular signal-regulated kinase (ERK) activation. UVB radiation induced AQP3 downregulation in HaCaT cells, and it was found that EPA treatment attenuated UVB-induced AQP3 reduction and the associated cell death. UVB-induced downregulation of AQP3 was blocked by EPA and p38 inhibitor SB203580. Collectively, the present results show that EPA increased AQP3 expression and that this led to a reduction UVB-induced photodamage.

A polymethoxyflavone mixture, extracted from orange peels, suppresses the UVB-induced expression of MMP-1.

PubMed

Yoshizaki, Norihiro; Fujii, Takahiro; Hashizume, Ron; Masaki, Hitoshi

2016-08-01

Ultraviolet (UV) B is the main cause of skin photoageing, which has characteristic features such as deep wrinkles. UVB increases the expression of matrix metalloproteinases (MMPs) in the skin and can cause wrinkles by disrupting components of the extracellular matrix, such as collagen fibres. We now report that a polymethoxyflavone (PMF) mixture, extracted from orange peels, suppresses the UVB-induced expression of MMP-1 that involves the inhibition of c-jun N-terminal kinase (JNK) activity. Furthermore, the PMF mixture also inhibits the UVB-induced phosphorylation of JNK. Therefore, the results suggest that the PMF mixture suppresses the UVB-induced expression of MMP-1 through the inhibition of JNK phosphorylation and should be useful as an antiphotoageing agent. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Roles of PCNA ubiquitination and TLS polymerases κ and η in the bypass of methyl methanesulfonate-induced DNA damage

PubMed Central

Wit, Niek; Buoninfante, Olimpia Alessandra; van den Berk, Paul C.M.; Jansen, Jacob G.; Hogenbirk, Marc A.; de Wind, Niels; Jacobs, Heinz

2015-01-01

Translesion synthesis (TLS) provides a highly conserved mechanism that enables DNA synthesis on a damaged template. TLS is performed by specialized DNA polymerases of which polymerase (Pol) κ is important for the cellular response to DNA damage induced by benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), ultraviolet (UV) light and the alkylating agent methyl methanesulfonate (MMS). As TLS polymerases are intrinsically error-prone, tight regulation of their activity is required. One level of control is provided by ubiquitination of the homotrimeric DNA clamp PCNA at lysine residue 164 (PCNA-Ub). We here show that Polκ can function independently of PCNA modification and that Polη can function as a backup during TLS of MMS-induced lesions. Compared to cell lines deficient for PCNA modification (PcnaK164R) or Polκ, double mutant cell lines display hypersensitivity to MMS but not to BPDE or UV-C. Double mutant cells also displayed delayed post-replicative TLS, accumulate higher levels of replication stress and delayed S-phase progression. Furthermore, we show that Polη and Polκ are redundant in the DNA damage bypass of MMS-induced DNA damage. Taken together, we provide evidence for PCNA-Ub-independent activation of Polκ and establish Polη as an important backup polymerase in the absence of Polκ in response to MMS-induced DNA damage. PMID:25505145

The organophosphate insecticide chlorpyrifos confers its genotoxic effects by inducing DNA damage and cell apoptosis.

PubMed

Li, Diqiu; Huang, Qingchun; Lu, Miaoqing; Zhang, Lei; Yang, Zhichuan; Zong, Mimi; Tao, Liming

2015-09-01

The organophosphate insecticide chlorpyrifos (CPF) is known to induce neurological effects, malformation and micronucleus formation, persistent developmental disorders, and maternal toxicity in rats and mice. The binding of chlorpyrifos with DNA to produce DNA adducts leads to an increasing social concern about the genotoxic risk of CPF in human, but CPF-induced cytotoxicity through DNA damage and cell apoptosis is not well understood. Here, we quantified the cytotoxicity and potential genotoxicity of CPF using the alkaline comet assay, γH2AX foci formation, and the DNA laddering assay in order to detect DNA damage and apoptosis in human HeLa and HEK293 cells in vitro. Drosophila S2 cells were used as a positive control. The alkaline comet assay showed that sublethal concentrations of CPF induced significant concentration-dependent increases in single-strand DNA breaks in the treated cells compared with the control. The percentage of γH2AX-positive HeLa cells revealed that CPF also causes DNA double-strand breaks in a time-dependent manner. Moreover, DNA fragmentation analysis demonstrated that exposure to CPF induced a significant concentration- and time-dependent increase in cell apoptosis. We conclude that CPF is a strongly genotoxic agent that induces DNA damage and cell apoptosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phenylbutyrate inhibits homologous recombination induced by camptothecin and methyl methanesulfonate.

PubMed

Kaiser, Gitte S; Germann, Susanne M; Westergaard, Tine; Lisby, Michael

2011-08-01

Homologous recombination is accompanied by extensive changes to chromatin organization at the site of DNA damage. Some of these changes are mediated through acetylation/deacetylation of histones. Here, we show that recombinational repair of DNA damage induced by the anti-cancer drug camptothecin (CPT) and the alkylating agent methyl methanesulfonate (MMS) is blocked by sodium phenylbutyrate (PBA) in the budding yeast Saccharomyces cerevisiae. In particular, PBA suppresses CPT- and MMS-induced genetic recombination as well as DNA double-strand break repair during mating-type interconversion. Treatment with PBA is accompanied by a dramatic reduction in histone H4 lysine 8 acetylation. Live cell imaging of homologous recombination proteins indicates that repair of CPT-induced DNA damage is redirected to a non-recombinogenic pathway in the presence of PBA without loss in cell viability. In contrast, the suppression of MMS-induced recombination by PBA is accompanied by a dramatic loss in cell viability. Taken together, our results demonstrate that PBA inhibits DNA damage-induced homologous recombination likely by mediating changes in chromatin acetylation. Moreover, the combination of PBA with genotoxic agents can lead to different cell fates depending on the type of DNA damage inflicted. 2011 Elsevier B.V. All rights reserved.

Caffeine decreases phospho-Chk1 (Ser317) and increases mitotic cells with cyclin B1 and caspase 3 in tumors from UVB-treated mice.

PubMed

Lu, Yao-Ping; Lou, You-Rong; Peng, Qing-Yun; Nghiem, Paul; Conney, Allan H

2011-07-01

Oral administration of caffeine to mice inhibits UVB-induced carcinogenesis, and these results are paralleled by epidemiology studies indicating that caffeinated coffee and tea intake (but not decaffeinated beverage intake) is associated with decreased incidence of nonmelanoma skin cancer. Topical applications of caffeine to the skin of SKH-1 mice that had previously been treated with UVB inhibited subsequent skin tumor development and stimulated apoptosis in tumors but not in nontumor areas of the epidermis. This study sought to determine the basis of these differential effects on tumor versus nontumor sites that can be induced by caffeine, long after all UVB treatment has ceased. The activation status of the ATR/Chk1 pathway in UVB-induced tumors and uninvolved skin was determined by quantitating phospho-Chk1 (Ser317) and induction of lethal mitosis in vivo in the presence and absence of topical caffeine treatment. In the absence of caffeine, we found that UVB-induced tumors often had islands of phospho-Chk1 (Ser317) staining cells that were not present in nontumor areas of the epidermis. Treatment of mice with topical caffeine significantly diminished phospho-Chk1 (Ser317) staining and increased the number of mitotic cells that expressed cyclin B1 and caspase 3 in tumors, consistent with caffeine-induced lethal mitosis selectively in tumors. We hypothesize that compared with adjacent uninvolved skin, UVB-induced skin tumors have elevated activation of, and dependence on, the ATR/Chk1 pathway long after UVB exposure has ceased and that caffeine can induce apoptosis selectively in tumors by inhibiting this pathway and promoting lethal mitosis.

Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells.

PubMed

Ganesan, Shanthi; Keating, Aileen F

2015-02-01

Phosphoramide mustard (PM), the ovotoxic metabolite of the anti-cancer agent cyclophosphamide (CPA), destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage. A previous study demonstrated that PM induces ovarian DNA damage in rat ovaries. To investigate whether PM induces DNA adduct formation, DNA damage and induction of the DNA repair response, rat spontaneously immortalized granulosa cells (SIGCs) were treated with vehicle control (1% DMSO) or PM (3 or 6μM) for 24 or 48h. Cell viability was reduced (P<0.05) after 48h of exposure to 3 or 6μM PM. The NOR-G-OH DNA adduct was detected after 24h of 6μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48h by exposure to both PM concentrations. Phosphorylated H2AX (γH2AX), a marker of DNA double stranded break occurrence, was also increased by PM exposure, coincident with DNA adduct formation. Additionally, induction of genes (Atm, Parp1, Prkdc, Xrcc6, and Brca1) and proteins (ATM, γH2AX, PARP-1, PRKDC, XRCC6, and BRCA1) involved in DNA repair were observed in both a time- and dose-dependent manner. These data support that PM induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response. Copyright © 2014 Elsevier Inc. All rights reserved.

Fractionated laser resurfacing corrects the inappropriate UVB response in geriatric skin.

PubMed

Spandau, Dan F; Lewis, Davina A; Somani, Ally-Khan; Travers, Jeffrey B

2012-06-01

Non-melanoma skin cancer is a disease primarily afflicting geriatric patients as evidenced by the fact that 80% of all non-melanoma skin cancers are diagnosed in patients over the age of 60 years. As such, geriatric skin responds to cancer-inducing UVB irradiation in a manner that allows the establishment of tumor cells. Currently, the only effective treatment for non-melanoma skin cancer is the removal of the tumors after they appear, indicating the need for a more cost-effective prophylactic therapy. Geriatric volunteers were treated with fractionated laser resurfacing therapy on either sun-protected (upper buttocks) or chronically sun-exposed (dorsal forearm) skin. Fractionated laser resurfacing therapy was shown to decrease the occurrence of senescent fibroblasts in geriatric dermis, increase the dermal expression of IGF-1, and correct the inappropriate UVB response observed in untreated geriatric skin. These responses to fractionated laser resurfacing were equal to the effects seen previously using the more aggressive wounding following dermabrasion. Furthermore, fractionated laser resurfacing was equally effective in both sun-protected and sun-exposed skin. The ability of fractionated laser resurfacing treatment to protect against the occurrence of UVB-damaged proliferating keratinocytes indicates the potential of fractionated laser resurfacing to reduce or prevent aging-associated non-melanoma skin cancer.

Fractionated laser resurfacing corrects the inappropriate UVB response in geriatric skin

PubMed Central

Spandau, Dan F; Lewis, Davina A.; Somani, Ally-Khan; Travers, Jeffrey B.

2012-01-01

Non-melanoma skin cancer is a disease primarily afflicting geriatric patients as evidenced by the fact that 80% of all non-melanoma skin cancers are diagnosed in patients over the age of 60 years. As such, geriatric skin responds to cancer-inducing UVB irradiation in a manner that allows the establishment of tumor cells. Currently, the only effective treatment for non-melanoma skin cancer is the removal of the tumors after they appear, indicating the need for a more cost-effective prophylactic therapy. Geriatric volunteers were treated with fractionated laser resurfacing therapy on either sun-protected (upper buttocks) or chronically sun-exposed (dorsal forearm) skin. Fractionated laser resurfacing therapy was demonstrated to decrease the occurrence of senescent fibroblasts in geriatric dermis, increase the dermal expression of insulin-like growth factor-1, and correct the inappropriate UVB response observed in untreated geriatric skin. These responses to fractionated laser resurfacing were equal to the effects seen previously using the more aggressive wounding following dermabrasion. Furthermore, fractionated laser resurfacing was equally effective in both sun-protected and sun-exposed skin. The ability of fractionated laser resurfacing treatment to protect against the occurrence of UVB-damaged proliferating keratinocytes indicates the potential of fractionated laser resurfacing to reduce or prevent aging-associated non-melanoma skin cancer. PMID:22377757

Solar irradiance changes and photobiological effects at earth's surface following astrophysical ionizing radiation events.

PubMed

Thomas, Brian C; Neale, Patrick J; Snyder, Brock R

2015-03-01

Astrophysical ionizing radiation events have been recognized as a potential threat to life on Earth, primarily through depletion of stratospheric ozone and subsequent increase in surface-level solar ultraviolet radiation. Simulations of the atmospheric effects of a variety of events (such as supernovae, gamma-ray bursts, and solar proton events) have been previously published, along with estimates of biological damage at Earth's surface. In this work, we employed the Tropospheric Ultraviolet and Visible (TUV) radiative transfer model to expand and improve calculations of surface-level irradiance and biological impacts following an ionizing radiation event. We considered changes in surface-level UVB, UVA, and photosynthetically active radiation (visible light) for clear-sky conditions and fixed aerosol parameter values. We also considered a wide range of biological effects on organisms ranging from humans to phytoplankton. We found that past work overestimated UVB irradiance but that relative estimates for increase in exposure to DNA-damaging radiation are still similar to our improved calculations. We also found that the intensity of biologically damaging radiation varies widely with organism and specific impact considered; these results have implications for biosphere-level damage following astrophysical ionizing radiation events. When considering changes in surface-level visible light irradiance, we found that, contrary to previous assumptions, a decrease in irradiance is only present for a short time in very limited geographical areas; instead we found a net increase for most of the modeled time-space region. This result has implications for proposed climate changes associated with ionizing radiation events.

Growth of antarctic cyanobacteria under ultraviolet radiation: UVA counteracts UVB inhibition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quesada, A.; Mouget, J.L.; Vincent, W.F.

A mat-forming cyanobacterium (Phormidium murayi West and West) isolated from an ice-shelf pond in Antarctica was grown under white light combined with a range of UVA and UVB irradiance. The 4-day growth rate decreased under increasing ultraviolet (UV) radiation, with a ninefold greater response to UVB relative to UVA. In vivo absorbance spectra showed that UVA and to a greater extent UVB caused a decrease in phycocyanin/chlorophyll a and an increase in carotenoids/chlorophyll a. The phycocyanin/chlorophyll a ratio was closely and positively correlated to the UVB-inhibited growth rate. Under fixed spectral gradients of UV radiation, the growth inhibition effect wasmore » dominated by UVB. However, at specific UVB irradiances the inhibition of growth depended on the ratio of UVB to UVA, and growth rates increased linearly with increasing UVA. These results are consistent with the view that UVB inhibition represents the balance between damage and repair processes that are each controlled by separate wavebands. They also underscore the need to consider UV spectral balance in laboratory and field assays of UVB toxicity. 49 refs., 6 figs.« less

Impact of Nrf2 on UVB-induced skin inflammation/photoprotection and photoprotective effect of sulforaphane.

PubMed

Saw, Constance L; Huang, Mou-Tuan; Liu, Yue; Khor, Tin Oo; Conney, Allan H; Kong, Ah-Ng

2011-06-01

Ultraviolet (UV) of sunlight is a complete carcinogen that can burn skin, enhance inflammation, and drive skin carcinogenesis. Previously, we have shown that sulforaphane (SFN) inhibited chemically induced skin carcinogenesis via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and others have shown that broccoli sprout extracts containing high SFN protected against UV-induced skin carcinogenesis in SKH-1 hairless mice. A recent study showed that there was no difference between Nrf2 knockout (Nrf2 KO) and Nrf2 wild-type (WT) BALB/C mice after exposing to high dose of UVB. Since Nrf2 plays critical roles in the anti-oxidative stress/anti-inflammatory responses, it is relevant to assess the role of Nrf2 for photoprotection against UV. In this context, the role of Nrf2 in UVB-induced skin inflammation in Nrf2 WT and Nrf2 KO C57BL/6 mice was studied. A single dose of UVB (300 mJ/cm(2)) resulted in skin inflammation in both WT and Nrf2 KO (-/-) mice (KO mice) at 8 h and 8 d following UVB irradiation. In the WT mice inflammation returned to the basal level to a greater extent when compared to the KO mice. SFN treatment of Nrf2 WT but not Nrf2 KO mice restored the number of sunburn cells back to their basal level by 8 d after UVB irradiation. Additionally, UVB-induced short-term inflammatory biomarkers (interleukin-1β and interleukin-6) were increased in the KO mice and UVB-induced apoptotic cells in the KO mice were significantly higher as compared to that in the WT. Taken together, our results show that functional Nrf2 confers a protective effect against UVB-induced inflammation, sunburn reaction, and SFN-mediated photoprotective effects in the skin. Copyright © 2010 Wiley-Liss, Inc.

Cytochrome P450 2A13 enhances the sensitivity of human bronchial epithelial cells to aflatoxin B1-induced DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Xuejiao; Jiaojiang District Center for Disease Control and Prevention, 518 Jingdong Rd., Taizhou 318000; Zhang, Zhan

Cytochrome P450 2A13 (CYP2A13) mainly expresses in human respiratory system and mediates the metabolic activation of aflatoxin B1 (AFB1). Our previous study suggested that CYP2A13 could increase the cytotoxic and apoptotic effects of AFB1 in immortalized human bronchial epithelial cells (BEAS-2B). However, the role of CYP2A13 in AFB1-induced DNA damage is unclear. Using BEAS-2B cells that stably express CYP2A13 (B-2A13), CYP1A2 (B-1A2), and CYP2A6 (B-2A6), we compared their effects in AFB1-induced DNA adducts, DNA damage, and cell cycle changes. BEAS-2B cells that were transfected with vector (B-vector) were used as a control. The results showed that AFB1 (5–80 nM) dose-more » and time-dependently induced DNA damage in B-2A13 cells. AFB1 at 10 and 80 nM significantly augmented this effect in B-2A13 and B-1A2 cells, respectively. B-2A6 cells showed no obvious DNA damage, similar to B-vector cells and the vehicle control. Similarly, compared with B-vector, B-1A2 or B-2A6 cells, B-2A13 cells showed more sensitivity in AFB1-induced γH2AX expression, DNA adduct 8-hydroxy-deoxyguanosine formation, and S-phase cell-cycle arrest. Furthermore, AFB1 activated the proteins related to DNA damage responses, such as ATM, ATR, Chk2, p53, BRCA1, and H2AX, rather than the proteins related to DNA repair. These effects could be almost completely inhibited by 100 μM nicotine (a substrate of CYP2A13) or 1 μM 8-methoxypsoralen (8-MOP; an inhibitor of CYP enzyme). Collectively, these findings suggest that CYP2A13 plays an important role in low-concentration AFB1-induced DNA damage, possibly linking environmental airborne AFB1 to genetic injury in human respiratory system. - Highlights: • CYP2A13 plays a critical role in low concentration of AFB1-induced DNA damage. • B-2A13 cells were more sensitive to AFB1 than B-1A2 cells and B-2A6 cells. • AFB1 dose- and time-dependently induced DNA damage in B-2A13 cells • AFB1-induced DNA adducts and damage can be inhibited by nicotine and 8-MOP.« less

Aeroallergens Induce Reactive Oxygen Species Production and DNA Damage and Dampen Antioxidant Responses in Bronchial Epithelial Cells.

PubMed

Chan, Tze Khee; Tan, W S Daniel; Peh, Hong Yong; Wong, W S Fred

2017-07-01

Exposure to environmental allergens is a major risk factor for asthma development. Allergens possess proteolytic activity that is capable of disrupting the airway epithelium. Although there is increasing evidence pointing to asthma as an epithelial disease, the underlying mechanism that drives asthma has not been fully elucidated. In this study, we investigated the direct DNA damage potential of aeroallergens on human bronchial epithelial cells and elucidated the mechanisms mediating the damage. Human bronchial epithelial cells, BEAS-2B, directly exposed to house dust mites (HDM) resulted in enhanced DNA damage, as measured by the CometChip and the staining of DNA double-strand break marker, γH2AX. HDM stimulated cellular reactive oxygen species production, increased mitochondrial oxidative stress, and promoted nitrosative stress. Notably, expression of nuclear factor erythroid 2-related factor 2-dependent antioxidant genes was reduced immediately after HDM exposure, suggesting that HDM altered antioxidant responses. HDM exposure also reduced cell proliferation and induced cell death. Importantly, HDM-induced DNA damage can be prevented by the antioxidants glutathione and catalase, suggesting that HDM-induced reactive oxygen and nitrogen species can be neutralized by antioxidants. Mechanistic studies revealed that HDM-induced cellular injury is NADPH oxidase (NOX)-dependent, and apocynin, a NOX inhibitor, protected cells from double-strand breaks induced by HDM. Our results show that direct exposure of bronchial epithelial cells to HDM leads to the production of reactive oxygen and nitrogen species that damage DNA and induce cytotoxicity. Antioxidants and NOX inhibitors can prevent HDM-induced DNA damage, revealing a novel role for antioxidants and NOX inhibitors in mitigating allergic airway disease. Copyright © 2017 by The American Association of Immunologists, Inc.

Changes of MMP-1 and collagen type Ialpha1 by UVA, UVB and IRA are differentially regulated by Trx-1.

PubMed

Buechner, Nicole; Schroeder, Peter; Jakob, Sascha; Kunze, Kerstin; Maresch, Tanja; Calles, Christian; Krutmann, Jean; Haendeler, Judith

2008-07-01

Exposure of human skin to solar radiation, which includes ultraviolet (UV) radiation (UVA and UVB) visible light and infrared radiation, induces skin aging. The effects of light have been attributed to irradiation-induced reactive oxygen species (ROS) formation, but the specific signaling pathways are not well understood. Detrimental effects of solar radiation are dermal diseases and photoaging. Exposure of cultured human dermal fibroblasts to UVA, UVB or IRA increased ROS formation in vitro. One important redox regulator is the oxidoreductase thioredoxin-1 (Trx). Trx is ubiquitously expressed and has anti-oxidative and anti-apoptotic properties. Besides its function to reduce H(2)O(2), Trx binds to and regulates transcription factors. The aim of this study was to investigate whether Trx influences the regulation of MMP-1 and collagen Ialpha1 by UVA, UVB and IRA. We irradiated human dermal fibroblasts with UVA, UVB and IRA. UVA, UVB and IRA upregulated MMP-1 expression. Trx inhibited UVA-induced MMP-1 upregulation in a NFkappaB dependent manner. UVA, UVB and IRA reduced collagen Ialpha1 expression. Incubation with Trx inhibited the effects of UVB and IRA on collagen Ialpha1 expression. In conclusion, MMP-1 and collagen Ialpha1, which play important roles in aging processes, seems to be regulated by different transcriptional mechanisms and Trx can only influence distinct signaling pathways induced by UVA, UVB and probably IRA. Thus, Trx may serve as an important contributor to an "anti-aging therapeutic cocktail".

The relevance of the vitamin D endocrine system (VDES) for tumorigenesis, prevention, and treatment of non-melanoma skin cancer (NMSC)

PubMed Central

Reichrath, Jörg; Reichrath, Sandra

2013-01-01

Solar UV (UV)-B-radiation exerts both beneficial and adverse effects on human health. On the one hand, it is the most important environmental risk factor for the development of non-melanoma skin cancer [NMSC; most importantly basal (BCC) and squamous (SCC) cell carcinomas], that represent the most common malignancies in Caucasian populations. On the other hand, the human body’s requirements of vitamin D are mainly achieved by UV-B-induced cutaneous photosynthesis. This dilemma represents a serious problem in many populations, for an association of vitamin D-deficiency and multiple independent diseases including various types of cancer has been convincingly demonstrated. In line with these findings, epidemiologic and laboratory investigations now indicate that vitamin D and its metabolites have a risk reducing effect for NMSC. Potential mechanisms of action include inhibition of the hedgehog signaling pathway (BCC) and modulation of p53-mediated DNA damage response (SCC). As a consequence of these new findings it can be concluded that UV-B-radiation exerts both beneficial and adverse effects on risk and prognosis of NMSC. It can be assumed that many independent factors, including frequency and dose of UV-B exposure, skin area exposed, and individual factors (such as skin type and genetic determinants of the skin`s vitamin D status and of signaling pathways that are involved in the tumorigenesis of NMSC) determine whether UV-B exposure promotes or inhibits tumorigenesis of NMSC. Moreover, these findings may help to explain many of the differential effects of UV-B radiation on risk of NMSC, including variation in the dose-dependent risk for development of SCC in situ (actinic keratosis, AK), invasive SCC, and BCC. In this review, we analyze the relevance of the vitamin D endocrine system (VDES) for tumorigenesis, prevention, and treatment of NMSC and give an overview of present concepts and future perspectives. PMID:24494041