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Sample records for oxygen species promote

  1. Reactive oxygen species promote raft formation in T lymphocytes.

    PubMed

    Lu, Shu-Ping; Lin Feng, Ming-Hsien; Huang, Huey-Lan; Huang, Ya-Ching; Tsou, Wen-I; Lai, Ming-Zong

    2007-04-01

    Lipid rafts are involved in many cell biology events, yet the molecular mechanisms on how rafts are formed are poorly understood. In this study we probed the possible requirement of reactive oxygen species (ROS) for T-cell receptor (TCR)-induced lipid raft formation. Microscopy and biochemical analyses illustrated that blockage of ROS production, by superoxide dismutase-mimic MnTBAP, significantly reduced partitioning of LAT, phospho-LAT, and PLC-gamma in lipid rafts. Another antioxidant N-acetylcysteine (NAC) displayed a similar suppressive effect on the entry of phospho-LAT into raft microdomains. The involvement of ROS in TCR-mediated raft assembly was observed in T-cell hybridomas, T leukemia cells, and normal T cells. Removal of ROS was accompanied by an attenuated activation of LAT and PKCtheta, with reduced production of IL-2. Consistently, treating T cells with the ROS-producer tert-butyl hydrogen peroxide (TBHP) greatly enhanced membrane raft formation, distribution of phospho-LAT into lipid rafts, and increased IL-2 production. Our results indicate for the first time that ROS contribute to TCR-induced membrane raft formation. PMID:17349922

  2. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)

    PubMed Central

    Ristow, Michael; Schmeisser, Kathrin

    2014-01-01

    Increasing evidence indicates that reactive oxygen species (ROS), consisting of superoxide, hydrogen peroxide, and multiple others, do not only cause oxidative stress, but rather may function as signaling molecules that promote health by preventing or delaying a number of chronic diseases, and ultimately extend lifespan. While high levels of ROS are generally accepted to cause cellular damage and to promote aging, low levels of these may rather improve systemic defense mechanisms by inducing an adaptive response. This concept has been named mitochondrial hormesis or mitohormesis. We here evaluate and summarize more than 500 publications from current literature regarding such ROS-mediated low-dose signaling events, including calorie restriction, hypoxia, temperature stress, and physical activity, as well as signaling events downstream of insulin/IGF-1 receptors, AMP-dependent kinase (AMPK), target-of-rapamycin (TOR), and lastly sirtuins to culminate in control of proteostasis, unfolded protein response (UPR), stem cell maintenance and stress resistance. Additionally, consequences of interfering with such ROS signals by pharmacological or natural compounds are being discussed, concluding that particularly antioxidants are useless or even harmful. PMID:24910588

  3. PKCα promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma

    SciTech Connect

    Wang, Jiajun; Shao, Miaomiao; Liu, Min; Peng, Peike; Li, Lili; Wu, Weicheng; Wang, Lan; Duan, Fangfang; Zhang, Mingming; Song, Shushu; Jia, Dongwei; Ruan, Yuanyuan; Gu, Jianxin

    2015-08-07

    Hepatocellular carcinoma (HCC) remains the second leading cause of cancer-related death worldwide, and elevated rates of reactive oxygen species (ROS) have long been considered as a hallmark of almost all types of cancer including HCC. Protein kinase C alpha (PKCα), a serine/threonine kinase among conventional PKC family, is recognized as a major player in signal transduction and tumor progression. Overexpression of PKCα is commonly observed in human HCC and associated with its poor prognosis. However, how PKCα is involved in hepatocellular carcinogenesis remains not fully understood. In this study, we found that among the members of conventional PKC family, PKCα, but not PKCβI or βII, promoted ROS production in HCC cells. PKCα stimulated generation of ROS by up-regulating DUOX2 at post-transcriptional level. Depletion of DUOX2 abrogated PKCα-induced activation of AKT/MAPK pathways as well as cell proliferation, migration and invasion in HCC cells. Moreover, the expression of DUOX2 and PKCα was well positively correlated in both HCC cell lines and patient samples. Collectively, our findings demonstrate that PKCα plays a critical role in HCC development by inducing DUOX2 expression and ROS generation, and propose a strategy to target PKCα/DUOX2 as a potential adjuvant therapy for HCC treatment. - Highlights: • PKCα promotes the generation of ROS in hepatocellular carcinoma. • PKCα induces ROS production by up-regulating DUOX2 at post-transcriptional level. • DUOX2 is required for PKCα-induced AKT/MAPK activation and tumor progression in HCC. • The expression of PKCα is positively correlated with DUOX2 in HCC.

  4. Reactive oxygen species promote caspase-12 expression and tubular apoptosis in diabetic nephropathy.

    PubMed

    Brezniceanu, Marie-Luise; Lau, Cara J; Godin, Nicolas; Chénier, Isabelle; Duclos, Alain; Ethier, Jean; Filep, Janos G; Ingelfinger, Julie R; Zhang, Shao-Ling; Chan, John S D

    2010-06-01

    Apoptosis of tubular epithelial cells contributes to the tubular atrophy that accompanies diabetic nephropathy. Reactive oxygen species (ROS) promote tubular apoptosis, but the mechanisms by which this occurs are incompletely understood. Here, we sought proapoptotic genes that ROS differentially upregulate in renal proximal tubular cells of diabetic (db/db) mice. We performed microarray analysis using total RNA from freshly isolated renal proximal tubules of nondiabetic, diabetic, and diabetic transgenic mice overexpressing catalase in the proximal tubule (thereby attenuating ROS). We observed greater expression of caspase-12 in the proximal tubules of the diabetic mice compared with the nondiabetic and diabetic transgenic mice. Quantitative PCR and immunohistochemistry confirmed the enhanced expression of caspase-12, as well as members of the endoplasmic reticulum stress-induced apoptotic pathway. Ex vivo, albumin induced caspase-12 activity and expression (protein and mRNA) and mRNA expression of the CCAT/enhancer-binding protein homologous protein in freshly isolated wild-type proximal tubules but not in catalase-overexpressing proximal tubules. In vitro, albumin stimulated activity of both caspase-12 and caspase-3 as well as expression of caspase-12 and CCAT/enhancer-binding protein homologous protein in a human proximal tubule cell line (HK-2). The free radical scavenger tiron inhibited these effects. Furthermore, knockdown of caspase-12 with small interfering RNA reduced albumin-induced apoptosis in HK-2 cells. Taken together, these studies demonstrate that albuminuria may induce tubular apoptosis through generation of ROS and the subsequent expression and activation of endoplasmic reticulum stress genes in the diabetic kidney. PMID:20299359

  5. Khat (Catha edulis) generates reactive oxygen species and promotes hepatic cell apoptosis via MAPK activation.

    PubMed

    Abid, Morad Dirhem Naji; Chen, Juan; Xiang, Min; Zhou, Jie; Chen, Xiaoping; Gong, Feili

    2013-08-01

    A number of studies have suggested an association between khat (Catha edulis) chewing and acute liver lesions or chronic liver disease. However, little is known about the effects of khat on hepatic cells. In the current study, we investigated the mechanism behind khat-induced apoptosis in the L02 human hepatic cell line. We used cell growth inhibition assay, flow cytometry and Hoechst 33258 staining to measure hepatocyte apoptosis induced by khat. Western blot analysis was used to detect the expression levels of caspase-8 and -9, as well as those of Bax and Bcl-2. We also measured reactive oxygen species production. The results indicated that khat induced significant hepatocyte apoptosis in L02 cells. We found that khat activated caspase-8 and -9, upregulated Bax protein expression and downregulated Bcl-2 expression levels, which resulted in the coordination of apoptotic signals. Khat-induced hepatocyte apoptosis is primarily regulated through the sustained activation of the c-Jun NH2-terminal kinase (JNK) pathway and only partially via the extracellular signal-regulated kinase (ERK) cascade. Furthermore, the khat-induced reactive oxygen species (ROS) production and the activation of the ROS scavenger, N-acetyl-L-cysteine (NAC), attenuated the khat-induced activation of JNK and ERK. Our results demonstrate that khat triggers the generation of intracellular ROS and sequentially induces the sustainable activation of JNK, which in turn results in a decrease in cell viability and an increase in cell apoptosis. PMID:23708648

  6. Hemoglobin fructation promotes heme degradation through the generation of endogenous reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Goodarzi, M.; Moosavi-Movahedi, A. A.; Habibi-Rezaei, M.; Shourian, M.; Ghourchian, H.; Ahmad, F.; Farhadi, M.; Saboury, A. A.; Sheibani, N.

    2014-09-01

    Protein glycation is a cascade of nonenzymatic reactions between reducing sugars and amino groups of proteins. It is referred to as fructation when the reducing monosaccharide is fructose. Some potential mechanisms have been suggested for the generation of reactive oxygen species (ROS) by protein glycation reactions in the presence of glucose. In this state, glucose autoxidation, ketoamine, and oxidative advance glycation end products (AGEs) formation are considered as major sources of ROS and perhaps heme degradation during hemoglobin glycation. However, whether fructose mediated glycation produces ROS and heme degradation is unknown. Here we report that ROS (H2O2) production occurred during hemoglobin fructation in vitro using chemiluminescence methods. The enhanced heme exposure and degradation were determined using UV-Vis and fluorescence spectrophotometry. Following accumulation of ROS, heme degradation products were accumulated reaching a plateau along with the detected ROS. Thus, fructose may make a significant contribution to the production of ROS, glycation of proteins, and heme degradation during diabetes.

  7. Reactive oxygen species promote heat shock protein 90-mediated HBV capsid assembly.

    PubMed

    Kim, Yoon Sik; Seo, Hyun Wook; Jung, Guhung

    2015-02-13

    Hepatitis B virus (HBV) infection induces reactive oxygen species (ROS) production and has been associated with the development of hepatocellular carcinoma (HCC). ROS are also an important factor in HCC because the accumulated ROS leads to abnormal cell proliferation and chromosome mutation. In oxidative stress, heat shock protein 90 (Hsp90) and glutathione (GSH) function as part of the defense mechanism. Hsp90 prevents cellular component from oxidative stress, and GSH acts as antioxidants scavenging ROS in the cell. However, it is not known whether molecules regulated by oxidative stress are involved in HBV capsid assembly. Based on the previous study that Hsp90 facilitates HBV capsid assembly, which is an important step for the packing of viral particles, here, we show that ROS enrich Hsp90-driven HBV capsid formation. In cell-free system, HBV capsid assembly was facilitated by ROS with Hsp90, whereas it was decreased without Hsp90. In addition, GSH inhibited the function of Hsp90 to decrease HBV capsid assembly. Consistent with the result of cell-free system, ROS and buthionine sulfoximine (BS), an inhibitor of GSH synthesis, increased HBV capsid formation in HepG2.2.15 cells. Thus, our study uncovers the interplay between ROS and Hsp90 during HBV capsid assembly. PMID:25576869

  8. Suppression of Cancer Growth by Nonviral Gene Therapy Based on a Novel Reactive Oxygen Species-responsive Promoter

    PubMed Central

    Policastro, Lucía L; Ibañez, Irene L; Durán, Hebe A; Soria, Gastón; Gottifredi, Vanesa; Podhajcer, Osvaldo L

    2009-01-01

    Increased reactive oxygen species (ROS) production has been reported as a distinctive feature of different pathologies including cancer. Therefore, we assessed whether increased ROS production in the cancer microenvironment could be selectively exploited to develop a selective anticancer therapy. For this purpose, we constructed a novel chimeric promoter, based on a ROS-response motif located in the VEGF gene promoter placed, in turn, downstream of a second ROS-response motif obtained from the early growth response 1 (Egr-1) gene promoter. The activity of the chimeric promoter was largely dependent on variations in intracellular ROS levels and showed a high inducible response to exogenous H2O2. Transient expression of the thymidine kinase (TK) gene driven by the chimeric promoter, followed by gancyclovir (GCV) administration, inhibited human colorectal cancer and melanoma cell growth in vitro and in vivo. Moreover, electrotransfer of the TK gene followed by GCV administration exerted a potent therapeutic effect on established tumors. This response was improved when combined with chemotherapeutic drugs. Thus, we show for the first time that a distinctive pro-oxidant state can be used to develop new selective gene therapeutics for cancer. PMID:19436270

  9. Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species promote cerebral artery dilation

    PubMed Central

    Sullivan, Michelle N.; Gonzales, Albert L.; Pires, Paulo W.; Bruhl, Allison; Leo, M. Dennis; Li, Wencheng; Oulidi, Agathe; Boop, Frederick A.; Feng, Yumei; Jaggar, Jonathan H.; Welsh, Donald G.; Earley, Scott

    2016-01-01

    Reactive oxygen species (ROS) can have divergent effects in cerebral and peripheral circulations. We found that Ca2+-permeable transient receptor potential ankyrin 1 (TRPA1) channels were present and colocalized with NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase 2 (NOX2), a major source of ROS, in the endothelium of cerebral arteries but not in other vascular beds. We recorded and characterized ROS-triggered Ca2+ signals representing Ca2+ influx through single TRPA1 channels, which we called “TRPA1 sparklets.” TRPA1 sparklet activity was low under basal conditions but was stimulated by NOX-generated ROS. Ca2+ entry during a single TRPA1 sparklet was twice that of a TRPV4 sparklet and ~200 times that of an L-type Ca2+ channel sparklet. TRPA1 sparklets representing the simultaneous opening of two TRPA1 channels were more common in endothelial cells than in human embryonic kidney (HEK) 293 cells expressing TRPA1. The NOX-induced TRPA1 sparklets activated intermediate-conductance, Ca2+-sensitive K+ channels, resulting in smooth muscle hyperpolarization and vasodilation. NOX-induced activation of TRPA1 sparklets and vasodilation required generation of hydrogen peroxide and lipid-peroxidizing hydroxyl radicals as intermediates. 4-Hydroxy-nonenal, a metabolite of lipid peroxidation, also increased TRPA1 sparklet frequency and dilated cerebral arteries. These data suggest that in the cerebral circulation, lipid peroxidation metabolites generated by ROS activate Ca2+ influx through TRPA1 channels in the endothelium of cerebral arteries to cause dilation. PMID:25564678

  10. Reactive oxygen species promote heat shock protein 90-mediated HBV capsid assembly

    SciTech Connect

    Kim, Yoon Sik Seo, Hyun Wook Jung, Guhung

    2015-02-13

    Hepatitis B virus (HBV) infection induces reactive oxygen species (ROS) production and has been associated with the development of hepatocellular carcinoma (HCC). ROS are also an important factor in HCC because the accumulated ROS leads to abnormal cell proliferation and chromosome mutation. In oxidative stress, heat shock protein 90 (Hsp90) and glutathione (GSH) function as part of the defense mechanism. Hsp90 prevents cellular component from oxidative stress, and GSH acts as antioxidants scavenging ROS in the cell. However, it is not known whether molecules regulated by oxidative stress are involved in HBV capsid assembly. Based on the previous study that Hsp90 facilitates HBV capsid assembly, which is an important step for the packing of viral particles, here, we show that ROS enrich Hsp90-driven HBV capsid formation. In cell-free system, HBV capsid assembly was facilitated by ROS with Hsp90, whereas it was decreased without Hsp90. In addition, GSH inhibited the function of Hsp90 to decrease HBV capsid assembly. Consistent with the result of cell-free system, ROS and buthionine sulfoximine (BS), an inhibitor of GSH synthesis, increased HBV capsid formation in HepG2.2.15 cells. Thus, our study uncovers the interplay between ROS and Hsp90 during HBV capsid assembly. - Highlights: • We examined H{sub 2}O{sub 2} and GSH modulate HBV capsid assembly. • H{sub 2}O{sub 2} facilitates HBV capsid assembly in the presence of Hsp90. • GSH inhibits function of Hsp90 in facilitating HBV capsid assembly. • H{sub 2}O{sub 2} and GSH induce conformation change of Hsp90.

  11. Ras-induced reactive oxygen species promote growth factor-independent proliferation in human CD34+ hematopoietic progenitor cells.

    PubMed

    Hole, Paul S; Pearn, Lorna; Tonks, Amanda J; James, Philip E; Burnett, Alan K; Darley, Richard L; Tonks, Alex

    2010-02-11

    Excessive production of reactive oxygen species (ROS) is a feature of human malignancy and is often triggered by activation of oncogenes such as activated Ras. ROS act as second messengers and can influence a variety of cellular process including growth factor responses and cell survival. We have examined the contribution of ROS production to the effects of N-Ras(G12D) and H-Ras(G12V) on normal human CD34(+) progenitor cells. Activated Ras strongly up-regulated the production of both superoxide and hydrogen peroxide through the stimulation of NADPH oxidase (NOX) activity, without affecting the expression of endogenous antioxidants or the production of mitochondrially derived ROS. Activated Ras also promoted both the survival and the growth factor-independent proliferation of CD34(+) cells. Using oxidase inhibitors and antioxidants, we found that excessive ROS production by these cells did not contribute to their enhanced survival; rather, ROS promoted their growth factor-independent proliferation. Although Ras-induced ROS production specifically activated the p38(MAPK) oxidative stress response, this failed to induce expression of the cell-cycle inhibitor, p16(INK4A); instead, ROS promoted the expression of D cyclins. These data are the first to show that excessive ROS production in the context of oncogene activation can promote proliferative responses in normal human hematopoietic progenitor cells. PMID:20007804

  12. In vitro incubation of human spermatozoa promotes reactive oxygen species generation and DNA fragmentation.

    PubMed

    Cicaré, J; Caille, A; Zumoffen, C; Ghersevich, S; Bahamondes, L; Munuce, M J

    2015-10-01

    The aim of this study was to investigate the oxidative process associated with sperm capacitation and its impact on DNA fragmentation and sperm function. Redox activity and lipid peroxidation were analysed in human spermatozoa after 3, 6 and 22 h of incubation in Ham's F10 medium plus bovine albumin at 37° and 5% CO2 for capacitation. DNA status, tyrosine phosphorylation pattern and induced acrosome reaction were evaluated after capacitating conditions. At 22 h of incubation, there was a significant (P < 0.05) increase in oxygen-free radicals and lipid peroxidation, with no effect on sperm viability. There also was a significant (P < 0.001) increase in fragmented DNA in capacitated spermatozoa compared to semen values with higher rates being found after the occurrence of the induced acrosome reaction. Protein tyrosine phosphorylation pattern confirms that capacitation took place in parallel with the occurrence of DNA fragmentation. These results indicate that when spermatozoa are incubated for several hours (22 h), a common practice in assisted reproductive techniques, an increase in oxidative sperm metabolism and in the proportion of fragmented DNA should be expected. However, there was no effect on any of the other functional parameters associated with sperm fertilising capacity. PMID:25233794

  13. Constitutive NF-κB activation and tumor-growth promotion by Romo1-mediated reactive oxygen species production

    SciTech Connect

    Chung, Jin Sil; Lee, Sora; Yoo, Young Do

    2014-08-08

    Highlights: • Romo1 expression is required for constitutive nuclear DNA-binding activity of NF-κB. • Romo1 depletion suppresses tumor growth in vivo. • Romo1 presents a potential therapeutic target for diseases. - Abstract: Deregulation of nuclear factor-κB (NF-κB) and related pathways contribute to tumor cell proliferation and invasion. Mechanisms for constitutive NF-κB activation are not fully explained; however, the underlying defects appear to generate and maintain pro-oxidative conditions. In hepatocellular carcinoma (HCC) tissues, up-regulation of reactive oxygen species modulator 1 (Romo1) correlates positively with tumor size. In the present study, we showed that Romo1 expression is required to maintain constitutive nuclear DNA-binding activity of NF-κB and transcriptional activity through constitutive IκBα phosphorylation. Overexpression of Romo1 promoted p65 nuclear translocation and DNA-binding activity. We also show that Romo1 depletion suppressed anchorage-independent colony formation by HCC cells and suppressed tumor growth in vivo. Based on these findings, Romo1 may be a principal regulatory factor in the maintenance of constitutive NF-κB activation in tumor cells. In the interest of anti-proliferative treatments for cancer, Romo1 may also present a productive target for drug development.

  14. Induction of reactive oxygen species generation inhibits epithelial-mesenchymal transition and promotes growth arrest in prostate cancer cells.

    PubMed

    Das, Trinath P; Suman, Suman; Damodaran, Chendil

    2014-07-01

    Oxidative stress is one causative factor of the pathogenesis and aggressiveness of most of the cancer types, including prostate cancer (CaP). A moderate increase in reactive oxygen species (ROS) induces cell proliferation whereas excessive amounts of ROS promote apoptosis. In this study, we explored the pro-oxidant property of 3,9-dihydroxy-2-prenylcoumestan (psoralidin [pso]), a dietary agent, on CaP (PC-3 and C4-2B) cells. Pso greatly induced ROS generation (more than 20-fold) that resulted in the growth inhibition of CaP cells. Overexpression of anti-oxidant enzymes superoxide dismutase 1 (SOD1), SOD2, and catalase, or pretreatment with the pharmacological inhibitor N-acetylcysteine (NAC) significantly attenuated both pso-mediated ROS generation and pso-mediated growth inhibition in CaP cells. Furthermore, pso administration significantly inhibited the migratory and invasive property of CaP cells by decreasing the transcription of β-catenin, and slug, which promote epithelial-mesenchymal transition (EMT), and by concurrently inducing E-cadherin expression in CaP cells. Pso-induced ROS generation in CaP cells resulted in loss of mitochondrial membrane potential, cytochrome-c release, and activation of caspase-3 and -9 and poly (ADP-ribose) polymerase (PARP), which led to apoptosis. On the other hand, overexpression of anti-oxidants rescued pso-mediated effects on CaP cells. These findings suggest that increasing the threshold of intracellular ROS could prevent or treat CaP growth and metastasis. PMID:23475579

  15. Reactive oxygen species promotes cellular senescence in normal human epidermal keratinocytes through epigenetic regulation of p16(INK4a.).

    PubMed

    Sasaki, Mina; Kajiya, Hiroshi; Ozeki, Satoru; Okabe, Koji; Ikebe, Tetsuro

    2014-09-26

    Reactive oxygen species (ROS) can cause severe damage to DNA, proteins and lipids in normal cells, contributing to carcinogenesis and various pathological conditions. While cellular senescence arrests the early phase of cell cycle without any detectable telomere loss or dysfunction. ROS is reported to contribute to induction of cellular senescence, as evidence by its premature onset upon treatment with antioxidants or inhibitors of cellular oxidant scavengers. Although cellular senescence is known to be implicated in tumor suppression, it remains unknown whether ROS initially contributed to be cellular senescence in normal human epidermal keratinocytes (NHEK) and their malignant counterparts. To clarify whether ROS induce cellular senescence in NHEKs, we examined the effect of hydrogen peroxide (H2O2) on the expression of cellular senescence-associated molecules in NHEKs, compared to in squamous carcinoma cells (SCCs). Hydrogen peroxide increased the number of cells positive in senescence associated-β-galactosidase (SA-β-Gal) activity in NHEKs, but not SCCs. The expression of cyclin-dependent kinase (CDK) inhibitors, especially p16(INK4a) was upregulated in NHEKs treated with H2O2. Interestingly, H2O2 suppressed the methylation of p16(INK4a), promoter region in NHEKs, but not in SCCs. Hydrogen peroxide also suppressed the expression of phosphorylated Rb and CDK4, resulting in arrest in G0/G1 phase in NHEKs, but not SCCs. Our results indicate that the ROS-induced cellular senescence in NHEKs was caused by the upregulation p16(INK4a) through demethylation in its promoter region, which is not detected in SCCs, suggesting that ROS-induced cellular senescence contributes to tumor suppression of NHEKs. PMID:25181340

  16. A mutation in the mitochondrial protein UQCRB promotes angiogenesis through the generation of mitochondrial reactive oxygen species

    SciTech Connect

    Chang, Junghwa; Jung, Hye Jin; Jeong, Seung Hun; Kim, Hyoung Kyu; Han, Jin; Kwon, Ho Jeong

    2014-12-12

    Highlights: • We constructed mitochondrial protein UQCRB mutant stable cell lines on the basis of a human case report. • These mutant cell lines exhibit pro-angiogenic activity with enhanced VEGF expression. • Proliferation of mutant cell lines was regulated by UQCRB inhibitors. • UQCRB may have a functional role in angiogenesis. - Abstract: Ubiquinol-cytochrome c reductase binding protein (UQCRB) is one of the subunits of mitochondrial complex III and is a target protein of the natural anti-angiogenic small molecule terpestacin. Previously, the biological role of UQCRB was thought to be limited to the maintenance of complex III. However, the identification and validation of UQCRB as a target protein of terpestacin enabled the role of UQCRB in oxygen sensing and angiogenesis to be elucidated. To explore the biological role of this protein further, UQCRB mutant stable cell lines were generated on the basis of a human case report. We demonstrated that these cell lines exhibited glycolytic and pro-angiogenic activities via mitochondrial reactive oxygen species (mROS)-mediated HIF1 signal transduction. Furthermore, a morphological abnormality in mitochondria was detected in UQCRB mutant stable cell lines. In addition, the proliferative effect of the UQCRB mutants was significantly regulated by the UQCRB inhibitors terpestacin and A1938. Collectively, these results provide a molecular basis for UQCRB-related biological processes and reveal potential key roles of UQCRB in angiogenesis and mitochondria-mediated metabolic disorders.

  17. Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity.

    PubMed

    Petersen Shay, Kate; Moreau, Régis F; Smith, Eric J; Hagen, Tory M

    2008-06-01

    The chemical reduction and oxidation (redox) properties of alpha-lipoic acid (LA) suggest that it may have potent antioxidant potential. A significant number of studies now show that LA and its reduced form, dihydrolipoic acid (DHLA), directly scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) species and protect cells against a host of insults where oxidative stress is part of the underlying etiology. However, owing to its limited and transient accumulation in tissues following oral intake, the efficacy of nonprotein-bound LA to function as a physiological antioxidant has been questioned. Herein, we review the evidence that the micronutrient functions of LA may be more as an effector of important cellular stress response pathways that ultimately influence endogenous cellular antioxidant levels and reduce proinflammatory mechanisms. This would promote a sustained improvement in cellular resistance to pathologies where oxidative stress is involved, which would not be forthcoming if LA solely acted as a transient ROS scavenger. PMID:18409172

  18. Promoting Active Species Generation by Plasmon-Induced Hot-Electron Excitation for Efficient Electrocatalytic Oxygen Evolution.

    PubMed

    Liu, Guigao; Li, Peng; Zhao, Guixia; Wang, Xin; Kong, Jintao; Liu, Huimin; Zhang, Huabin; Chang, Kun; Meng, Xianguang; Kako, Tetsuya; Ye, Jinhua

    2016-07-27

    Water splitting represents a promising technology for renewable energy conversion and storage, but it is greatly hindered by the kinetically sluggish oxygen evolution reaction (OER). Here, using Au-nanoparticle-decorated Ni(OH)2 nanosheets [Ni(OH)2-Au] as catalysts, we demonstrate that the photon-induced surface plasmon resonance (SPR) excitation on Au nanoparticles could significantly activate the OER catalysis, specifically achieving a more than 4-fold enhanced activity and meanwhile affording a markedly decreased overpotential of 270 mV at the current density of 10 mA cm(-2) and a small Tafel slope of 35 mV dec(-1) (no iR-correction), which is much better than those of the benchmark IrO2 and RuO2, as well as most Ni-based OER catalysts reported to date. The synergy of the enhanced generation of Ni(III/IV) active species and the improved charge transfer, both induced by hot-electron excitation on Au nanoparticles, is proposed to account for such a markedly increased activity. The SPR-enhanced OER catalysis could also be observed over cobalt oxide (CoO)-Au and iron oxy-hydroxide (FeOOH)-Au catalysts, suggesting the generality of this strategy. These findings highlight the possibility of activating OER catalysis by plasmonic excitation and could open new avenues toward the design of more-energy-efficient catalytic water oxidation systems with the assistance of light energy. PMID:27380539

  19. Reactive Oxygen Species and Cellular Oxygen Sensing

    PubMed Central

    Cash, Timothy P; Pan, Yi; Simon, M. Celeste

    2008-01-01

    Many organisms activate adaptive transcriptional programs to help them cope with decreased oxygen levels, or hypoxia, in their environment. These responses are triggered by various oxygen sensing systems in bacteria, yeast and metazoans. In metazoans, the hypoxia inducible factors (HIFs) mediate the adaptive transcriptional response to hypoxia by upregulating genes involved in maintaining bioenergetic homeostasis. The HIFs in turn are regulated by HIF-specific prolyl hydroxlase activity, which is sensitive to cellular oxygen levels and other factors such as tricarboxylic acid cycle metabolites and reactive oxygen species (ROS). Establishing a role for ROS in cellular oxygen sensing has been challenging since ROS are intrinsically unstable and difficult to measure. However, recent advances in fluorescence energy transfer resonance (FRET)-based methods for measuring ROS are alleviating some of the previous difficulties associated with dyes and luminescent chemicals. In addition, new genetic models have demonstrated that functional mitochondrial electron transport and associated ROS production during hypoxia are required for HIF stabilization in mammalian cells. Current efforts are directed at how ROS mediate prolyl hydroxylase activity and hypoxic HIF stabilization. Progress in understanding this process has been enhanced by the development of the FRET-based ROS probe, an vivo prolyl hydroxylase reporter and various genetic models harboring mutations in components of the mitochondrial electron transport chain. PMID:17893032

  20. Extracellular ATP promotes stomatal opening of Arabidopsis thaliana through heterotrimeric G protein α subunit and reactive oxygen species.

    PubMed

    Hao, Li-Hua; Wang, Wei-Xia; Chen, Chen; Wang, Yu-Fang; Liu, Ting; Li, Xia; Shang, Zhong-Lin

    2012-07-01

    In recent years, adenosine tri-phosphate (ATP) has been reported to exist in apoplasts of plant cells as a signal molecule. Extracellular ATP (eATP) plays important roles in plant growth, development, and stress tolerance. Here, extracellular ATP was found to promote stomatal opening of Arabidopsis thaliana in light and darkness. ADP, GTP, and weakly hydrolyzable ATP analogs (ATPγS, Bz-ATP, and 2meATP) showed similar effects, whereas AMP and adenosine did not affect stomatal movement. Apyrase inhibited stomatal opening. ATP-promoted stomatal opening was blocked by an NADPH oxidase inhibitor (diphenylene iodonium) or deoxidizer (dithiothreitol), and was impaired in null mutant of NADPH oxidase (atrbohD/F). Added ATP triggered ROS generation in guard cells via NADPH oxidase. ATP also induced Ca(2+) influx and H(+) efflux in guard cells. In atrbohD/F, ATP-induced ion flux was strongly suppressed. In null mutants of the heterotrimeric G protein α subunit, ATP-promoted stomatal opening, cytoplasmic ROS generation, Ca(2+) influx, and H(+) efflux were all suppressed. These results indicated that eATP-promoted stomatal opening possibly involves the heterotrimeric G protein, ROS, cytosolic Ca(2+), and plasma membrane H(+)-ATPase. PMID:22138967

  1. 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

  2. UV-B Induced Generation of Reactive Oxygen Species Promotes Formation of BFA-Induced Compartments in Cells of Arabidopsis Root Apices.

    PubMed

    Yokawa, Ken; Kagenishi, Tomoko; Baluška, František

    2015-01-01

    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

  3. DUOX2 promotes the elimination of the Klebsiella pneumoniae strain K5 from T24 cells through the reactive oxygen species pathway.

    PubMed

    Lu, Huixia; Wu, Qi; Yang, Huijun

    2015-08-01

    Dual oxidase 2 (DUOX2) plays a major role in host defense in intestinal and airway epithelial cells through the reactive oxygen species (ROS) pathway. Klebsiella pneumoniae is a uropathogen that causes urinary tract infections. It is not known whether DUOX2 plays a role in host defense in bladder cancer epithelial cells. It is also not known whether Klebsiella pneumoniae invades T24 human bladder carcinoma cells and whether DUOX2 plays a role in eliminating the Klebsiella pneumoniae strain K5 through the ROS pathway in T24 cells. Thus, in the present study, we aimed to investigate the infectious capability of the Klebsiella pneumoniae K5 strain and the immunity-promoting capability of DUOX2 in T24 cells. We quantified the number of viable intracellular bacteria using the plate count method. DUOX2 expression was evaluated by western blot analysis and reverse transcription-quantitative PCR (RT-qPCR) following treatment with or without multiple cytokines, phorbol 12-myristate 13-acetate (PMA), muramyl dipeptide (MDP), N-acetylmuramyl-D-alanyl-D-isoglutamine (MDP-DD), H2O2 inhibitor, catalase (CAT), the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) oxidase inhibitor, diphenyleneiodonium (DPI), or siRNA targeting DUOX2 (siDUOX2). The levels of ROS in the T24 cells infected with the K5 strain were examined following treatment with DPI, CAT or siDUOX2. Our results revealed that DUOX2 expression increased and the number of viable intracellular bacteria decreased in the T24 cells following infection with the K4 bacteria. Treatment with the cytokines and MDP and PMA also induced DUOX2 expression and decreased the number of viable intracellular bacteria. The levels of ROS also increased following treatment with the cytokines and MDP and PMA. However, when the cells were treated with the inhibitors (DPI or CAT), these effects were all reversed. Our data demonstrated that DUOX2 played an important role in innate immunity against bacterial cytoinvasion through the

  4. Reactive oxygen species induce MMP12-dependent degradation of collagen 5 and fibronectin to promote the motility of human umbilical cord-derived mesenchymal stem cells

    PubMed Central

    Yun, Seung Pil; Lee, Sei-Jung; Oh, Sang Yub; Jung, Young Hyun; Ryu, Jung Min; Suh, Han Na; Kim, Mi Ok; Oh, Keon Bong; Han, Ho Jae

    2014-01-01

    BACKGROUND AND PURPOSE Reactive oxygen species (ROS) are potent regulators of stem cell behaviour; however, their physiological significance as regards MMP-mediated regulation of the motility of human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) has not been characterized. In the present study, we investigated the role of hydrogen peroxide (H2O2) and associated signalling pathways in promoting UCB-MSCs motility. EXPERIMENTAL APPROACH The regulatory effects of H2O2 on the activation of PKC, MAPKs, NF-κB and β-catenin were determined. The expressions of MMP and extracellular matrix proteins were examined. Pharmacological inhibitors and gene-specific siRNA were used to identify the signalling pathways of H2O2 that affect UCB-MSCs motility. An experimental skin wound-healing model was used to confirm the functional role of UCB-MSCs treated with H2O2 in ICR mice. KEY RESULTS H2O2 increased the motility of UCB-MSCs by activating PKCα via a calcium influx mechanism. H2O2 activated ERK and p38 MAPK, which are responsible for the distinct activation of transcription factors NF-κB and β-catenin. UCB-MSCs expressed eight MMP genes, but only MMP12 expression was uniquely regulated by NF-κB and β-catenin activation. H2O2 increased the MMP12-dependent degradation of collagen 5 (COL-5) and fibronectin (FN) associated with UCB-MSCs motility. Finally, topical transplantation of UCB-MSCs treated with H2O2 enhanced skin wound healing in mice. CONCLUSIONS AND IMPLICATIONS H2O2 stimulated UCB-MSCs motility by increasing MMP12-dependent degradation of COL-5 and FN through the activation of NF-κB and glycogen synthase kinase-3β/β-catenin, which is critical for providing a suitable microenvironment for MSCs transplantation and re-epithelialization of skin wounds in mice. PMID:24627968

  5. Long-Acting Progestin-Only Contraceptives Enhance Human Endometrial Stromal Cell Expressed Neuronal Pentraxin-1 and Reactive Oxygen Species to Promote Endothelial Cell Apoptosis

    PubMed Central

    Guzeloglu-Kayisli, O.; Basar, M.; Shapiro, J. P.; Semerci, N.; Huang, J. S.; Schatz, F.

    2014-01-01

    Context: Despite the absence of progesterone receptor protein in human endometrial endothelial cells (HEECs), endometria of women receiving long-acting progestin-only contraceptives (LAPCs) display reduced uterine blood flow, elevated reactive oxygen species generation, increased angiogenesis, and irregularly distributed, enlarged, fragile microvessels resulting in abnormal uterine bleeding. Objective: We propose that paracrine factors from LAPC-treated human endometrial stromal cells (HESCs) impair HEEC functions by shifting the balance between HEEC viability and death in favor of the latter. Design and Setting: Proliferation, apoptosis, and transcriptome analyses were performed in HEECs treated with conditioned medium supernatant (CMS) derived from HESCs treated with estradiol (E2) ± medroxyprogesterone acetate or etonogestrel under normoxia or hypoxia. Mass spectrometry interrogated the CMS secretome while immunostaining for neuronal pentraxin-1 (NPTX1), cleaved caspase-3, and cytochrome c was performed in cultured HEECs and paired endometria from women using LAPCs. Main Outcome: HEEC apoptosis and its underlying mechanism. Results: HESC CMS from E2 + medroxyprogesterone acetate or E2 + etonogestrel incubations under hypoxia induced HEEC apoptosis (P < .05), whereas mass spectrometry of the CMS revealed increased NPTX1 secretion (P < .05). Endothelial cleaved caspase-3 and stromal NPTX1 immunoreactivity were significantly higher in LAPC-treated endometria (P < .001). Transcriptomics revealed AKT signaling inhibition and mitochondrial dysfunction in HEECs incubated with HESC CMS. In vitro analyses proved that CMS decreased HEEC AKT phosphorylation (P < .05) and that recombinant NPTX1 (P < .05) or NPTX1 + H2O2 (P < .001) increase HEEC apoptosis and cytosolic cytochrome c levels. Conclusions: LAPC-enhanced NPTX1 secretion and reactive oxygen species generation in HESCs impair HEEC survival resulting in a loss in vascular integrity, demonstrating a novel paracrine

  6. Constitutive activation of epidermal growth factor receptor promotes tumorigenesis of Cr(VI)-transformed cells through decreased reactive oxygen species and apoptosis resistance development.

    PubMed

    Kim, Donghern; Dai, Jin; Fai, Leonard Yenwong; Yao, Hua; Son, Young-Ok; Wang, Lei; Pratheeshkumar, Poyil; Kondo, Kazuya; Shi, Xianglin; Zhang, Zhuo

    2015-01-23

    Hexavalent chromium (Cr(VI)) compounds are well-established lung carcinogens. Epidermal growth factor receptor (EGFR) is a tyrosine kinase transmembrane receptor that regulates cell survival, tumor invasion, and angiogenesis. Our results show that chronic exposure of human bronchial epithelial (BEAS-2B) cells to Cr(VI) is able to cause malignant cell transformation. These transformed cells exhibit apoptosis resistance with reduced poly ADP-ribose polymerase cleavage (C-PARP) and Bax expression and enhanced expressions of Bcl-2 and Bcl-xL. These transformed cells also exhibit reduced capacity of reactive oxygen species (ROS) generation along with elevated expression of antioxidant manganese superoxide dismutase 2 (SOD2). The expression of this antioxidant was also elevated in lung tumor tissue from a worker exposed to Cr(VI) for 19 years. EGFR was activated in Cr(VI)-transformed BEAS-2B cells, lung tissue from animals exposed to Cr(VI) particles, and human lung tumor tissue. Further study indicates that constitutive activation of EGFR in Cr(VI)-transformed cells was due to increased binding to its ligand amphiregulin (AREG). Inhibition of EGFR or AREG increased Bax expression and reduced Bcl-2 expression, resulting in reduced apoptosis resistance. Furthermore, inhibition of AREG or EGFR restored capacity of ROS generation and decreased SOD2 expression. PI3K/AKT was activated, which depended on EGFR in Cr(VI)-transformed BEAS-2B cells. Inhibition of PI3K/AKT increased ROS generation and reduced SOD2 expression, resulting in reduced apoptosis resistance with commitment increase in Bax expression and reduction of Bcl-2 expression. Xenograft mouse tumor study further demonstrates the essential role of EGFR in tumorigenesis of Cr(VI)-transformed cells. In summary, the present study suggests that ligand-dependent constitutive activation of EGFR causes reduced ROS generation and increased antioxidant expression, leading to development of apoptosis resistance, contributing

  7. Physical exercise, reactive oxygen species and neuroprotection.

    PubMed

    Radak, Zsolt; Suzuki, Katsuhiko; Higuchi, Mitsuru; Balogh, Laszlo; Boldogh, Istvan; Koltai, Erika

    2016-09-01

    Regular exercise has systemic beneficial effects, including the promotion of brain function. The adaptive response to regular exercise involves the up-regulation of the enzymatic antioxidant system and modulation of oxidative damage. Reactive oxygen species (ROS) are important regulators of cell signaling. Exercise, via intensity-dependent modulation of metabolism and/or directly activated ROS generating enzymes, regulates the cellular redox state of the brain. ROS are also involved in the self-renewal and differentiation of neuronal stem cells and the exercise-mediated neurogenesis could be partly associated with ROS production. Exercise has strong effects on the immune system and readily alters the production of cytokines. Certain cytokines, especially IL-6, IL-1, TNF-α, IL-18 and IFN gamma, are actively involved in the modulation of synaptic plasticity and neurogenesis. Cytokines can also contribute to ROS production. ROS-mediated alteration of lipids, protein, and DNA could directly affect brain function, while exercise modulates the accumulation of oxidative damage. Oxidative alteration of macromolecules can activate signaling processes, membrane remodeling, and gene transcription. The well known neuroprotective effects of exercise are partly due to redox-associated adaptation. PMID:26828019

  8. Reactive oxygen species and anti-proteinases.

    PubMed

    Siddiqui, Tooba; Zia, Mohammad Khalid; Ali, Syed Saqib; Rehman, Ahmed Abdur; Ahsan, Haseeb; Khan, Fahim Halim

    2016-01-01

    Reactive oxygen species (ROS) cause damage to macromolecules such as proteins, lipids and DNA and alters their structure and function. When generated outside the cell, ROS can induce damage to anti-proteinases. Anti-proteinases are proteins that are involved in the control and regulation of proteolytic enzymes. The damage caused to anti-proteinase barrier disturbs the proteinase-anti-proteinases balance and uncontrolled proteolysis at the site of injury promotes tissue damage. Studies have shown that ROS damages anti-proteinase shield of the body by inactivating key members such as alpha-2-macroglobulin, alpha-1-antitrypsin. Hypochlorous acid inactivates α-1-antitrypsin by oxidizing a critical reactive methionine residue. Superoxide and hypochlorous acid are physiological inactivators of alpha-2-macroglobulin. The damage to anti-proteinase barrier induced by ROS is a hallmark of diseases such as atherosclerosis, emphysema and rheumatoid arthritis. Thus, understanding the behaviour of ROS-induced damage to anti-proteinases may helps us in development of strategies that could control these inflammatory reactions and diseases. PMID:26699123

  9. Rosacea, Reactive Oxygen Species, and Azelaic Acid

    PubMed Central

    2009-01-01

    Rosacea is a common skin condition thought to be primarily an inflammatory disorder. Neutrophils, in particular, have been implicated in the inflammation associated with rosacea and mediate many of their effects through the release of reactive oxygen species. Recently, the role of reactive oxygen species in the pathophysiology of rosacea has been recognized. Many effective agents for rosacea, including topical azelaic acid and topical metronidazole, have anti-inflammatory properties. in-vitro models have demonstrated the potent antioxidant effects of azelaic acid, providing a potential mechanistic explanation for its efficacy in the treatment of rosacea. PMID:20967185

  10. Reactive oxygen species formed in organic lithium-oxygen batteries.

    PubMed

    Schwager, Patrick; Dongmo, Saustin; Fenske, Daniela; Wittstock, Gunther

    2016-04-20

    Li-oxygen batteries with organic electrolytes are of general interest because of their theoretically high gravimetric energy density. Among the great challenges for this storage technology is the generation of reactive oxygen species such as superoxides and peroxides that may react with the organic solvent molecules and other cell components. The generation of such species has been assumed to occur during the charging reaction. Here we show that superoxide is formed also during the discharge reaction in lithium ion-containing dimethyl sulfoxide electrolytes and is released into the solution. This is shown independently by fluorescence microscopy after reaction with the selective reagent 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole and by local detection using a microelectrode of a scanning electrochemcial microscope positioned in a defined distance of 10 to 90 μm above the gas diffusion electrode. PMID:26911793

  11. Formation and Detoxification of Reactive Oxygen Species

    ERIC Educational Resources Information Center

    Kuciel, Radoslawa; Mazurkiewicz, Aleksandra

    2004-01-01

    A model of reactive oxygen species metabolism is proposed as a laboratory exercise for students. The superoxide ion in this model is generated during the reaction of oxidation of xanthine, catalyzed by xanthine oxidase. The effect of catalase, superoxide dismutase, and allopurinol on superoxide ion generation and removal in this system is also…

  12. REACTIVE OXYGEN SPECIES: IMPACT ON SKELETAL MUSCLE

    PubMed Central

    Powers, Scott K.; Ji, Li Li; Kavazis, Andreas N.; Jackson, Malcolm J.

    2014-01-01

    It is well established that contracting muscles produce both reactive oxygen and nitrogen species. Although the sources of oxidant production during exercise continue to be debated, growing evidence suggests that mitochondria are not the dominant source. Regardless of the sources of oxidants in contracting muscles, intense and prolonged exercise can result in oxidative damage to both proteins and lipids in the contracting myocytes. Further, oxidants regulate numerous cell signaling pathways and modulate the expression of many genes. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels. Furthermore, numerous products associated with oxidant-modulated genes have been identified and include antioxidant enzymes, stress proteins, and mitochondrial electron transport proteins. Interestingly, low and physiological levels of reactive oxygen species are required for normal force production in skeletal muscle, but high levels of reactive oxygen species result in contractile dysfunction and fatigue. Ongoing research continues to explore the redox-sensitive targets in muscle that are responsible for both redox-regulation of muscle adaptation and oxidant-mediated muscle fatigue. PMID:23737208

  13. Interaction of insulin with methyl tert-butyl ether promotes molten globule-like state and production of reactive oxygen species.

    PubMed

    Valipour, Masoumeh; Maghami, Parvaneh; Habibi-Rezaei, Mehran; Sadeghpour, Mostafa; Khademian, Mohamad Ali; Mosavi, Khadijeh; Sheibani, Nader; Moosavi-Movahedi, Ali Akbar

    2015-09-01

    Interaction of methyl tert-butyl ether (MTBE) with proteins is a new look at its potential adverse biological effects. When MTBE is released to the environment it enters the blood stream through inhalation, and could affect the properties of various proteins. Here we investigated the interaction of MTBE with insulin and its effect on insulin structural changes. Our results showed that insulin formed a molten globule (MG)-like structure in the presence of 8 μM MTBE under physiological pH. The insulin structural changes were studied using spectroscopy methods, viscosity calculation, dynamic light scattering and differential scanning calorimetry. To delineate the mechanisms involved in MTBE-protein interactions, the formation of reactive oxygen specious (ROS) and formation of protein aggregates were measured. The chemiluminscence experiments revealed an increase in ROS production in the presence of MTBE especially in the MG-like state. These results were further confirmed by the aggregation tests, which indicated more aggregation of insulin at 40 μM MTBE compared with 8 μM. Thus, the formation of initial aggregates and exposure of the hydrophobic patches upon formation of the MG-like state in the presence of MTBE drives protein oxidation and ROS generation. PMID:26193678

  14. Senescence, Stress, and Reactive Oxygen Species

    PubMed Central

    Jajic, Ivan; Sarna, Tadeusz; Strzalka, Kazimierz

    2015-01-01

    Generation of reactive oxygen species (ROS) is one of the earliest responses of plant cells to various biotic and abiotic stresses. ROS are capable of inducing cellular damage by oxidation of proteins, inactivation of enzymes, alterations in the gene expression, and decomposition of biomembranes. On the other hand, they also have a signaling role and changes in production of ROS can act as signals that change the transcription of genes that favor the acclimation of plants to abiotic stresses. Among the ROS, it is believed that H2O2 causes the largest changes in the levels of gene expression in plants. A wide range of plant responses has been found to be triggered by H2O2 such as acclimation to drought, photooxidative stress, and induction of senescence. Our knowledge on signaling roles of singlet oxygen (1O2) has been limited by its short lifetime, but recent experiments with a flu mutant demonstrated that singlet oxygen does not act primarily as a toxin but rather as a signal that activates several stress-response pathways. In this review we summarize the latest progress on the signaling roles of ROS during senescence and abiotic stresses and we give a short overview of the methods that can be used for their assessment. PMID:27135335

  15. Endophytic Bacterium-Triggered Reactive Oxygen Species Directly Increase Oxygenous Sesquiterpenoid Content and Diversity in Atractylodes lancea.

    PubMed

    Zhou, Jia-Yu; Yuan, Jie; Li, Xia; Ning, Yi-Fan; Dai, Chuan-Chao

    2016-03-01

    Oxygenous terpenoids are active components of many medicinal plants. However, current studies that have focused on enzymatic oxidation reactions cannot comprehensively clarify the mechanisms of oxygenous terpenoid synthesis and diversity. This study shows that an endophytic bacterium can trigger the generation of reactive oxygen species (ROS) that directly increase oxygenous sesquiterpenoid content and diversity in Atractylodes lancea. A. lancea is a famous but endangered Chinese medicinal plant that contains abundant oxygenous sesquiterpenoids. Geo-authentic A. lancea produces a wider range and a greater abundance of oxygenous sesquiterpenoids than the cultivated herb. Our previous studies have shown the mechanisms behind endophytic promotion of the production of sesquiterpenoid hydrocarbon scaffolds; however, how endophytes promote the formation of oxygenous sesquiterpenoids and their diversity is unclear. After colonization by Pseudomonas fluorescens ALEB7B, oxidative burst and oxygenous sesquiterpenoid accumulation in A. lancea occur synchronously. Treatment with exogenous hydrogen peroxide (H2O2) or singlet oxygen induces oxidative burst and promotes oxygenous sesquiterpenoid accumulation in planta. Conversely, pretreatment of plantlets with the ROS scavenger ascorbic acid significantly inhibits the oxidative burst and oxygenous sesquiterpenoid accumulation induced by P. fluorescens ALEB7B. Further in vitro oxidation experiments show that several oxygenous sesquiterpenoids can be obtained from direct oxidation caused by H2O2 or singlet oxygen. In summary, this study demonstrates that endophytic bacterium-triggered ROS can directly oxidize oxygen-free sesquiterpenoids and increase the oxygenous sesquiterpenoid content and diversity in A. lancea, providing a novel explanation of the mechanisms of oxygenous terpenoid synthesis in planta and an essential complementarity to enzymatic oxidation reactions. PMID:26712554

  16. Endophytic Bacterium-Triggered Reactive Oxygen Species Directly Increase Oxygenous Sesquiterpenoid Content and Diversity in Atractylodes lancea

    PubMed Central

    Zhou, Jia-Yu; Yuan, Jie; Li, Xia; Ning, Yi-Fan

    2015-01-01

    Oxygenous terpenoids are active components of many medicinal plants. However, current studies that have focused on enzymatic oxidation reactions cannot comprehensively clarify the mechanisms of oxygenous terpenoid synthesis and diversity. This study shows that an endophytic bacterium can trigger the generation of reactive oxygen species (ROS) that directly increase oxygenous sesquiterpenoid content and diversity in Atractylodes lancea. A. lancea is a famous but endangered Chinese medicinal plant that contains abundant oxygenous sesquiterpenoids. Geo-authentic A. lancea produces a wider range and a greater abundance of oxygenous sesquiterpenoids than the cultivated herb. Our previous studies have shown the mechanisms behind endophytic promotion of the production of sesquiterpenoid hydrocarbon scaffolds; however, how endophytes promote the formation of oxygenous sesquiterpenoids and their diversity is unclear. After colonization by Pseudomonas fluorescens ALEB7B, oxidative burst and oxygenous sesquiterpenoid accumulation in A. lancea occur synchronously. Treatment with exogenous hydrogen peroxide (H2O2) or singlet oxygen induces oxidative burst and promotes oxygenous sesquiterpenoid accumulation in planta. Conversely, pretreatment of plantlets with the ROS scavenger ascorbic acid significantly inhibits the oxidative burst and oxygenous sesquiterpenoid accumulation induced by P. fluorescens ALEB7B. Further in vitro oxidation experiments show that several oxygenous sesquiterpenoids can be obtained from direct oxidation caused by H2O2 or singlet oxygen. In summary, this study demonstrates that endophytic bacterium-triggered ROS can directly oxidize oxygen-free sesquiterpenoids and increase the oxygenous sesquiterpenoid content and diversity in A. lancea, providing a novel explanation of the mechanisms of oxygenous terpenoid synthesis in planta and an essential complementarity to enzymatic oxidation reactions. PMID:26712554

  17. [The two faces of reactive oxygen species].

    PubMed

    Zabłocka, Agnieszka; Janusz, Maria

    2008-01-01

    Oxidative stress has been implicated in playing a crucial role in aging and in the pathogeneses of a number of diseases, including neurodegenerative disorders such as Alzheimer's disease. Oxidative stress occurs due to an imbalance in prooxidant and antioxidant levels. Reactive oxygen species (ROS) are highly reactive and may modify and inactivate proteins, lipids, DNA, and RNA and induce cellular dysfunctions. To prevent free radical-induced cellular damage, the organism has developed a defense mechanism, the antioxidative system. This system includes antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), and glutathione reductase (GSSGR) and low-molecular antioxidants such as glutathion and plasma proteins. Glutathion plays a key role in maintaining the physiological balance between prooxidants and antioxidants. Plasma proteins can inhibit ROS generation and lipid peroxidation by chelating free transition metals. The major exogenous antioxidants are vitamins E, C, and A. PMID:18388851

  18. REACTIVE OXYGEN SPECIES AND COLORECTAL CANCER

    PubMed Central

    Sreevalsan, Sandeep; Safe, Stephen

    2013-01-01

    Several agents used for treatment of colon and other cancers induce reactive oxygen species (ROS) and this plays an important role in their anticancer activities. In addition to the well-known proapoptotic effects of ROS inducers, these compounds also decrease expression of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 and several pro-oncogenic Spregulated genes important for cancer cell proliferation, survival and metastasis. The mechanism of these responses involve ROS-dependent downregulation of microRNA-27a (miR-27a) or miR-20a (and paralogs) and induction of two Sp-repressors, ZBTB10 and ZBTB4 respectively. This pathway significantly contributes to the anticancer activity of ROS inducers and should be considered in development of drug combinations for cancer chemotherapy. PMID:25584043

  19. Downregulation of Reactive Oxygen Species in Apoptosis

    PubMed Central

    Jeong, Chul-Ho; Joo, Sang Hoon

    2016-01-01

    Generation of reactive oxygen species (ROS) by diverse anti-cancer drugs or phytochemicals has been closely related with the induction of apoptosis in cancers. Also, the downregulation of ROS by these chemicals has been found to block initiation of carcinogenesis. Therefore, modulation of ROS by phytochemicals emerges as a crucial mechanism to regulate apoptosis in cancer prevention or therapy. This review summarizes the current understanding of the selected chemical compounds and related cellular components that modulate ROS during apoptotic process. Metformin, quercetin, curcumin, vitamin C, and other compounds have been shown to downregulate ROS in the cellular apoptotic process, and some of them even induce apoptosis in cancer cells. The cellular components mediating the downregulation of ROS include nuclear factor erythroid 2-related factor 2 antioxidant signaling pathway, thioredoxin, catalase, glutathione, heme oxygenase-1, and uncoupling proteins. The present review provides information on the relationship between these compounds and the cellular components in modulating ROS in apoptotic cancer cells. PMID:27051644

  20. Reactive oxygen species in abiotic stress signaling.

    PubMed

    Jaspers, Pinja; Kangasjärvi, Jaakko

    2010-04-01

    Reactive oxygen species (ROS) are known to accumulate during abiotic stresses, and different cellular compartments respond to them by distinctive profiles of ROS formation. In contrast to earlier views, it is becoming increasingly evident that even during stress, ROS production is not necessarily a symptom of cellular dysfunction but might represent a necessary signal in adjusting the cellular machinery to the altered conditions. ROS can modulate many signal transduction pathways, such as mitogen-activated protein kinase cascades, and ultimately influence the activity of transcription factors. However, the picture of ROS-mediated signaling is still fragmentary and the issues of ROS perception as well as the signaling specificity remain open. Here, we review some of the recent advances in plant abiotic stress signaling with emphasis on processes known to be affected heavily by ROS. PMID:20028478

  1. Reactive oxygen species, ageing and the hormesis police.

    PubMed

    Ludovico, Paula; Burhans, William C

    2014-02-01

    For more than 50 years, the free radical theory served as the paradigm guiding most investigations of ageing. However, recent studies in a variety of organisms have identified conceptual and practical limitations to this theory. Some of these limitations are related to the recent discovery that caloric restriction and other experimental manipulations promote longevity by inducing hormesis effects in association with increased reactive oxygen species (ROS). The beneficial role of ROS in lifespan extension is consistent with the essential role of these molecules in cell signalling. However, the identity of specific forms of ROS that promote longevity remains unclear. In this article, we argue that in several model systems, hydrogen peroxide plays a crucial role in the induction of hormesis. PMID:23965186

  2. Reactive oxygen species: their relation to pneumoconiosis and carcinogenesis.

    PubMed

    Vallyathan, V; Shi, X; Castranova, V

    1998-10-01

    Occupational exposures to mineral particles cause pneumoconiosis and other diseases, including cancer. Recent studies have suggested that reactive oxygen species (ROS) may play a key role in the mechanisms of disease initiation and progression following exposure to these particles. ROS-induced primary stimuli result in the increased secretion of proinflammatory cytokines and other mediators, promoting events that appear to be important in the progression of cell injury and pulmonary disease. We have provided evidence supporting the hypothesis that inhalation of insoluble particles such as asbestos, agricultural dusts, coal, crystalline silica, and inorganic dust can be involved in facilitating multiple pathways for persistent generation of ROS, which may lead to a continuum of inflammation leading to progression of disease. This article briefly summarizes some of the recent findings from our laboratories with emphasis on the molecular events by which ROS are involved in promoting pneumoconiosis and carcinogenesis. PMID:9788890

  3. Reactive Oxygen Species and Neutrophil Function.

    PubMed

    Winterbourn, Christine C; Kettle, Anthony J; Hampton, Mark B

    2016-06-01

    Neutrophils are essential for killing bacteria and other microorganisms, and they also have a significant role in regulating the inflammatory response. Stimulated neutrophils activate their NADPH oxidase (NOX2) to generate large amounts of superoxide, which acts as a precursor of hydrogen peroxide and other reactive oxygen species that are generated by their heme enzyme myeloperoxidase. When neutrophils engulf bacteria they enclose them in small vesicles (phagosomes) into which superoxide is released by activated NOX2 on the internalized neutrophil membrane. The superoxide dismutates to hydrogen peroxide, which is used by myeloperoxidase to generate other oxidants, including the highly microbicidal species hypochlorous acid. NOX activation occurs at other sites in the cell, where it is considered to have a regulatory function. Neutrophils also release oxidants, which can modify extracellular targets and affect the function of neighboring cells. We discuss the identity and chemical properties of the specific oxidants produced by neutrophils in different situations, and what is known about oxidative mechanisms of microbial killing, inflammatory tissue damage, and signaling. PMID:27050287

  4. Influence of reactive oxygen species on the sterilization of microbes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The influence of reactive oxygen species on living cells, including various microbes, is discussed. A sterilization experiment with bacterial endospores reveals that an argoneoxygen plasma jet very effectively kills endospores of Bacillus atrophaeus (ATCC 9372), thereby indicating that oxygen radic...

  5. Production and Consumption of Reactive Oxygen Species by Fullerenes

    EPA Science Inventory

    Reactive oxygen species (ROS) are one of the most important intermediates in chemical, photochemical, and biological processes. To understand the environmental exposure and toxicity of fullerenes better, the production and consumption of ROS (singlet oxygen, superoxide, hydrogen ...

  6. Reactive Oxygen Species in Cancer Stem Cells

    PubMed Central

    Shi, Xiaoke; Zhang, Yan; Zheng, Junheng

    2012-01-01

    Abstract Significance: Reactive oxygen species (ROS), byproducts of aerobic metabolism, are increased in many types of cancer cells. Increased endogenous ROS lead to adaptive changes and may play pivotal roles in tumorigenesis, metastasis, and resistance to radiation and chemotherapy. In contrast, the ROS generated by xenobiotics disturb the redox balance and may selectively kill cancer cells but spare normal cells. Recent Advances: Cancer stem cells (CSCs) are integral parts of pathophysiological mechanisms of tumor progression, metastasis, and chemo/radio resistance. Currently, intracellular ROS in CSCs is an active field of research. Critical Issues: Normal stem cells such as hematopoietic stem cells reside in niches characterized by hypoxia and low ROS, both of which are critical for maintaining the potential for self-renewal and stemness. However, the roles of ROS in CSCs remain poorly understood. Future Directions: Based on the regulation of ROS levels in normal stem cells and CSCs, future research may evaluate the potential therapeutic application of ROS elevation by exogenous xenobiotics to eliminate CSCs. Antioxid. Redox Signal. 16, 1215–1228. PMID:22316005

  7. Reactive oxygen species as glomerular autacoids.

    PubMed

    Baud, L; Fouqueray, B; Philippe, C; Ardaillou, R

    1992-04-01

    There is considerable evidence suggesting that reactive oxygen species (ROS; superoxide anion, hydrogen peroxide, hydroxyl radical, hypochlorous acid) are implicated in the pathogenesis of toxic, ischemic, and immunologically mediated glomerular injury. The capacity of glomerular cells, especially mesangial cells, to generate ROS in response to several stimuli suggests that these autacoids may play a role in models of glomerular injury that are independent of infiltrating polymorphonuclear leukocytes and monocytes. The mechanisms whereby ROS formation results in morphologic lesions and in modifications of glomerular permeability, blood flow, and filtration rate have been inferred from in vitro studies. They involve direct and indirect injury to resident cells (mesangiolysis) and glomerular basement membrane (in concert with metalloproteases) and alteration of both the release and binding of vasoactive substances, such as bioactive lipids (e.g., prostaglandin E2, prostacyclin, thromboxane), cytokines (e.g., tumor necrosis factor alpha), and possibly endothelium-derived relaxing factor. The importance of such processes appears to be modulated by the intrinsic antioxidant defenses of the glomeruli. Further studies are needed to address the role of ROS in human glomerular diseases. PMID:1600128

  8. Reactive oxygen species in leaf abscission signaling

    PubMed Central

    Sakamoto, Masaru; Munemura, Ikuko; Tomita, Reiko

    2008-01-01

    Reactive oxygen species (ROS) are produced in response to many environmental stresses, such as UV, chilling, salt and pathogen attack. These stresses also accompany leaf abscission in some plants, however, the relationship between these stresses and abscission is poorly understood. In our recent report, we developed an in vitro abscission system that reproduces stress-induced pepper leaf abscission in planta. Using this system, we demonstrated that continuous production of hydrogen peroxide (H2O2) is involved in leaf abscission signaling. Continuous H2O2 production is required to induce expression of the cell wall-degrading enzyme, cellulase and functions downstream of ethylene in abscission signaling. Furthermore, enhanced production of H2O2 occurs at the execution phase of abscission, suggesting that H2O2 also plays a role in the cell-wall degradation process. These data suggest that H2O2 has several roles in leaf abscission signaling. Here, we propose a model for these roles. PMID:19704438

  9. Ovarian toxicity from reactive oxygen species.

    PubMed

    Luderer, Ulrike

    2014-01-01

    Oxidative stress occurs when cellular mechanisms to regulate levels of reactive oxygen species (ROS) are overwhelmed due to overproduction of ROS and/or deficiency of antioxidants. This chapter describes accumulating evidence that oxidative stress is involved in ovarian toxicity caused by diverse stimuli, including environmental toxicants. There is strong evidence that ROS are involved in initiation of apoptosis in antral follicles caused by several chemical and physical agents. Although less attention has been focused on the roles of ROS in primordial and primary follicle death, several studies have shown protective effects of antioxidants and/or evidence of oxidative damage, suggesting that ROS may play a role in these smaller follicles as well. Oxidative damage to lipids in the oocyte has been implicated as a cause of persistently poor oocyte quality after early life exposure to several toxicants. Developing germ cells in the fetal ovary have also been shown to be sensitive to toxicants and ionizing radiation, which induce oxidative stress. Recent studies have begun to elucidate the mechanisms by which ROS mediate ovarian toxicity. PMID:24388188

  10. Reactive Oxygen Species in Combustion Aerosols

    NASA Astrophysics Data System (ADS)

    Balasubramanian, R.; See, S.

    2007-12-01

    Research on airborne particulate matter (PM) has received increased concern in recent years after it was identified as a major component of the air pollution mix that is strongly associated with premature mortality and morbidity. Particular attention has been paid to understanding the potential health impacts of fine particles (PM2.5), which primarily originate from combustion sources. One group of particulate-bound chemical components of health concern is reactive oxygen species (ROS), which include molecules such as hydrogen peroxide (H2O2), ions such as hypochlorite ion (OCl-), free radicals such as hydroxyl radical (·OH) and superoxide anion (·O2-) which is both an ion and a radical. However, the formation of ROS in PM is not clearly understood yet. Furthermore, the concentration of ROS in combustion particles of different origin has not been quantified. The primary objective of this work is to study the effect of transition metals on the production of ROS in PM2.5 by determining the concentrations of ROS and metals. Both soluble and total metals were measured to evaluate their respective associations with ROS. PM2.5 samples were collected from several outdoor and indoor combustion sources, including those emitted from on-road vehicles, food cooking, incense sticks, and cigarette smoke. PM2.5 samples were also collected from the background air in both the ambient outdoor and indoor environments to assess the levels of particulate-bound transition metals and ROS with no combustion activities in the vicinity of sampling locations. Results obtained from this comprehensive study on particulate-bound ROS will be presented and discussed.

  11. Reactive oxygen species and boar sperm function.

    PubMed

    Awda, Basim J; Mackenzie-Bell, Meghan; Buhr, Mary M

    2009-09-01

    Boar spermatozoa are very susceptible to reactive oxygen species (ROS), but ROS involvement in damage and/or capacitation is unclear. The impact of exposing fresh boar spermatozoa to an ROS-generating system (xanthine/xanthine oxidase; XA/XO) on sperm ROS content, membrane lipid peroxidation, phospholipase (PL) A activity, and motility, viability, and capacitation was contrasted to ROS content and sperm function after cryopreservation. Exposing boar sperm (n = 4-5 ejaculates) to the ROS-generating system for 30 min rapidly increased hydrogen peroxide (H2O2) and lipid peroxidation in all sperm, increased PLA in dead sperm, and did not affect intracellular O2- (flow cytometry of sperm labeled with 2',7'-dichlorodihydrofluorscein diacetate, BODIPY 581/591 C11, bis-BODIPY-FL C11, hydroethidine, respectively; counterstained for viability). Sperm viability remained high, but sperm became immotile. Cryopreservation decreased sperm motility, viability, and intracellular O2- significantly, but did not affect H2O2. As expected, more sperm incubated in capacitating media than Beltsville thawing solution buffer underwent acrosome reactions and protein tyrosine phosphorylation (four proteins, 58-174 kDa); which proteins were tyrosine phosphorylated was pH dependent. Pre-exposing sperm to the ROS-generating system increased the percentage of sperm that underwent acrosome reactions after incubation in capacitating conditions (P < 0.025), and decreased capacitation-dependent increases in two tyrosine-phosphorylated proteins (P < or = 0.035). In summary, H2O2 is the major free radical mediating direct ROS effects, but not cryopreservation changes, on boar sperm. Boar sperm motility, acrosome integrity, and lipid peroxidation are more sensitive indicators of oxidative stress than viability and PLA activity. ROS may stimulate the acrosome reaction in boar sperm through membrane lipid peroxidation and PLA activation. PMID:19357363

  12. Skin, Reactive Oxygen Species, and Circadian Clocks

    PubMed Central

    Ndiaye, Mary A.; Nihal, Minakshi; Wood, Gary S.

    2014-01-01

    Abstract Significance: Skin, a complex organ and the body's first line of defense against environmental insults, plays a critical role in maintaining homeostasis in an organism. This balance is maintained through a complex network of cellular machinery and signaling events, including those regulating oxidative stress and circadian rhythms. These regulatory mechanisms have developed integral systems to protect skin cells and to signal to the rest of the body in the event of internal and environmental stresses. Recent Advances: Interestingly, several signaling pathways and many bioactive molecules have been found to be involved and even important in the regulation of oxidative stress and circadian rhythms, especially in the skin. It is becoming increasingly evident that these two regulatory systems may, in fact, be interconnected in the regulation of homeostasis. Important examples of molecules that connect the two systems include serotonin, melatonin, vitamin D, and vitamin A. Critical Issues: Excessive reactive oxygen species and/or dysregulation of antioxidant system and circadian rhythms can cause critical errors in maintaining proper barrier function and skin health, as well as overall homeostasis. Unfortunately, the modern lifestyle seems to contribute to increasing alterations in redox balance and circadian rhythms, thereby posing a critical problem for normal functioning of the living system. Future Directions: Since the oxidative stress and circadian rhythm systems seem to have areas of overlap, future research needs to be focused on defining the interactions between these two important systems. This may be especially important in the skin where both systems play critical roles in protecting the whole body. Antioxid. Redox Signal. 20, 2982–2996. PMID:24111846

  13. REACTIVE OXYGEN SPECIES IN PULMONARY VASCULAR REMODELING

    PubMed Central

    Aggarwal, Saurabh; Gross, Christine M.; Sharma, Shruti; Fineman, Jeffrey R.; Black, Stephen M.

    2014-01-01

    The pathogenesis of pulmonary hypertension is a complex multifactorial process that involves the remodeling of pulmonary arteries. This remodeling process encompasses concentric medial thickening of small arterioles, neomuscularization of previously nonmuscular capillary-like vessels, and structural wall changes in larger pulmonary arteries. The pulmonary arterial muscularization is characterized by vascular smooth muscle cell (SMC) hyperplasia and hypertrophy. In addition, in uncontrolled pulmonary hypertension, the clonal expansion of apoptosis-resistant endothelial cells leads to the formation of plexiform lesions. Based upon a large number of studies in animal models, the three major stimuli that drive the vascular remodeling process are inflammation, shear stress and hypoxia. Although, the precise mechanisms by which these stimuli impair pulmonary vascular function and structure are unknown, reactive oxygen species (ROS)-mediated oxidative damage appears to play an important role. ROS are highly reactive due to their unpaired valence shell electron. Oxidative damage occurs when the production of ROS exceeds the quenching capacity of the anti-oxidant mechanisms of the cell. ROS can be produced from complexes in the cell membrane (nicotinamide adenine dinucleotide phosphate-oxidase), cellular organelles (peroxisomes and mitochondria), and in the cytoplasm (xanthine oxidase). Furthermore, low levels of tetrahydrobiopterin (BH4) and L-arginine the rate limiting co-factor and substrate for endothelial nitric oxide synthase (eNOS), can cause the uncoupling of eNOS, resulting in decreased NO production and increased ROS production. This review will focus on the ROS generation systems, scavenger antioxidants, and oxidative stress associated alterations in vascular remodeling in pulmonary hypertension. PMID:23897679

  14. Reactive oxygen species-targeted therapeutic interventions for atrial fibrillation

    PubMed Central

    Sovari, Ali A.; Dudley, Samuel C.

    2012-01-01

    Atrial fibrillation (AF) is the most common arrhythmia that requires medical attention, and its incidence is increasing. Current ion channel blockade therapies and catheter ablation have significant limitations in treatment of AF, mainly because they do not address the underlying pathophysiology of the disease. Oxidative stress has been implicated as a major underlying pathology that promotes AF; however, conventional antioxidants have not shown impressive therapeutic effects. A more careful design of antioxidant therapies and better selection of patients likely are required to treat effectively AF with antioxidant agents. Current evidence suggest inhibition of prominent cardiac sources of reactive oxygen species (ROS) such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and targeting subcellular compartments with the highest levels of ROS may prove to be effective therapies for AF. Increased serum markers of oxidative stress may be an important guide in selecting the AF patients who will most likely respond to antioxidant therapy. PMID:22934062

  15. Reactive Oxygen Species in Inflammation and Tissue Injury

    PubMed Central

    Mittal, Manish; Siddiqui, Mohammad Rizwan; Tran, Khiem; Reddy, Sekhar P.

    2014-01-01

    Abstract Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury. Antioxid. Redox Signal. 20, 1126–1167. PMID:23991888

  16. Are Reactive Oxygen Species Always Detrimental to Pathogens?

    PubMed Central

    Bozza, Marcelo T.

    2014-01-01

    Abstract Reactive oxygen species (ROS) are deadly weapons used by phagocytes and other cell types, such as lung epithelial cells, against pathogens. ROS can kill pathogens directly by causing oxidative damage to biocompounds or indirectly by stimulating pathogen elimination by various nonoxidative mechanisms, including pattern recognition receptors signaling, autophagy, neutrophil extracellular trap formation, and T-lymphocyte responses. Thus, one should expect that the inhibition of ROS production promote infection. Increasing evidences support that in certain particular infections, antioxidants decrease and prooxidants increase pathogen burden. In this study, we review the classic infections that are controlled by ROS and the cases in which ROS appear as promoters of infection, challenging the paradigm. We discuss the possible mechanisms by which ROS could promote particular infections. These mechanisms are still not completely clear but include the metabolic effects of ROS on pathogen physiology, ROS-induced damage to the immune system, and ROS-induced activation of immune defense mechanisms that are subsequently hijacked by particular pathogens to act against more effective microbicidal mechanisms of the immune system. The effective use of antioxidants as therapeutic agents against certain infections is a realistic possibility that is beginning to be applied against viruses. Antioxid. Redox Signal. 20, 1000–1037. PMID:23992156

  17. Cytotoxic and Antitumor Activity of Sulforaphane: The Role of Reactive Oxygen Species

    PubMed Central

    Sestili, Piero; Fimognari, Carmela

    2015-01-01

    According to recent estimates, cancer continues to remain the second leading cause of death and is becoming the leading one in old age. Failure and high systemic toxicity of conventional cancer therapies have accelerated the identification and development of innovative preventive as well as therapeutic strategies to contrast cancer-associated morbidity and mortality. In recent years, increasing body of in vitro and in vivo studies has underscored the cancer preventive and therapeutic efficacy of the isothiocyanate sulforaphane. In this review article, we highlight that sulforaphane cytotoxicity derives from complex, concurring, and multiple mechanisms, among which the generation of reactive oxygen species has been identified as playing a central role in promoting apoptosis and autophagy of target cells. We also discuss the site and the mechanism of reactive oxygen species' formation by sulforaphane, the toxicological relevance of sulforaphane-formed reactive oxygen species, and the death pathways triggered by sulforaphane-derived reactive oxygen species. PMID:26185755

  18. Reactive oxygen species: their relation to pneumoconiosis and carcinogenesis.

    PubMed Central

    Vallyathan, V; Shi, X; Castranova, V

    1998-01-01

    Occupational exposures to mineral particles cause pneumoconiosis and other diseases, including cancer. Recent studies have suggested that reactive oxygen species (ROS) may play a key role in the mechanisms of disease initiation and progression following exposure to these particles. ROS-induced primary stimuli result in the increased secretion of proinflammatory cytokines and other mediators, promoting events that appear to be important in the progression of cell injury and pulmonary disease. We have provided evidence supporting the hypothesis that inhalation of insoluble particles such as asbestos, agricultural dusts, coal, crystalline silica, and inorganic dust can be involved in facilitating multiple pathways for persistent generation of ROS, which may lead to a continuum of inflammation leading to progression of disease. This article briefly summarizes some of the recent findings from our laboratories with emphasis on the molecular events by which ROS are involved in promoting pneumoconiosis and carcinogenesis. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 Figure 7 Figure 8 PMID:9788890

  19. Reactive oxygen species delay control of lymphocytic choriomeningitis virus

    PubMed Central

    Lang, P A; Xu, H C; Grusdat, M; McIlwain, D R; Pandyra, A A; Harris, I S; Shaabani, N; Honke, N; Kumar Maney, S; Lang, E; Pozdeev, V I; Recher, M; Odermatt, B; Brenner, D; Häussinger, D; Ohashi, P S; Hengartner, H; Zinkernagel, R M; Mak, T W; Lang, K S

    2013-01-01

    Cluster of differentiation (CD)8+ T cells are like a double edged sword during chronic viral infections because they not only promote virus elimination but also induce virus-mediated immunopathology. Elevated levels of reactive oxygen species (ROS) have been reported during virus infections. However, the role of ROS in T-cell-mediated immunopathology remains unclear. Here we used the murine lymphocytic choriomeningitis virus to explore the role of ROS during the processes of virus elimination and induction of immunopathology. We found that virus infection led to elevated levels of ROS producing granulocytes and macrophages in virus-infected liver and spleen tissues that were triggered by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Lack of the regulatory subunit p47phox of the NADPH oxidase diminished ROS production in these cells. While CD8+ T cells exhibited ROS production that was independent of NADPH oxidase expression, survival and T-cell function was elevated in p47phox-deficient (Ncf1−/−) mice. In the absence of p47phox, enhanced T-cell immunity promoted virus elimination and blunted corresponding immunopathology. In conclusion, we find that NADPH-mediated production of ROS critically impairs the immune response, impacting elimination of virus and outcome of liver cell damage. PMID:23328631

  20. Balancing the generation and elimination of reactive oxygen species

    USGS Publications Warehouse

    Rodriguez, Rusty; Redman, Regina

    2005-01-01

    Fossil records suggest that bacteria developed the ability to photosynthesize ≈3,500 million years ago (mya), initiating a very slow accumulation of atmospheric oxygen (1). Recent geochemical models suggest that atmospheric oxygen did not accumulate to levels conducive for aerobic life until 500–1,000 mya (2, 3). The oxygenation of Earth's atmosphere resulted in the emergence of aerobic organisms followed by a great diversification of biological species and the eventual evolution of humans.

  1. The oxygen isotope equilibrium fractionation between sulfite species and water

    NASA Astrophysics Data System (ADS)

    Müller, Inigo A.; Brunner, Benjamin; Breuer, Christian; Coleman, Max; Bach, Wolfgang

    2013-11-01

    Sulfite is an important sulfoxy intermediate in oxidative and reductive sulfur cycling in the marine and terrestrial environment. Different aqueous sulfite species exist, such as dissolved sulfur dioxide (SO2), bisulfite (HSO3-), pyrosulfite (S2O52-) and sulfite sensu stricto (SO32-), whereas their relative abundance in solution depends on the concentration and the pH. Conversion of one species into another is rapid and involves in many cases incorporation of oxygen from, or release of oxygen to, water (e.g. SO2 + H2O ↔ HSO3- + H+), resulting in rapid oxygen isotope exchange between sulfite species and water. Consequently, the oxygen isotope composition of sulfite is strongly influenced by the oxygen isotope composition of water. Since sulfate does not exchange oxygen isotopes with water under most earth surface conditions, it can preserve the sulfite oxygen isotope signature that it inherits via oxidative and reductive sulfur cycling. Therefore, interpretation of δO values strongly hinges on the oxygen isotope equilibrium fractionation between sulfite and water which is poorly constrained. This is in large part due to technical difficulties in extraction of sulfite from solution for oxygen isotope analysis.

  2. Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer

    PubMed Central

    2016-01-01

    Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Reactive oxygen species (ROS) are generally increased in pancreatic cancer cells compared with normal cells. ROS plays a vital role in various cellular biological activities including proliferation, growth, apoptosis, and invasion. Besides, ROS participates in tumor microenvironment orchestration. The role of ROS is a doubled-edged sword in pancreatic cancer. The dual roles of ROS depend on the concentration. ROS facilitates carcinogenesis and cancer progression with mild-to-moderate elevated levels, while excessive ROS damages cancer cells dramatically and leads to cell death. Based on the recent knowledge, either promoting ROS generation to increase the concentration of ROS with extremely high levels or enhancing ROS scavenging ability to decrease ROS levels may benefit the treatment of pancreatic cancer. However, when faced with oxidative stress, the antioxidant programs of cancer cells have been activated to help cancer cells to survive in the adverse condition. Furthermore, ROS signaling and antioxidant programs play the vital roles in the progression of pancreatic cancer and in the response to cancer treatment. Eventually, it may be the novel target for various strategies and drugs to modulate ROS levels in pancreatic cancer therapy. PMID:26881012

  3. Tamoxifen reduces fat mass by boosting reactive oxygen species

    PubMed Central

    Liu, L; Zou, P; Zheng, L; Linarelli, L E; Amarell, S; Passaro, A; Liu, D; Cheng, Z

    2015-01-01

    As the pandemic of obesity is growing, a variety of animal models have been generated to study the mechanisms underlying the increased adiposity and development of metabolic disorders. Tamoxifen (Tam) is widely used to activate Cre recombinase that spatiotemporally controls target gene expression and regulates adiposity in laboratory animals. However, a critical question remains as to whether Tam itself affects adiposity and possibly confounds the functional study of target genes in adipose tissue. Here we administered Tam to Cre-absent forkhead box O1 (FoxO1) floxed mice (f-FoxO1) and insulin receptor substrate Irs1/Irs2 double floxed mice (df-Irs) and found that Tam induced approximately 30% reduction (P<0.05) in fat mass with insignificant change in body weight. Mechanistically, Tam promoted reactive oxygen species (ROS) production, apoptosis and autophagy, which was associated with downregulation of adipogenic regulator peroxisome proliferator-activated receptor gamma and dedifferentiation of mature adipocytes. However, normalization of ROS potently suppressed Tam-induced apoptosis, autophagy and adipocyte dedifferentiation, suggesting that ROS may account, at least in part, for the changes. Importantly, Tam-induced ROS production and fat mass reduction lasted for 4–5 weeks in the f-FoxO1 and df-Irs mice. Our data suggest that Tam reduces fat mass via boosting ROS, thus making a recovery period crucial for posttreatment study. PMID:25569103

  4. Co-cultures of human coronary smooth muscle cells and dimethyl sulfoxide-differentiated HL60 cells upregulate ProMMP9 activity and promote mobility-modulation by reactive oxygen species.

    PubMed

    Bernard, Yohann; Melchior, Chantal; Tschirhart, Eric; Bueb, Jean-Luc

    2008-10-01

    Vascular cells and leukocytes, involved in the development of atherosclerosis, produce cytokines and/or reactive oxygen species (ROS) and matrix metalloproteinases (MMPs) implicated in cell mobility. We investigated by co-culture experiments the effects of human coronary smooth muscle cells (HCSMC) on MMPs characteristics and mobility of neutrophil-like dimethyl sulfoxide-differentiated HL60 cells (not equal HL60). The effects of superoxide dismutase (SOD) and catalase were also analyzed. All the studied MMP2 characteristics remained unchanged. HCSMC stimulated MMP9 protein level, activity and mobility of not equal HL60 cells and expressed and secreted a variety of cytokines implicated in atherosclerosis. SOD and catalase increased MMP9 expression, protein level and activity of not equal HL60, but migration of not equal HL60 cells was only decreased by catalase, demonstrating that ROS are more efficient in modulating MMP9 activity of not equal HL60 than their mobility. Finally, HCSMC being able to stimulate not equal HL60, their co-cultures may represent an in vitro approach to study cellular interactions occurring in vivo during atherosclerosis. PMID:18665441

  5. Comparison of two strategies for detection of reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Gao, Weidong; Zhou, Yuanshu; Gu, Yueqing

    2014-09-01

    Photodynamic therapy (PDT) is a clinically approved treatment that was applied to oncology , dermatology, and ophthalmology. Reactive oxygen species (ROS) play a important role in the efficacy of PDT. Online monitoring of reactive oxygen species is the key to understand effect of PDT treatment. We used Fluorescence probes DPBF and luminescent probe luminal to measure the ROS in cells. And we revaluate the relationship between the amount of light and cell survival. There is strongly correlated between the amount of light and cell kill.

  6. Reactive oxygen species production by catechol stabilized copper nanoparticles

    NASA Astrophysics Data System (ADS)

    Chen, Cheng; Ahmed, Ishtiaq; Fruk, Ljiljana

    2013-11-01

    Stable Cu nanoparticles (NPs) prepared using catechol containing dopamine-based linkers could generate reactive oxygen species (ROS) that can activate peroxidase enzymes and catalyze the degradation of fluorescent dye pollutants.Stable Cu nanoparticles (NPs) prepared using catechol containing dopamine-based linkers could generate reactive oxygen species (ROS) that can activate peroxidase enzymes and catalyze the degradation of fluorescent dye pollutants. Electronic supplementary information (ESI) available: Details of the synthesis of dopamine linkers and Cu NPs, peroxidase activity tests, H2O2 calibration and degradation tests for resorufin, RB and MB. See DOI: 10.1039/c3nr03563h

  7. Role of reactive oxygen species in myocardial remodeling.

    PubMed

    Zhang, Min; Shah, Ajay M

    2007-03-01

    Adverse cardiac remodeling is a fundamental process in the progression to chronic heart failure. Although the mechanisms underlying cardiac remodeling are multi-factorial, a significant body of evidence points to the crucial roles of increased reactive oxygen species. This article reviews recent advances in delineating the different sources of production for reactive oxygen species (namely mitochondria, xanthine oxidase, uncoupled nitric oxide synthases, and NADPH oxidases) that may be involved in cardiac remodeling and the aspects of the remodeling process that they affect. These data could suggest new ways of targeting redox pathways for the prevention and treatment of adverse cardiac remodeling. PMID:17386182

  8. The chlorinated AHR ligand 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) promotes reactive oxygen species (ROS) production during embryonic development in the killifish (Fundulus heteroclitus)

    USGS Publications Warehouse

    Arzuaga, Xabier; Wassenberg, Deena; Giulio, Richard D.; Elskus, Adria

    2006-01-01

    Exposure to dioxin-like chemicals that activate the aryl hydrocarbon receptor (AHR) can result in increased cellular and tissue production of reactive oxygen species (ROS). Little is known of these effects during early fish development. We used the fish model, Fundulus heteroclitus, to determine if the AHR ligand and pro-oxidant 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) can increase ROS production during killifish development, and to test a novel method for measuring ROS non-invasively in a living organism. The superoxide-sensitive fluorescent dye, dihydroethidium (DHE), was used to detect in ovo ROS production microscopically in developing killifish exposed to PCB126 or vehicle. Both in ovo CYP1A activity (ethoxyresorufin-o-deethylase, EROD) and in ovo ROS were induced by PCB126. In ovo CYP1A activity was inducible by PCB126 concentrations as low as 0.003 nM, with maximal induction occurring at 0.3 nM PCB126. These PCB126 concentrations also significantly increased in ovo ROS production in embryonic liver, ROS being detectable as early as 5 days post-fertilization. These data demonstrate that the pro-oxidant and CYP1A inducer, PCB126, increases both CYP1A activity and ROS production in developing killifish embryos. The superoxide detection assay (SoDA) described in this paper provides a semi-quantitative, easily measured, early indicator of altered ROS production that can be used in conjunction with simultaneous in ovo measurements of CYP1A activity and embryo development to explore functional relationships among biochemical, physiological and developmental responses to AHR ligands.

  9. Reactive oxygen species at phospholipid bilayers: distribution, mobility and permeation.

    PubMed

    Cordeiro, Rodrigo M

    2014-01-01

    Reactive oxygen species (ROS) are involved in biochemical processes such as redox signaling, aging, carcinogenesis and neurodegeneration. Although biomembranes are targets for reactive oxygen species attack, little is known about the role of their specific interactions. Here, molecular dynamics simulations were employed to determine the distribution, mobility and residence times of various reactive oxygen species at the membrane-water interface. Simulations showed that molecular oxygen (O2) accumulated at the membrane interior. The applicability of this result to singlet oxygen ((1)O2) was discussed. Conversely, superoxide (O2(-)) radicals and hydrogen peroxide (H2O2) remained at the aqueous phase. Both hydroxyl (HO) and hydroperoxyl (HO2) radicals were able to penetrate deep into the lipid headgroups region. Due to membrane fluidity and disorder, these radicals had access to potential peroxidation sites along the lipid hydrocarbon chains, without having to overcome the permeation free energy barrier. Strikingly, HO2 radicals were an order of magnitude more concentrated in the headgroups region than in water, implying a large shift in the acid-base equilibrium between HO2 and O2(-). In comparison with O2, both HO and HO2 radicals had lower lateral mobility at the membrane. Simulations revealed that there were intermittent interruptions in the H-bond network around the HO radicals at the headgroups region. This effect is expected to be unfavorable for the H-transfer mechanism involved in HO diffusion. The implications for lipid peroxidation and for the effectiveness of membrane antioxidants were evaluated. PMID:24095673

  10. Oxygen chemistry of shocked interstellar clouds. III - Sulfur and oxygen species in dense clouds

    NASA Technical Reports Server (NTRS)

    Leen, T. M.; Graff, M. M.

    1988-01-01

    The chemical evolution of oxygen and sulfur species in shocked dense clouds is studied. Reaction rate constants for several important neutral reactions are examined, and revised values are suggested. The one-fluid magnetohydrodynamic shock structure and postshock chemical evolution are calculated for shocks of velocity v(s) = 10 km/s through clouds of initial number density n(0) = 100,000/cu cm and of molecule/atom ratios H2/H = 10, 1000, and 100,000 with most sulfur contained initially in molecules SO2 and SO. Abundances of SO2, SO, CS, and OCS remain near their preshock values, except in clouds containing substantial amounts of atomic hydrogen, where significant destruction of sulfur-oxygen species occurs. Abundances of shock-enhanced molecules HS and H2O are sensitive to the molecule/atom ratio. Nonthermal oxygen-hydrogen chemistry has a minor effect on oxygen-sulfur molecules in the case H2/H = 10.

  11. Role of reactive oxygen species in low level light therapy

    NASA Astrophysics Data System (ADS)

    Chen, Aaron Chi-Hao; Huang, Ying-Ying; Arany, Praveen R.; Hamblin, Michael R.

    2009-02-01

    This review will focus on the role of reactive oxygen species in the cellular and tissue effects of low level light therapy (LLLT). Coincidentally with the increase in electron transport and in ATP, there has also been observed by intracellular fluorescent probes and electron spin resonance an increase in intracellular reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, singlet oxygen and hydroxyl radical. ROS scavengers, antioxidants and ROS quenchers block many LLLT processes. It has been proposed that light between 400-500- nm may produce ROS by a photosensitization process involving flavins, while longer wavelengths may directly produce ROS from the mitochondria. Several redox-sensitive transcription factors are known such as NF-kB and AP1, that are able to initiate transcription of genes involved in protective responses to oxidative stress. It may be the case that LLLT can be pro-oxidant in the short-term, but anti-oxidant in the long-term.

  12. BIOMONITORING OF REACTIVE OXYGEN SPECIES IN BIOLOGICAL FLUIDS

    EPA Science Inventory

    Elevated levels of reactive oxygen species (ROS) are associated with several disease processes in humans, including cancer, asthma, diabetes, and cardiac disease. We have explored whether ROS can be measured directly in human fluids, and their value as a biomarker of exposure an...

  13. Reactive oxygen species in cancer: a dance with the devil.

    PubMed

    Schumacker, Paul T

    2015-02-01

    Reactive oxygen species (ROS) can initiate cancer, but oxidant generation in tumors leaves them vulnerable to further stresses. In this issue of Cancer Cell, Harris and colleagues show that augmenting oxidant stress in normal cells limits tumor initiation and progression. Hence, strategic targeting of antioxidant systems may undermine survival of new tumor cells. PMID:25670075

  14. A role for reactive oxygen species in postharvest biocontrol

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reactive oxygen species (ROS) play an important role in plant defense responses against pathogens. There is evidence that microbial biocontrol agents also induce a transient production of ROS in a host plant which triggers local and systemic defense responses. In this study, we explored the abilit...

  15. Adipose dysfunction, interaction of reactive oxygen species, and inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This American Society for Nutrition sponsored symposium summary contains information about the symposium focus and the general content of speaker presentation. The focus of the symposium was to delineate the significance of obesity-associated reactive oxygen species (ROS), inflammation, and adipose ...

  16. Kinetics of oxygen species in an electrically driven singlet oxygen generator

    NASA Astrophysics Data System (ADS)

    Azyazov, V. N.; Torbin, A. P.; Pershin, A. A.; Mikheyev, P. A.; Heaven, M. C.

    2015-12-01

    The kinetics of oxygen species in the gaseous medium of a discharge singlet oxygen generator has been revisited. Vibrationally excited ozone O3(υ) formed in O + O2 recombination is thought to be a significant agent in the deactivation of singlet oxygen O2(a1Δ), oxygen atom removal and ozone formation. It is shown that the process O3(υ ⩾ 2) + O2(a1Δ) → 2O2 + O is the main O2(a1Δ) deactivation channel in the post-discharge zone. If no measures are taken to decrease the oxygen atom concentration, the contribution of this process to the overall O2(a1Δ) removal is significant, even in the discharge zone. A simplified model for the kinetics of vibrationally excited ozone is proposed. Calculations based on this model yield results that are in good agreement with the experimental data.

  17. CONSERVATION PROGRAMS THAT PROMOTE INVASIVE SPECIES

    EPA Science Inventory

    Invasive plant species are degrading the structure and function of ecosystems throughout the world. Although most state and federal conservation agencies in the U.S. attempt to reduce the impact of invasive species, some agency activities can contribute to the spread of invasive...

  18. Vitiligo, reactive oxygen species and T-cells.

    PubMed

    Glassman, Steven J

    2011-02-01

    The acquired depigmenting disorder of vitiligo affects an estimated 1% of the world population and constitutes one of the commonest dermatoses. Although essentially asymptomatic, the psychosocial impact of vitiligo can be severe. The cause of vitiligo remains enigmatic, hampering efforts at successful therapy. The underlying pathogenesis of the pigment loss has, however, been clarified to some extent in recent years, offering the prospect of effective treatment, accurate prognosis and rational preventative strategies. Vitiligo occurs when functioning melanocytes disappear from the epidermis. A single dominant pathway is unlikely to account for all cases of melanocyte loss in vitiligo; rather, it is the result of complex interactions of biochemical, environmental and immunological events, in a permissive genetic milieu. ROS (reactive oxygen species) and H2O2 in excess can damage biological processes, and this situation has been documented in active vitiligo skin. Tyrosinase activity is impaired by excess H2O2 through oxidation of methionine residues in this key melanogenic enzyme. Mechanisms for repairing this oxidant damage are also damaged by H2O2, compounding the effect. Numerous proteins and peptides, in addition to tyrosinase, are similarly affected. It is possible that oxidant stress is the principal cause of vitiligo. However, there is also ample evidence of immunological phenomena in vitiligo, particularly in established chronic and progressive disease. Both innate and adaptive arms of the immune system are involved, with a dominant role for T-cells. Sensitized CD8+ T-cells are targeted to melanocyte differentiation antigens and destroy melanocytes either as the primary event in vitiligo or as a secondary promotive consequence. There is speculation on the interplay, if any, between ROS and the immune system in the pathogenesis of vitiligo. The present review focuses on the scientific evidence linking alterations in ROS and/or T-cells to vitiligo. PMID

  19. The formation of metal--oxygen species at low temperatures

    SciTech Connect

    Qiu, S.L.; Lin, C.L.; Chen, J.; Strongin, M. )

    1990-05-01

    The interaction of solid molecular oxygen with Li, Cs, K, La, Ag, Cu, and Ba has been studied at 35 K or below using photoemission. A feature near 535 eV in the O 1{ital s} core-level spectra was observed when Li, Cs, K, and La were deposited on solid oxygen. This feature was identified with one electron being donated to an oxygen molecule, i.e., the superoxide species, which as far as we know has not been previously reported for La and Li. A feature at about 531.5--533 eV was identified as a peroxide species where two electrons were donated to an oxygen molecule. Finally, features at about 528--530.5 eV were identified as oxide phases where the molecular oxygen was dissociated into atomic O with formal oxidation state of {minus}2. These identifications are crucial in the determinations of the exotic features in the x-ray photoelectron spectroscopy (XPS) O 1{ital s} spectra of the high {ital T}{sub {ital c}} superconductors.

  20. Properties of reactive oxygen species by quantum Monte Carlo

    SciTech Connect

    Zen, Andrea; Trout, Bernhardt L.; Guidoni, Leonardo

    2014-07-07

    The electronic properties of the oxygen molecule, in its singlet and triplet states, and of many small oxygen-containing radicals and anions have important roles in different fields of chemistry, biology, and atmospheric science. Nevertheless, the electronic structure of such species is a challenge for ab initio computational approaches because of the difficulties to correctly describe the statical and dynamical correlation effects in presence of one or more unpaired electrons. Only the highest-level quantum chemical approaches can yield reliable characterizations of their molecular properties, such as binding energies, equilibrium structures, molecular vibrations, charge distribution, and polarizabilities. In this work we use the variational Monte Carlo (VMC) and the lattice regularized Monte Carlo (LRDMC) methods to investigate the equilibrium geometries and molecular properties of oxygen and oxygen reactive species. Quantum Monte Carlo methods are used in combination with the Jastrow Antisymmetrized Geminal Power (JAGP) wave function ansatz, which has been recently shown to effectively describe the statical and dynamical correlation of different molecular systems. In particular, we have studied the oxygen molecule, the superoxide anion, the nitric oxide radical and anion, the hydroxyl and hydroperoxyl radicals and their corresponding anions, and the hydrotrioxyl radical. Overall, the methodology was able to correctly describe the geometrical and electronic properties of these systems, through compact but fully-optimised basis sets and with a computational cost which scales as N{sup 3} − N{sup 4}, where N is the number of electrons. This work is therefore opening the way to the accurate study of the energetics and of the reactivity of large and complex oxygen species by first principles.

  1. Properties of reactive oxygen species by quantum Monte Carlo.

    PubMed

    Zen, Andrea; Trout, Bernhardt L; Guidoni, Leonardo

    2014-07-01

    The electronic properties of the oxygen molecule, in its singlet and triplet states, and of many small oxygen-containing radicals and anions have important roles in different fields of chemistry, biology, and atmospheric science. Nevertheless, the electronic structure of such species is a challenge for ab initio computational approaches because of the difficulties to correctly describe the statical and dynamical correlation effects in presence of one or more unpaired electrons. Only the highest-level quantum chemical approaches can yield reliable characterizations of their molecular properties, such as binding energies, equilibrium structures, molecular vibrations, charge distribution, and polarizabilities. In this work we use the variational Monte Carlo (VMC) and the lattice regularized Monte Carlo (LRDMC) methods to investigate the equilibrium geometries and molecular properties of oxygen and oxygen reactive species. Quantum Monte Carlo methods are used in combination with the Jastrow Antisymmetrized Geminal Power (JAGP) wave function ansatz, which has been recently shown to effectively describe the statical and dynamical correlation of different molecular systems. In particular, we have studied the oxygen molecule, the superoxide anion, the nitric oxide radical and anion, the hydroxyl and hydroperoxyl radicals and their corresponding anions, and the hydrotrioxyl radical. Overall, the methodology was able to correctly describe the geometrical and electronic properties of these systems, through compact but fully-optimised basis sets and with a computational cost which scales as N(3) - N(4), where N is the number of electrons. This work is therefore opening the way to the accurate study of the energetics and of the reactivity of large and complex oxygen species by first principles. PMID:25005287

  2. Properties of reactive oxygen species by quantum Monte Carlo

    NASA Astrophysics Data System (ADS)

    Zen, Andrea; Trout, Bernhardt L.; Guidoni, Leonardo

    2014-07-01

    The electronic properties of the oxygen molecule, in its singlet and triplet states, and of many small oxygen-containing radicals and anions have important roles in different fields of chemistry, biology, and atmospheric science. Nevertheless, the electronic structure of such species is a challenge for ab initio computational approaches because of the difficulties to correctly describe the statical and dynamical correlation effects in presence of one or more unpaired electrons. Only the highest-level quantum chemical approaches can yield reliable characterizations of their molecular properties, such as binding energies, equilibrium structures, molecular vibrations, charge distribution, and polarizabilities. In this work we use the variational Monte Carlo (VMC) and the lattice regularized Monte Carlo (LRDMC) methods to investigate the equilibrium geometries and molecular properties of oxygen and oxygen reactive species. Quantum Monte Carlo methods are used in combination with the Jastrow Antisymmetrized Geminal Power (JAGP) wave function ansatz, which has been recently shown to effectively describe the statical and dynamical correlation of different molecular systems. In particular, we have studied the oxygen molecule, the superoxide anion, the nitric oxide radical and anion, the hydroxyl and hydroperoxyl radicals and their corresponding anions, and the hydrotrioxyl radical. Overall, the methodology was able to correctly describe the geometrical and electronic properties of these systems, through compact but fully-optimised basis sets and with a computational cost which scales as N3 - N4, where N is the number of electrons. This work is therefore opening the way to the accurate study of the energetics and of the reactivity of large and complex oxygen species by first principles.

  3. Reactive oxygen species generation and signaling in plants

    PubMed Central

    Tripathy, Baishnab Charan; Oelmüller, Ralf

    2012-01-01

    The introduction of molecular oxygen into the atmosphere was accompanied by the generation of reactive oxygen species (ROS) as side products of many biochemical reactions. ROS are permanently generated in plastids, peroxisomes, mitochiondria, the cytosol and the apoplast. Imbalance between ROS generation and safe detoxification generates oxidative stress and the accumulating ROS are harmful for the plants. On the other hand, specific ROS function as signaling molecules and activate signal transduction processes in response to various stresses. Here, we summarize the generation of ROS in the different cellular compartments and the signaling processes which are induced by ROS. PMID:23072988

  4. Chemical pathway analysis of Titan's upper atmosphere: Oxygen species

    NASA Astrophysics Data System (ADS)

    Stock, J. W.; Lara, L. M.; Lehmann, R.

    2014-04-01

    CO, CO2, and H2O are the only oxygen bearing species in Titan's atmosphere which have been clearly detected so far. Their abundances are controlled by the interaction of external and internal sources, photochemistry and condensation. In this contribution, we determine all significant chemical pathways responsible for the production and consumption of CO, CO2, and H2O. Furthermore, we investigate the effects of different oxygen sources on the efficiencies of the pathways. In order to achieve this, we apply a unique algorithm, called the Pathway Analysis Program - PAP to the results of a 1D photochemical model of Titan's atmosphere.

  5. ARSENIC SPECIES CAUSE RELEASE OF IRON FROM FERRITIN GENERATING REACTIVIE OXYGEN SPECIES

    EPA Science Inventory

    ARSENIC SPECIES. CAUSE RELEASE OF IRON , FROM FERRITIN GENERATING REACTIVE OXYGEN SPECIES

    Arsenic-associated cancer (lung, bladder, skin, liver, kidney) remains a significant world- wide public health problem (e.g., Taiwan, Chile, Bangladesh, India, China and Thailand). R...

  6. ARSENIC SPECIES CAUSE RELEASE OF IRON FROM FERRITIN GENERATING REACTIVE OXYGEN SPECIES

    EPA Science Inventory

    ARSENIC SPECIES CAUSE RELEASE OF IRON FROM FERRITIN GENERATING REACTIVE OXYGEN SPECIES

    Arsenic-associated cancer (lung, bladder, skin, liver, kidney) remains a significant world- wide public health problem (e.g., Taiwan, Chile, Bangladesh, India, China and Thailand). Rece...

  7. Upsides and Downsides of Reactive Oxygen Species for Cancer: The Roles of Reactive Oxygen Species in Tumorigenesis, Prevention, and Therapy

    PubMed Central

    Gupta, Subash C.; Hevia, David; Patchva, Sridevi; Park, Byoungduck; Koh, Wonil

    2012-01-01

    Abstract Significance: Extensive research during the last quarter century has revealed that reactive oxygen species (ROS) produced in the body, primarily by the mitochondria, play a major role in various cell-signaling pathways. Most risk factors associated with chronic diseases (e.g., cancer), such as stress, tobacco, environmental pollutants, radiation, viral infection, diet, and bacterial infection, interact with cells through the generation of ROS. Recent Advances: ROS, in turn, activate various transcription factors (e.g., nuclear factor kappa-light-chain-enhancer of activated B cells [NF-κB], activator protein-1, hypoxia-inducible factor-1α, and signal transducer and activator of transcription 3), resulting in the expression of proteins that control inflammation, cellular transformation, tumor cell survival, tumor cell proliferation and invasion, angiogenesis, and metastasis. Paradoxically, ROS also control the expression of various tumor suppressor genes (p53, Rb, and PTEN). Similarly, γ-radiation and various chemotherapeutic agents used to treat cancer mediate their effects through the production of ROS. Interestingly, ROS have also been implicated in the chemopreventive and anti-tumor action of nutraceuticals derived from fruits, vegetables, spices, and other natural products used in traditional medicine. Critical Issues: These statements suggest both “upside” (cancer-suppressing) and “downside” (cancer-promoting) actions of the ROS. Thus, similar to tumor necrosis factor-α, inflammation, and NF-κB, ROS act as a double-edged sword. This paradox provides a great challenge for researchers whose aim is to exploit ROS stress for the development of cancer therapies. Future Directions: The various mechanisms by which ROS mediate paradoxical effects are discussed in this article. The outstanding questions and future directions raised by our current understanding are discussed. Antioxid. Redox Signal. 16, 1295–1322. PMID:22117137

  8. Reaction Pathways for Oxygen Evolution Promoted by Cobalt Catalyst

    PubMed Central

    Mattioli, Giuseppe; Giannozzi, Paolo; Bonapasta, Aldo Amore; Guidoni, Leonardo

    2014-01-01

    The in-depth understanding of the molecular mechanisms regulating the water oxidation catalysis is of key relevance for the rationalization and the design of efficient oxygen evolution catalysts based on earth-abundant transition metals. Performing ab initio DFT+U molecular dynamics calculations of cluster models in explicit water solution, we provide insight into the pathways for oxygen evolution of a cobalt-based catalyst (CoCat). The fast motion of protons at the CoCat/water interface and the occurrence of cubane-like Co-oxo units at the catalyst boundaries are the keys to unlock the fast formation of O–O bonds. Along the resulting pathways, we identified the formation of Co(IV)-oxyl species as the driving ingredient for the activation of the catalytic mechanism, followed by their geminal coupling with O atoms coordinated by the same Co. Concurrent nucleophilic attack of water molecules coming directly from the water solution is discouraged by high activation barriers. The achieved results suggest also interesting similarities between the CoCat and the Mn4Ca-oxo oxygen evolving complex of photosystem II. PMID:24044778

  9. Natural antioxidants as inhibitors of oxygen species induced mutagenicity.

    PubMed

    Minnunni, M; Wolleb, U; Mueller, O; Pfeifer, A; Aeschbacher, H U

    1992-10-01

    A ternary antioxidant vitamin mix consisting of ascorbic acid, alpha-tocopherol and lecithin as well as a rosemary extract with carnosic acid and carnosol as the two major active ingredients were shown to exhibit strong antimutagenic effects in Ames tester strain TA102. This strain has been shown to be highly sensitive to reactive oxygen species. Mutagenicity was induced by the generation of oxygen radicals by tert-butyl-hydroperoxide (tBOOH) or hydrogen peroxide (H2O2); therefore, the antimutagenic property of the above substances was attributed to their antioxidant properties. In the case of the vitamin mix, ascorbic acid was held responsible for this inhibitory property, whereas for the rosemary extract carnosic acid was identified as the antimutagenic agent. Since oxygen radicals are known to be involved in the multiprocess of carcinogenicity, it is concluded that these antioxidants might exhibit anticarcinogenic properties. PMID:1383702

  10. Pyrroloquinoline-quinone: a reactive oxygen species scavenger in bacteria.

    PubMed

    Misra, Hari S; Khairnar, Nivedita P; Barik, Atanu; Indira Priyadarsini, K; Mohan, Hari; Apte, Shree K

    2004-12-01

    Transgenic Escherichia coli expressing pyrroloquinoline-quinone (PQQ) synthase gene from Deinococcus radiodurans showed superior survival during Rose Bengal induced oxidative stress. Such cells showed significantly low levels of protein carbonylation as compared to non-transgenic control. In vitro, PQQ reacted with reactive oxygen species with rate constants comparable to other well known antioxidants, producing non-reactive molecular products. PQQ also protected plasmid DNA and proteins from the oxidative damage caused by gamma-irradiation in solution. The data suggest that radioprotective/oxidative stress protective ability of PQQ in bacteria may be consequent to scavenging of reactive oxygen species per se and induction of other free radical scavenging mechanism. PMID:15581610

  11. Reactive oxygen species and antioxidant vitamins: mechanisms of action.

    PubMed

    Frei, B

    1994-09-26

    This article is a brief overview of the mechanisms of production of reactive oxygen species in biologic systems, and the various antioxidant defense systems that provide protection against oxidative damage to biologic macromolecules. The mechanisms of lipid peroxidation and antioxidant protection are explained using a specific example, viz., oxidative modification of human low density lipoprotein and its prevention by vitamin C, vitamin E, and beta-carotene. PMID:8085584

  12. Reactive oxygen species: The good, the bad, and the enigma

    PubMed Central

    Ogrunc, Müge

    2014-01-01

    Work carried out primarily in the laboratory of Fabrizio d’Adda di Fagagna unveils the mitogenic properties of Ras-induced reactive oxygen species (ROS) and their relationship with the DNA damage response. Combined data from studies of cultured cells, zebrafish models, and clinical material consistently support a role of the RAS-RAC1-NOX4 axis in ROS induction, hyperproliferation, and senescence. PMID:27308352

  13. Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis.

    PubMed

    Khan, Saeed R

    2014-09-01

    Calcium oxalate (CaOx) kidney stones are formed attached to Randall's plaques (RPs) or Randall's plugs. Mechanisms involved in the formation and growth are poorly understood. It is our hypothesis that stone formation is a form of pathological biomineralization or ectopic calcification. Pathological calcification and plaque formation in the body is triggered by reactive oxygen species (ROS) and the development of oxidative stress (OS). This review explores clinical and experimental data in support of ROS involvement in the formation of CaOx kidney stones. Under normal conditions the production of ROS is tightly controlled, increasing when and where needed. Results of clinical and experimental studies show that renal epithelial exposure to high oxalate and crystals of CaOx/calcium phosphate (CaP) generates excess ROS, causing injury and inflammation. Major markers of OS and inflammation are detectable in urine of stone patients as well as rats with experimentally induced CaOx nephrolithiasis. Antioxidant treatments reduce crystal and oxalate induced injury in tissue culture and animal models. Significantly lower serum levels of antioxidants, alpha-carotene, beta-carotene and beta-cryptoxanthine have been found in individuals with a history of kidney stones. A diet rich in antioxidants has been shown to reduce stone episodes. ROS regulate crystal formation, growth and retention through the timely production of crystallization modulators. In the presence of abnormal calcium, citrate, oxalate, and/or phosphate, however, there is an overproduction of ROS and a decrease in the antioxidant capacity resulting in OS, renal injury and inflammation. Cellular degradation products in the urine promote crystallization in the tubular lumen at a faster rate thus blocking the tubule and plugging the tubular openings at the papillary tips forming Randall's plugs. Renal epithelial cells lining the loops of Henle/collecting ducts may become osteogenic, producing membrane vesicles at

  14. Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis

    PubMed Central

    2014-01-01

    Calcium oxalate (CaOx) kidney stones are formed attached to Randall’s plaques (RPs) or Randall’s plugs. Mechanisms involved in the formation and growth are poorly understood. It is our hypothesis that stone formation is a form of pathological biomineralization or ectopic calcification. Pathological calcification and plaque formation in the body is triggered by reactive oxygen species (ROS) and the development of oxidative stress (OS). This review explores clinical and experimental data in support of ROS involvement in the formation of CaOx kidney stones. Under normal conditions the production of ROS is tightly controlled, increasing when and where needed. Results of clinical and experimental studies show that renal epithelial exposure to high oxalate and crystals of CaOx/calcium phosphate (CaP) generates excess ROS, causing injury and inflammation. Major markers of OS and inflammation are detectable in urine of stone patients as well as rats with experimentally induced CaOx nephrolithiasis. Antioxidant treatments reduce crystal and oxalate induced injury in tissue culture and animal models. Significantly lower serum levels of antioxidants, alpha-carotene, beta-carotene and beta-cryptoxanthine have been found in individuals with a history of kidney stones. A diet rich in antioxidants has been shown to reduce stone episodes. ROS regulate crystal formation, growth and retention through the timely production of crystallization modulators. In the presence of abnormal calcium, citrate, oxalate, and/or phosphate, however, there is an overproduction of ROS and a decrease in the antioxidant capacity resulting in OS, renal injury and inflammation. Cellular degradation products in the urine promote crystallization in the tubular lumen at a faster rate thus blocking the tubule and plugging the tubular openings at the papillary tips forming Randall’s plugs. Renal epithelial cells lining the loops of Henle/collecting ducts may become osteogenic, producing membrane vesicles

  15. [Reactive oxygen species and fibrosis in tissues and organs - review].

    PubMed

    Meng, Juan-Xia; Zhao, Ming-Feng

    2012-10-01

    Reactive oxygen species (ROS) is a kind of molecules derived by oxygen in the metabolic process of aerobic cells, which mainly includes superoxide, hydroxyl radicals, alkoxyl, hydrogen peroxide, hypochlorous acid, ozone, etc. They can destroy the structure and function of cells through the damage of biological macromolecules such as DNA, proteins and the lipid peroxidation. ROS also can regulate the proliferation, differentiation and apoptosis of cells through several signaling pathways and participate in fibrogenesis of many organs including hepatic and pulmonary fibrosis. Recent study shows that ROS might have an important effect on the forming of myelofibrosis. Consequently, ROS plays a significant role in the fibrogenesis of tissues and organs. In this review, the relevance between ROS and common tissues and organs fibrosis is summarized. PMID:23114165

  16. Reactive oxygen species and energy machinery: an integrated dynamic model.

    PubMed

    Korla, Kalyani

    2016-08-01

    The role of several important reactive oxygen species (ROS) on the Krebs cycle, the electron transport chain (ETC) and the two important shuttles has been modelled. Major part of the ROS is produced during oxygen reduction in the ETC, which has been kinetically simulated, and the changes in the final concentrations of several important metabolites were found. The simulation is based on chemical kinetics equation, and the associated set of differential equations was solved by the ordinary differential equation package in Octave. The validity of the model is checked by comparing the experimental results available in the literature with the simulations when a part of the ETC is blocked (80%) in the script. The present approach is versatile and flexible and has potential applications in various simulations. It is easy to study the change in concentrations of various metabolites when a particular enzyme or pathway is blocked (say by a drug). The Octave script is presented in the text. PMID:26309069

  17. Implications for reactive oxygen species in schizophrenia pathogenesis.

    PubMed

    Koga, Minori; Serritella, Anthony V; Sawa, Akira; Sedlak, Thomas W

    2016-09-01

    Oxidative stress is a well-recognized participant in the pathophysiology of multiple brain disorders, particularly neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. While not a dementia, a wide body of evidence has also been accumulating for aberrant reactive oxygen species and inflammation in schizophrenia. Here we highlight roles for oxidative stress as a common mechanism by which varied genetic and epidemiologic risk factors impact upon neurodevelopmental processes that underlie the schizophrenia syndrome. While there is longstanding evidence that schizophrenia may not have a single causative lesion, a common pathway involving oxidative stress opens the possibility for intervention at susceptible phases. PMID:26589391

  18. Redox Processes in Neurodegenerative Disease Involving Reactive Oxygen Species

    PubMed Central

    Kovacic, Peter; Somanathan, Ratnasamy

    2012-01-01

    Much attention has been devoted to neurodegenerative diseases involving redox processes. This review comprises an update involving redox processes reported in the considerable literature in recent years. The mechanism involves reactive oxygen species and oxidative stress, usually in the brain. There are many examples including Parkinson’s, Huntington’s, Alzheimer’s, prions, Down’s syndrome, ataxia, multiple sclerosis, Creutzfeldt-Jacob disease, amyotrophic lateral sclerosis, schizophrenia, and Tardive Dyskinesia. Evidence indicates a protective role for antioxidants, which may have clinical implications. A multifaceted approach to mode of action appears reasonable. PMID:23730253

  19. Cellular reactive oxygen species inhibit MPYS induction of IFNβ.

    PubMed

    Jin, Lei; Lenz, Laurel L; Cambier, John C

    2010-01-01

    Many inflammatory diseases, as well as infections, are accompanied by elevation in cellular levels of Reactive Oxygen Species (ROS). Here we report that MPYS, a.k.a. STING, which was recently shown to mediate activation of IFNβ expression during infection, is a ROS sensor. ROS induce intermolecular disulfide bonds formation in MPYS homodimer and inhibit MPYS IFNβ stimulatory activity. Cys-64, -148, -292, -309 and the potential C₈₈xxC₉₁ redox motif in MPYS are indispensable for IFNβ stimulation and IRF3 activation. Thus, our results identify a novel mechanism for ROS regulation of IFNβ stimulation. PMID:21170271

  20. Mechanisms of group A Streptococcus resistance to reactive oxygen species.

    PubMed

    Henningham, Anna; Döhrmann, Simon; Nizet, Victor; Cole, Jason N

    2015-07-01

    Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the 'top 10' causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•(-)), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress. PMID:25670736

  1. Vibrio vulnificus VvpE Stimulates IL-1β Production by the Hypomethylation of the IL-1β Promoter and NF-κB Activation via Lipid Raft-Dependent ANXA2 Recruitment and Reactive Oxygen Species Signaling in Intestinal Epithelial Cells.

    PubMed

    Lee, Sei-Jung; Jung, Young Hyun; Song, Eun Ju; Jang, Kyung Ku; Choi, Sang Ho; Han, Ho Jae

    2015-09-01

    An inflammatory response is a hallmark of necrosis evoked by bacterial pathogens. Vibrio vulnificus, VvpE, is an elastase that is responsible for tissue necrosis and inflammation; however, the molecular mechanism by which it regulates host cell death has not been characterized. In the present study, we investigate the cellular mechanism of VvpE with regard to host cell death and the inflammatory response of human intestinal epithelial (INT-407) cells. The recombinant protein (r)VvpE (50 pg/ml) caused cytotoxicity mainly via necrosis coupled with IL-1β production. The necrotic cell death induced by rVvpE is highly susceptible to the knockdown of annexin A (ANXA)2 and the sequestration of membrane cholesterol. We found that rVvpE induces the recruitment of NADPH oxidase 2 and neutrophil cytosolic factor 1 into membrane lipid rafts coupled with ANXA2 to facilitate the production of reactive oxygen species (ROS). The bacterial signaling of rVvpE through ROS production is uniquely mediated by the phosphorylation of redox-sensitive transcription factor NF-κB. The silencing of NF-κB inhibited IL-1β production during necrosis. rVvpE induced hypomethylation and region-specific transcriptional occupancy by NF-κB in the IL-1β promoter and has the ability to induce pyroptosis via NOD-, LRR-, and pyrin domain-containing 3 inflammasome. In a mouse model of V. vulnificus infection, the mutation of the vvpE gene from V. vulnificus negated the proinflammatory responses and maintained the physiological levels of the proliferation and migration of enterocytes. These results demonstrate that VvpE induces the hypomethylation of the IL-1β promoter and the transcriptional regulation of NF-κB through lipid raft-dependent ANXA2 recruitment and ROS signaling to promote IL-1β production in intestinal epithelial cells. PMID:26223656

  2. Scavenging of reactive oxygen species by silibinin dihemisuccinate.

    PubMed

    Mira, L; Silva, M; Manso, C F

    1994-08-17

    Silibinin dihemisuccinate (SDH) is a flavonoid of plant origin with hepatoprotective effects which have been partially attributed to its ability to scavenge oxygen free radicals. In the present paper the antioxidant properties of SDH were evaluated by studying the ability of this drug to react with relevant biological oxidants such as superoxide anion radical (O2-), hydrogen peroxide (H2O2), hydroxyl radical (HO.) and hypochlorous acid (HOCl). In addition, its effect on lipid peroxidation was investigated. SDH is not a good scavenger of O2- and no reaction with H2O2 was detected within the sensitivity limit of our assay. However, it reacts rapidly with HO. radicals in free solution at approximately diffusion-controlled rate (K = (1.0-1.2) x 10(10)/M/sec) and appears to be a weak iron ion chelator. SDH at concentrations in the micromolar range protected alpha 1-antiproteinase against inactivation by HOCl, showing that it is a potent scavenger of this oxidizing species. Luminol-dependent chemiluminescence induced by HOCl was also inhibited by SDH. The reaction of SDH with HOCl was monitored by the modification of the UV-visible spectrum of SDH. The studies on rat liver microsome lipid peroxidation induced by Fe(III)/ascorbate showed that SDH has an inhibitory effect, which is dependent on its concentration and the magnitude of lipid peroxidation. This work supports the reactive oxygen species scavenger action ascribed to SDH. PMID:8080448

  3. Singlet Oxygen Is the Major Reactive Oxygen Species Involved in Photooxidative Damage to Plants1[W

    PubMed Central

    Triantaphylidès, Christian; Krischke, Markus; Hoeberichts, Frank Alfons; Ksas, Brigitte; Gresser, Gabriele; Havaux, Michel; Van Breusegem, Frank; Mueller, Martin Johannes

    2008-01-01

    Reactive oxygen species act as signaling molecules but can also directly provoke cellular damage by rapidly oxidizing cellular components, including lipids. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry-based quantitative method that allowed us to discriminate between free radical (type I)- and singlet oxygen (1O2; type II)-mediated lipid peroxidation (LPO) signatures by using hydroxy fatty acids as specific reporters. Using this method, we observed that in nonphotosynthesizing Arabidopsis (Arabidopsis thaliana) tissues, nonenzymatic LPO was almost exclusively catalyzed by free radicals both under normal and oxidative stress conditions. However, in leaf tissues under optimal growth conditions, 1O2 was responsible for more than 80% of the nonenzymatic LPO. In Arabidopsis mutants favoring 1O2 production, photooxidative stress led to a dramatic increase of 1O2 (type II) LPO that preceded cell death. Furthermore, under all conditions and in mutants that favor the production of superoxide and hydrogen peroxide (two sources for type I LPO reactions), plant cell death was nevertheless always preceded by an increase in 1O2-dependent (type II) LPO. Thus, besides triggering a genetic cell death program, as demonstrated previously with the Arabidopsis fluorescent mutant, 1O2 plays a major destructive role during the execution of reactive oxygen species-induced cell death in leaf tissues. PMID:18676660

  4. Functional implications of mitochondrial reactive oxygen species generated by oncogenic viruses

    PubMed Central

    Choi, Young Bong; Harhaj, Edward William

    2014-01-01

    Between 15–20% of human cancers are associated with infection by oncogenic viruses. Oncogenic viruses, including HPV, HBV, HCV and HTLV-1, target mitochondria to influence cell proliferation and survival. Oncogenic viral gene products also trigger the production of reactive oxygen species which can elicit oxidative DNA damage and potentiate oncogenic host signaling pathways. Viral oncogenes may also subvert mitochondria quality control mechanisms such as mitophagy and metabolic adaptation pathways to promote virus replication. Here, we will review recent progress on viral regulation of mitophagy and metabolic adaptation and their roles in viral oncogenesis. PMID:25580106

  5. Beyond oxidative stress: an immunologist’s guide to reactive oxygen species

    PubMed Central

    Nathan, Carl; Cunningham-Bussel, Amy

    2014-01-01

    Reactive oxygen species (ROS) react preferentially with certain atoms to modulate functions ranging from cell homeostasis to cell death. Molecular actions include both inhibition and activation of proteins, mutagenesis of DNA and activation of gene transcription. Cellular actions include promotion or suppression of inflammation, immunity and carcinogenesis. ROS help the host to compete against microorganisms and are also involved in intermicrobial competition. ROS chemistry and their pleiotropy make them difficult to localize, to quantify and to manipulate — challenges we must overcome to translate ROS biology into medical advances. PMID:23618831

  6. Oxygen sensitivity of the nifLA promoter of Klebsiella pneumoniae

    SciTech Connect

    Kong, Q.T.; Wu, Q.L.; Ma, Z.F.; Shen, S.C.

    1986-05-01

    Oxygen sensitivity of the nifLA promoter of Klebsiella pneumoniae has been demonstrated. Studies on the oxygen regulation of nifB-lacZ and nifH-lacZ fusions in the presence of the nifLA operon, which contains either an intact or a deleted nifL gene, indicate that possible both the nifL promoter and the nifL product are responsible for nif repression by oxygen.

  7. Hyperbaric oxygen therapy. Promoting healing in difficult cases

    SciTech Connect

    Cohn, G.H.

    1986-02-01

    Inhalation of pressurized 100% oxygen is a helpful adjunctive treatment for certain patients, because the increased oxygen carried by the blood to the tissue enhances new growth of microcirculation and, thus, healing. Patients with tissue breakdown after radiation therapy, refractory osteomyelitis, gas gangrene, soft-tissue infection with necrosis from mixed aerobic and anaerobic organisms, crush injuries resulting in acute ischemia, and compromised skin grafts or non-healing wounds are likely to benefit from hyperbaric oxygen therapy.

  8. Reactive Oxygen Species in Normal and Tumor Stem Cells

    PubMed Central

    Zhou, Daohong; Shao, Lijian; Spitz, Douglas R.

    2014-01-01

    Reactive oxygen species (ROS) play an important role in determining the fate of normal stem cells. Low levels of ROS are required for stem cells to maintain quiescence and self-renewal. Increases in ROS production cause stem cell proliferation/differentiation, senescence, and apoptosis in a dose-dependent manner, leading to their exhaustion. Therefore, the production of ROS in stem cells is tightly regulated to ensure that they have the ability to maintain tissue homeostasis and repair damaged tissues for the life span of an organism. In this chapter, we discuss how the production of ROS in normal stem cells is regulated by various intrinsic and extrinsic factors and how the fate of these cells is altered by the dysregulation of ROS production under various pathological conditions. In addition, the implications of the aberrant production of ROS by tumor stem cells for tumor progression and treatment are also discussed. PMID:24974178

  9. Reactive oxygen species in eradicating acute myeloid leukemic stem cells

    PubMed Central

    Zhang, Hui; Fang, Hai

    2014-01-01

    Leukemic stem cells (LSCs) have been proven to drive leukemia initiation, progression and relapse, and are increasingly being used as a critical target for therapeutic intervention. As an essential feature in LSCs, reactive oxygen species (ROS) homeostasis has been extensively exploited in the past decade for targeting LSCs in acute myeloid leukemia (AML). Most, if not all, agents that show therapeutic benefits are able to alter redox status by inducing ROS, which confers selectivity in eradicating AML stem cells but sparing normal counterparts. In this review, we provide the comprehensive update of ROS-generating agents in the context of their impacts on our understanding of the pathogenesis of AML and its therapy. We anticipate that further characterizing these ROS agents will help us combat against AML in the coming era of LSC-targeting strategy.

  10. Reactive oxygen species and hydrogen peroxide generation in cell migration

    PubMed Central

    Rudzka, Dominika A; Cameron, Jenifer M; Olson, Michael F

    2015-01-01

    Directional cell migration is a complex process that requires spatially and temporally co-ordinated regulation of actin cytoskeleton dynamics. In response to external cues, signals are transduced to elicit cytoskeletal responses. It has emerged that reactive oxygen species, including hydrogen peroxide, are important second messengers in pathways that influence the actin cytoskeleton, although the identities of key proteins regulated by hydrogen peroxide are largely unknown. We recently showed that oxidation of cofilin1 is elevated in migrating cells relative to stationary cells, and that the effect of this post-translational modification is to reduce cofilin1-actin binding and to inhibit filamentous-actin severing by cofilin1. These studies revealed that cofilin1 regulation by hydrogen peroxide contributes to directional cell migration, and established a template for discovering additional proteins that are regulated in an analogous manner. PMID:27066166

  11. Reactive Oxygen Species Driven Angiogenesis by Inorganic Nanorods

    PubMed Central

    Patra, Chitta Ranjan; Kim, Jong Ho; Pramanik, Kallal; d’Uscio, Livius V.; Patra, Sujata; Pal, Krishnendu; Ramchandran, Ramani; Strano, Michael S; Mukhopadhyay, Debabrata

    2011-01-01

    The exact mechanism of angiogenesis by europium hydroxide nanorods was unclear. In this study we have showed that formation of reactive oxygen species (H2O2 and O2•−) are involved in redox signaling pathways during angiogenesis, important for cardiovascular and ischemic diseases. Here we used single-walled carbon nanotube (SWNT) sensor array to measure the single-molecule efflux of H2O2 and a HPLC method for the determination of O2•− from endothelial cells in response to pro-angiogenic factors. Additionally, ROS-mediated angiogenesis using inorganic nanorods was observed in transgenic (fli1a:EGFP) zebrafish embryos. PMID:21967244

  12. Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity

    PubMed Central

    Beckhauser, Thiago Fernando; Francis-Oliveira, José; De Pasquale, Roberto

    2016-01-01

    In the mammalian central nervous system, reactive oxygen species (ROS) generation is counterbalanced by antioxidant defenses. When large amounts of ROS accumulate, antioxidant mechanisms become overwhelmed and oxidative cellular stress may occur. Therefore, ROS are typically characterized as toxic molecules, oxidizing membrane lipids, changing the conformation of proteins, damaging nucleic acids, and causing deficits in synaptic plasticity. High ROS concentrations are associated with a decline in cognitive functions, as observed in some neurodegenerative disorders and age-dependent decay of neuroplasticity. Nevertheless, controlled ROS production provides the optimal redox state for the activation of transductional pathways involved in synaptic changes. Since ROS may regulate neuronal activity and elicit negative effects at the same time, the distinction between beneficial and deleterious consequences is unclear. In this regard, this review assesses current research and describes the main sources of ROS in neurons, specifying their involvement in synaptic plasticity and distinguishing between physiological and pathological processes implicated. PMID:27625575

  13. Reactive oxygen species, essential molecules, during plant-pathogen interactions.

    PubMed

    Camejo, Daymi; Guzmán-Cedeño, Ángel; Moreno, Alexander

    2016-06-01

    Reactive oxygen species (ROS) are continually generated as a consequence of the normal metabolism in aerobic organisms. Accumulation and release of ROS into cell take place in response to a wide variety of adverse environmental conditions including salt, temperature, cold stresses and pathogen attack, among others. In plants, peroxidases class III, NADPH oxidase (NOX) locates in cell wall and plasma membrane, respectively, may be mainly enzymatic systems involving ROS generation. It is well documented that ROS play a dual role into cells, acting as important signal transduction molecules and as toxic molecules with strong oxidant power, however some aspects related to its function during plant-pathogen interactions remain unclear. This review focuses on the principal enzymatic systems involving ROS generation addressing the role of ROS as signal molecules during plant-pathogen interactions. We described how the chloroplasts, mitochondria and peroxisomes perceive the external stimuli as pathogen invasion, and trigger resistance response using ROS as signal molecule. PMID:26950921

  14. Reactive oxygen species production and discontinuous gas exchange in insects

    PubMed Central

    Boardman, Leigh; Terblanche, John S.; Hetz, Stefan K.; Marais, Elrike; Chown, Steven L.

    2012-01-01

    While biochemical mechanisms are typically used by animals to reduce oxidative damage, insects are suspected to employ a higher organizational level, discontinuous gas exchange mechanism to do so. Using a combination of real-time, flow-through respirometry and live-cell fluorescence microscopy, we show that spiracular control associated with the discontinuous gas exchange cycle (DGC) in Samia cynthia pupae is related to reactive oxygen species (ROS). Hyperoxia fails to increase mean ROS production, although minima are elevated above normoxic levels. Furthermore, a negative relationship between mean and mean ROS production indicates that higher ROS production is generally associated with lower . Our results, therefore, suggest a possible signalling role for ROS in DGC, rather than supporting the idea that DGC acts to reduce oxidative damage by regulating ROS production. PMID:21865257

  15. Reactive oxygen species in organ-specific autoimmunity.

    PubMed

    Di Dalmazi, Giulia; Hirshberg, Jason; Lyle, Daniel; Freij, Joudeh B; Caturegli, Patrizio

    2016-12-01

    Reactive oxygen species (ROS) have been extensively studied in the induction of inflammation and tissue damage, especially as it relates to aging. In more recent years, ROS have been implicated in the pathogenesis of autoimmune diseases. Here, ROS accumulation leads to apoptosis and autoantigen structural changes that result in novel specificities. ROS have been implicated not only in the initiation of the autoimmune response but also in its amplification and spreading to novel epitopes, through the unmasking of cryptic determinants. This review will examine the contribution of ROS to the pathogenesis of four organ specific autoimmune diseases (Hashimoto thyroiditis, inflammatory bowel disease, multiple sclerosis, and vitiligo), and compare it to that of a better characterized systemic autoimmune disease (rheumatoid arthritis). It will also discuss tobacco smoking as an environmental factor endowed with both pro-oxidant and anti-oxidant properties, thus capable of differentially modulating the autoimmune response. PMID:27491295

  16. Reactive oxygen species-activated nanomaterials as theranostic agents.

    PubMed

    Kim, Kye S; Lee, Dongwon; Song, Chul Gyu; Kang, Peter M

    2015-01-01

    Reactive oxygen species (ROS) are generated from the endogenous oxidative metabolism or from exogenous pro-oxidant exposure. Oxidative stress occurs when there is excessive production of ROS, outweighing the antioxidant defense mechanisms which may lead to disease states. Hydrogen peroxide (H2O2) is one of the most abundant and stable forms of ROS, implicated in inflammation, cellular dysfunction and apoptosis, which ultimately lead to tissue and organ damage. This review is an overview of the role of ROS in different diseases. We will also examine ROS-activated nanomaterials with emphasis on hydrogen peroxide, and their potential medical implications. Further development of the biocompatible, stimuli-activated agent responding to disease causing oxidative stress, may lead to a promising clinical use. PMID:26328770

  17. Reactive Oxygen Species, Apoptosis, and Mitochondrial Dysfunction in Hearing Loss

    PubMed Central

    Fujimoto, Chisato

    2015-01-01

    Reactive oxygen species (ROS) production is involved in several apoptotic and necrotic cell death pathways in auditory tissues. These pathways are the major causes of most types of sensorineural hearing loss, including age-related hearing loss, hereditary hearing loss, ototoxic drug-induced hearing loss, and noise-induced hearing loss. ROS production can be triggered by dysfunctional mitochondrial oxidative phosphorylation and increases or decreases in ROS-related enzymes. Although apoptotic cell death pathways are mostly activated by ROS production, there are other pathways involved in hearing loss that do not depend on ROS production. Further studies of other pathways, such as endoplasmic reticulum stress and necrotic cell death, are required. PMID:25874222

  18. Reactive oxygen species in development and infection processes.

    PubMed

    Marschall, Robert; Tudzynski, Paul

    2016-09-01

    Reactive oxygen species (ROS) are important signaling molecules that affect vegetative and pathogenic processes in pathogenic fungi. There is growing evidence that ROS are not only secreted during the interaction of host and pathogen but also involved in tightly controlled intracellular processes. The major ROS producing enzymes are NADPH oxidases (Nox). Recent investigations in fungi revealed that Nox-activity is responsible for the formation of infection structures, cytoskeleton architecture as well as interhyphal communication. However, information about the localization and site of action of the Nox complexes in fungi is limited and signaling pathways and intracellular processes affected by ROS have not been fully elucidated. This review focuses on the role of ROS as signaling molecules in fungal "model" organisms: it examines the role of ROS in vegetative and pathogenic processes and gives special attention to Nox complexes and their function as important signaling hubs. PMID:27039026

  19. The Role of Reactive Oxygen Species in Microvascular Remodeling

    PubMed Central

    Staiculescu, Marius C.; Foote, Christopher; Meininger, Gerald A.; Martinez-Lemus, Luis A.

    2014-01-01

    The microcirculation is a portion of the vascular circulatory system that consists of resistance arteries, arterioles, capillaries and venules. It is the place where gases and nutrients are exchanged between blood and tissues. In addition the microcirculation is the major contributor to blood flow resistance and consequently to regulation of blood pressure. Therefore, structural remodeling of this section of the vascular tree has profound implications on cardiovascular pathophysiology. This review is focused on the role that reactive oxygen species (ROS) play on changing the structural characteristics of vessels within the microcirculation. Particular attention is given to the resistance arteries and the functional pathways that are affected by ROS in these vessels and subsequently induce vascular remodeling. The primary sources of ROS in the microcirculation are identified and the effects of ROS on other microcirculatory remodeling phenomena such as rarefaction and collateralization are briefly reviewed. PMID:25535075

  20. Reactive oxygen species-activated nanomaterials as theranostic agents

    PubMed Central

    Kim, Kye S; Lee, Dongwon; Song, Chul Gyu; Kang, Peter M

    2015-01-01

    Reactive oxygen species (ROS) are generated from the endogenous oxidative metabolism or from exogenous pro-oxidant exposure. Oxidative stress occurs when there is excessive production of ROS, outweighing the antioxidant defense mechanisms which may lead to disease states. Hydrogen peroxide (H2O2) is one of the most abundant and stable forms of ROS, implicated in inflammation, cellular dysfunction and apoptosis, which ultimately lead to tissue and organ damage. This review is an overview of the role of ROS in different diseases. We will also examine ROS-activated nanomaterials with emphasis on hydrogen peroxide, and their potential medical implications. Further development of the biocompatible, stimuli-activated agent responding to disease causing oxidative stress, may lead to a promising clinical use. PMID:26328770

  1. Mitochondrial Reactive Oxygen Species Modulate Mosquito Susceptibility to Plasmodium Infection

    PubMed Central

    Oliveira, Giselle A.; Andersen, John F.; Oliveira, Marcus F.; Oliveira, Pedro L.; Barillas-Mury, Carolina

    2012-01-01

    Background Mitochondria perform multiple roles in cell biology, acting as the site of aerobic energy-transducing pathways and as an important source of reactive oxygen species (ROS) that modulate redox metabolism. Methodology/Principal Findings We demonstrate that a novel member of the mitochondrial transporter protein family, Anopheles gambiae mitochondrial carrier 1 (AgMC1), is required to maintain mitochondrial membrane potential in mosquito midgut cells and modulates epithelial responses to Plasmodium infection. AgMC1 silencing reduces mitochondrial membrane potential, resulting in increased proton-leak and uncoupling of oxidative phosphorylation. These metabolic changes reduce midgut ROS generation and increase A. gambiae susceptibility to Plasmodium infection. Conclusion We provide direct experimental evidence indicating that ROS derived from mitochondria can modulate mosquito epithelial responses to Plasmodium infection. PMID:22815925

  2. Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity.

    PubMed

    Beckhauser, Thiago Fernando; Francis-Oliveira, José; De Pasquale, Roberto

    2016-01-01

    In the mammalian central nervous system, reactive oxygen species (ROS) generation is counterbalanced by antioxidant defenses. When large amounts of ROS accumulate, antioxidant mechanisms become overwhelmed and oxidative cellular stress may occur. Therefore, ROS are typically characterized as toxic molecules, oxidizing membrane lipids, changing the conformation of proteins, damaging nucleic acids, and causing deficits in synaptic plasticity. High ROS concentrations are associated with a decline in cognitive functions, as observed in some neurodegenerative disorders and age-dependent decay of neuroplasticity. Nevertheless, controlled ROS production provides the optimal redox state for the activation of transductional pathways involved in synaptic changes. Since ROS may regulate neuronal activity and elicit negative effects at the same time, the distinction between beneficial and deleterious consequences is unclear. In this regard, this review assesses current research and describes the main sources of ROS in neurons, specifying their involvement in synaptic plasticity and distinguishing between physiological and pathological processes implicated. PMID:27625575

  3. Bioreductively Activated Reactive Oxygen Species (ROS) Generators as MRSA Inhibitors.

    PubMed

    Khodade, Vinayak S; Sharath Chandra, Mallojjala; Banerjee, Ankita; Lahiri, Surobhi; Pulipeta, Mallikarjuna; Rangarajan, Radha; Chakrapani, Harinath

    2014-07-10

    The number of cases of drug resistant Staphylococcus aureus infections is on the rise globally and new strategies to identify drug candidates with novel mechanisms of action are in urgent need. Here, we report the synthesis and evaluation of a series of benzo[b]phenanthridine-5,7,12(6H)-triones, which were designed based on redox-active natural products. We find that the in vitro inhibitory activity of 6-(prop-2-ynyl)benzo[b]phenanthridine-5,7,12(6H)-trione (1f) against methicillin-resistant Staphylococcus aureus (MRSA), including a panel of patient-derived strains, is comparable or better than vancomycin. We show that the lead compound generates reactive oxygen species (ROS) in the cell, contributing to its antibacterial activity. PMID:25050164

  4. Reactive oxygen species production and discontinuous gas exchange in insects.

    PubMed

    Boardman, Leigh; Terblanche, John S; Hetz, Stefan K; Marais, Elrike; Chown, Steven L

    2012-03-01

    While biochemical mechanisms are typically used by animals to reduce oxidative damage, insects are suspected to employ a higher organizational level, discontinuous gas exchange mechanism to do so. Using a combination of real-time, flow-through respirometry and live-cell fluorescence microscopy, we show that spiracular control associated with the discontinuous gas exchange cycle (DGC) in Samia cynthia pupae is related to reactive oxygen species (ROS). Hyperoxia fails to increase mean ROS production, although minima are elevated above normoxic levels. Furthermore, a negative relationship between mean and mean ROS production indicates that higher ROS production is generally associated with lower . Our results, therefore, suggest a possible signalling role for ROS in DGC, rather than supporting the idea that DGC acts to reduce oxidative damage by regulating ROS production. PMID:21865257

  5. NADPH oxidase-derived reactive oxygen species in cardiac pathophysiology

    PubMed Central

    Cave, Alison; Grieve, David; Johar, Sofian; Zhang, Min; Shah, Ajay M

    2005-01-01

    Chronic heart failure, secondary to left ventricular hypertrophy or myocardial infarction, is a condition with increasing morbidity and mortality. Although the mechanisms underlying the development and progression of this condition remain a subject of intense interest, there is now growing evidence that redox-sensitive pathways play an important role. This article focuses on the involvement of reactive oxygen species derived from a family of superoxide-generating enzymes, termed NADPH oxidases (NOXs), in the pathophysiology of ventricular hypertrophy, the accompanying interstitial fibrosis and subsequent heart failure. In particular, the apparent ability of the different NADPH oxidase isoforms to define the response of a cell to a range of physiological and pathophysiological stimuli is reviewed. If confirmed, these data would suggest that independently targeting different members of the NOX family may hold the potential for therapeutic intervention in the treatment of cardiac disease. PMID:16321803

  6. Photosensitizing Nanoparticles and The Modulation of Reactive Oxygen Species generation

    NASA Astrophysics Data System (ADS)

    Tada, Dayane; Baptista, Mauricio

    2015-05-01

    The association of PhotoSensitizer (PS) molecules with nanoparticles (NPs) forming photosensitizing NPs, has emerged as a therapeutic strategy to improve PS tumor targeting, to protect PS from deactivation reactions and to enhance both PS solubility and circulation time. Since association with NPs usually alters PS photophysical and photochemical properties, photosensitizing NPs are an important tool to modulate reactive oxygen species (ROS) generation. Depending on the design of the photosensitizing NP, i.e., type of PS, the NP material and the method applied for the construction of the photosensitizing NP, the deactivation routes of the excited state can be controlled, allowing the generation of either singlet oxygen or other ROS. Controlling the type of generated ROS is desirable not only in biomedical applications, as in Photodynamic Therapy where the type of ROS affects therapeutic efficiency, but also in other technological relevant fields like energy conversion, where the electron and energy transfer processes are necessary to increase the efficiency of photoconversion cells. The current review highlights some of the recent developments in the design of Photosensitizing NPs aimed at modulating the primary photochemical events after light absorption.

  7. Reactive oxygen species mediate growth and death in submerged plants

    PubMed Central

    Steffens, Bianka; Steffen-Heins, Anja; Sauter, Margret

    2013-01-01

    Aquatic and semi-aquatic plants are well adapted to survive partial or complete submergence which is commonly accompanied by oxygen deprivation. The gaseous hormone ethylene controls a number of adaptive responses to submergence including adventitious root growth and aerenchyma formation. Reactive oxygen species (ROS) act as signaling intermediates in ethylene-controlled submergence adaptation and possibly also independent of ethylene. ROS levels are controlled by synthesis, enzymatic metabolism, and non-enzymatic scavenging. While the actors are by and large known, we still have to learn about altered ROS at the subcellular level and how they are brought about, and the signaling cascades that trigger a specific response. This review briefly summarizes our knowledge on the contribution of ROS to submergence adaptation and describes spectrophotometrical, histochemical, and live cell imaging detection methods that have been used to study changes in ROS abundance. Electron paramagnetic resonance (EPR) spectroscopy is introduced as a method that allows identification and quantification of specific ROS in cell compartments. The use of advanced technologies such as EPR spectroscopy will be necessary to untangle the intricate and partially interwoven signaling networks of ethylene and ROS. PMID:23761805

  8. Reactive Oxygen Species Mediated Activation of a Dormant Singlet Oxygen Photosensitizer: From Autocatalytic Singlet Oxygen Amplification to Chemicontrolled Photodynamic Therapy.

    PubMed

    Durantini, Andrés M; Greene, Lana E; Lincoln, Richard; Martínez, Sol R; Cosa, Gonzalo

    2016-02-01

    Here we show the design, preparation, and characterization of a dormant singlet oxygen ((1)O2) photosensitizer that is activated upon its reaction with reactive oxygen species (ROS), including (1)O2 itself, in what constitutes an autocatalytic process. The compound is based on a two segment photosensitizer-trap molecule where the photosensitizer segment consists of a Br-substituted boron-dipyrromethene (BODIPY) dye. The trap segment consists of the chromanol ring of α-tocopherol, the most potent naturally occurring lipid soluble antioxidant. Time-resolved absorption, fluorescence, and (1)O2 phosphorescence studies together with fluorescence and (1)O2 phosphorescence emission quantum yields collected on Br2B-PMHC and related bromo and iodo-substituted BODIPY dyes show that the trap segment provides a total of three layers of intramolecular suppression of (1)O2 production. Oxidation of the trap segment with ROS restores the sensitizing properties of the photosensitizer segment resulting in ∼40-fold enhancement in (1)O2 production. The juxtaposed antioxidant (chromanol) and prooxidant (Br-BODIPY) antagonistic chemical activities of the two-segment compound enable the autocatalytic, and in general ROS-mediated, activation of (1)O2 sensitization providing a chemical cue for the spatiotemporal control of (1)O2.The usefulness of this approach to selectively photoactivate the production of singlet oxygen in ROS stressed vs regular cells was successfully tested via the photodynamic inactivation of a ROS stressed Gram negative Escherichia coli strain. PMID:26789198

  9. Role of reactive oxygen species produced by NADPH oxidase in gibberellin biosynthesis during barley seed germination.

    PubMed

    Kai, Kyohei; Kasa, Shinsuke; Sakamoto, Masatsugu; Aoki, Nozomi; Watabe, Gaku; Yuasa, Takashi; Iwaya-Inoue, Mari; Ishibashi, Yushi

    2016-05-01

    NADPH oxidase catalyzes the production of the superoxide anion (O2(-)), a reactive oxygen species (ROS), and regulates the germination of barley (Hordeum vulgare L.). Diphenyleneiodonium (DPI) chloride, an NADPH oxidase inhibitor, delayed barley germination, and exogenous H2O2 (an ROS) partially rescued it. Six enzymes, ent-copalyl diphosphate synthase (CPS), ent-kaurene synthase (KS), ent-kaurene oxidase (KO), ent-kaurenoic acid oxidase (KAO), GA20-oxidase (GA20ox) and GA3-oxidase (GA3ox), catalyze the transformation of trans-geranylgeranyl diphosphate to active gibberellin, which promotes germination. Exogenous H2O2 promoted the expressions of HvKAO1 and HvGA3ox1 in barley embryos. These results suggest that ROS produced by NADPH oxidase are involved in gibberellin biosynthesis through the regulation of HvKAO1 and HvGA3ox1. PMID:27110861

  10. Role of reactive oxygen and nitrogen species in acute respiratory distress syndrome.

    PubMed

    Fink, Mitchell P

    2002-02-01

    Reactive oxygen species are reactive, partially reduced derivatives of molecular oxygen (O 2 ). Important reactive oxygen species in biologic systems include superoxide radical anion, hydrogen peroxide, and hydroxyl radical. Closely related species include the hypohalous acids, particularly hypochlorous acid; chloramine and substituted chloramines; and singlet oxygen. Reactive nitrogen species are derived from the simple diatomic gas, nitric oxide. Peroxynitrite and its protonated form, peroxynitrous acid, are the most significant reactive nitrogen species in biologic systems. A variety of enzymatic and nonenzymatic processes can generate reactive oxygen species and reactive nitrogen species in mammalian cells. An extensive body of experimental evidence from studies using animal models supports the view that reactive oxygen species and reactive nitrogen species are important in the pathogenesis of acute respiratory distress syndrome. This view is further supported by data from clinical studies that correlate biochemical evidence of reactive oxygen species-mediated or reactive nitrogen species-mediated stress with the development of acute respiratory distress syndrome. Despite these data, pharmacologic strategies directed at minimizing reactive oxygen species-mediated or reactive nitrogen species-mediated damage have yet to be successfully introduced into clinical practice. The most extensively studied compound in this regard is N -acetylcysteine; unfortunately, clinical trials with this compound in patients with acute respiratory distress syndrome have yielded disappointing results. PMID:12205400

  11. Effects of reactive oxygen species on sperm function.

    PubMed

    Guthrie, H D; Welch, G R

    2012-11-01

    Reactive oxygen species (ROS) formation and membrane lipid peroxidation have been recognized as problems for sperm survival and fertility. The precise roles and detection of superoxide (SO), hydrogen peroxide (HP), and membrane lipid peroxidation have been problematic, because of the low specificity and sensitivity of the established chemiluminescence assay technologies. We developed flow cytometric assays to measure SO, HP, membrane lipid peroxidation, and inner mitochondrial transmembrane potential in boar sperm. These methods were sufficiently sensitive to permit detection of early changes in ROS formation in sperm cells that were still viable. Basal ROS formation and membrane lipid peroxidation in the absence of ROS generators were low in viable sperm of both fresh and frozen-thawed boar semen, affecting less than 4% of the sperm cells on average. However, this is not the case in other species, as human, bovine, and poultry sperm have large increases in sperm ROS formation, lipid peroxidation, loss of motility, and death in vitro. Closer study of the effects of ROS formation on the relationship between sperm motility and ATP content in boar sperm was conducted using menadione (mitochondrial SO generator) and HP treatment. Menadione or HP caused an immediate disruption of motility with delayed or no decrease in sperm ATP content, respectively. Overall, the inhibitory effects of ROS on motility point to a mitochondrial-independent mechanism. The reduction in motility may have been due to a ROS-induced lesion in ATP utilization or in the contractile apparatus of the flagellum. PMID:22704396

  12. Cell signaling by reactive nitrogen and oxygen species in atherosclerosis

    NASA Technical Reports Server (NTRS)

    Patel, R. P.; Moellering, D.; Murphy-Ullrich, J.; Jo, H.; Beckman, J. S.; Darley-Usmar, V. M.

    2000-01-01

    The production of reactive oxygen and nitrogen species has been implicated in atherosclerosis principally as means of damaging low-density lipoprotein that in turn initiates the accumulation of cholesterol in macrophages. The diversity of novel oxidative modifications to lipids and proteins recently identified in atherosclerotic lesions has revealed surprising complexity in the mechanisms of oxidative damage and their potential role in atherosclerosis. Oxidative or nitrosative stress does not completely consume intracellular antioxidants leading to cell death as previously thought. Rather, oxidative and nitrosative stress have a more subtle impact on the atherogenic process by modulating intracellular signaling pathways in vascular tissues to affect inflammatory cell adhesion, migration, proliferation, and differentiation. Furthermore, cellular responses can affect the production of nitric oxide, which in turn can strongly influence the nature of oxidative modifications occurring in atherosclerosis. The dynamic interactions between endogenous low concentrations of oxidants or reactive nitrogen species with intracellular signaling pathways may have a general role in processes affecting wound healing to apoptosis, which can provide novel insights into the pathogenesis of atherosclerosis.

  13. Reactive oxygen species in bovine embryo in vitro production.

    PubMed

    Dalvit, G C; Cetica, P D; Pintos, L N; Beconi, M T

    2005-08-01

    Oxidative modifications of cell components due to the action of reactive oxygen species (ROS) is one of the most potentially damaging processes for proper cell function. However, in the last few years it has been observed that ROS participate in physiological processes. The aim of this work was to determine ROS generation during in vitro production of bovine embryos. Cumulus-oocyte complexes were recovered by aspiration of antral follicles from ovaries obtained from slaughtered cows and cultured in medium 199 for 22 h at 39 degrees C in 5% CO2: 95% humidified air. In vitro fertilization was carried out in IVF-mSOF with frozen-thawed semen in the same culture conditions and embryo in vitro culture in IVC-mSOF at 90% N2: 5% CO2: 5% O2. ROS was determined in denuded oocytes and embryos at successive stages of development by the 2',7'-dichlorodihydrofluorescein diacetate fluorescent assay. ROS production was not modified during oocyte maturation. However, a gradual increase in ROS production was observed up to the late morula stage during embryo in vitro culture (P < 0.05). In expanded blastocysts, ROS level decreased to reach values similar to the corresponding in oocytes. In the bovine species, the variation in ROS level during the complete process of embryo in vitro production was determined for the first time. PMID:16187501

  14. Enzymatic Production of Extracellular Reactive Oxygen Species by Marine Microorganisms

    NASA Astrophysics Data System (ADS)

    Diaz, J. M.; Andeer, P. F.; Hansel, C. M.

    2014-12-01

    Reactive oxygen species (ROS) serve as intermediates in a myriad of biogeochemically important processes, including cell signaling pathways, cellular oxidative stress responses, and the transformation of both nutrient and toxic metals such as iron and mercury. Abiotic reactions involving the photo-oxidation of organic matter were once considered the only important sources of ROS in the environment. However, the recent discovery of substantial biological ROS production in marine systems has fundamentally shifted this paradigm. Within the last few decades, marine phytoplankton, including diatoms of the genus Thalassiosira, were discovered to produce ample extracellular quantities of the ROS superoxide. Even more recently, we discovered widespread production of extracellular superoxide by phylogenetically and ecologically diverse heterotrophic bacteria at environmentally significant levels (up to 20 amol cell-1 hr-1), which has introduced the revolutionary potential for substantial "dark" cycling of ROS. Despite the profound biogeochemical importance of extracellular biogenic ROS, the cellular mechanisms underlying the production of this ROS have remained elusive. Through the development of a gel-based assay to identify extracellular ROS-producing proteins, we have recently found that enzymes typically involved in antioxidant activity also produce superoxide when molecular oxygen is the only available electron acceptor. For example, large (~3600 amino acids) heme peroxidases are involved in extracellular superoxide production by a bacterium within the widespread Roseobacter clade. In Thalassiosira spp., extracellular superoxide is produced by flavoproteins such as glutathione reductase and ferredoxin NADP+ reductase. Thus, extracellular ROS production may occur via secreted and/or cell surface enzymes that modulate between producing and degrading ROS depending on prevailing geochemical and/or ecological conditions.

  15. Manipulation of environmental oxygen modifies reactive oxygen and nitrogen species generation during myogenesis

    PubMed Central

    McCormick, Rachel; Pearson, Timothy; Vasilaki, Aphrodite

    2016-01-01

    Regulated changes in reactive oxygen and nitrogen species (RONS) activities are important in maintaining the normal sequence and development of myogenesis. Both excessive formation and reduction in RONS have been shown to affect muscle differentiation in a negative way. Cultured cells are typically grown in 20% O2 but this is not an appropriate physiological concentration for a number of cell types, including skeletal muscle. The aim was to examine the generation of RONS in cultured skeletal muscle cells under a physiological oxygen concentration condition (6% O2) and determine the effect on muscle myogenesis. Primary mouse satellite cells were grown in 20% or 6% O2 environments and RONS activity was measured at different stages of myogenesis by real-time fluorescent microscopy using fluorescent probes with different specificities i.e. dihydroethidium (DHE), 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate (DAF-FM DA) and 5-(and-6)-chloromethyl-2′,7′ -dichlorodihydrofluorescein diacetate (CM-DCFH-DA). Data demonstrate that satellite cell proliferation increased when cells were grown in 6% O2 compared with 20% O2. Myoblasts grown in 20% O2 showed an increase in DCF fluorescence and DHE oxidation compared with myoblasts grown at 6% O2. Myotubes grown in 20% O2 also showed an increase in DCF and DAF-FM fluorescence and DHE oxidation compared with myotubes grown in 6% O2. The catalase and MnSOD contents were also increased in myoblasts and myotubes that were maintained in 20% O2 compared with myoblasts and myotubes grown in 6% O2. These data indicate that intracellular RONS activities in myoblasts and myotubes at rest are influenced by changes in environmental oxygen concentration and that the increased ROS may influence myogenesis in a negative manner. PMID:26827127

  16. Manipulation of environmental oxygen modifies reactive oxygen and nitrogen species generation during myogenesis.

    PubMed

    McCormick, Rachel; Pearson, Timothy; Vasilaki, Aphrodite

    2016-08-01

    Regulated changes in reactive oxygen and nitrogen species (RONS) activities are important in maintaining the normal sequence and development of myogenesis. Both excessive formation and reduction in RONS have been shown to affect muscle differentiation in a negative way. Cultured cells are typically grown in 20% O2 but this is not an appropriate physiological concentration for a number of cell types, including skeletal muscle. The aim was to examine the generation of RONS in cultured skeletal muscle cells under a physiological oxygen concentration condition (6% O2) and determine the effect on muscle myogenesis. Primary mouse satellite cells were grown in 20% or 6% O2 environments and RONS activity was measured at different stages of myogenesis by real-time fluorescent microscopy using fluorescent probes with different specificities i.e. dihydroethidium (DHE), 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM DA) and 5-(and-6)-chloromethyl-2',7' -dichlorodihydrofluorescein diacetate (CM-DCFH-DA). Data demonstrate that satellite cell proliferation increased when cells were grown in 6% O2 compared with 20% O2. Myoblasts grown in 20% O2 showed an increase in DCF fluorescence and DHE oxidation compared with myoblasts grown at 6% O2. Myotubes grown in 20% O2 also showed an increase in DCF and DAF-FM fluorescence and DHE oxidation compared with myotubes grown in 6% O2. The catalase and MnSOD contents were also increased in myoblasts and myotubes that were maintained in 20% O2 compared with myoblasts and myotubes grown in 6% O2. These data indicate that intracellular RONS activities in myoblasts and myotubes at rest are influenced by changes in environmental oxygen concentration and that the increased ROS may influence myogenesis in a negative manner. PMID:26827127

  17. REACTIVE OXYGEN AND NITROGEN SPECIES IN PULMONARY HYPERTENSION

    PubMed Central

    Tabima, Diana M.; Frizzell, Sheila; Gladwin, Mark T.

    2013-01-01

    Pulmonary vascular disease can be defined as either a disease affecting the pulmonary capillaries and pulmonary arterioles, termed pulmonary arterial hypertension, or as a disease affecting the left ventricle, called pulmonary venous hypertension. Pulmonary arterial hypertension (PAH) is a disorder of the pulmonary circulation characterized by endothelial dysfunction, as well as intimal and smooth muscle proliferation. Progressive increases in pulmonary vascular resistance and pressure impair the performance of the right ventricle, resulting in declining cardiac output, reduced exercise capacity, right heart failure, and ultimately death. While the primary and heritable forms of the disease are thought to affect over 5,000 patients in the U.S., the disease can occur secondary to congenital heart disease, most advanced lung diseases, and many systemic diseases. Multiple studies implicate oxidative stress in the development of PAH. Further, this oxidative stress has been shown to be associated with alterations in reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO) signaling pathways, whereby bioavailable NO is decreased and ROS and RNS production are increased. Many canonical ROS and NO signaling pathways are simultaneously disrupted in PAH, with increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and xanthine oxidoreductase, uncoupling of endothelial NO synthase (eNOS), and reduction in mitochondrial number, as well as impaired mitochondrial function. Upstream dysregulation of ROS/NO redox homeostasis impairs vascular tone and contributes to the pathological activation of anti-apoptotic and mitogenic pathways, leading to cell proliferation and obliteration of the vasculature. This manuscript will review the available data regarding the role of oxidative and nitrosative stress and endothelial dysfunction in the pathophysiology of pulmonary hypertension, and provide a description of targeted therapies

  18. Plasma-generated reactive oxygen species for biomedical applications

    NASA Astrophysics Data System (ADS)

    Sousa, J. S.; Hammer, M. U.; Winter, J.; Tresp, H.; Duennbier, M.; Iseni, S.; Martin, V.; Puech, V.; Weltmann, K. D.; Reuter, S.

    2012-10-01

    To get a better insight into the effects of reactive oxygen species (ROS) on cellular components, fundamental studies are essential to determine the nature and concentration of plasma-generated ROS, and the chemistry induced in biological liquids by those ROS. In this context, we have measured the absolute density of the main ROS created in three different atmospheric pressure plasma sources: two geometrically distinct RF-driven microplasma jets (μ-APPJ [1] and kinpen [2]), and an array of microcathode sustained discharges [3]. Optical diagnostics of the plasma volumes and effluent regions have been performed: UV absorption for O3 and IR emission for O2(a^1δ) [4]. High concentrations of both ROS have been obtained (10^14--10^17cm-3). The effect of different parameters, such as gas flows and mixtures and power coupled to the plasmas, has been studied. For plasma biomedicine, the determination of the reactive species present in plasma-treated liquids is of great importance. In this work, we focused on the measurement of the concentration of H2O2 and NOX radicals, generated in physiological solutions like NaCl and PBS.[4pt] [1] N. Knake et al., J. Phys. D: App. Phys. 41, 194006 (2008)[0pt] [2] K.D. Weltmann et al., Pure Appl. Chem. 82, 1223 (2010)[0pt] [3] J.S. Sousa et al., Appl. Phys. Lett. 97, 141502 (2010)[0pt] [4] J.S. Sousa et al., Appl. Phys. Lett. 93, 011502 (2008)

  19. Reactive oxygen species regulate alkaloid metabolism in undifferentiated N. tabacum cells.

    PubMed

    Sachan, Nita; Rogers, Dennis T; Yun, Kil-Young; Littleton, John M; Falcone, Deane L

    2010-05-01

    Plants produce an immense number of natural products and undifferentiated cells from various plant tissues have long been considered an ideal source for their synthesis. However, undifferentiated plant cells often either lose their biosynthetic capacity over time or exhibit immediate repression of the required pathways once dedifferentiated. In this study, freshly prepared callus tissue was employed to further investigate the regulation of a natural product pathway in undifferentiated tobacco cells. Putrescine N-methyltransferase (PMT) is a pathway-specific enzyme required in nicotinic alkaloid production in Nicotiana species. Callus derived from transgenic Nicotiana tabacum plants harboring PMT promoter-GUS fusions were used to study factors that influence PMT expression. Under normal callus growth conditions in the presence of light and auxin, PMT promoter activity was strongly repressed. Conversely, dark conditions and the absence of auxin were found to upregulate PMT promoter activity, with light being dominant to the repressive effects of auxin. Since reactive oxygen species (ROS) are known by-products of photosynthesis and have been implicated in signaling, their involvement was investigated in transgenic callus by treatment with the ROS scavenger, dimethylthiourea, or catalase. Under highly repressive conditions for alkaloid synthesis, including normal culture conditions in the light, both ROS scavengers resulted in significant induction of PMT promoter activity. Moreover, treatment of callus with catalase resulted in the upregulation of PMT promoter activity and alkaloid accumulation in this tissue. These results suggest that ROS impact the regulation of the alkaloid pathway in undifferentiated cells and have implications for regulation of the pathway in other plant tissues. PMID:20217418

  20. Male infertility testing: reactive oxygen species and antioxidant capacity.

    PubMed

    Ko, Edmund Y; Sabanegh, Edmund S; Agarwal, Ashok

    2014-12-01

    Reactive oxygen species (ROS) are an integral component of sperm developmental physiology, capacitation, and function. Elevated ROS levels, from processes such as infection or inflammation, can be associated with aberrations of sperm development, function, and fertilizing capacity. We review the impact of ROS on sperm physiology, its place in infertility evaluation, the implications for reproductive outcomes, and antioxidant therapy. Our systematic review of PubMed literature from the last 3 decades focuses on the physiology and etiology of ROS and oxidative stress (OS), evaluation of ROS, and antioxidants. ROS is normally produced physiologically and is used to maintain cellular processes such as sperm maturation, capacitation, and sperm-oocyte interaction. When ROS production exceeds the buffering capacity of antioxidants, OS occurs and can have a negative impact on sperm and fertility. ROS and antioxidant capacity testing can potentially add additional prognostic information to standard laboratory testing for the infertile male, although its role as standard part of an evaluation has yet to be determined. Elevated ROS levels have been implicated with abnormal semen parameters and male infertility, but the impact of ROS on fertilization rates and pregnancy is controversial. This is partly because of the lack of consensus on what type of patients may be suitable for ROS testing and assay standardization. Routine ROS testing for the infertile male is not currently recommended. PMID:25458618

  1. Reactive oxygen species: players in the cardiovascular effects of testosterone.

    PubMed

    Tostes, Rita C; Carneiro, Fernando S; Carvalho, Maria Helena C; Reckelhoff, Jane F

    2016-01-01

    Androgens are essential for the development and maintenance of male reproductive tissues and sexual function and for overall health and well being. Testosterone, the predominant and most important androgen, not only affects the male reproductive system, but also influences the activity of many other organs. In the cardiovascular system, the actions of testosterone are still controversial, its effects ranging from protective to deleterious. While early studies showed that testosterone replacement therapy exerted beneficial effects on cardiovascular disease, some recent safety studies point to a positive association between endogenous and supraphysiological levels of androgens/testosterone and cardiovascular disease risk. Among the possible mechanisms involved in the actions of testosterone on the cardiovascular system, indirect actions (changes in the lipid profile, insulin sensitivity, and hemostatic mechanisms, modulation of the sympathetic nervous system and renin-angiotensin-aldosterone system), as well as direct actions (modulatory effects on proinflammatory enzymes, on the generation of reactive oxygen species, nitric oxide bioavailability, and on vasoconstrictor signaling pathways) have been reported. This mini-review focuses on evidence indicating that testosterone has prooxidative actions that may contribute to its deleterious actions in the cardiovascular system. The controversial effects of testosterone on ROS generation and oxidant status, both prooxidant and antioxidant, in the cardiovascular system and in cells and tissues of other systems are reviewed. PMID:26538238

  2. Redox Roles of Reactive Oxygen Species in Cardiovascular Diseases

    PubMed Central

    He, Feng; Zuo, Li

    2015-01-01

    Cardiovascular disease (CVD), a major cause of mortality in the world, has been extensively studied over the past decade. However, the exact mechanism underlying its pathogenesis has not been fully elucidated. Reactive oxygen species (ROS) play a pivotal role in the progression of CVD. Particularly, ROS are commonly engaged in developing typical characteristics of atherosclerosis, one of the dominant CVDs. This review will discuss the involvement of ROS in atherosclerosis, specifically their effect on inflammation, disturbed blood flow and arterial wall remodeling. Pharmacological interventions target ROS in order to alleviate oxidative stress and CVD symptoms, yet results are varied due to the paradoxical role of ROS in CVD. Lack of effectiveness in clinical trials suggests that understanding the exact role of ROS in the pathophysiology of CVD and developing novel treatments, such as antioxidant gene therapy and nanotechnology-related antioxidant delivery, could provide a therapeutic advance in treating CVDs. While genetic therapies focusing on specific antioxidant expression seem promising in CVD treatments, multiple technological challenges exist precluding its immediate clinical applications. PMID:26610475

  3. NSAIDs and Cardiovascular Diseases: Role of Reactive Oxygen Species

    PubMed Central

    Ghosh, Rajeshwary; Alajbegovic, Azra; Gomes, Aldrin V.

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs worldwide. NSAIDs are used for a variety of conditions including pain, rheumatoid arthritis, and musculoskeletal disorders. The beneficial effects of NSAIDs in reducing or relieving pain are well established, and other benefits such as reducing inflammation and anticancer effects are also documented. The undesirable side effects of NSAIDs include ulcers, internal bleeding, kidney failure, and increased risk of heart attack and stroke. Some of these side effects may be due to the oxidative stress induced by NSAIDs in different tissues. NSAIDs have been shown to induce reactive oxygen species (ROS) in different cell types including cardiac and cardiovascular related cells. Increases in ROS result in increased levels of oxidized proteins which alters key intracellular signaling pathways. One of these key pathways is apoptosis which causes cell death when significantly activated. This review discusses the relationship between NSAIDs and cardiovascular diseases (CVD) and the role of NSAID-induced ROS in CVD. PMID:26457127

  4. UV-induced reactive oxygen species in photocarcinogenesis and photoaging.

    PubMed

    Scharffetter-Kochanek, K; Wlaschek, M; Brenneisen, P; Schauen, M; Blaudschun, R; Wenk, J

    1997-11-01

    The increase in UV irradiation on earth due to the stratospheric ozone depletion represents a major environmental threat to the skin increasing its risk of photooxidative damage by UV-induced reactive oxygen species (ROS). Increased ROS load has been implicated in several pathological states including photoaging and photocarcinogenesis of the skin. Large efforts have been made to better define the involvement of distinct ROS in photocarcinogenesis and photoaging. Both pathological processes share common features; however, they reveal unique molecular characteristics which finally determine the fate of the cell and its host. As well as causing permanent genetic changes involving protooncogenes and tumor suppressor genes, ROS activate cytoplasmic signal transduction pathways that are related to growth differentiation, senescence, transformation and tissue degradation. This review focuses on the role of UV-induced ROS in the photodamage of the skin resulting in biochemical and clinical characteristics of photocarcinogenesis and photoaging. A decrease in the ROS load by efficient sunscreens and/or otherwise protective agents may represent a promising strategy to prevent or at least minimize ROS induced cutaneous pathological states. PMID:9426184

  5. Reactive oxygen species in response of plants to gravity stress

    NASA Astrophysics Data System (ADS)

    Jadko, Sergiy

    2016-07-01

    Reactive oxygen species (ROS) as second messengers can induce stress response of plants. Thioredoxins (Trx) and peroxiredoxins (Prx) can function as sensors and transmitters of the ROS in stress signaling and antioxidant response. 12-14 days old tissue culture of Arabidopsis thaliana have been investigated. Hypergravity stress was induced by centrifugation at 10 and 20 g during 30 and 90 min and than intensity of spontaneous chemiluminescence (SChL/ROS content), Trx and Prx activities were determined. All experiments were repeated from 3 to 5 times and the obtained data were statistically treated. In the tissue culture under development of the stress there were an increase in intensity of SChL and Trx and Prx activities. Thus, under hypergravity stress in the plant occurred early increase in the ROS level and the ROS induced the increase in the Trx and Prx activities. Prx and Trx can also participate in the formation of stress respons as acceptors and transducers of the redox signals. Increase in the activity of these enzymes primarily aimed at increasing of the total antioxidant activity in the cells to prevent of the plant to development of oxidative degradation by ROS.

  6. Reactive oxygen species (ROS): involvement in bovine follicular cysts etiopathogenesis.

    PubMed

    Rizzo, Annalisa; Minoia, Giuseppe; Trisolini, Carmelinda; Mutinati, Maddalena; Spedicato, Massimo; Jirillo, Felicita; Sciorsci, Raffaele Luigi

    2009-01-01

    Ovulation is compared to an acute inflammatory process during which vasoactive agents, prostanoids, leukotrienes and Reactive Oxygen Species (ROS) develop. The aim of this study was to evaluate the levels of ROS in cystic and follicular fluid, in order to establish their involvement in the etiopathogenesis of Cystic Ovarian Follicle (COF) in dairy cows. The study was conducted in 30 healthy cows (group C) and 30 cows affected by COF (group COF). The fluid of follicular cysts and of preovulatory follicles was drawn by means of ultrasound guided aspiration from the cows of both groups. The fluid obtained was analyzed by a photometric analytical system to detect ROS level. ROS concentration was statistically lower in the cystic fluid than in the follicular one (62.4 +/- 13.36 U.Carr vs. 84.89 +/- 26.99 U.Carr) (p<0.05), thus suggesting that an alteration of the cascade responsible for ROS production may be implicated in the complex etipathogenesis of COF. PMID:19874233

  7. Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Induced Transcription

    NASA Astrophysics Data System (ADS)

    Chandel, N. S.; Maltepe, E.; Goldwasser, E.; Mathieu, C. E.; Simon, M. C.; Schumacker, P. T.

    1998-09-01

    Transcriptional activation of erythropoietin, glycolytic enzymes, and vascular endothelial growth factor occurs during hypoxia or in response to cobalt chloride (CoCl2) in Hep3B cells. However, neither the mechanism of cellular O2 sensing nor that of cobalt is fully understood. We tested whether mitochondria act as O2 sensors during hypoxia and whether hypoxia and cobalt activate transcription by increasing generation of reactive oxygen species (ROS). Results show (i) wild-type Hep3B cells increase ROS generation during hypoxia (1.5% O2) or CoCl2 incubation, (ii) Hep3B cells depleted of mitochondrial DNA (ρ 0 cells) fail to respire, fail to activate mRNA for erythropoietin, glycolytic enzymes, or vascular endothelial growth factor during hypoxia, and fail to increase ROS generation during hypoxia; (iii) ρ 0 cells increase ROS generation in response to CoCl2 and retain the ability to induce expression of these genes; and (iv) the antioxidants pyrrolidine dithiocarbamate and ebselen abolish transcriptional activation of these genes during hypoxia or CoCl2 in wild-type cells, and abolish the response to CoCl2 in ρ 0 cells. Thus, hypoxia activates transcription via a mitochondria-dependent signaling process involving increased ROS, whereas CoCl2 activates transcription by stimulating ROS generation via a mitochondria-independent mechanism.

  8. Methods for Detection of Mitochondrial and Cellular Reactive Oxygen Species

    PubMed Central

    Harrison, David G.

    2014-01-01

    Abstract Significance: Mitochondrial and cellular reactive oxygen species (ROS) play important roles in both physiological and pathological processes. Different ROS, such as superoxide (O2•−), hydrogen peroxide, and peroxynitrite (ONOO•−), stimulate distinct cell-signaling pathways and lead to diverse outcomes depending on their amount and subcellular localization. A variety of methods have been developed for ROS detection; however, many of these methods are not specific, do not allow subcellular localization, and can produce artifacts. In this review, we will critically analyze ROS detection and present advantages and the shortcomings of several available methods. Recent Advances: In the past decade, a number of new fluorescent probes, electron-spin resonance approaches, and immunoassays have been developed. These new state-of-the-art methods provide improved selectivity and subcellular resolution for ROS detection. Critical Issues: Although new methods for HPLC superoxide detection, application of fluorescent boronate-containing probes, use of cell-targeted hydroxylamine spin probes, and immunospin trapping have been available for several years, there has been lack of translation of these into biomedical research, limiting their widespread use. Future Directions: Additional studies to translate these new technologies from the test tube to physiological applications are needed and could lead to a wider application of these approaches to study mitochondrial and cellular ROS. Antioxid. Redox Signal. 20, 372–382. PMID:22978713

  9. Reactive oxygen species in diabetic nephropathy: friend or foe?

    PubMed

    Bondeva, Tzvetanka; Wolf, Gunter

    2014-11-01

    Based on the numerous cellular and animal studies over the last decades, it has been postulated that reactive oxygen species (ROS) are important secondary messengers for signalling pathways associated with apoptosis, proliferation, damage and inflammation. Their adverse effects were considered to play a leading role in the onset and progression of type 1 and type 2 diabetes mellitus as well as in the complication of diabetic disease leading to vascular-, cardiac-, neuro-degeneration, diabetic retinopathy and diabetic nephropathy. All these complications were mostly linked to the generation of the superoxide anion, due to a prolonged hyperglycaemia in diabetes, and this anion was almost 'blamed for everything', despite the fact that its measurement and detection in life systems is extremely complicated due to the short lifespan of the superoxide anion. Therefore, a tremendous amount of research has been focused on finding ways to suppress ROS production. However, a recent report from Dugan et al. shed new insights into the life detection of superoxide generation in diabetes and raised the question of whether we treat the diabetes-related complications correctly or the target is somewhat different as thought. This review will focus on some aspects of this novel concept for the role of ROS in diabetic nephropathy. PMID:24589719

  10. Generation of Reactive Oxygen Species from Silicon Nanowires

    PubMed Central

    Leonard, Stephen S; Cohen, Guy M; Kenyon, Allison J; Schwegler-Berry, Diane; Fix, Natalie R; Bangsaruntip, Sarunya; Roberts, Jenny R

    2014-01-01

    Processing and synthesis of purified nanomaterials of diverse composition, size, and properties is an evolving process. Studies have demonstrated that some nanomaterials have potential toxic effects and have led to toxicity research focusing on nanotoxicology. About two million workers will be employed in the field of nanotechnology over the next 10 years. The unknown effects of nanomaterials create a need for research and development of techniques to identify possible toxicity. Through a cooperative effort between National Institute for Occupational Safety and Health and IBM to address possible occupational exposures, silicon-based nanowires (SiNWs) were obtained for our study. These SiNWs are anisotropic filamentary crystals of silicon, synthesized by the vapor–liquid–solid method and used in bio-sensors, gas sensors, and field effect transistors. Reactive oxygen species (ROS) can be generated when organisms are exposed to a material causing cellular responses, such as lipid peroxidation, H2O2 production, and DNA damage. SiNWs were assessed using three different in vitro environments (H2O2, RAW 264.7 cells, and rat alveolar macrophages) for ROS generation and possible toxicity identification. We used electron spin resonance, analysis of lipid peroxidation, measurement of H2O2 production, and the comet assay to assess generation of ROS from SiNW and define possible mechanisms. Our results demonstrate that SiNWs do not appear to be significant generators of free radicals. PMID:25452695

  11. Salicylic acid signaling inhibits apoplastic reactive oxygen species signaling

    PubMed Central

    2014-01-01

    Background Reactive oxygen species (ROS) are used by plants as signaling molecules during stress and development. Given the amount of possible challenges a plant face from their environment, plants need to activate and prioritize between potentially conflicting defense signaling pathways. Until recently, most studies on signal interactions have focused on phytohormone interaction, such as the antagonistic relationship between salicylic acid (SA)-jasmonic acid and cytokinin-auxin. Results In this study, we report an antagonistic interaction between SA signaling and apoplastic ROS signaling. Treatment with ozone (O3) leads to a ROS burst in the apoplast and induces extensive changes in gene expression and elevation of defense hormones. However, Arabidopsis thaliana dnd1 (defense no death1) exhibited an attenuated response to O3. In addition, the dnd1 mutant displayed constitutive expression of defense genes and spontaneous cell death. To determine the exact process which blocks the apoplastic ROS signaling, double and triple mutants involved in various signaling pathway were generated in dnd1 background. Simultaneous elimination of SA-dependent and SA-independent signaling components from dnd1 restored its responsiveness to O3. Conversely, pre-treatment of plants with SA or using mutants that constitutively activate SA signaling led to an attenuation of changes in gene expression elicited by O3. Conclusions Based upon these findings, we conclude that plants are able to prioritize the response between ROS and SA via an antagonistic action of SA and SA signaling on apoplastic ROS signaling. PMID:24898702

  12. Imaging Reactive Oxygen Species-Induced Modifications in Living Systems

    PubMed Central

    Maulucci, Giuseppe; Bačić, Goran; Bridal, Lori; Schmidt, Harald H.H.W.; Tavitian, Bertrand; Viel, Thomas; Utsumi, Hideo; Yalçın, A. Süha

    2016-01-01

    Abstract Significance: Reactive Oxygen Species (ROS) may regulate signaling, ion channels, transcription factors, and biosynthetic processes. ROS-related diseases can be due to either a shortage or an excess of ROS. Recent Advances: Since the biological activity of ROS depends on not only concentration but also spatiotemporal distribution, real-time imaging of ROS, possibly in vivo, has become a need for scientists, with potential for clinical translation. New imaging techniques as well as new contrast agents in clinically established modalities were developed in the previous decade. Critical Issues: An ideal imaging technique should determine ROS changes with high spatio-temporal resolution, detect physiologically relevant variations in ROS concentration, and provide specificity toward different redox couples. Furthermore, for in vivo applications, bioavailability of sensors, tissue penetration, and a high signal-to-noise ratio are additional requirements to be satisfied. Future Directions: None of the presented techniques fulfill all requirements for clinical translation. The obvious way forward is to incorporate anatomical and functional imaging into a common hybrid-imaging platform. Antioxid. Redox Signal. 24, 939–958. PMID:27139586

  13. NSAIDs and Cardiovascular Diseases: Role of Reactive Oxygen Species.

    PubMed

    Ghosh, Rajeshwary; Alajbegovic, Azra; Gomes, Aldrin V

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs worldwide. NSAIDs are used for a variety of conditions including pain, rheumatoid arthritis, and musculoskeletal disorders. The beneficial effects of NSAIDs in reducing or relieving pain are well established, and other benefits such as reducing inflammation and anticancer effects are also documented. The undesirable side effects of NSAIDs include ulcers, internal bleeding, kidney failure, and increased risk of heart attack and stroke. Some of these side effects may be due to the oxidative stress induced by NSAIDs in different tissues. NSAIDs have been shown to induce reactive oxygen species (ROS) in different cell types including cardiac and cardiovascular related cells. Increases in ROS result in increased levels of oxidized proteins which alters key intracellular signaling pathways. One of these key pathways is apoptosis which causes cell death when significantly activated. This review discusses the relationship between NSAIDs and cardiovascular diseases (CVD) and the role of NSAID-induced ROS in CVD. PMID:26457127

  14. Matairesinol inhibits angiogenesis via suppression of mitochondrial reactive oxygen species

    SciTech Connect

    Lee, Boram; Kim, Ki Hyun; Jung, Hye Jin; Kwon, Ho Jeong

    2012-04-27

    Highlights: Black-Right-Pointing-Pointer Matairesinol suppresses mitochondrial ROS generation during hypoxia. Black-Right-Pointing-Pointer Matairesinol exhibits potent anti-angiogenic activity both in vitro and in vivo. Black-Right-Pointing-Pointer Matairesinol could be a basis for the development of novel anti-angiogenic agents. -- Abstract: Mitochondrial reactive oxygen species (mROS) are involved in cancer initiation and progression and function as signaling molecules in many aspects of hypoxia and growth factor-mediated signaling. Here we report that matairesinol, a natural small molecule identified from the cell-based screening of 200 natural plants, suppresses mROS generation resulting in anti-angiogenic activity. A non-toxic concentration of matairesinol inhibited the proliferation of human umbilical vein endothelial cells. The compound also suppressed in vitro angiogenesis of tube formation and chemoinvasion, as well as in vivo angiogenesis of the chorioallantoic membrane at non-toxic doses. Furthermore, matairesinol decreased hypoxia-inducible factor-1{alpha} in hypoxic HeLa cells. These results demonstrate that matairesinol could function as a novel angiogenesis inhibitor by suppressing mROS signaling.

  15. Reactive Oxygen Species, Apoptosis, Antimicrobial Peptides and Human Inflammatory Diseases

    PubMed Central

    Oyinloye, Babatunji Emmanuel; Adenowo, Abiola Fatimah; Kappo, Abidemi Paul

    2015-01-01

    Excessive free radical generation, especially reactive oxygen species (ROS) leading to oxidative stress in the biological system, has been implicated in the pathogenesis and pathological conditions associated with diverse human inflammatory diseases (HIDs). Although inflammation which is considered advantageous is a defensive mechanism in response to xenobiotics and foreign pathogen; as a result of cellular damage arising from oxidative stress, if uncontrolled, it may degenerate to chronic inflammation when the ROS levels exceed the antioxidant capacity. Therefore, in the normal resolution of inflammatory reactions, apoptosis is acknowledged to play a crucial role, while on the other hand, dysregulation in the induction of apoptosis by enhanced ROS production could also result in excessive apoptosis identified in the pathogenesis of HIDs. Apparently, a careful balance must be maintained in this complex environment. Antimicrobial peptides (AMPs) have been proposed in this review as an excellent candidate capable of playing prominent roles in maintaining this balance. Consequently, in novel drug design for the treatment and management of HIDs, AMPs are promising candidates owing to their size and multidimensional properties as well as their wide spectrum of activities and indications of reduced rate of resistance. PMID:25850012

  16. Reactive oxygen species a double-edged sword for mesothelioma

    PubMed Central

    Catalani, Simona; Galati, Rossella

    2015-01-01

    It is well known that oxidative stress can lead to chronic inflammation which, in turn, could mediate most chronic diseases including cancer. Oxidants have been implicated in the activity of crocidolite and amosite, the most powerful types of asbestos associated to the occurrence of mesothelioma. Currently rates of mesothelioma are rising and estimates indicate that the incidence of mesothelioma will peak within the next 10–15 years in the western world, while in Japan the peak is predicted not to occur until 40 years from now. Although the use of asbestos has been banned in many countries around the world, production of and the potentially hazardous exposure to asbestos is still present with locally high incidences of mesothelioma. Today a new man-made material, carbon nanotubes, has arisen as a concern; carbon nanotubes may display ‘asbestos-like’ pathogenicity with mesothelioma induction potential. Carbon nanotubes resulted in the greatest reactive oxygen species generation. How oxidative stress activates inflammatory pathways leading to the transformation of a normal cell to a tumor cell, to tumor cell survival, proliferation, invasion, angiogenesis, chemoresistance, and radioresistance, is the aim of this review. PMID:26078352

  17. Role of Reactive Oxygen Species in Neonatal Pulmonary Vascular Disease

    PubMed Central

    Steinhorn, Robin H.

    2014-01-01

    Abstract Significance: Abnormal lung development in the perinatal period can result in severe neonatal complications, including persistent pulmonary hypertension (PH) of the newborn and bronchopulmonary dysplasia. Reactive oxygen species (ROS) play a substantive role in the development of PH associated with these diseases. ROS impair the normal pulmonary artery (PA) relaxation in response to vasodilators, and ROS are also implicated in pulmonary arterial remodeling, both of which can increase the severity of PH. Recent Advances: PA ROS levels are elevated when endogenous ROS-generating enzymes are activated and/or when endogenous ROS scavengers are inactivated. Animal models have provided valuable insights into ROS generators and scavengers that are dysregulated in different forms of neonatal PH, thus identifying potential therapeutic targets. Critical Issues: General antioxidant therapy has proved ineffective in reversing PH, suggesting that it is necessary to target specific signaling pathways for successful therapy. Future Directions: Development of novel selective pharmacologic inhibitors along with nonantioxidant therapies may improve the treatment outcomes of patients with PH, while further investigation of the underlying mechanisms may enable earlier detection of the disease. Antioxid. Redox Signal. 21, 1926–1942. PMID:24350610

  18. Reactive Oxygen Species (Ros-Induced) Ros Release

    PubMed Central

    Zorov, Dmitry B.; Filburn, Charles R.; Klotz, Lars-Oliver; Zweier, Jay L.; Sollott, Steven J.

    2000-01-01

    We sought to understand the relationship between reactive oxygen species (ROS) and the mitochondrial permeability transition (MPT) in cardiac myocytes based on the observation of increased ROS production at sites of spontaneously deenergized mitochondria. We devised a new model enabling incremental ROS accumulation in individual mitochondria in isolated cardiac myocytes via photoactivation of tetramethylrhodamine derivatives, which also served to report the mitochondrial transmembrane potential, ΔΨ. This ROS accumulation reproducibly triggered abrupt (and sometimes reversible) mitochondrial depolarization. This phenomenon was ascribed to MPT induction because (a) bongkrekic acid prevented it and (b) mitochondria became permeable for calcein (∼620 daltons) concurrently with depolarization. These photodynamically produced “triggering” ROS caused the MPT induction, as the ROS scavenger Trolox prevented it. The time required for triggering ROS to induce the MPT was dependent on intrinsic cellular ROS-scavenging redox mechanisms, particularly glutathione. MPT induction caused by triggering ROS coincided with a burst of mitochondrial ROS generation, as measured by dichlorofluorescein fluorescence, which we have termed mitochondrial “ROS-induced ROS release” (RIRR). This MPT induction/RIRR phenomenon in cardiac myocytes often occurred synchronously and reversibly among long chains of adjacent mitochondria demonstrating apparent cooperativity. The observed link between MPT and RIRR could be a fundamental phenomenon in mitochondrial and cell biology. PMID:11015441

  19. Reactive oxygen species at the crossroads of inflammasome and inflammation

    PubMed Central

    Harijith, Anantha; Ebenezer, David L.; Natarajan, Viswanathan

    2014-01-01

    Inflammasomes form a crucial part of the innate immune system. These are multi-protein oligomer platforms that are composed of intracellular sensors which are coupled with caspase and interleukin activating systems. Nod-like receptor protein (NLRP) 3, and 6 and NLRC4 and AIM2 are the prominent members of the inflammasome family. Inflammasome activation leads to pyroptosis, a process of programmed cell death distinct from apoptosis through activation of Caspase and further downstream targets such as IL-1β and IL-18 leading to activation of inflammatory cascade. Reactive oxygen species (ROS) serves as important inflammasome activating signals. ROS activates inflammasome through mitogen-activated protein kinases (MAPK) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). Dysregulation of inflammasome plays a significant role in various pathological processes. Viral infections such as Dengue and Respiratory syncytial virus activate inflammasomes. Crystal compounds in silicosis and gout also activate ROS. In diabetes, inhibition of autophagy with resultant accumulation of dysfunctional mitochondria leads to enhanced ROS production activating inflammasomes. Activation of inflammasomes can be dampened by antioxidants such as SIRT-1. Inflammasome and related cascade could serve as future therapeutic targets for various pathological conditions. PMID:25324778

  20. Are reactive oxygen species still the basis for diabetic complications?

    PubMed

    Di Marco, Elyse; Jha, Jay C; Sharma, Arpeeta; Wilkinson-Berka, Jennifer L; Jandeleit-Dahm, Karin A; de Haan, Judy B

    2015-07-01

    Despite the wealth of pre-clinical support for a role for reactive oxygen and nitrogen species (ROS/RNS) in the aetiology of diabetic complications, enthusiasm for antioxidant therapeutic approaches has been dampened by less favourable outcomes in large clinical trials. This has necessitated a re-evaluation of pre-clinical evidence and a more rational approach to antioxidant therapy. The present review considers current evidence, from both pre-clinical and clinical studies, to address the benefits of antioxidant therapy. The main focus of the present review is on the effects of direct targeting of ROS-producing enzymes, the bolstering of antioxidant defences and mechanisms to improve nitric oxide availability. Current evidence suggests that a more nuanced approach to antioxidant therapy is more likely to yield positive reductions in end-organ injury, with considerations required for the types of ROS/RNS involved, the timing and dosage of antioxidant therapy, and the selective targeting of cell populations. This is likely to influence future strategies to lessen the burden of diabetic complications such as diabetes-associated atherosclerosis, diabetic nephropathy and diabetic retinopathy. PMID:25927680

  1. Reactive oxygen species and mitochondria: A nexus of cellular homeostasis

    PubMed Central

    Dan Dunn, Joe; Alvarez, Luis AJ; Zhang, Xuezhi; Soldati, Thierry

    2015-01-01

    Reactive oxygen species (ROS) are integral components of multiple cellular pathways even though excessive or inappropriately localized ROS damage cells. ROS function as anti-microbial effector molecules and as signaling molecules that regulate such processes as NF-kB transcriptional activity, the production of DNA-based neutrophil extracellular traps (NETs), and autophagy. The main sources of cellular ROS are mitochondria and NADPH oxidases (NOXs). In contrast to NOX-generated ROS, ROS produced in the mitochondria (mtROS) were initially considered to be unwanted by-products of oxidative metabolism. Increasing evidence indicates that mtROS have been incorporated into signaling pathways including those regulating immune responses and autophagy. As metabolic hubs, mitochondria facilitate crosstalk between the metabolic state of the cell with these pathways. Mitochondria and ROS are thus a nexus of multiple pathways that determine the response of cells to disruptions in cellular homeostasis such as infection, sterile damage, and metabolic imbalance. In this review, we discuss the roles of mitochondria in the generation of ROS-derived anti-microbial effectors, the interplay of mitochondria and ROS with autophagy and the formation of DNA extracellular traps, and activation of the NLRP3 inflammasome by ROS and mitochondria. PMID:26432659

  2. Reactive oxygen species and mitochondria: A nexus of cellular homeostasis.

    PubMed

    Dan Dunn, Joe; Alvarez, Luis Aj; Zhang, Xuezhi; Soldati, Thierry

    2015-12-01

    Reactive oxygen species (ROS) are integral components of multiple cellular pathways even though excessive or inappropriately localized ROS damage cells. ROS function as anti-microbial effector molecules and as signaling molecules that regulate such processes as NF-kB transcriptional activity, the production of DNA-based neutrophil extracellular traps (NETs), and autophagy. The main sources of cellular ROS are mitochondria and NADPH oxidases (NOXs). In contrast to NOX-generated ROS, ROS produced in the mitochondria (mtROS) were initially considered to be unwanted by-products of oxidative metabolism. Increasing evidence indicates that mtROS have been incorporated into signaling pathways including those regulating immune responses and autophagy. As metabolic hubs, mitochondria facilitate crosstalk between the metabolic state of the cell with these pathways. Mitochondria and ROS are thus a nexus of multiple pathways that determine the response of cells to disruptions in cellular homeostasis such as infection, sterile damage, and metabolic imbalance. In this review, we discuss the roles of mitochondria in the generation of ROS-derived anti-microbial effectors, the interplay of mitochondria and ROS with autophagy and the formation of DNA extracellular traps, and activation of the NLRP3 inflammasome by ROS and mitochondria. PMID:26432659

  3. Reactive oxygen species, nutrition, hypoxia and diseases: Problems solved?

    PubMed Central

    Görlach, Agnes; Dimova, Elitsa Y.; Petry, Andreas; Martínez-Ruiz, Antonio; Hernansanz-Agustín, Pablo; Rolo, Anabela P.; Palmeira, Carlos M.; Kietzmann, Thomas

    2015-01-01

    Within the last twenty years the view on reactive oxygen species (ROS) has changed; they are no longer only considered to be harmful but also necessary for cellular communication and homeostasis in different organisms ranging from bacteria to mammals. In the latter, ROS were shown to modulate diverse physiological processes including the regulation of growth factor signaling, the hypoxic response, inflammation and the immune response. During the last 60–100 years the life style, at least in the Western world, has changed enormously. This became obvious with an increase in caloric intake, decreased energy expenditure as well as the appearance of alcoholism and smoking; These changes were shown to contribute to generation of ROS which are, at least in part, associated with the occurrence of several chronic diseases like adiposity, atherosclerosis, type II diabetes, and cancer. In this review we discuss aspects and problems on the role of intracellular ROS formation and nutrition with the link to diseases and their problematic therapeutical issues. PMID:26339717

  4. Reactive Oxygen Species and Respiratory Plasticity Following Intermittent Hypoxia

    PubMed Central

    MacFarlane, P.M.; Wilkerson, J.E.R.; Lovett-Barr, M.R.; Mitchell, G.S.

    2008-01-01

    The neural network controlling breathing exhibits plasticity in response to environmental or physiological challenges. For example, while hypoxia initiates rapid and robust increases in respiratory motor output to defend against hypoxemia, it also triggers persistent changes, or plasticity, in chemosensory neurons and integrative pathways that transmit brainstem respiratory activity to respiratory motor neurons. Frequently studied models of hypoxia-induced respiratory plasticity include: 1) carotid chemosensory plasticity and metaplasticity induced by chronic intermittent hypoxia (CIH), and 2) acute intermittent hypoxia (AIH) induced phrenic long-term facilitation (pLTF) in naïve and CIH preconditioned rats. These forms of plasticity share some mechanistic elements, although they differ in anatomical location and the requirement for CIH preconditioning. Both forms of plasticity require serotonin receptor activation and formation of reactive oxygen species (ROS). While the cellular sources and targets of ROS are not well known, recent evidence suggests that ROS modify the balance of protein phosphatase and kinase activities, shifting the balance towards net phosphorylation and favoring cellular reactions that induce and/or maintain plasticity. Here, we review possible sources of ROS, and the impact of ROS on phosphorylation events relevant to respiratory plasticity. PMID:18692605

  5. Pharmacological modulation of reactive oxygen species in cancer treatment.

    PubMed

    Ribas, Judit; Mattiolo, Paolo; Boix, Jacint

    2015-01-01

    Aerobic metabolism of mammalian cells leads to the generation of reactive oxygen species (ROS). To cope with this toxicity, evolution provided cells with effective antioxidant systems like glutathione. Current anticancer therapies focus on the cancer dependence on oncogenes and non-oncogenes. Tumors trigger mechanisms to circumvent the oncogenic stress and to escape cell death. In this context we have studied 2-phenylethinesulfoxamine (PES), which disables the cell protective mechanisms to confront the proteotoxicity of damaged and unfolded proteins. Proteotoxic stress is increased in tumor cells, thus providing an explanation for the anticancer selectivity of PES. In addition, we have found that PES induces a severe oxidative stress and the activation of p53. The reduction of the cell content in glutathione by means of L-buthionine-sulfoximine (BSO) synergizes with PES. In conclusion, we have found that ROS constitutes a central element in a series of positive feed-back loops in the cell. ROS, p53, proteotoxicity, autophagy and mitochondrial dynamics are interconnected with the mechanisms leading to cell death, either apoptotic or necrotic. This network of interactions provides multiple targets for drug discovery and development in cancer. PMID:25395102

  6. Redox Roles of Reactive Oxygen Species in Cardiovascular Diseases.

    PubMed

    He, Feng; Zuo, Li

    2015-01-01

    Cardiovascular disease (CVD), a major cause of mortality in the world, has been extensively studied over the past decade. However, the exact mechanism underlying its pathogenesis has not been fully elucidated. Reactive oxygen species (ROS) play a pivotal role in the progression of CVD. Particularly, ROS are commonly engaged in developing typical characteristics of atherosclerosis, one of the dominant CVDs. This review will discuss the involvement of ROS in atherosclerosis, specifically their effect on inflammation, disturbed blood flow and arterial wall remodeling. Pharmacological interventions target ROS in order to alleviate oxidative stress and CVD symptoms, yet results are varied due to the paradoxical role of ROS in CVD. Lack of effectiveness in clinical trials suggests that understanding the exact role of ROS in the pathophysiology of CVD and developing novel treatments, such as antioxidant gene therapy and nanotechnology-related antioxidant delivery, could provide a therapeutic advance in treating CVDs. While genetic therapies focusing on specific antioxidant expression seem promising in CVD treatments, multiple technological challenges exist precluding its immediate clinical applications. PMID:26610475

  7. Reactive Oxygen Species and the Brain in Sleep Apnea

    PubMed Central

    Wang, Yang; Zhang, Shelley XL; Gozal, David

    2010-01-01

    Rodents exposed to intermittent hypoxia (IH), a model of obstructive sleep apnea (OSA), manifest impaired learning and memory and somnolence. Increased levels of reactive oxygen species (ROS), oxidative tissue damage, and apoptotic neuronal cell death are associated with the presence of IH-induced CNS dysfunction. Furthermore, treatment with antioxidants or overexpression of antioxidant enzymes is neuroprotective during IH. These findings mimic clinical cases of OSA and suggest that ROS may play a key causal role in OSA-induced neuropathology. Controlled production of ROS occurs in multiple subcellular compartments of normal cells and de-regulation of such processes may result in excessive ROS production. The mitochondrial electron transport chain, especially complexes I and III, and the NADPH oxidase in the cellular membrane are the two main sources of ROS in brain cells, although other systems, including xanthine oxidase, phospholipase A2, lipoxygenase, cyclooxygenase, and cytochrome P450, may all play a role. The initial evidence for NADPH oxidase and mitochondrial involvement in IH-induced ROS production and neuronal injury unquestionably warrants future research efforts. PMID:20833273

  8. Reactive Oxygen Species (ROS) generation by lunar simulants

    NASA Astrophysics Data System (ADS)

    Kaur, Jasmeet; Rickman, Douglas; Schoonen, Martin A.

    2016-05-01

    The current interest in human exploration of the Moon and past experiences of Apollo astronauts has rekindled interest into the possible harmful effects of lunar dust on human health. In comparison to the Apollo-era explorations, human explorers may be weeks on the Moon, which will raise the risk of inhalation exposure. The mineralogical composition of lunar dust is well documented, but its effects on human health are not fully understood. With the aim of understanding the reactivity of dusts that may be encountered on geologically different lunar terrains, we have studied Reactive Oxygen Species (ROS) generation by a suite of lunar simulants of different mineralogical-chemical composition dispersed in water and Simulated Lung Fluid (SLF). To further explore the reactivity of simulants under lunar environmental conditions, we compared the reactivity of simulants both in air and inert atmosphere. As the impact of micrometeorites with consequent shock-induced stresses is a major environmental factor on the Moon, we also studied the effect of mechanical stress on samples. Mechanical stress was induced by hand crushing the samples both in air and inert atmosphere. The reactivity of samples after crushing was analyzed for a period of up to nine days. Hydrogen peroxide (H2O2) in water and SLF was analyzed by an in situ electrochemical probe and hydroxyl radical (•OH) by Electron Spin Resonance (ESR) spectroscopy and Adenine probe. Out of all simulants, CSM-CL-S was found to be the most reactive simulant followed by OB-1 and then JSC-1A simulant. The overall reactivity of samples in the inert atmosphere was higher than in air. Fresh crushed samples showed a higher level of reactivity than uncrushed samples. Simulant samples treated to create agglutination, including the formation of zero-valent iron, showed less reactivity than untreated simulants. ROS generation in SLF is initially slower than in deionized water (DI), but the ROS formation is sustained for as long as 7

  9. A case of mistaken identity: are reactive oxygen species actually reactive sulfide species?

    PubMed

    DeLeon, Eric R; Gao, Yan; Huang, Evelyn; Arif, Maaz; Arora, Nitin; Divietro, Alexander; Patel, Shivali; Olson, Kenneth R

    2016-04-01

    Stepwise one-electron reduction of oxygen to water produces reactive oxygen species (ROS) that are chemically and biochemically similar to reactive sulfide species (RSS) derived from one-electron oxidations of hydrogen sulfide to elemental sulfur. Both ROS and RSS are endogenously generated and signal via protein thiols. Given the similarities between ROS and RSS, we wondered whether extant methods for measuring the former would also detect the latter. Here, we compared ROS to RSS sensitivity of five common ROS methods: redox-sensitive green fluorescent protein (roGFP), 2', 7'-dihydrodichlorofluorescein, MitoSox Red, Amplex Red, and amperometric electrodes. All methods detected RSS and were as, or more, sensitive to RSS than to ROS. roGFP, arguably the "gold standard" for ROS measurement, was more than 200-fold more sensitive to the mixed polysulfide H2Sn(n = 1-8) than to H2O2 These findings suggest that RSS may be far more prevalent in intracellular signaling than previously appreciated and that the contribution of ROS may be overestimated. This conclusion is further supported by the observation that estimated daily sulfur metabolism and ROS production are approximately equal and the fact that both RSS and antioxidant mechanisms have been present since the origin of life, nearly 4 billion years ago, long before the rise in environmental oxygen 600 million years ago. Although ROS are assumed to be the most biologically relevant oxidants, our results question this paradigm. We also anticipate our findings will direct attention toward development of novel and clinically relevant anti-(RSS)-oxidants. PMID:26764057

  10. Involvement of Cytochrome P450 in Reactive Oxygen Species Formation and Cancer.

    PubMed

    Hrycay, Eugene G; Bandiera, Stelvio M

    2015-01-01

    This review examines the involvement of cytochrome P450 (CYP) enzymes in the formation of reactive oxygen species in biological systems and discusses the possible involvement of reactive oxygen species and CYP enzymes in cancer. Reactive oxygen species are formed in biological systems as byproducts of the reduction of molecular oxygen and include the superoxide radical anion (∙O2-), hydrogen peroxide (H2O2), hydroxyl radical (∙OH), hydroperoxyl radical (HOO∙), singlet oxygen ((1)O2), and peroxyl radical (ROO∙). Two endogenous sources of reactive oxygen species are the mammalian CYP-dependent microsomal electron transport system and the mitochondrial electron transport chain. CYP enzymes catalyze the oxygenation of an organic substrate and the simultaneous reduction of molecular oxygen. If the transfer of oxygen to a substrate is not tightly controlled, uncoupling occurs and leads to the formation of reactive oxygen species. Reactive oxygen species are capable of causing oxidative damage to cellular membranes and macromolecules that can lead to the development of human diseases such as cancer. In normal cells, intracellular levels of reactive oxygen species are maintained in balance with intracellular biochemical antioxidants to prevent cellular damage. Oxidative stress occurs when this critical balance is disrupted. Topics covered in this review include the role of reactive oxygen species in intracellular cell signaling and the relationship between CYP enzymes and cancer. Outlines of CYP expression in neoplastic tissues, CYP enzyme polymorphism and cancer risk, CYP enzymes in cancer therapy and the metabolic activation of chemical procarcinogens by CYP enzymes are also provided. PMID:26233903

  11. Hyperbaric Oxygen Promotes Proximal Bone Regeneration and Organized Collagen Composition during Digit Regeneration

    PubMed Central

    Sammarco, Mimi C.; Simkin, Jennifer; Cammack, Alexander J.; Fassler, Danielle; Gossmann, Alexej; Marrero, Luis; Lacey, Michelle; Van Meter, Keith; Muneoka, Ken

    2015-01-01

    Oxygen is critical for optimal bone regeneration. While axolotls and salamanders have retained the ability to regenerate whole limbs, mammalian regeneration is restricted to the distal tip of the digit (P3) in mice, primates, and humans. Our previous study revealed the oxygen microenvironment during regeneration is dynamic and temporally influential in building and degrading bone. Given that regeneration is dependent on a dynamic and changing oxygen environment, a better understanding of the effects of oxygen during wounding, scarring, and regeneration, and better ways to artificially generate both hypoxic and oxygen replete microenvironments are essential to promote regeneration beyond wounding or scarring. To explore the influence of increased oxygen on digit regeneration in vivo daily treatments of hyperbaric oxygen were administered to mice during all phases of the entire regenerative process. Micro-Computed Tomography (μCT) and histological analysis showed that the daily application of hyperbaric oxygen elicited the same enhanced bone degradation response as two individual pulses of oxygen applied during the blastema phase. We expand past these findings to show histologically that the continuous application of hyperbaric oxygen during digit regeneration results in delayed blastema formation at a much more proximal location after amputation, and the deposition of better organized collagen fibers during bone formation. The application of sustained hyperbaric oxygen also delays wound closure and enhances bone degradation after digit amputation. Thus, hyperbaric oxygen shows the potential for positive influential control on the various phases of an epimorphic regenerative response. PMID:26452224

  12. Reactive Oxygen Species in the Paraventricular Nucleus of the Hypothalamus Alter Sympathetic Activity During Metabolic Syndrome

    PubMed Central

    Cruz, Josiane C.; Flôr, Atalia F. L.; França-Silva, Maria S.; Balarini, Camille M.; Braga, Valdir A.

    2015-01-01

    The paraventricular nucleus of the hypothalamus (PVN) contains heterogeneous populations of neurons involved in autonomic and neuroendocrine regulation. The PVN plays an important role in the sympathoexcitatory response to increasing circulating levels of angiotensin II (Ang-II), which activates AT1 receptors in the circumventricular organs (OCVs), mainly in the subfornical organ (SFO). Circulating Ang-II induces a de novo synthesis of Ang-II in SFO neurons projecting to pre-autonomic PVN neurons. Activation of AT1 receptors induces intracellular increases in reactive oxygen species (ROS), leading to increases in sympathetic nerve activity (SNA). Chronic sympathetic nerve activation promotes a series of metabolic disorders that characterizes the metabolic syndrome (MetS): dyslipidemia, hyperinsulinemia, glucose intolerance, hyperleptinemia and elevated plasma hormone levels, such as noradrenaline, glucocorticoids, leptin, insulin, and Ang-II. This review will discuss the contribution of our laboratory and others regarding the sympathoexcitation caused by peripheral Ang-II-induced reactive oxygen species along the subfornical organ and paraventricular nucleus of the hypothalamus. We hypothesize that this mechanism could be involved in metabolic disorders underlying MetS. PMID:26779026

  13. Formation of reactive oxygen species in rat epithelial cells upon stimulation with fly ash.

    PubMed

    Voelkel, K; Krug, H F; Diabaté, S

    2003-02-01

    Fly ash was used as a model for ambient particulate matter which is under suspicion to cause adverse pulmonary health effects. The fly ash was pre-sized and contained only particles < 20 microm including an ultrafine fraction (< 100 nm) that contributed 31% to the particle number. In our study, we investigated the influence of fly ash on the promotion of early inflammatory reactions like the formation of reactive oxygen species (ROS) in rat lung epithelial cells (RLE-6TN). Furthermore, we determined the formation of nitric oxide (NO). The cells show a clear dose-response relationship concerning the formation of ROS with regard to the mass of particles applied. Lipopolysaccharide (LPS) added as a co-stimulus did not increase the formation of ROS induced by fly ash. Furthermore, in LPS (0.1 microg/ml) and tumour necrosis factor-alpha (TNF-alpha; 1 ng/ml) pre-treated cells no increase in reactive oxygen species comparable to fly ash alone is observable. In presence of the metal chelator, desferrioxamine (DFO), ROS formation can be significantly reduced. Neither fly ash nor LPS induced a significant NO release in RLE-6TN cells. PMID:12682424

  14. Tree species richness promotes productivity in temperate forests through strong complementarity between species.

    PubMed

    Morin, Xavier; Fahse, Lorenz; Scherer-Lorenzen, Michael; Bugmann, Harald

    2011-12-01

    Understanding the link between biodiversity and ecosystem functioning (BEF) is pivotal in the context of global biodiversity loss. Yet, long-term effects have been explored only weakly, especially for forests, and no clear evidence has been found regarding the underlying mechanisms. We explore the long-term relationship between diversity and productivity using a forest succession model. Extensive simulations show that tree species richness promotes productivity in European temperate forests across a large climatic gradient, mostly through strong complementarity between species. We show that this biodiversity effect emerges because increasing species richness promotes higher diversity in shade tolerance and growth ability, which results in forests responding faster to small-scale mortality events. Our study generalises results from short-term experiments in grasslands to forest ecosystems and demonstrates that competition for light alone induces a positive effect of biodiversity on productivity, thus providing a new angle for explaining BEF relationships. PMID:21955682

  15. Growth enhancement and gene expression of Arabidopsis thaliana irradiated with active oxygen species

    NASA Astrophysics Data System (ADS)

    Watanabe, Satoshi; Ono, Reoto; Hayashi, Nobuya; Shiratani, Masaharu; Tashiro, Kosuke; Kuhara, Satoru; Inoue, Asami; Yasuda, Kaori; Hagiwara, Hiroko

    2016-07-01

    The characteristics of plant growth enhancement effect and the mechanism of the enhancement induced by plasma irradiation are investigated using various active species in plasma. Active oxygen species in oxygen plasma are effective for growth enhancement of plants. DNA microarray analysis of Arabidopsis thaliana indicates that the genes coding proteins that counter oxidative stresses by eliminating active oxygen species are expressed at significantly high levels. The size of plant cells increases owing to oxygen plasma irradiation. The increases in gene expression levels and cell size suggest that the increase in the expression level of the expansin protein is essential for plant growth enhancement phenomena.

  16. Reactive Oxygen Species Alter Autocrine and Paracrine Signaling

    SciTech Connect

    Zangar, Richard C.; Bollinger, Nikki; Weber, Thomas J.; Tan, Ruimin; Markillie, Lye Meng; Karin, Norman J.

    2011-12-01

    Cytochrome P450 (P450) 3A4 (CYP3A4) is the most abundant P450 protein in human liver and intestine and is highly inducible by a variety of drugs and other compounds. The P450 catalytic cycle is known to uncouple and release reactive oxygen species (ROS), but the effects of ROS from P450 and other enzymes in the endo-plasmic reticulum have been poorly studied from the perspective of effects on cell biology. In this study, we expressed low levels of CYP3A4 in HepG2 cells, a human hepatocarcinoma cell line, and examined effects on intracellular levels of ROS and on the secretion of a variety of growth factors that are important in extracellular communication. Using the redox-sensitive dye RedoxSensor red, we demonstrate that CYP3A4 expression increases levels of ROS in viable cells. A customELISA microarray platform was employed to demonstrate that expression of CYP3A4 increased secretion of amphiregulin, intracellular adhesion molecule 1, matrix metalloprotease 2, platelet-derived growth factor (PDGF), and vascular endothelial growth factor, but suppressed secretion of CD14. The antioxidant N-acetylcysteine suppressed all P450-dependent changes in protein secretion except for CD14. Quantitative RT-PCR demonstrated that changes in protein secretion were consistently associated with corresponding changes in gene expression. Inhibition of the NF-{kappa}B pathway blocked P450 effects on PDGF secretion. CYP3A4 expression also altered protein secretion in human mammary epithelial cells and C10 mouse lung cells. Overall, these results suggest that increased ROS production in the endoplasmic reticulum alters the secretion of proteins that have key roles in paracrine and autocrine signaling.

  17. Are mitochondrial reactive oxygen species required for autophagy?

    SciTech Connect

    Jiang, Jianfei; Maeda, Akihiro; Ji, Jing; Baty, Catherine J.; Watkins, Simon C.; Greenberger, Joel S.; Kagan, Valerian E.

    2011-08-19

    Highlights: {yields} Autophageal and apoptotic pathways were dissected in cytochrome c deficient cells. {yields} Staurosporine (STS)-induced autophagy was not accompanied by ROS generation. {yields} Autophagy was detectable in mitochondrial DNA deficient {rho}{sup 0} cells. {yields} Mitochondrial ROS are not required for the STS-induced autophagy in HeLa cells. -- Abstract: Reactive oxygen species (ROS) are said to participate in the autophagy signaling. Supporting evidence is obscured by interference of autophagy and apoptosis, whereby the latter heavily relies on ROS signaling. To dissect autophagy from apoptosis we knocked down expression of cytochrome c, the key component of mitochondria-dependent apoptosis, in HeLa cells using shRNA. In cytochrome c deficient HeLa1.2 cells, electron transport was compromised due to the lack of electron shuttle between mitochondrial respiratory complexes III and IV. A rapid and robust LC3-I/II conversion and mitochondria degradation were observed in HeLa1.2 cells treated with staurosporine (STS). Neither generation of superoxide nor accumulation of H{sub 2}O{sub 2} was detected in STS-treated HeLa1.2 cells. A membrane permeable antioxidant, PEG-SOD, plus catalase exerted no effect on STS-induced LC3-I/II conversion and mitochondria degradation. Further, STS caused autophagy in mitochondria DNA-deficient {rho}{sup o} HeLa1.2 cells in which both electron transport and ROS generation were completely disrupted. Counter to the widespread view, we conclude that mitochondrial ROS are not required for the induction of autophagy.

  18. Development of fluorometric reactive oxygen species assay for photosafety evaluation.

    PubMed

    Seto, Yoshiki; Ohtake, Hiroto; Kato, Masashi; Onoue, Satomi

    2016-08-01

    The present investigation involved an attempt to develop a new reactive oxygen species (ROS) assay system for the photosafety assessment of chemicals using 1,3-diphenylisobenzofuran (DPBF), a fluorescent probe for monitoring ROS generation. The assay conditions of the fluorometric ROS (fROS) assay were optimized focusing on the solvent system, concentration of DPBF, fluorescent determination, screening run time and reproducibility. The photoreactivity of 21 phototoxic and 11 non-phototoxic compounds was assessed by fROS assay, and the obtained ROS data were compared with the results from a micellar ROS (mROS) assay and in vitro/in vivo phototoxicity information to confirm the predictive capacity of the fROS assay. In the optimized fROS assay, intra-day and inter-day precision levels (coefficient of variation) were found to be below 5%, and the Z'-factor for DPBF fluorescence quenching showed a large separation between positive and negative controls. Of all tested compounds, 3 false positive and 7 false negative predictions were observed in the fROS assay, and the negative predictivity for the fROS assay was found to be lower than that for the mROS assay. Although the fROS assay has some limitations, the procedures for it were highly simplified with a marked reduction in screening run time and one analytical sample for monitoring ROS generation from compounds. The fROS assay has the potential to become a new tool for photosafety assessment at an early stage of product development. PMID:27058001

  19. Reactive oxygen species generated from skeletal muscles are required for gecko tail regeneration.

    PubMed

    Zhang, Qing; Wang, Yingjie; Man, Lili; Zhu, Ziwen; Bai, Xue; Wei, Sumei; Liu, Yan; Liu, Mei; Wang, Xiaochuan; Gu, Xiaosong; Wang, Yongjun

    2016-01-01

    Reactive oxygen species (ROS) participate in various physiological and pathological functions following generation from different types of cells. Here we explore ROS functions on spontaneous tail regeneration using gecko model. ROS were mainly produced in the skeletal muscle after tail amputation, showing a temporal increase as the regeneration proceeded. Inhibition of the ROS production influenced the formation of autophagy in the skeletal muscles, and as a consequence, the length of the regenerating tail. Transcriptome analysis has shown that NADPH oxidase (NOX2) and the subunits (p40(phox) and p47(phox)) are involved in the ROS production. ROS promoted the formation of autophagy through regulation of both ULK and MAPK activities. Our results suggest that ROS produced by skeletal muscles are required for the successful gecko tail regeneration. PMID:26853930

  20. The regulatory roles of ethylene and reactive oxygen species (ROS) in plant salt stress responses.

    PubMed

    Zhang, Ming; Smith, J Andrew C; Harberd, Nicholas P; Jiang, Caifu

    2016-08-01

    Soil salinity is one of the most commonly encountered environmental stresses affecting plant growth and crop productivity. Accordingly, plants have evolved a variety of morphological, physiological and biochemical strategies that enable them to adapt to saline growth conditions. For example, it has long been known that salinity-stress increases both the production of the gaseous stress hormone ethylene and the in planta accumulation of reactive oxygen species (ROS). Recently, there has been significant progress in understanding how the fine-tuning of ethylene biosynthesis and signaling transduction can promote salinity tolerance, and how salinity-induced ROS accumulation also acts as a signal in the mediation of salinity tolerance. Furthermore, recent advances have indicated that ethylene signaling modulates salinity responses largely via regulation of ROS-generating and ROS-scavenging mechanisms. This review focuses on these recent advances in understanding the linked roles of ethylene and ROS in salt tolerance. PMID:27233644

  1. Mitochondrial reactive oxygen species regulate the strength of inhibitory GABA-mediated synaptic transmission

    PubMed Central

    Accardi, Michael V.; Daniels, Bryan A.; Brown, Patricia M.G.E.; Fritschy, Jean-Marc; Tyagarajan, Shiva K.; Bowie, Derek

    2016-01-01

    Neuronal communication imposes a heavy metabolic burden in maintaining ionic gradients essential for action potential firing and synaptic signaling. Although cellular metabolism is known to regulate excitatory neurotransmission, it is still unclear whether the brain’s energy supply affects inhibitory signaling. Here we show that mitochondrial-derived reactive oxygen species (mROS) regulate the strength of postsynaptic GABAA receptors at inhibitory synapses of cerebellar stellate cells. Inhibition is strengthened through a mechanism that selectively recruits α3-containing GABAA receptors into synapses with no discernible effect on resident α1-containing receptors. Since mROS promotes the emergence of postsynaptic events with unique kinetic properties, we conclude that newly-recruited α3-containing GABAA receptors are activated by neurotransmitter released onto discrete postsynaptic sites. Although traditionally associated with oxidative stress in neurodegenerative disease, our data identifies mROS as a putative homeostatic signaling molecule coupling cellular metabolism to the strength of inhibitory transmission. PMID:24430741

  2. Reactive oxygen species generated from skeletal muscles are required for gecko tail regeneration

    PubMed Central

    Zhang, Qing; Wang, Yingjie; Man, Lili; Zhu, Ziwen; Bai, Xue; Wei, Sumei; Liu, Yan; Liu, Mei; Wang, Xiaochuan; Gu, Xiaosong; Wang, Yongjun

    2016-01-01

    Reactive oxygen species (ROS) participate in various physiological and pathological functions following generation from different types of cells. Here we explore ROS functions on spontaneous tail regeneration using gecko model. ROS were mainly produced in the skeletal muscle after tail amputation, showing a temporal increase as the regeneration proceeded. Inhibition of the ROS production influenced the formation of autophagy in the skeletal muscles, and as a consequence, the length of the regenerating tail. Transcriptome analysis has shown that NADPH oxidase (NOX2) and the subunits (p40phox and p47phox) are involved in the ROS production. ROS promoted the formation of autophagy through regulation of both ULK and MAPK activities. Our results suggest that ROS produced by skeletal muscles are required for the successful gecko tail regeneration. PMID:26853930

  3. Mitochondrial reactive oxygen species regulate the strength of inhibitory GABA-mediated synaptic transmission

    NASA Astrophysics Data System (ADS)

    Accardi, Michael V.; Daniels, Bryan A.; Brown, Patricia M. G. E.; Fritschy, Jean-Marc; Tyagarajan, Shiva K.; Bowie, Derek

    2014-01-01

    Neuronal communication imposes a heavy metabolic burden in maintaining ionic gradients essential for action potential firing and synaptic signalling. Although cellular metabolism is known to regulate excitatory neurotransmission, it is still unclear whether the brain’s energy supply affects inhibitory signalling. Here we show that mitochondrial-derived reactive oxygen species (mROS) regulate the strength of postsynaptic GABAA receptors at inhibitory synapses of cerebellar stellate cells. Inhibition is strengthened through a mechanism that selectively recruits α3-containing GABAA receptors into synapses with no discernible effect on resident α1-containing receptors. Since mROS promotes the emergence of postsynaptic events with unique kinetic properties, we conclude that newly recruited α3-containing GABAA receptors are activated by neurotransmitter released onto discrete postsynaptic sites. Although traditionally associated with oxidative stress in neurodegenerative disease, our data identify mROS as a putative homeostatic signalling molecule coupling cellular metabolism to the strength of inhibitory transmission.

  4. Effects of the Oxygenation level on Formation of Different Reactive Oxygen Species During Photodynamic Therapy

    PubMed Central

    Price, Michael; Heilbrun, Lance; Kessel, David

    2012-01-01

    We examined the effect of the oxygenation level on efficacy of two photosensitizing agents, both of which target lysosomes for photodamage but via different photochemical pathways. Upon irradiation, the chlorin termed NPe6 forms singlet oxygen in high yield while the bacteriopheophorbide WST11 forms only oxygen radicals (in an aqueous environment). Photokilling efficacy by WST11 in cell culture was impaired when the atmospheric oxygen concentration was reduced from 20% to 1%, while photokilling by NPe6 was unaffected. Studies in a cell-free system revealed that rates of photobleaching of these agents, as a function of the oxygenation level, were correlated with results described above. Moreover, the rate of formation of oxygen radicals by either agent was more sensitive to the level of oxygenation than was singlet oxygen formation by NPe6. These data indicate that the photochemical process that leads to oxygen radical formation is more dependent on the oxygenation level than is the pathway leading to formation of singlet oxygen. PMID:23216021

  5. Reactive Oxygen Species are involved in BMP-Induced Dendritic Growth in Cultured Rat Sympathetic Neurons

    PubMed Central

    Chandrasekaran, Vidya; Lea, Charlotte; Sosa, Jose Carlo; Higgins, Dennis; Lein, Pamela J.

    2015-01-01

    Previous studies have shown that bone morphogenetic proteins (BMPs) promote dendritic growth in sympathetic neurons; however, the downstream signaling molecules that mediate the dendrite promoting activity of BMPs are not well characterized. Here we test the hypothesis that reactive oxygen species (ROS)-mediated signaling links BMP receptor activation to dendritic growth. In cultured rat sympathetic neurons, exposure to any of three mechanistically distinct antioxidants, diphenylene iodinium (DPI), nordihydroguiaretic acid (NGA) or desferroxamine (DFO), blocked de novo BMP-induced dendritic growth. Addition of DPI to cultures previously induced with BMP to extend dendrites caused dendritic retraction while DFO and NGA prevented further growth of dendrites. The inhibition of the dendrite promoting activity of BMPs by antioxidants was concentration-dependent and occurred without altering axonal growth or neuronal cell survival. Antioxidant treatment did not block BMP activation of SMAD 1,5 as determined by nuclear localization of these SMADs. While BMP treatment did not cause a detectable increase in intracellular ROS in cultured sympathetic neurons as assessed using fluorescent indicator dyes, BMP treatment increased the oxygen consumption rate in cultured sympathetic neurons as determined using the Seahorse XF24 Analyzer, suggesting increased mitochondrial activity. In addition, BMPs upregulated expression of NADPH oxidase 2 (NOX2) and either pharmacological inhibition or siRNA knockdown of NOX2 significantly decreased BMP-7 induced dendritic growth. Collectively, these data support the hypothesis that ROS are involved in the downstream signaling events that mediate BMP7-induced dendritic growth in sympathetic neurons, and suggest that ROS-mediated signaling positively modulates dendritic complexity in peripheral neurons. PMID:26079955

  6. Hyperbaric oxygen therapy promotes neurogenesis: where do we stand?

    PubMed Central

    2011-01-01

    Neurogenesis in adults, initiated by injury to the central nervous system (CNS) presents an autologous repair mechanism. It has been suggested that hyperbaric oxygen therapy (HBOT) enhances neurogenesis which accordingly may improve functional outcome after CNS injury. In this present article we aim to review experimental as well as clinical studies on the subject of HBOT and neurogenesis. We demonstrate hypothetical mechanism of HBOT on cellular transcription factors including hypoxia-inducible factors (HIFs) and cAMP response element binding (CREB). We furthermore reveal the discrepancy between experimental findings and clinical trials in regards of HBOT. Further translational preclinical studies followed by improved clinical trials are needed to elucidate potential benefits of HBOT. PMID:22146131

  7. KRIT1 Regulates the Homeostasis of Intracellular Reactive Oxygen Species

    PubMed Central

    Goitre, Luca; Balzac, Fiorella; Degani, Simona; Degan, Paolo; Marchi, Saverio; Pinton, Paolo; Retta, Saverio Francesco

    2010-01-01

    KRIT1 is a gene responsible for Cerebral Cavernous Malformations (CCM), a major cerebrovascular disease characterized by abnormally enlarged and leaky capillaries that predispose to seizures, focal neurological deficits, and fatal intracerebral hemorrhage. Comprehensive analysis of the KRIT1 gene in CCM patients has suggested that KRIT1 functions need to be severely impaired for pathogenesis. However, the molecular and cellular functions of KRIT1 as well as CCM pathogenesis mechanisms are still research challenges. We found that KRIT1 plays an important role in molecular mechanisms involved in the maintenance of the intracellular Reactive Oxygen Species (ROS) homeostasis to prevent oxidative cellular damage. In particular, we demonstrate that KRIT1 loss/down-regulation is associated with a significant increase in intracellular ROS levels. Conversely, ROS levels in KRIT1−/− cells are significantly and dose-dependently reduced after restoration of KRIT1 expression. Moreover, we show that the modulation of intracellular ROS levels by KRIT1 loss/restoration is strictly correlated with the modulation of the expression of the antioxidant protein SOD2 as well as of the transcriptional factor FoxO1, a master regulator of cell responses to oxidative stress and a modulator of SOD2 levels. Furthermore, we show that the KRIT1-dependent maintenance of low ROS levels facilitates the downregulation of cyclin D1 expression required for cell transition from proliferative growth to quiescence. Finally, we demonstrate that the enhanced ROS levels in KRIT1−/− cells are associated with an increased cell susceptibility to oxidative DNA damage and a marked induction of the DNA damage sensor and repair gene Gadd45α, as well as with a decline of mitochondrial energy metabolism. Taken together, our results point to a new model where KRIT1 limits the accumulation of intracellular oxidants and prevents oxidative stress-mediated cellular dysfunction and DNA damage by enhancing the

  8. Regenerable MgO promoted metal oxide oxygen carriers for chemical looping combustion

    DOEpatents

    Siriwardane, Ranjani V.; Miller, Duane D.

    2014-08-19

    The disclosure provides an oxygen carrier comprised of a plurality of metal oxide particles in contact with a plurality of MgO promoter particles. The MgO promoter particles increase the reaction rate and oxygen utilization of the metal oxide when contacting with a gaseous hydrocarbon at a temperature greater than about 725.degree. C. The promoted oxide solid is generally comprised of less than about 25 wt. % MgO, and may be prepared by physical mixing, incipient wetness impregnation, or other methods known in the art. The oxygen carrier exhibits a crystalline structure of the metal oxide and a crystalline structure of MgO under XRD crystallography, and retains these crystalline structures over subsequent redox cycles. In an embodiment, the metal oxide is Fe.sub.2O.sub.3, and the gaseous hydrocarbon is comprised of methane.

  9. Blood radicals: reactive nitrogen species, reactive oxygen species, transition metal ions, and the vascular system.

    PubMed

    Darley-Usmar, V; Halliwell, B

    1996-05-01

    Free radicals, such as superoxide, hydroxyl and nitric oxide, and other "reactive species", such as hydrogen peroxide, hypochlorous acid and peroxynitrite, are formed in vivo. Some of these molecules, e.g. superoxide and nitric oxide, can be physiologically useful, but they can also cause damage under certain circumstances. Excess production of reactive oxygen or nitrogen species (ROS, RNS), their production in inappropriate relative amounts (especially superoxide and NO) or deficiencies in antioxidant defences may result in pathological stress to cells and tissues. This oxidative stress can have multiple effects. It can induce defence systems, and render tissues more resistant to subsequent insult. If oxidative stress is excessive or if defence and repair responses are inadequate, cell injury can be caused by such mechanisms as oxidative damage to essential proteins, lipid peroxidation, DNA strand breakage and base modification, and rises in the concentration of intracellular "free" Ca(2+). Considerable evidence supports the view that oxidative damage involving both ROS and RNS is an important contributor to the development of atherosclerosis. Peroxynitrite (derived by reaction of superoxide with nitric oxide) and transition metal ions (perhaps released by injury to the vessel wall) may contribute to lipid peroxidation in atherosclerotic lesions. PMID:8860419

  10. Reactive oxygen species scavenging activity of Jixueteng evaluated by electron spin resonance (ESR) and photon emission.

    PubMed

    Toyama, Toshizo; Wada-Takahashi, Satoko; Takamichi, Maomi; Watanabe, Kiyoko; Yoshida, Ayaka; Yoshino, Fumihiko; Miyamoto, Chihiro; Maehata, Yojiro; Sugiyama, Shuta; Takahashi, Shun-Suke; Todoki, Kazuo; Lee, Masaichi-Chang-Il; Hamada, Nobushiro

    2014-12-01

    Jixueteng, the dried stem of Spatholobus suberectus Dunn (Leguminosae), is a traditional Chinese herbal medicine that is commonly classified as a herb that promotes blood circulation and can be used to treat blood stasis. The aim of this study was to examine the reactive oxygen species (ROS) scavenging activity of Jixueteng and other herbal medicines. The ROS scavenging activities of the water extracts of Jixueteng, Cnidium officinale and Salvia miltiorrhiza were examined using an electron spin resonance (ESR) technique and faint luminescence measurement. The ESR signal intensities of the superoxide anion (O2·) and hydroxyl radical (HO·) were reduced more by Jixueteng than the other herbal medicines we tested. High photon emission intensity to hydrogen peroxide (H202) and HO· was observed in Jixueteng using the XYZ chemiluminescence system that was used as faint luminescence measurement and analysis. The results of the present study revealed that the ROS scavenging activity of 8% Jixueteng was the strongest among the herbal medicines we tested. It has been reported that Jixueteng includes various polyphenols. In the ROS scavenging activity by Jixueteng, it is supposed that the antioxidant activity caused by these polyphenols would contribute greatly. In conclusion, a water extract component of Jixueteng had potent free radical scavenging activity and an antioxidative effect that inhibited the oxidative actions of O2·⁻, H2O2 and HO·. Therefore, Jixueteng represents a promising therapeutic drug for reactive oxygen-associated pathologies. PMID:25632478

  11. Reactive oxygen species controllable non-thermal helium plasmas for evaluation of plasmid DNA strand breaks

    NASA Astrophysics Data System (ADS)

    Young Kim, Jae; Lee, Dong-Hoon; Ballato, John; Cao, Weiguo; Kim, Sung-O.

    2012-11-01

    Non-thermal, oxygen-rich helium plasmas were investigated to achieve an enhanced reactive oxygen species concentration at low voltage driving conditions. A non-thermal plasma device was fabricated based on a theta-shaped tube, and its potential was investigated for use in topological alteration of plasmid DNA. The optical emission spectra of the plasma showed that the oxygen flow affected the plasma properties, even though an oxygen plasma was not produced. The plasmid DNA strand breaks became more significant with the addition of oxygen flow to the helium in a single hollow, theta-shaped tube with other experimental conditions being unchanged.

  12. Quantitative assessment of reactive oxygen species generation by cavitation incepted efficiently using nonlinear propagation effect

    NASA Astrophysics Data System (ADS)

    Yasuda, Jun; Yoshizawa, Shin; Umemura, Shin-ichiro

    2015-10-01

    Sonodynamic treatment is a treatment method that uses chemical bio-effect of cavitation bubbles. Reactive oxygen species that can kill cancerous tissue is induced by such chemical effect of cavitation bubbles and it is important to generate them efficiently for effective sonodynamic treatment. Cavitation cloud can be formed by an effect of nonlinear propagation and focus and in this study, it was experimentally investigated if cavitation cloud was useful for efficient generation of reactive oxygen species. As a result, it was demonstrated that cavitation cloud would be useful for efficient generation of reactive oxygen species.

  13. Frequency effects on the production of reactive oxygen species in atmospheric radio frequency helium-oxygen discharges

    SciTech Connect

    Zhang, Yuantao T.; He Jin

    2013-01-15

    Several experimental and computational studies have shown that increasing frequency can effectively enhance the discharge stability in atmospheric radio-frequency (rf) discharges, but the frequency effects on the reactivity of rf discharges, represented by the densities of reactive oxygen species (ROS), are still far from fully understood. In this paper, a one-dimensional fluid model with 17 species and 65 reactions taken into account is used to explore the influences of the driving frequency on the production and destruction of ROS in atmospheric rf helium-oxygen discharges. From the computational results, with an increase in the frequency the densities of ROS decrease always at a constant power density, however, in the relatively higher frequency discharges the densities of ROS can be effectively improved by increasing the input power density with an expanded oxygen admixture range, while the discharges operate in the {alpha} mode, and the numerical data also show the optimal oxygen admixture for ground state atomic oxygen, at which the peak atomic oxygen density can be obtained, increases with the driving frequency.

  14. Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes

    SciTech Connect

    Radogna, Flavia; Paternoster, Laura; De Nicola, Milena; Cerella, Claudia; Ammendola, Sergio; Bedini, Annalida; Tarzia, Giorgio; Aquilano, Katia; Ciriolo, Maria; Ghibelli, Lina

    2009-08-15

    Melatonin is a modified tryptophan with potent biological activity, exerted by stimulation of specific plasma membrane (MT1/MT2) receptors, by lower affinity intracellular enzymatic targets (quinone reductase, calmodulin), or through its strong anti-oxidant ability. Scattered studies also report a perplexing pro-oxidant activity, showing that melatonin is able to stimulate production of intracellular reactive oxygen species (ROS). Here we show that on U937 human monocytes melatonin promotes intracellular ROS in a fast (< 1 min) and transient (up to 5-6 h) way. Melatonin equally elicits its pro-radical effect on a set of normal or tumor leukocytes; intriguingly, ROS production does not lead to oxidative stress, as shown by absence of protein carbonylation, maintenance of free thiols, preservation of viability and regular proliferation rate. ROS production is independent from MT1/MT2 receptor interaction, since a) requires micromolar (as opposed to nanomolar) doses of melatonin; b) is not contrasted by the specific MT1/MT2 antagonist luzindole; c) is not mimicked by a set of MT1/MT2 high affinity melatonin analogues. Instead, chlorpromazine, the calmodulin inhibitor shown to prevent melatonin-calmodulin interaction, also prevents melatonin pro-radical effect, suggesting that the low affinity binding to calmodulin (in the micromolar range) may promote ROS production.

  15. Susceptibility of brown adipocytes to pro-inflammatory cytokine toxicity and reactive oxygen species

    PubMed Central

    Rebiger, Lars; Lenzen, Sigurd; Mehmeti, Ilir

    2016-01-01

    Brown adipose tissue (BAT) cells have a very high oxidative capacity. On the other hand, in obesity and obesity-related diabetes, levels of pro-inflammatory cytokines are elevated, which might promote BAT dysfunction and consequently impair carbohydrate metabolism and thereby exacerbate cellular dysfunction and promote diabetes progression. Therefore, the antioxidative enzyme status of a brown adipocyte cell line and its susceptibility towards pro-inflammatory cytokines, which participate in the pathogenesis of diabetes, and reactive oxygen species (ROS) were analysed. Mature brown adipocytes exhibited significantly higher levels of expression of mitochondrially and peroxisomally located antioxidative enzymes compared with non-differentiated brown adipocytes. Pro-inflammatory cytokines induced a significant decrease in the viability of differentiated brown adipocytes, which was accompanied by a massive ROS production and down-regulation of BAT-specific markers, such as uncoupling protein 1 (UCP-1) and β-Klotho. Taken together, the results strongly indicate that pro-inflammatory cytokines cause brown adipocyte dysfunction and death through suppression of BAT-specific proteins, especially of UCP-1 and β-Klotho, and consequently increased oxidative stress. PMID:26795216

  16. CCL11 enhances excitotoxic neuronal death by producing reactive oxygen species in microglia.

    PubMed

    Parajuli, Bijay; Horiuchi, Hiroshi; Mizuno, Tetsuya; Takeuchi, Hideyuki; Suzumura, Akio

    2015-12-01

    The chemokine CCL11 (also known as eotaxin-1) is a potent eosinophil chemoattractant that mediates allergic diseases such as asthma, atopic dermatitis, and inflammatory bowel diseases. Previous studies demonstrated that concentrations of CCL11 are elevated in the sera and cerebrospinal fluids (CSF) of patients with neuroinflammatory disorders, including multiple sclerosis. Moreover, the levels of CCL11 in plasma and CSF increase with age, and CCL11 suppresses adult neurogenesis in the central nervous system (CNS), resulting in memory impairment. However, the precise source and function of CCL11 in the CNS are not fully understood. In this study, we found that activated astrocytes release CCL11, whereas microglia predominantly express the CCL11 receptor. CCL11 significantly promoted the migration of microglia, and induced microglial production of reactive oxygen species by upregulating nicotinamide adenine dinucleotide phosphate-oxidase 1 (NOX1), thereby promoting excitotoxic neuronal death. These effects were reversed by inhibition of NOX1. Our findings suggest that CCL11 released from activated astrocytes triggers oxidative stress via microglial NOX1 activation and potentiates glutamate-mediated neurotoxicity, which may be involved in the pathogenesis of various neurological disorders. PMID:26184677

  17. Solar light-induced production of reactive oxygen species by single walled carbon nanotubes in water

    EPA Science Inventory

    Photosensitizing processes of engineered nanomaterials (ENMs) which include photo-induced production of reactive oxygen species (ROS) convert light energy into oxidizing chemical energy that mediates transformations of nanomaterials. The oxidative stress associated with ROS may p...

  18. COMPARATIVE ANALYSIS OF REACTIVE OXYGEN SPECIES IN HUMAN PLASMA AND BLOOD

    EPA Science Inventory

    Reactive oxygen species (ROS) are commonly associated with diseased states (including asthma, cardiovascular disease, cancer) infections, and exposure to various toxicants in humans. It is of interest in epidemiology studies to characterize the association of oxidative stress in...

  19. The Effect of Oxygen Potential on the Sulfide Capacity for Slags Containing Multivalent Species

    NASA Astrophysics Data System (ADS)

    Allertz, Carl; Selleby, Malin; Sichen, Du

    2016-06-01

    The dependence of sulfide capacity on the oxygen partial pressure for slags containing multivalent species was investigated experimentally using a slag containing vanadium oxide. Copper-slag equilibration experiments were carried out at 1873 K (1600 °C) in the approximate oxygen partial pressure range 10-15.4 to 10-9 atm. The sulfide capacity was found to be strongly dependent on the oxygen potential in this slag system, increasing with the oxygen partial pressure. The sulfide capacity changed by more than two orders of magnitude over the oxygen partial pressure range. The effect of changing oxygen partial pressure was found to be much greater than the effect of changing slag composition at a fixed oxygen partial pressure.

  20. Species-level variability in extracellular production rates of reactive oxygen species by diatoms

    NASA Astrophysics Data System (ADS)

    Schneider, Robin; Roe, Kelly; Hansel, Colleen; Voelker, Bettina

    2016-03-01

    Biological production and decay of the reactive oxygen species (ROS) hydrogen peroxide (H2O2) and superoxide (O2-) likely have significant effects on the cycling of trace metals and carbon in marine systems. In this study, extracellular production rates of H2O2 and O2- were determined for five species of marine diatoms in the presence and absence of light. Production of both ROS was measured in parallel by suspending cells on filters and measuring the ROS downstream using chemiluminescence probes. In addition, the ability of these organisms to break down O2- and H2O2 was examined by measuring recovery of O2- and H2O2 added to the influent medium. O2- production rates ranged from undetectable to 7.3 x 10-16 mol cell-1 hr-1, while H2O2 production rates ranged from undetectable to 3.4 x 10-16 mol cell-1 hr-1. Results suggest that extracellular ROS production occurs through a variety of pathways even amongst organisms of the same genus. Thalassiosira spp. produced more O2- in light than dark, even when the organisms were killed, indicating that O2- is produced via a passive photochemical process on the cell surface. The ratio of H2O¬2 to O2- production rates was consistent with production of H2O2 solely through dismutation of O2- for T. oceanica, while T. pseudonana made much more H2O2 than O2 . T. weissflogii only produced H2O2 when stressed or killed. P. tricornutum cells did not make cell-associated ROS, but did secrete H2O2-producing substances into the growth medium. In all organisms, recovery rates for killed cultures (94-100% H2O2; 10-80% O2-) were consistently higher than those for live cultures (65-95% H2O2; 10-50% O2-). While recovery rates for killed cultures in H2O2 indicate that nearly all H2O2 was degraded by active cell processes, O2- decay appeared to occur via a combination of active and passive processes. Overall, this study shows that the rates and pathways for ROS production and decay vary greatly among diatom species, even between those that are

  1. Species-Level Variability in Extracellular Production Rates of Reactive Oxygen Species by Diatoms

    PubMed Central

    Schneider, Robin J.; Roe, Kelly L.; Hansel, Colleen M.; Voelker, Bettina M.

    2016-01-01

    Biological production and decay of the reactive oxygen species (ROS) hydrogen peroxide (H2O2) and superoxide (O2-) likely have significant effects on the cycling of trace metals and carbon in marine systems. In this study, extracellular production rates of H2O2 and O2- were determined for five species of marine diatoms in the presence and absence of light. Production of both ROS was measured in parallel by suspending cells on filters and measuring the ROS downstream using chemiluminescence probes. In addition, the ability of these organisms to break down O2- and H2O2 was examined by measuring recovery of O2- and H2O2 added to the influent medium. O2- production rates ranged from undetectable to 7.3 × 10−16 mol cell−1 h−1, while H2O2 production rates ranged from undetectable to 3.4 × 10−16 mol cell−1 h−1. Results suggest that extracellular ROS production occurs through a variety of pathways even amongst organisms of the same genus. Thalassiosira spp. produced more O2- in light than dark, even when the organisms were killed, indicating that O2- is produced via a passive photochemical process on the cell surface. The ratio of H2O2 to O2- production rates was consistent with production of H2O2 solely through dismutation of O2- for T. oceanica, while T. pseudonana made much more H2O2 than O2-. T. weissflogii only produced H2O2 when stressed or killed. P. tricornutum cells did not make cell-associated ROS, but did secrete H2O2-producing substances into the growth medium. In all organisms, recovery rates for killed cultures (94–100% H2O2; 10–80% O2-) were consistently higher than those for live cultures (65–95% H2O2; 10–50% O2-). While recovery rates for killed cultures in H2O2 indicate that nearly all H2O2 was degraded by active cell processes, O2- decay appeared to occur via a combination of active and passive processes. Overall, this study shows that the rates and pathways for ROS production and decay vary greatly among diatom species, even

  2. Species-Level Variability in Extracellular Production Rates of Reactive Oxygen Species by Diatoms.

    PubMed

    Schneider, Robin J; Roe, Kelly L; Hansel, Colleen M; Voelker, Bettina M

    2016-01-01

    Biological production and decay of the reactive oxygen species (ROS) hydrogen peroxide (H2O2) and superoxide (O[Formula: see text]) likely have significant effects on the cycling of trace metals and carbon in marine systems. In this study, extracellular production rates of H2O2 and O[Formula: see text] were determined for five species of marine diatoms in the presence and absence of light. Production of both ROS was measured in parallel by suspending cells on filters and measuring the ROS downstream using chemiluminescence probes. In addition, the ability of these organisms to break down O[Formula: see text] and H2O2 was examined by measuring recovery of O[Formula: see text] and H2O2 added to the influent medium. O[Formula: see text] production rates ranged from undetectable to 7.3 × 10(-16) mol cell(-1) h(-1), while H2O2 production rates ranged from undetectable to 3.4 × 10(-16) mol cell(-1) h(-1). Results suggest that extracellular ROS production occurs through a variety of pathways even amongst organisms of the same genus. Thalassiosira spp. produced more O[Formula: see text] in light than dark, even when the organisms were killed, indicating that O[Formula: see text] is produced via a passive photochemical process on the cell surface. The ratio of H2O2 to O[Formula: see text] production rates was consistent with production of H2O2 solely through dismutation of O[Formula: see text] for T. oceanica, while T. pseudonana made much more H2O2 than O[Formula: see text]. T. weissflogii only produced H2O2 when stressed or killed. P. tricornutum cells did not make cell-associated ROS, but did secrete H2O2-producing substances into the growth medium. In all organisms, recovery rates for killed cultures (94-100% H2O2; 10-80% O[Formula: see text]) were consistently higher than those for live cultures (65-95% H2O2; 10-50% O[Formula: see text]). While recovery rates for killed cultures in H2O2 indicate that nearly all H2O2 was degraded by active cell processes, O

  3. Activation of molecular oxygen and the nature of the active oxygen species for CO oxidation on oxide supported Au catalysts.

    PubMed

    Widmann, D; Behm, R J

    2014-03-18

    Although highly dispersed Au catalysts with Au nanoparticles (NPs) of a few nanometers in diameter are well-known for their high catalytic activity for several oxidation and reduction reactions already at rather low temperatures for almost 30 years, central aspects of the reaction mechanism are still unresolved. While most studies focused on the active site, the active Au species, and the effect of the support material, the most crucial step during oxidation reactions, the activation of molecular oxygen and the nature of the resulting active oxygen species (Oact), received more attention just recently. This is topic of this Account, which focuses on the formation, location, and nature of the Oact species present on metal oxide supported Au catalysts under typical reaction conditions, at room temperature and above. It is mainly based on quantitative temporal analysis of products (TAP) reactor measurements, which different from most spectroscopic techniques are able to detect and quantify these species even at the extremely low concentrations present under realistic reaction conditions. Different types of pulse experiments were performed, during which the highly dispersed, realistic powder catalysts are exposed to very low amounts of reactants, CO and/or O2, in order to form and reactively remove Oact species and gain information on their formation, nature, and the active site for Oact formation. Our investigations have shown that the active oxygen species for CO oxidation on Au/TiO2 for reaction at 80 °C and higher is a highly stable atomic species, which at 80 °C is formed only at the perimeter of the Au-oxide interface and whose reactive removal by CO is activated, but not its formation. From these findings, it is concluded that surface lattice oxygen represents the Oact species for the CO oxidation. Accordingly, the CO oxidation proceeds via a Au-assisted Mars-van Krevelen mechanism, during which surface lattice oxygen close to the Au NPs is removed by reaction

  4. Reactive oxygen species are involved in gibberellin/abscisic acid signaling in barley aleurone cells.

    PubMed

    Ishibashi, Yushi; Tawaratsumida, Tomoya; Kondo, Koji; Kasa, Shinsuke; Sakamoto, Masatsugu; Aoki, Nozomi; Zheng, Shao-Hui; Yuasa, Takashi; Iwaya-Inoue, Mari

    2012-04-01

    Reactive oxygen species (ROS) act as signal molecules for a variety of processes in plants. However, many questions about the roles of ROS in plants remain to be clarified. Here, we report the role of ROS in gibberellin (GA) and abscisic acid (ABA) signaling in barley (Hordeum vulgare) aleurone cells. The production of hydrogen peroxide (H2O2), a type of ROS, was induced by GA in aleurone cells but suppressed by ABA. Furthermore, exogenous H2O2 appeared to promote the induction of α-amylases by GA. In contrast, antioxidants suppressed the induction of α-amylases. Therefore, H2O2 seems to function in GA and ABA signaling, and in regulation of α-amylase production, in aleurone cells. To identify the target of H2O2 in GA and ABA signaling, we analyzed the interrelationships between H2O2 and DELLA proteins Slender1 (SLN1), GA-regulated Myb transcription factor (GAmyb), and ABA-responsive protein kinase (PKABA) and their roles in GA and ABA signaling in aleurone cells. In the presence of GA, exogenous H2O2 had little effect on the degradation of SLN1, the primary transcriptional repressor mediating GA signaling, but it promoted the production of the mRNA encoding GAMyb, which acts downstream of SLN1 and involves induction of α-amylase mRNA. Additionally, H2O2 suppressed the production of PKABA mRNA, which is induced by ABA:PKABA represses the production of GAMyb mRNA. From these observations, we concluded that H2O2 released the repression of GAMyb mRNA by PKABA and consequently promoted the production of α-amylase mRNA, thus suggesting that the H2O2 generated by GA in aleurone cells is a signal molecule that antagonizes ABA signaling. PMID:22291200

  5. Detection of reactive oxygen species in primary cultures of cerebellar granule cells.

    PubMed

    Atlante, A; Passarella, S

    1999-12-01

    The aim of this work was to develop a novel procedure useful to detect the formation of two reactive oxygen species, i.e. superoxide and singlet oxygen, in neuron monolayer primary cultures, thus, making possible the investigation of the effect of certain compounds on reactive oxygen species formation. Thus, use was made of two reactive oxygen species detecting systems consisting of ferricytochrome c (Fe-cyt c) and imidazole-RNO (N, N-dimethyl-4-nitrosoaniline) which allow for the photometric detection of superoxide anion and singlet oxygen, respectively. Both of them were used to assess the formation of reactive oxygen species in cerebellar granule cells exposed to glutamate: both superoxide anion and singlet oxygen proved to be generated in glutamate neurotoxicity in a way sensitive to glutamate NMDA-receptor inhibitor, MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a, d)cyclohepten-5,10-imine hydrogen maleate), to Ca(2+) complexing agent, EGTA, and to certain antioxidants. In principle, the reported protocol can be applied to any cell type in culture. PMID:10592334

  6. Virion disruption by ozone-mediated reactive oxygen species.

    PubMed

    Murray, Byron K; Ohmine, Seiga; Tomer, David P; Jensen, Kendal J; Johnson, F Brent; Kirsi, Jorma J; Robison, Richard A; O'Neill, Kim L

    2008-10-01

    It is well documented in the scientific literature that ozone-oxygen mixtures inactivate microorganisms including bacteria, fungi and viruses (Hoff, J.C., 1986. Inactivation of microbial agents by chemical disinfectants. EPA 600 S2-86 067. Office of Water, U.S. Environmental Protection Agency, Washington, DC; Khadre, M.A., Yousef, A.E., Kim, J.-G., 2001. Microbiological aspects of ozone applications in food: a review. J. Food Sci. 66, 1242-1252). In the current study, delivery and absorption of precisely known concentrations of ozone (in liquid media) were used to inactivate virus infectivity. An ozone-oxygen delivery system capable of monitoring and recording ozone concentrations in real time was used to inactivate a series of enveloped and non-enveloped viruses including herpes simplex virus type-1 (HHV-1, strain McIntyre), vesicular stomatitis Indiana virus (VSIV), vaccinia virus (VACV, strain Elstree), adenovirus type-2 (HAdV-2), and the PR8 strain of influenza A virus (FLUAVA/PR/8/34/H1N1; FLUAV). The results of the study showed that ozone exposure reduced viral infectivity by lipid peroxidation and subsequent lipid envelope and protein shell damage. These data suggest that a wide range of virus types can be inactivated in an environment of known ozone exposure. PMID:18598719

  7. Using oxygen species to measure marine production in Drake Passage

    NASA Astrophysics Data System (ADS)

    Castro Morales, Karel; Cassar, Nicolas; Bender, Michael; Kaiser, Jan

    2010-05-01

    Marine biological production is key to understanding the global carbon cycle, particularly the role of the Southern Ocean as a sink of CO2. Measurements of oxygen in the surface ocean allow quantifying marine biological productivity, since CO2 and O2 are linked via photosynthesis and respiration. Measurements of O2/Ar ratios and dissolved O2 isotopologues, together with wind-speed gas exchange parameterizations, give estimates of biological oxygen air-sea fluxes (Fbio) and gross photosynthetic production (G) in the mixed layer (zmix). In the absence of vertical mixing, Fbio can be used as a proxy for net community production (N). O2/Ar ratios and O2 concentrations were measured continuously in the uncontaminated seawater supply on board the RRS James Clark Ross along two sections across Drake Passage (DP). The DP1 section (southbound, 27 February-3 March 2007) represented mid-summer; DP2 represented early autumn (northbound, 12-15 April, 2007). The time difference between the two transects was 40 days. Weighted average gas exchange rates were calculated using the WOCE-NODC ocean mixed layer depth climatology and ECMWF wind speeds over 60 days prior to sample collection. The WOCE-NODC climatology shows a deepening of the zmix by on average 46 m within 40 days. The sea surface temperature decreased about 2.4 °C from DP1 to DP2. This reflects the seasonal transition from late summer to early autumn. In agreement with previous observations, we observed a strong north-south gradient of biological oxygen production in the DP. Our results also show high temporal variability over the course of 40 days. During late summer, the physical supersaturation contributes to about 3.6% of the total O2 supersaturation (?O2) for the Subantarctic and Polar Frontal Zones (SAZ and PFZ, respectively). In the other hand, the biological O2 supersaturation (?O2/Ar) showed mainly positive and homogeneous values (~1%) along the Antarctic Zone and Southern Antarctic Circumpolar Current Zone

  8. Nanopore formation process in artificial cell membrane induced by plasma-generated reactive oxygen species.

    PubMed

    Tero, Ryugo; Yamashita, Ryuma; Hashizume, Hiroshi; Suda, Yoshiyuki; Takikawa, Hirofumi; Hori, Masaru; Ito, Masafumi

    2016-09-01

    We investigated morphological change of an artificial lipid bilayer membrane induced by oxygen radicals which were generated by non-equilibrium atmospheric pressure plasma. Neutral oxygen species, O((3)Pj) and O2((1)Δg), were irradiated of a supported lipid bilayer existing under a buffer solution at various conditions of dose time and distances, at which the dose amounts of the oxygen species were calculated quantitatively. Observation using an atomic force microscope and a fluorescence microscope revealed that dose of the neutral oxygen species generated nanopores with the diameter of 10-50 nm in a phospholipid bilayer, and finally destructed the bilayer structure. We found that protrusions appeared on the lipid bilayer surface prior to the formation of nanopores, and we attributed the protrusions to the precursor of the nanopores. We propose a mechanism of the pore formation induced by lipid oxidation on the basis of previous experimental and theoretical studies. PMID:27216034

  9. Sensitivity of primary fibroblasts in culture to atmospheric oxygen does not correlate with species lifespan

    PubMed Central

    Patrick, Alison; Seluanov, Michael; Hwang, Chaewon; Tam, Jonathan; Khan, Tanya; Morgenstern, Ari; Wiener, Lauren; Vazquez, Juan M.; Zafar, Hiba; Wen, Robert; Muratkalyeva, Malika; Doerig, Katherine; Zagorulya, Maria; Cole, Lauren; Catalano, Sophia; Lobo Ladd, Aliny AB; Coppi, A. Augusto; Coşkun, Yüksel; Tian, Xiao; Ablaeva, Julia; Nevo, Eviatar; Gladyshev, Vadim N.; Zhang, Zhengdong D.; Vijg, Jan; Seluanov, Andrei; Gorbunova, Vera

    2016-01-01

    Differences in the way human and mouse fibroblasts experience senescence in culture had long puzzled researchers. While senescence of human cells is mediated by telomere shortening, Parrinello et al. demonstrated that senescence of mouse cells is caused by extreme oxygen sensitivity. It was hypothesized that the striking difference in oxygen sensitivity between mouse and human cells explains their different rates of aging. To test if this hypothesis is broadly applicable, we cultured cells from 16 rodent species with diverse lifespans in 3% and 21% oxygen and compared their growth rates. Unexpectedly, fibroblasts derived from laboratory mouse strains were the only cells demonstrating extreme sensitivity to oxygen. Cells from hamster, muskrat, woodchuck, capybara, blind mole rat, paca, squirrel, beaver, naked mole rat and wild-caught mice were mildly sensitive to oxygen, while cells from rat, gerbil, deer mouse, chipmunk, guinea pig and chinchilla showed no difference in the growth rate between 3% and 21% oxygen. We conclude that, although the growth of primary fibroblasts is generally improved by maintaining cells in 3% oxygen, the extreme oxygen sensitivity is a peculiarity of laboratory mouse strains, possibly related to their very long telomeres, and fibroblast oxygen sensitivity does not directly correlate with species' lifespan. PMID:27163160

  10. Sensitivity of primary fibroblasts in culture to atmospheric oxygen does not correlate with species lifespan.

    PubMed

    Patrick, Alison; Seluanov, Michael; Hwang, Chaewon; Tam, Jonathan; Khan, Tanya; Morgenstern, Ari; Wiener, Lauren; Vazquez, Juan M; Zafar, Hiba; Wen, Robert; Muratkalyeva, Malika; Doerig, Katherine; Zagorulya, Maria; Cole, Lauren; Catalano, Sophia; Lobo Ladd, Aliny Ab; Coppi, A Augusto; Coşkun, Yüksel; Tian, Xiao; Ablaeva, Julia; Nevo, Eviatar; Gladyshev, Vadim N; Zhang, Zhengdong D; Vijg, Jan; Seluanov, Andrei; Gorbunova, Vera

    2016-05-01

    Differences in the way human and mouse fibroblasts experience senescence in culture had long puzzled researchers. While senescence of human cells is mediated by telomere shortening, Parrinello et al. demonstrated that senescence of mouse cells is caused by extreme oxygen sensitivity. It was hypothesized that the striking difference in oxygen sensitivity between mouse and human cells explains their different rates of aging. To test if this hypothesis is broadly applicable, we cultured cells from 16 rodent species with diverse lifespans in 3% and 21% oxygen and compared their growth rates. Unexpectedly, fibroblasts derived from laboratory mouse strains were the only cells demonstrating extreme sensitivity to oxygen. Cells from hamster, muskrat, woodchuck, capybara, blind mole rat, paca, squirrel, beaver, naked mole rat and wild-caught mice were mildly sensitive to oxygen, while cells from rat, gerbil, deer mouse, chipmunk, guinea pig and chinchilla showed no difference in the growth rate between 3% and 21% oxygen. We conclude that, although the growth of primary fibroblasts is generally improved by maintaining cells in 3% oxygen, the extreme oxygen sensitivity is a peculiarity of laboratory mouse strains, possibly related to their very long telomeres, and fibroblast oxygen sensitivity does not directly correlate with species' lifespan. PMID:27163160

  11. Storage capacity and oxygen mobility in mixed oxides from transition metals promoted by cerium

    NASA Astrophysics Data System (ADS)

    Perdomo, Camilo; Pérez, Alejandro; Molina, Rafael; Moreno, Sonia

    2016-10-01

    The oxygen mobility and storage capacity of Ce-Co/Cu-MgAl or Ce-MgAl mixed oxides, obtained by hydrotalcite precursors, were evaluated using Toluene-temperature-programmed-reaction, 18O2 isotopic exchange and O2-H2 titration. The presence of oxygen vacancies-related species was evaluated by means of Electron Paramagnetic Resonance. A correlation was found between the studied properties and the catalytic activity of the oxides in total oxidation processes. It was evidenced that catalytic activity depends on two related processes: the facility with which the solid can be reduced and its ability to regenerate itself in the presence of molecular oxygen in the gas phase. These processes are enhanced by Cu-Co cooperative effect in the mixed oxides. Additionally, the incorporation of Ce in the Co-Cu catalysts improved their oxygen transport properties.

  12. Oxygen promotes biofilm formation of Shewanella putrefaciens CN32 through a diguanylate cyclase and an adhesin

    PubMed Central

    Wu, Chao; Cheng, Yuan-Yuan; Yin, Hao; Song, Xiang-Ning; Li, Wen-Wei; Zhou, Xian-Xuan; Zhao, Li-Ping; Tian, Li-Jiao; Han, Jun-Cheng; Yu, Han-Qing

    2013-01-01

    Although oxygen has been reported to regulate biofilm formation by several Shewanella species, the exact regulatory mechanism mostly remains unclear. Here, we identify a direct oxygen-sensing diguanylate cyclase (DosD) and reveal its regulatory role in biofilm formation by Shewanella putrefaciens CN32 under aerobic conditions. In vitro and in vivo analyses revealed that the activity of DosD culminates to synthesis of cyclic diguanylate (c-di-GMP) in the presence of oxygen. DosD regulates the transcription of bpfA operon which encodes seven proteins including a large repetitive adhesin BpfA and its cognate type I secretion system (TISS). Regulation of DosD in aerobic biofilms is heavily dependent on an adhesin BpfA and the TISS. This study offers an insight into the molecular mechanism of oxygen-stimulated biofilm formation by S. putrefaciens CN32. PMID:23736081

  13. Promoted Ignition and Burning Tests of Stainless Steel in Flowing and Nonflowing Oxygen

    NASA Technical Reports Server (NTRS)

    Forsyth, Elliot T.; Maes, Miguel; Stoltzfus, Joel M.; Bachelier, Frederic

    2003-01-01

    The Industry-Sponsored Metals Combustion Test Program 96-1 was coordinated through Wendell Hull & Associates, Inc. on behalf of several contributing companies, and all design and testing was performed at the NASA White Sands Test Facility. Phase I of this test program studied the threshold pressure for self-sustained burning of various types and sizes of stain less steel rods in nonflowing oxygen, as observed in Standard Test Method for Determining the Combustion Behavior of Metallic Materials in Oxygen-Enriched Atmospheres (ASTM G 124-95). Phase II studied the ignition and propagation of burning of 316L stainless steel rods and pipe in flowing gaseous oxygen. The test sample configurations were chosen to replicate previous promoted ignition and burning tests as well as to represent geometries and cross-sectional thicknesses common in industrial piping applications. The gas pressw'es and velocities for the test matrix were selected to generally compare with CGA G-4.4 guidelines for the use of stain less steel in oxygen service. This paper summarizes the results from the Phase I nonflowing oxygen tests and presents in detail the results of the Phase II flowing oxygen tests. The maximum sample burn-length is shown as a function of test pressure in Phase 1 and also as a function of gas velocity in Phase IT. These results indicate that flowing oxygen, under the given test conditions, significantly affects maximum sample burn length as compared to nonflowing oxygen. Supplementary flowing oxygen test data on stainless steel rods from a follow-up test program are consistent with these results and are presented herein.

  14. Oxidative DNA adducts after Cu(2+)-mediated activation of dihydroxy PCBs: role of reactive oxygen species.

    PubMed

    Spencer, Wendy A; Lehmler, Hans-Joachim; Robertson, Larry W; Gupta, Ramesh C

    2009-05-15

    Polychlorinated biphenyls (PCBs) are toxic industrial chemicals, complete carcinogens, and efficacious tumor promoters. However, the mechanism(s) of PCB-mediated carcinogenicity remains largely undefined. One likely pathway by which these agents may play a role in carcinogenesis is the generation of oxidative DNA damage by redox cycling of dihydroxylated PCB metabolites. We have now employed a new (32)P-postlabeling system to examine novel oxidative DNA lesions induced by Cu(2+)-mediated activation of PCB metabolites. (32)P postlabeling of DNA incubated with various PCB metabolites resulted in over a dozen novel polar oxidative DNA adducts that were chromatographically similar for all active agents. The most potent metabolites tested were the hydroquinones (hydroxyl groups arranged para to each other), yielding polar oxidative adduct levels ranging from 55 to 142 adducts/10(6) nucleotides. PCB catechols, or ortho-dihydroxy metabolites, were up to 40% less active than their corresponding hydroquinone congeners, whereas monohydroxylated and quinone metabolites did not produce detectable oxidative damage over that of vehicle. With the exception of 2,4,5-Cl-2',5'-dihydroxybiphenyl, this oxidative DNA damage seemed to be inversely related to chlorine content: no chlorine approximately mono->di->trichlorinated metabolites. Importantly, copper, but not iron, was essential for activation of the PCB metabolites to these polar oxidative DNA adducts, because in its absence or in the presence of the Cu(+)-specific scavenger bathocuproine, no adducts were detected. Intervention studies with known reactive oxygen species (ROS) modifiers suggested that H(2)O(2), singlet oxygen, hydroxyl radical, and superoxide may also be involved in this PCB-mediated oxidative DNA damage. These data indicate a mechanistic role for several ROS, in addition to copper, in PCB-induced DNA damage and provide further support for oxidative DNA damage in PCB-mediated carcinogenesis. PMID:19233261

  15. Reactive Oxygen Species on the Early Earth and Survival of Bacteria

    NASA Technical Reports Server (NTRS)

    Balk, Melikea; Mason, Paul; Stams, Alfons J. M.; Smidt, Hauke; Freund, Friedemann; Rothschild, Lynn

    2011-01-01

    An oxygen-rich atmosphere appears to have been a prerequisite for complex, multicellular life to evolve on Earth and possibly elsewhere in the Universe. However it remains unclear how free oxygen first became available on the early Earth. A potentially important, and as yet poorly constrained pathway, is the production of oxygen through the weathering of rocks and release into the near-surface environment. Reactive Oxygen Species (ROS), as precursors to molecular oxygen, are a key step in this process, and may have had a decisive impact on the evolution of life, present and past. ROS are generated from minerals in igneous rocks during hydrolysis of peroxy defects, which consist of pairs of oxygen anions oxidized to the valence state -1 and during (bio) transformations of iron sulphide minerals. ROS are produced and consumed by intracellular and extracellular reactions of Fe, Mn, C, N, and S species. We propose that, despite an overall reducing or neutral oxidation state of the macroenvironment and the absence of free O2 in the atmosphere, organisms on the early Earth had to cope with ROS in their microenvironments. They were thus under evolutionary pressure to develop enzymatic and other defences against the potentially dangerous, even lethal effects of oxygen and its derived ROS. Conversely it appears that microorganisms learned to take advantage of the enormous reactive potential and energy gain provided by nascent oxygen. We investigate how oxygen might be released through weathering. We test microorganisms in contact with rock surfaces and iron sulphides. We model bacteria such as Deionococcus radiodurans and Desulfotomaculum, Moorella and Bacillus species for their ability to grow or survive in the presence of ROS. We examine how early Life might have adapted to oxygen.

  16. Roles of Reactive Oxygen and Nitrogen Species in Pain

    PubMed Central

    Salvemini, Daniela; Little, Joshua W.; Doyle, Timothy; Neumann, William L.

    2011-01-01

    Peroxynitrite (PN, ONOO−) and its reactive oxygen precursor superoxide (SO, O2·−), are critically important in the development of pain of several etiologies including in the development of pain associated with chronic use of opiates such as morphine (also known as opiate-induced hyperalgesia and antinociceptive tolerance). This is now an emerging field in which considerable progress has been made in terms of understanding the relative contribution of SO, PN, and nitroxidative stress in pain signaling at the molecular and biochemical levels. Aggressive research in this area is poised to provide the pharmacological basis for development of novel non-narcotic analgesics that are based upon the unique ability to selectively eliminate SO and/or PN. As we have a better understanding of the role of SO and PN in pathophysiological settings, targeting PN may be a better therapeutic strategy than targeting SO. This is due to the fact that unlike PN, which has no currently known beneficial role, SO may play a significant role in learning and memory [1]. Thus, the best approach may be to spare SO while directly targeting its downstream product, PN. Over the last 15 years, our team has spearheaded research concerning the roles of SO/PN in pain and these results are currently leading to the development of solid therapeutic strategies in this important area. PMID:21277369

  17. THE THEORIES OF AGING: REACTIVE OXYGEN SPECIES AND WHAT ELSE?

    PubMed

    Avantaggiato, A; Bertuzzi, G; Pascali, M; Candotto, V; Carinci, F

    2015-01-01

    This manuscript is a short review on the theories of aging, focusing mainly on the balance between the nutrient and the oxygen intake necessary for energy metabolism and the processes for neutralizing the negative consequences of energy production. The first section entitled “Why” provides brief historical details regarding the main group of aging theories, firstly the evolutionary theories and secondly the theories of aging related to humans, cells and biomolecules are discussed. The second section entitled ‘Where’ includes brief summaries of the many cellular levels at which aging damage can occur: replicative senescence with its genetic and epigenetic implications, cytoplasmic accumulation, mitochondrial respiratory chain dysfunction, peroxisome and membrane activity. In the third section entitled ‘How’ the linking mechanisms between the caloric restriction and the antioxidant intake on lifespan and aging in experimental models are discussed. The role of ROS is evaluated in relation to the mitochondria, the AMPK activated sirtuins, the hormesis, the target of rapamicin and the balance autophagy/apoptosis. PMID:26511196

  18. Antioxidant properties of UCP1 are evolutionarily conserved in mammals and buffer mitochondrial reactive oxygen species.

    PubMed

    Oelkrug, Rebecca; Goetze, Nadja; Meyer, Carola W; Jastroch, Martin

    2014-12-01

    Mitochondrial uncoupling reduces reactive oxygen species (ROS) production and appears to be important for cellular signaling/protection, making it a focus for the treatment of metabolic and age-related diseases. Whereas the physiological role of uncoupling protein 1 (UCP1) of brown adipose tissue is established for thermogenesis, the function of UCP1 in the reduction of ROS in cold-exposed animals is currently under debate. Here, we investigated the role of UCP1 in mitochondrial ROS handling in the Lesser hedgehog tenrec (Echinops telfairi), a unique protoendothermic Malagasy mammal with recently identified brown adipose tissue (BAT). We show that the reduction of ROS by UCP1 activity also occurs in BAT mitochondria of the tenrec, suggesting that the antioxidative role of UCP1 is an ancient mammalian trait. Our analysis shows that the quantity of UCP1 displays strong control over mitochondrial hydrogen peroxide release, whereas other factors, such as mild cold, nonshivering thermogenesis, oxidative capacity, and mitochondrial respiration, do not correlate. Furthermore, hydrogen peroxide release from recoupled BAT mitochondria was positively associated with mitochondrial membrane potential. These findings led to a model of UCP1 controlling mitochondrial ROS release and, presumably, being controlled by high membrane potential, as proposed in the canonical model of "mild uncoupling". Our study further promotes a conserved role for UCP1 in the prevention of oxidative stress, which was presumably established during evolution before UCP1 was physiologically integrated into nonshivering thermogenesis. PMID:25224037

  19. Roles of Reactive Oxygen Species in Anticancer Therapy with Salvia miltiorrhiza Bunge

    PubMed Central

    Pan, Tai-Long

    2016-01-01

    Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia miltiorrhiza Bunge (Danshen). Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen. PMID:27579153

  20. Reactive oxygen species stimulate mitochondrial allele segregation toward homoplasmy in human cells

    PubMed Central

    Ling, Feng; Niu, Rong; Hatakeyama, Hideyuki; Goto, Yu-ichi; Shibata, Takehiko; Yoshida, Minoru

    2016-01-01

    Mitochondria that contain a mixture of mutant and wild-type mitochondrial (mt) DNA copies are heteroplasmic. In humans, homoplasmy is restored during early oogenesis and reprogramming of somatic cells, but the mechanism of mt-allele segregation remains unknown. In budding yeast, homoplasmy is restored by head-to-tail concatemer formation in mother cells by reactive oxygen species (ROS)–induced rolling-circle replication and selective transmission of concatemers to daughter cells, but this mechanism is not obvious in higher eukaryotes. Here, using heteroplasmic m.3243A > G primary fibroblast cells derived from MELAS patients treated with hydrogen peroxide (H2O2), we show that an optimal ROS level promotes mt-allele segregation toward wild-type and mutant mtDNA homoplasmy. Enhanced ROS level reduced the amount of intact mtDNA replication templates but increased linear tandem multimers linked by head-to-tail unit-sized mtDNA (mtDNA concatemers). ROS-triggered mt-allele segregation correlated with mtDNA-concatemer production and enabled transmission of multiple identical mt-genome copies as a single unit. Our results support a mechanism by which mt-allele segregation toward mt-homoplasmy is mediated by concatemers. PMID:27009201

  1. Caveolin-1 is involved in reactive oxygen species-induced SHP-2 activation in astrocytes

    PubMed Central

    Yun, Ji Hee; Park, Soo Jung; Jo, Ara; Jou, Ilo; Park, Jung Soo

    2011-01-01

    Recent evidence supports a neuroprotective role of Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2) against ischemic brain injury. However, the molecular mechanisms of SHP-2 activation and those governing how SHP-2 exerts its function under oxidative stress conditions are not well understood. Recently we have reported that reactive oxygen species (ROS)-mediated oxidative stress promotes the phosphorylation of endogenous SHP-2 through lipid rafts, and that this phosphorylation strongly occurs in astrocytes, but not in microglia. To investigate the molecules involved in events leading to phosphorylation of SHP-2, raft proteins were analyzed using astrocytes and microglia. Interestingly, caveolin-1 and -2 were detected only in astrocytes but not in microglia, whereas flotillin-1 was expressed in both cell types. To examine whether the H2O2-dependent phosphorylation of SHP-2 is mediated by caveolin-1, we used specific small interfering RNA (siRNA) to downregulate caveolin-1 expression. In the presence of caveolin-1 siRNA, the level of SHP-2 phosphorylation induced by H2O2 was significantly decreased, compared with in the presence of control siRNA. Overexpression of caveolin-1 effectively increased H2O2-induced SHP-2 phosphorylation in microglia. Lastly, H2O2 induced extracellular signal-regulated kinase (ERK) activation in astrocytes through caveolin-1. Our results suggest that caveolin-1 is involved in astrocyte-specific intracellular responses linked to the SHP-2-mediated signaling cascade following ROS-induced oxidative stress. PMID:21918362

  2. Determination of photochemically-generated reactive oxygen species in natural water.

    PubMed

    Zhan, Manjun

    2009-01-01

    Reactive oxygen species (ROS) can be produced by interactions between sunlight and light-absorbing substances in natural water environment. ROS may participate in the indirect photolysis of trace organic pollutants, therefore resulting in changes in their environmental fates and ecological risks in natural water systems. Bisphenol A (BPA), an endocrine-disrupting chemical, exits widely in natural waters. The photodegradation of BPA promoted by ROS (*OH, 1O2, HO2*/O2(*-)), which were produced on the excitation of ubiquitous constituents (such as nitrate ion, humic substances and Fe(III)-oxalate complexes) in natural water under simulated solar radiation was investigated. Both molecular probe method and electron spin resonance (ESR) test were used for the characterization of the generated ROS. It was found that *OH was photochemically produced in the presence of nitrate ions, humic substances and Fe(III)-oxalate complexes and that 102 was produced with the presence of humic substances. The steady-state concentrations of *OH was 1.27x10(-14) mol/L in a nitrate solution, and the second-order rate constant of BPA with *OH was 1.01 x 10(10) L/(mol x s). PMID:19634440

  3. The bright side of reactive oxygen species: lifespan extension without cellular demise

    PubMed Central

    Maiese, Kenneth

    2016-01-01

    Oxidative stress and the generation of reactive oxygen species (ROS) can lead to mitochondrial dysfunction, DNA damage, protein misfolding, programmed cell death with apoptosis and autophagy, and the promotion of aging –dependent processes. Mitochondria control the processing of redox energy that yields adenosine triphosphate (ATP) through the oxidation of glucose, pyruvate, and nicotinamide adenine dinucleotide. Ultimately, the generation of ROS occurs with the aerobic production of ATP. Although reduced levels of ROS may lead to tolerance against metabolic, mechanical, and oxidative stressors and the generation of brief periods of ROS during ischemia-reperfusion models may limit cellular injury, under most circumstances ROS and mitochondrial dysfunction can lead to apoptotic caspase activation and autophagy induction that can result in cellular demise. Yet, new work suggests that ROS generation may have a positive impact through respiratory complex I reverse electron transport that can extend lifespan. Such mechanisms may bring new insight into clinically relevant disorders that are linked to cellular senescence and aging of the body’s system. Further investigation of the potential “bright side” of ROS and mitochondrial respiration is necessary to target specific pathways, such as the mechanistic target of rapamycin, nicotinamidases, sirtuins, mRNA decoupling and protein expression, and Wnt signaling, that can impact oxidative stress-ROS mechanisms to extend lifespan and eliminate disease onset. PMID:27200181

  4. Reactive oxygen species mediates homocysteine-induced mitochondrial biogenesis in human endothelial cells: Modulation by antioxidants

    SciTech Connect

    Perez-de-Arce, Karen; Foncea, Rocio . E-mail: rfoncea@med.puc.cl; Leighton, Federico

    2005-12-16

    It has been proposed that homocysteine (Hcy)-induces endothelial dysfunction and atherosclerosis by generation of reactive oxygen species (ROS). A previous report has shown that Hcy promotes mitochondrial damage. Considering that oxidative stress can affect mitochondrial biogenesis, we hypothesized that Hcy-induced ROS in endothelial cells may lead to increased mitochondrial biogenesis. We found that Hcy-induced ROS (1.85-fold), leading to a NF-{kappa}B activation and increase the formation of 3-nitrotyrosine. Furthermore, expression of the mitochondrial biogenesis factors, nuclear respiratory factor-1 and mitochondrial transcription factor A, was significantly elevated in Hcy-treated cells. These changes were accompanied by increase in mitochondrial mass and higher mRNA and protein expression of the subunit III of cytochrome c oxidase. These effects were significantly prevented by pretreatment with the antioxidants, catechin and trolox. Taken together, our results suggest that ROS is an important mediator of mitochondrial biogenesis induced by Hcy, and that modulation of oxidative stress by antioxidants may protect against the adverse vascular effects of Hcy.

  5. Impaired ADP channeling to mitochondria and elevated reactive oxygen species in hypertensive hearts.

    PubMed

    Power, Amelia S C; Pham, Toan; Loiselle, Denis S; Crossman, David H; Ward, Marie-Louise; Hickey, Anthony J

    2016-06-01

    Systemic hypertension initially promotes a compensatory cardiac hypertrophy, yet it progresses to heart failure (HF), and energetic deficits appear to be central to this failure. However, the transfer of energy between the mitochondria and the myofibrils is not often considered as part of the energetic equation. We compared hearts from old spontaneously hypertensive rats (SHRs) and normotensive Wistar controls. SHR hearts showed a 35% depression in mitochondrial function, yet produced at least double the amount of reactive oxygen species (ROS) in all respiration states in left ventricular (LV) homogenates. To test the connectivity between mitochondria and myofibrils, respiration was further tested in situ with LV permeabilized fibers by addition of multiple substrates and ATP, which requires hydrolysis to mediate oxidative phosphorylation. By trapping ADP using a pyruvate kinase enzyme system, we tested ADP channeling towards mitochondria, and this suppressed respiration and elevated ROS production more in the SHR fibers. The ADP-trapped state was also less relieved on creatine addition, likely reflecting the 30% depression in total CK activity in the SHR heart fibers. Confocal imaging identified a 34% longer distance between the centers of myofibril to mitochondria in the SHR hearts, which increases transverse metabolite diffusion distances (e.g., for ATP, ADP, and creatine phosphate). We propose that impaired connectivity between mitochondria and myofibrils may contribute to elevated ROS production. Impaired energy exchange could be the result of ultrastructural changes that occur with hypertrophy in this model of hypertension. PMID:27084386

  6. Ambient Fine Particulate Matter Induces Apoptosis of Endothelial Progenitor Cells Through Reactive Oxygen Species Formation

    PubMed Central

    Cui, Yuqi; Xie, Xiaoyun; Jia, Fengpeng; He, Jianfeng; Li, Zhihong; Fu, Minghuan; Hao, Hong; Liu, Ying; Liu, Jason Z.; Cowan, Peter J.; Zhu, Hua; Sun, Qinghua; Liu, Zhenguo

    2015-01-01

    Background/Aims Bone marrow (BM)-derived endothelial progenitor cells (EPCs) play a critical role in angiogenesis and vascular repair. Some environmental insults, like fine particulate matter (PM) exposure, significantly impair cardiovascular functions. However, the mechanisms for PM-induced adverse effects on cardiovascular system remain largely unknown. The present research was to study the detrimental effects of PM on EPCs and explore the potential mechanisms. Methods PM was intranasal-distilled into male C57BL/6 mice for one month. Flow cytometry was used to measure the number of EPCs, apoptosis level of circulating EPCs and intracellular reactive oxygen species (ROS) formation. Serum TNF-α and IL-1β were measured using ELISA. To determine the role of PM-induced ROS in EPC apoptosis, PM was co-administrated with the antioxidant N-acetylcysteine (NAC) in wild type mice or used in a triple transgenic mouse line (TG) with overexpression of antioxidant enzyme network (AON) composed of superoxide dismutase (SOD)1, SOD3, and glutathione peroxidase (Gpx-1) with decreased in vivo ROS production. Results PM treatment significantly decreased circulating EPC population, promoted apoptosis of EPCs in association with increased ROS production and serum TNF-α and IL-1β levels, which could be effectively reversed by either NAC treatment or overexpression of AON. Conclusion PM exposure significantly decreased circulating EPCs population due to increased apoptosis via ROS formation in mice. PMID:25591776

  7. TOR complex 2-Ypk1 signaling regulates actin polarization via reactive oxygen species.

    PubMed

    Niles, Brad J; Powers, Ted

    2014-12-01

    The evolutionarily conserved mTOR complex 2 (mTORC2) signaling pathway is an important regulator of actin cytoskeletal architecture and, as such, is a candidate target for preventing cancer cell motility and invasion. Remarkably, the precise mechanism(s) by which mTORC2 regulates the actin cytoskeleton have remained elusive. Here we show that in budding yeast, TORC2 and its downstream kinase Ypk1 regulate actin polarization by controlling reactive oxygen species (ROS) accumulation. Specifically, we find that TORC2-Ypk1 regulates actin polarization both by vacuole-related ROS, controlled by the phospholipid flippase kinase Fpk1 and sphingolipids, and by mitochondria-mediated ROS, controlled by the PKA subunit Tpk3. In addition, we find that the protein kinase C (Pkc1)/MAPK cascade, a well-established regulator of actin, acts downstream of Ypk1 to regulate ROS, in part by promoting degradation of the oxidative stress responsive repressor, cyclin C. Furthermore, we show that Ypk1 regulates Pkc1 activity through proper localization of Rom2 at the plasma membrane, which is also dependent on Fpk1 and sphingolipids. Together these findings demonstrate important links between TORC2/Ypk1 signaling, Fpk1, sphingolipids, Pkc1, and ROS as regulators of actin and suggest that ROS may play an important role in mTORC2-dependent dysregulation of the actin cytoskeleton in cancer cells. PMID:25253719

  8. Roles of Reactive Oxygen Species in Anticancer Therapy with Salvia miltiorrhiza Bunge.

    PubMed

    Hung, Yu-Chiang; Pan, Tai-Long; Hu, Wen-Long

    2016-01-01

    Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia miltiorrhiza Bunge (Danshen). Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen. PMID:27579153

  9. Reactive oxygen species stimulate mitochondrial allele segregation toward homoplasmy in human cells.

    PubMed

    Ling, Feng; Niu, Rong; Hatakeyama, Hideyuki; Goto, Yu-Ichi; Shibata, Takehiko; Yoshida, Minoru

    2016-05-15

    Mitochondria that contain a mixture of mutant and wild-type mitochondrial (mt) DNA copies are heteroplasmic. In humans, homoplasmy is restored during early oogenesis and reprogramming of somatic cells, but the mechanism of mt-allele segregation remains unknown. In budding yeast, homoplasmy is restored by head-to-tail concatemer formation in mother cells by reactive oxygen species (ROS)-induced rolling-circle replication and selective transmission of concatemers to daughter cells, but this mechanism is not obvious in higher eukaryotes. Here, using heteroplasmic m.3243A > G primary fibroblast cells derived from MELAS patients treated with hydrogen peroxide (H2O2), we show that an optimal ROS level promotes mt-allele segregation toward wild-type and mutant mtDNA homoplasmy. Enhanced ROS level reduced the amount of intact mtDNA replication templates but increased linear tandem multimers linked by head-to-tail unit-sized mtDNA (mtDNA concatemers). ROS-triggered mt-allele segregation correlated with mtDNA-concatemer production and enabled transmission of multiple identical mt-genome copies as a single unit. Our results support a mechanism by which mt-allele segregation toward mt-homoplasmy is mediated by concatemers. PMID:27009201

  10. Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

    SciTech Connect

    Watanabe, Tomoyuki; Saotome, Masao; Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi; Funaki, Makoto; Hayashi, Hideharu

    2014-05-01

    Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ{sub m}) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H{sub 2}O{sub 2}), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ{sub m} depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H{sub 2}O{sub 2}-induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ{sub m} depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin

  11. Reactive oxygen species regulate Smac mimetic/TNFα-induced necroptotic signaling and cell death.

    PubMed

    Schenk, B; Fulda, S

    2015-11-19

    Necroptosis represents a key programmed cell death pathway involved in various physiological and pathophysiological conditions. However, the role of reactive oxygen species (ROS) in necroptotic signaling has remained unclear. In the present study, we identify ROS as critical regulators of BV6/tumor necrosis factor-α (TNFα)-induced necroptotic signaling and cell death. We show that BV6/TNFα-induced cell death depends on ROS production, as several ROS scavengers such as butylated hydroxyanisole, N-acetylcysteine, α-tocopherol and ethyl pyruvate significantly rescue cell death. Before cell death, BV6/TNFα-stimulated ROS generation promotes stabilization of the receptor-interacting protein kinase 1 (RIP1)/RIP3 necrosome complex via a potential positive feedback loop, as on the one hand radical scavengers attenuate RIP1/RIP3 necrosome assembly and phosphorylation of mixed lineage kinase domain like (MLKL), but on the other hand silencing of RIP1 or RIP3 reduces ROS production. Although MLKL knockdown effectively decreases BV6/TNFα-induced cell death, it does not affect RIP1/RIP3 interaction and only partly reduces ROS generation. Moreover, the deubiquitinase cylindromatosis (CYLD) promotes BV6/TNFα-induced ROS generation and necrosome assembly even in the presence of BV6, as CYLD silencing attenuates these events. Genetic silencing of phosphoglycerate mutase 5 or dynamin-related protein 1 (Drp1) fails to protect against BV6/TNFα-induced cell death. By demonstrating that ROS are involved in regulating BV6/TNFα-induced necroptotic signaling, our study provides new insights into redox regulation of necroptosis. PMID:25867066

  12. Promoted Combustion of Metals in a High-Pressure, Flowing Oxygen Environment

    NASA Technical Reports Server (NTRS)

    Maes, M. J.; Stoltzfus, J. M.

    2001-01-01

    Traditional promoted combustion testing has used 0.125 inch diameter samples that are ignited in a pressurized, oxygen-enriched environment. Many years of testing this sample size have yielded useful data regarding threshold pressure, or the minimum oxygen pressure required to support self-sustained combustion. However, when a material is tested in a flowing system, the threshold pressure changes. White Sands Test Facility has developed a test system to burn samples in flowing gaseous oxygen. Current sample configurations are 0.5 inch diameter rods and 1.25 inch diameter pipes with pressures ranging up to 2000 psi and gas velocities reaching 200 ft/s. This paper describes the test apparatus, modifications made as the result of a fire, and a description of the tests currently being performed.

  13. Strong self-limitation promotes the persistence of rare species.

    PubMed

    Yenni, Glenda; Adler, Peter B; Ernest, S K Morgan

    2012-03-01

    Theory has recognized a combination of niche and neutral processes each contributing, with varying importance, to species coexistence. However, long-term persistence of rare species has been difficult to produce in trait-based models of coexistence that incorporate stochastic dynamics, raising questions about how rare species persist despite such variability. Following recent evidence that rare species may experience significantly different population dynamics than dominant species, we use a plant community model to simulate the effect of disproportionately strong negative frequency dependence on the long-term persistence of the rare species in a simulated community. This strong self-limitation produces long persistence times for the rare competitors, which otherwise succumb quickly to stochastic extinction. The results suggest that the mechanism causing species to be rare in this case is the same mechanism allowing those species to persist. PMID:22624200

  14. Combined effect of protein and oxygen on reactive oxygen and nitrogen species in the plasma treatment of tissue

    NASA Astrophysics Data System (ADS)

    Gaur, Nishtha; Szili, Endre J.; Oh, Jun-Seok; Hong, Sung-Ha; Michelmore, Andrew; Graves, David B.; Hatta, Akimitsu; Short, Robert D.

    2015-09-01

    The influence of protein and molecular, ground state oxygen (O2) on the plasma generation, and transport of reactive oxygen and nitrogen species (RONS) in tissue are investigated. A tissue target, comprising a 1 mm thick gelatin film (a surrogate for real tissue), is placed on top of a 96-well plate; each well is filled with phosphate buffered saline (PBS, pH 7.4) containing one fluorescent or colorimetric reporter that is specific for one of three RONS (i.e., H2O2, NO2-, or OH•) or a broad spectrum reactive oxygen species reporter (2,7-dichlorodihydrofluorescein). A helium cold atmospheric plasma (CAP) jet contacts the top of the gelatin surface, and the concentrations of RONS generated in PBS are measured on a microplate reader. The data show that H2O2, NO2-, or OH• are generated in PBS underneath the target. Independently, measurements are made of the O2 concentration in the PBS with and without the gelatin target. Adding bovine serum albumin protein to the PBS or gelatin shows that protein either raises or inhibits RONS depending upon the O2 concentration. Our results are discussed in the context of plasma-soft tissue interactions that are important in the development of CAP technology for medicine, biology, and food manufacturing.

  15. NADPH Oxidase 1 and Its Derived Reactive Oxygen Species Mediated Tissue Injury and Repair

    PubMed Central

    Fu, Xiu-Jun; Peng, Ying-Bo; Hu, Yi-Ping; Shi, You-Zhen; Yao, Min; Zhang, Xiong

    2014-01-01

    Reactive oxygen species are mostly viewed to cause oxidative damage to various cells and induce organ dysfunction after ischemia-reperfusion injury. However, they are also considered as crucial molecules for cellular signal transduction in biology. NADPH oxidase, whose only function is reactive oxygen species production, has been extensively investigated in many cell types especially phagocytes. The deficiency of NADPH oxidase extends the process of inflammation and delays tissue repair, which causes chronic granulomatous disease in patients. NADPH oxidase 1, one member of the NADPH oxidase family, is not only constitutively expressed in a variety of tissues, but also induced to increase expression in both mRNA and protein levels under many circumstances. NADPH oxidase 1 and its derived reactive oxygen species are suggested to be able to regulate inflammation reaction, cell proliferation and migration, and extracellular matrix synthesis, which contribute to the processes of tissue injury and repair. PMID:24669283

  16. The Relevance of Nrf2 Pathway and Autophagy in Pancreatic Cancer Cells upon Stimulation of Reactive Oxygen Species

    PubMed Central

    2016-01-01

    Nrf2 (NF-E2-related factor 2) pathway and autophagy both can respond to oxidative stress to promote cancer cells to survive in the tumor microenvironment. We, therefore, explored the relevance between Nrf2 pathway and autophagy in pancreatic cancer cells upon stimulation of reactive oxygen species (ROS). Pancreatic cancer cells were cultured under controlled ROS stressing condition or basal condition. Different inhibitors were used to prevent autophagy at particular stages. Nrf2 siRNA was used to inhibit Nrf2 pathway activation. Ad-mRFP-GFP-LC3 infection was used to monitor autophagic flux. The result shows that a small amount of exogenous hydrogen peroxide (H2O2) can significantly improve the level of intracellular ROS. Moreover, our findings indicate that ROS promotes the activation of both Nrf2 pathway and autophagy in pancreatic cancer cells. Moreover, our data demonstrate that suppression of autophagic activity at particular stages results in an increased promotion of Nrf2 pathway activation upon ROS stimulation. Furthermore, we found that silencing of Nrf2 promotes autophagy upon ROS stimulation. In addition, Nrf2 interference effectively promotes autophagic flux upon ROS stimulation. In summary, our findings suggest that Nrf2 pathway and autophagy have a negative interaction with each other upon ROS stimulation. PMID:26682003

  17. Effects of coordination number of Au catalyst on oxygen species and their catalytic roles

    NASA Astrophysics Data System (ADS)

    Ouyang, Gen; Zhu, Kong-Jie; Zhang, Lei; Cui, Peng-Fei; Teng, Bo-Tao; Wen, Xiao-Dong

    2016-11-01

    To explore the effects of coordination number of Au nanoparticles on oxygen species and their catalytic roles is very important in gold catalysis. Based on the systematic study of oxygen adsorption on Au(997) by density functional theory calculation, the quantitative correlation for different oxygen species with coverage and Au coordination number is established in theory. The only O adatoms near step area with relatively low Au coordination numbers exist at low coverage (<1/18 ML), O adatoms adsorb at terrace areas with relatively high Au coordination numbers at medium coverage (1/18-2/9 ML); while oxygen islands form at high coverage (>2/9 ML). The theoretical predictions are in good agreement with the experimental observations in TDS spectrum. On the basis of Langmuir-Hinschelwood and Eley-Rideal mechanisms for NO oxidation, the activities of the three different oxygen species also exhibit correlation with Au coordination number. The oxygen island shows the highest oxidation activity, followed by the O adatom at terrace surface; while the O adatom near step area has the lowest oxidative performance. This work will shed light into the understanding of gold catalysis.

  18. Inactivation of Pathogenic Bacteria on Seeds by Active Oxygen Species Generated in Low-Pressure Plasma

    NASA Astrophysics Data System (ADS)

    Ono, Reoto; Uchida, Shohei; Hayashi, Nobuya; Kosaka, Rina; Soeda, Yasutaka

    2015-09-01

    The inactivation of bacteria on seeds by active oxygen species generated by a low-pressure oxygen plasma is investigated. Species of active oxygen contributing to the inactivation of bacteria are attempted to be identified. Cylindrical stainless chamber with the internal volume of 17 L is used and RF antenna is set inside the chamber. The oxygen gas pressure is 20-100 Pa. RF power of 13.56 MHz is supplied to RF antenna and CCP is generated. After irradiation, bacteria are extracted from seeds and cultivated on nutrient agars. The number of colonies on these agars is counted after 48 h incubation. The number of bacteria on seeds decreases to less than 10-3 after plasma irradiation for 45 min comparing with that of control. The tendency of the reduction rate of bacteria on seeds has positive correlation with that of the light emission intensity of the singlet excited oxygen molecule as the oxygen gas pressure is varied. It is supposed that the singlet excited oxygen molecule would be one of the major factors for the inactivation of bacteria on seeds.

  19. Endotoxin Disrupts Circadian Rhythms in Macrophages via Reactive Oxygen Species

    PubMed Central

    Wang, Yusi; Pati, Paramita; Xu, Yiming; Chen, Feng; Stepp, David W.; Huo, Yuqing; Rudic, R. Daniel; Fulton, David J. R.

    2016-01-01

    The circadian clock is a transcriptional network that functions to regulate the expression of genes important in the anticipation of changes in cellular and organ function. Recent studies have revealed that the recognition of pathogens and subsequent initiation of inflammatory responses are strongly regulated by a macrophage-intrinsic circadian clock. We hypothesized that the circadian pattern of gene expression might be influenced by inflammatory stimuli and that loss of circadian function in immune cells can promote pro-inflammatory behavior. To investigate circadian rhythms in inflammatory cells, peritoneal macrophages were isolated from mPer2luciferase transgenic mice and circadian oscillations were studied in response to stimuli. Using Cosinor analysis, we found that LPS significantly altered the circadian period in peritoneal macrophages from mPer2luciferase mice while qPCR data suggested that the pattern of expression of the core circadian gene (Bmal1) was disrupted. Inhibition of TLR4 offered protection from the LPS-induced impairment in rhythm, suggesting a role for toll-like receptor signaling. To explore the mechanisms involved, we inhibited LPS-stimulated NO and superoxide. Inhibition of NO synthesis with L-NAME had no effect on circadian rhythms. In contrast, inhibition of superoxide with Tempol or PEG-SOD ameliorated the LPS-induced changes in circadian periodicity. In gain of function experiments, we found that overexpression of NOX5, a source of ROS, could significantly disrupt circadian function in a circadian reporter cell line (U2OS) whereas iNOS overexpression, a source of NO, was ineffective. To assess whether alteration of circadian rhythms influences macrophage function, peritoneal macrophages were isolated from Bmal1-KO and Per-TKO mice. Compared to WT macrophages, macrophages from circadian knockout mice exhibited altered balance between NO and ROS release, increased uptake of oxLDL and increased adhesion and migration. These results

  20. Scavenging activity of "beta catechin" on reactive oxygen species generated by photosensitization of riboflavin.

    PubMed

    Kumari, M V; Yoneda, T; Hiramatsu, M

    1996-05-01

    "beta CATECHIN", a preparation containing green tea extract, ascorbic acid, sunflower seed extract, dunaliella carotene and natural vitamin E, has been designed as a model "universal antioxidant" that offers protection via its scavenging action on a wide range of free radicals, both water-soluble and fat-soluble. Reactive oxygen species like singlet oxygen, hydroxyl and superoxide radicals, are often generated in biological systems during photosensitized oxidation reactions. We report on the simultaneous effect of "beta CATECHIN" on active oxygen species generated during the photosensitized oxidation of riboflavin using 2,2,6,6-tetramethyl-4-piperidone (TMPD) as a "spin-trapping" agent. The intensities of the resulting stable nitroxide radical adduct, 2,2,6,6-tetramethyl-4-piperidone-1-oxyl (TEMPONE), were detected by electron spin resonance (ESR) spectroscopy. Results show simultaneous, nonspecific and complete scavenging action of reactive oxygen species generated in our in vitro model system by "beta CATECHIN". It is therefore suggested that "beta CATECHIN" could offer protection against free radical insult and in preventing cancer and other diseases that are mediated by reactive oxygen species. PMID:8739038

  1. Studies of oxygen species in synthetic Todorokite-like manganese oxide octahedral molecular sieves

    SciTech Connect

    Yin, Yuan-Gen; Xu, Wen-Qing; Shen, Yan-Fei; Suib, S.L. ); O'Young, C.L. )

    1994-10-01

    Manganese oxide octahedral molecular sieves of 3 x 3 tunnel structure (OMS-1) doped with various cations possess high thermal stability and were studied by means of temperature-programmed desorption and reduction by H[sub 2] and CO. Different oxygen species can be discerned according to their peak positions in the temperature-programmed desorption and reduction and assigned to chemisorbed dioxygen, oxygen atoms bound to Mn[sup 2+], and those bound to Mn[sup 4+] ions in the framework. Differences in peak positions and availabilities of these species during TPD and TPR can be explained by creation of nascent Mn[sup 2+] ions during TPR. The effects of doping cations on the reactivity and availability of these oxygen species are demonstrated to be more pronounced in TPR in H[sub 2] or CO than in TPD. In some instances, the trends of changes in reactivity and availability of the oxygen species due to doping of Cu[sup 2+], Ni[sup 2+], Zn[sup 2+], and Mg[sup 2+] correlated with the changes in the heat of formation of oxides of these cations. Temperature-programmed reactions with methane show some reactivity of these doped OMS-1 materials. Pulse reactions with CO show higher reactivity of Cu-doped OM-1 than with butane. However, the recovery of Cu-doped OMS-1 by reoxidation with oxygen pulses seems rather incomplete at the same temperature. 27 refs., 9 figs.

  2. Wine metabolomics reveals new sulfonated products in bottled white wines, promoted by small amounts of oxygen.

    PubMed

    Arapitsas, Panagiotis; Ugliano, Maurizio; Perenzoni, Daniele; Angeli, Andrea; Pangrazzi, Paolo; Mattivi, Fulvio

    2016-01-15

    The impact of minute amounts of oxygen in the headspace on the post-bottling development of wine is generally considered to be very important, since oxygen can either damage or improve the quality of wine. This project aimed to gain new experimental evidence about the chemistry of the interaction between wine and oxygen. The experimental design included 216 bottles of 12 different white wines produced from 6 different cultivars (Inzolia, Muller Thurgau, Chardonnay, Grillo, Traminer and Pinot gris). Half of them were bottled using the standard industrial process with inert headspace and the other half without inert gas and with extra headspace. After 60 days of storage at room temperature, the wines were analysed using an untargeted LC-MS method. The use of a detailed holistic analysis workflow, with several levels of quality control and marker selection, gave 35 metabolites putatively induced by the different amounts of oxygen. These metabolite markers included ascorbic acid, tartaric acid and various sulfonated compounds observed in wine for the first time (e.g. S-sulfonated cysteine, glutathione and pantetheine; and sulfonated indole-3-lactic acid hexoside and tryptophol). The consumption of SO2 mediated by these sulfonation reactions was promoted by the presence of higher levels of oxygen on bottling. PMID:26709023

  3. Electron Spin Resonance (ESR) detection of active oxygen species and organic phases in Martian soils

    NASA Technical Reports Server (NTRS)

    Tsay, Fun-Dow; Kim, Soon Sam; Liang, Ranty H.

    1989-01-01

    The presence of active oxygen species (O(-), O2(-), O3(-)) and other strong oxidants (Fe2O3 and Fe3O4) was invoked in interpretations of the Viking biological experiments and a model was also suggested for Martian surface chemistry. The non-biological interpretations of the biological results gain futher support as no organic compounds were detected in the Viking pyrolysis-gas chromatography mass spectrometer (GCSM) experiments at concentrations as low as 10 ppb. Electron spin resonance (ESR) measures the absorption of microwaves by a paramagnetic and/or ferromagnetic center in the presence of an external field. In many instances, ESR has the advantage of detailed submicroscopic identification of the transient species and/or unstable reaction intermediates in their environments. Since the higly active oxygen species (O(-), O2(-), O3(-), and R-O-O(-)) are all paramagnetic in nature, they can be readily detected in native form by the ESR method. Active oxygen species likely to occur in the Martian surface samples were detected by ESR in UV-irradiated samples containing MgO. A miniaturized ESR spectrometer system can be developed for the Mars Rover Sample Return Mission. The instrument can perform the following in situ Martian samples analyses: detection of active oxygen species; characterization of Martian surface chemistry and photooxidation processes; and searching for organic compounds in the form of free radicals preserved in subsoils, and detection of microfossils with Martian carbonate sediments.

  4. Activity of Heat Shock Genes’ Promoters in Thermally Contrasting Animal Species

    PubMed Central

    Astakhova, Lyubov N.; Zatsepina, Olga G.; Funikov, Sergei Yu.; Zelentsova, Elena S.; Schostak, Natalia G.; Orishchenko, Konstantin E.; Evgen’ev, Michael B.; Garbuz, David G.

    2015-01-01

    Heat shock gene promoters represent a highly conserved and universal system for the rapid induction of transcription after various stressful stimuli. We chose pairs of mammalian and insect species that significantly differ in their thermoresistance and constitutive levels of Hsp70 to compare hsp promoter strength under normal conditions and after heat shock (HS). The first pair includes the HSPA1 gene promoter of camel (Camelus dromedarius) and humans. It was demonstrated that the camel HSPA1A and HSPA1L promoters function normally in vitro in human cell cultures and exceed the strength of orthologous human promoters under basal conditions. We used the same in vitro assay for Drosophila melanogaster Schneider-2 (S2) cells to compare the activity of the hsp70 and hsp83 promoters of the second species pair represented by Diptera, i.e., Stratiomys singularior and D. melanogaster, which dramatically differ in thermoresistance and the pattern of Hsp70 accumulation. Promoter strength was also monitored in vivo in D. melanogaster strains transformed with constructs containing the S. singularior hsp70 ORF driven either by its own promoter or an orthologous promoter from the D. melanogaster hsp70Aa gene. Analysis revealed low S. singularior hsp70 promoter activity in vitro and in vivo under basal conditions and after HS in comparison with the endogenous promoter in D. melanogaster cells, which correlates with the absence of canonical GAGA elements in the promoters of the former species. Indeed, the insertion of GAGA elements into the S. singularior hsp70 regulatory region resulted in a dramatic increase in promoter activity in vitro but only modestly enhanced the promoter strength in the larvae of the transformed strains. In contrast with hsp70 promoters, hsp83 promoters from both of the studied Diptera species demonstrated high conservation and universality. PMID:25700087

  5. Molecular Oxygen and Reactive Oxygen Species in Bread-making Processes: Scarce, but Nevertheless Important.

    PubMed

    Decamps, Karolien; Joye, Iris J; De Vos, Dirk E; Courtin, Christophe M; Delcour, Jan A

    2016-01-01

    In bread making, O2 is consumed by flour constituents, yeast, and, optionally, some additives optimizing dough processing and/or product quality. It plays a major role especially in the oxidation/reduction phenomena in dough, impacting gluten network structure. The O2 level is about 7.2 mmol/kg dough, of which a significant part stems from wheat flour. We speculate that O2 is quickly lost to the atmosphere during flour hydration. Later, when the gluten network structure develops, some O2 is incorporated in dough through mixing-in of air. O2 is consumed by yeast respiration and in a number of reactions catalyzed by a wide range of enzymes present or added. About 60% of the O2 consumption in yeastless dough is ascribed to oxidation of fatty acids by wheat lipoxygenase activity. In yeasted dough, about 70% of the O2 in dough is consumed by yeast and wheat lipoxygenase. This would leave only about 30% for other reactions. The severe competition between endogenous (and added) O2-consuming systems impacts the gluten network. Moreover, the scarce literature data available suggest that exogenous oxidative enzymes but not those in flour may promote crosslinking of arabinoxylan in yeastless dough. In any case, dough turns anaerobic during the first minutes of fermentation. PMID:26055405

  6. Associative oxygen species on the oxidized silver surface formed under O 2 microwave excitation

    NASA Astrophysics Data System (ADS)

    Boronin, A. I.; Koscheev, S. V.; Murzakhmetov, K. T.; Avdeev, V. I.; Zhidomirov, G. M.

    2000-09-01

    The experimental methods of X-ray and ultraviolet photoelectron spectroscopies (XPS and UPS, respectively) and the quantum mechanical calculations are applied for analysis of oxygen states on the silver oxide surface. At low temperatures ( T<470 K), the silver surface is intensively oxidized by a microwave oxygen discharge to form cuprite Ag 2O. Two adsorbed oxygen species of the atomic (dissociative) and molecular (associative) nature can be adsorbed on the cuprite Ag 2O surface. A comparison of the UPS data and the DFT calculations of molecular models Ag 2-O 2 and Ag 2-O 3 shows that the formation of ozonide-like structures is preferable to that of peroxide species. Thermal stability and the reaction probability of the adsorbed states are investigated.

  7. Deoxyamphimedine, a pyridoacridine alkaloid, damages DNA via the production of reactive oxygen species.

    PubMed

    Marshall, Kathryn M; Andjelic, Cynthia D; Tasdemir, Deniz; Concepción, Gisela P; Ireland, Chris M; Barrows, Louis R

    2009-01-01

    Marine pyridoacridines are a class of aromatic chemicals that share an 11H-pyrido[4,3,2-mn]acridine skeleton. Pyridoacridine alkaloids display diverse biological activities including cytotoxicity, fungicidal and bactericidal properties, production of reactive oxygen species (ROS) and topoisomerase inhibition. These activities are often dependent on slight modifications to the pyridoacridine skeleton. Here we demonstrate that while structurally similar to neoamphimedine and amphimedine, the biological activity of deoxyamphimedine differs greatly. Deoxyamphimedine damages DNA in vitro independent of topoisomerase enzymes through the generation of reactive oxygen species. Its activity was decreased in low oxygen, with the removal of a reducing agent and in the presence of anti-oxidants. Deoxyamphimedine also showed enhanced toxicity in cells sensitive to single or double strand DNA breaks, consistent with the in vitro activity. PMID:19597581

  8. NADPH Oxidase- and Mitochondria-derived Reactive Oxygen Species in Proinflammatory Microglial Activation: A Bipartisan Affair?

    PubMed Central

    Bordt, Evan A.; Polster, Brian M.

    2014-01-01

    Microglia are the resident immune cells of the brain and play major roles in central nervous system development, maintenance, and disease. Brain insults cause microglia to proliferate, migrate, and transform into one or more activated states. Classical M1 activation triggers the production of proinflammatory factors such as tumor necrosis factor- α (TNF-α), interleukin-1β (IL-1β), nitric oxide (NO), and reactive oxygen species which, in excess, can exacerbate brain injury. The mechanisms underlying microglial activation are not fully understood, yet reactive oxygen species are increasingly implicated as mediators of microglial activation. In this review, we highlight studies linking reactive oxygen species, in particular hydrogen peroxide derived from NADPH oxidase-generated superoxide, to the classical activation of microglia. In addition, we critically evaluate controversial evidence suggesting a specific role for mitochondrial reactive oxygen species in the activation of the NLRP3 inflammasome, a multiprotein complex that mediates the production of IL-1β and IL-18. Finally, the limitations of common techniques used to implicate mitochondrial ROS in microglial and inflammasome activation, such as the use of the mitochondrially-targeted ROS indicator MitoSOX and the mitochondrially-targeted antioxidant MitoTEMPO, are also discussed. PMID:25091898

  9. Mitochondrial function and reactive oxygen species action in relation to boar motility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flow cytometric assays were developed for reactive oxygen species (ROS) formation (ROS-induced oxidization of hydroethidine to ethidium), membrane lipid peroxidation (C11-BODIPY-581/591 oxidation), and mitochondrial transmembrane potential (MMP) (MMP-induced JC-1 aggregation, red fluorescence) in vi...

  10. Water-soluble fullerene materials for bioapplications: photoinduced reactive oxygen species generation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The photoinduced reactive oxygen species (ROS) generation from several water-soluble fullerenes was examined. Macromolecular or small molecular water-soluble fullerene complexes/derivatives were prepared and their 1O2 and O2•- generation abilities were evaluated by EPR spin-trapping methods. As a r...

  11. Release of elicitors from rice blast spores under the action of reactive oxygen species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of reactive oxygen species (ROS) on secretion of hypothesized elicitors from spores of rice blast causal fungus Magnaporthe grisea were studied. For spore exposure to exogenous ROS, they were germinated for 5 h in 50 µM H2O2 followed by addition of catalase E.C. 1.11.1.6 (to decompose pe...

  12. Effects of reactive oxygen species action on sperm function in spermatozoa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reactive oxygen species (ROS) formation and lipid peroxidation have been recognized as problems for sperm survival and fertility. The precise roles and detection of superoxide (SO), hydrogen peroxide (HP), and membrane lipid peroxidation have been problematic because of the low specificity and sens...

  13. Mitochondrial function and reactive oxygen species action in relation to boar motility.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flow cytometric assays of viable boar sperm were developed to measure reactive oxygen species (ROS) formation (oxidization of hydroethidine to ethidium), membrane lipid peroxidation (oxidation of lipophilic probe C11-BODIPY581/591), and mitochondrial inner transmembrane potential (aggregation of mit...

  14. Reactive Oxygen Species Are Involved in Plant Defense against a Gall Midge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reactive oxygen species (ROS) play a major role in plant defense against pathogens, but evidence for their role in defense against insects is still preliminary and inconsistent. In this study, we examined the potential role of ROS in defense of wheat and rice against Hessian fly (Mayetiola destruct...

  15. Iron and Reactive Oxygen Species: Friends or Foes of Cancer Cells?

    PubMed Central

    Bystrom, Laura M.

    2014-01-01

    Abstract Significance: In this review, the dual nature of both iron and reactive oxygen species (ROS) will be explored in normal and cancer cell metabolism. Although iron and ROS play important roles in cellular homeostasis, they may also contribute to carcinogenesis. On the other hand, many studies have indicated that abrogation of iron metabolism, elevation of ROS, or modification of redox regulatory mechanisms in cancer cells, should be considered as therapeutic approaches for cancer. Recent Advances: Drugs that target different aspects of iron metabolism may be promising therapeutics for cancer. The ability of iron chelators to cause iron depletion and/or elevate ROS levels indicates that these types of compounds have more potential as antitumor medicines than originally expected. Other natural and synthetic compounds that target pathways involved in ROS homeostasis also have potential value alone or in combination with current chemotherapeutics. Critical Issues: Although ROS induction and iron depletion may be targets for cancer therapies, the optimal therapeutic strategies have yet to be identified. This review highlights some of the research that strives to identify such therapeutics. Future Directions: More studies are needed to better understand the role of iron and ROS in carcinogenesis not only as cancer promoters, but also as cytotoxic agents to cancer cells and cancer stem cells (CSCs). Moreover, the structure–activity effects of iron chelators and other compounds that increase ROS and/or disrupt iron metabolism need to be further evaluated to assess the effectiveness and selectivity of these compounds against both cancer and CSCs. Antioxid. Redox Signal. 20, 1917–1924. PMID:23198911

  16. Ethylene-induced flavonol accumulation in guard cells suppresses reactive oxygen species and moderates stomatal aperture.

    PubMed

    Watkins, Justin M; Hechler, Paul J; Muday, Gloria K

    2014-04-01

    Guard cell swelling controls the aperture of stomata, pores that facilitate gas exchange and water loss from leaves. The hormone abscisic acid (ABA) has a central role in regulation of stomatal closure through synthesis of second messengers, which include reactive oxygen species (ROS). ROS accumulation must be minimized by antioxidants to keep concentrations from reaching damaging levels within the cell. Flavonols are plant metabolites that have been implicated as antioxidants; however, their antioxidant activity in planta has been debated. Flavonols accumulate in guard cells of Arabidopsis thaliana, but not surrounding pavement cells, as visualized with a flavonol-specific dye. The expression of a reporter driven by the promoter of CHALCONE SYNTHASE, a gene encoding a flavonol biosynthetic enzyme, in guard cells, but not pavement cells, suggests guard cell-specific flavonoid synthesis. Increased levels of ROS were detected using a fluorescent ROS sensor in guard cells of transparent testa4-2, which has a null mutation in CHALCONE SYNTHASE and therefore synthesizes no flavonol antioxidants. Guard cells of transparent testa4-2 show more rapid ABA-induced closure than the wild type, suggesting that flavonols may dampen the ABA-dependent ROS burst that drives stomatal closing. The levels of flavonols are positively regulated in guard cells by ethylene treatment in the wild type, but not in the ethylene-insensitive2-5 mutant. In addition, in both ethylene-overproducing1 and ethylene-treated wild-type plants, elevated flavonols lead to decreasing ROS and slower ABA-mediated stomatal closure. These results are consistent with flavonols suppressing ROS accumulation and decreasing the rate of ABA-dependent stomatal closure, with ethylene-induced increases in guard cell flavonols modulating these responses. PMID:24596331

  17. NADPH Oxidases: A Perspective on Reactive Oxygen Species Production in Tumor Biology

    PubMed Central

    Meitzler, Jennifer L.; Antony, Smitha; Wu, Yongzhong; Juhasz, Agnes; Liu, Han; Jiang, Guojian; Lu, Jiamo; Roy, Krishnendu

    2014-01-01

    Abstract Significance: Reactive oxygen species (ROS) promote genomic instability, altered signal transduction, and an environment that can sustain tumor formation and growth. The NOX family of NADPH oxidases, membrane-bound epithelial superoxide and hydrogen peroxide producers, plays a critical role in the maintenance of immune function, cell growth, and apoptosis. The impact of NOX enzymes in carcinogenesis is currently being defined and may directly link chronic inflammation and NOX ROS-mediated tumor formation. Recent Advances: Increased interest in the function of NOX enzymes in tumor biology has spurred a surge of investigative effort to understand the variability of NOX expression levels in tumors and the effect of NOX activity on tumor cell proliferation. These initial efforts have demonstrated a wide variance in NOX distribution and expression levels across numerous cancers as well as in common tumor cell lines, suggesting that much remains to be discovered about the unique role of NOX-related ROS production within each system. Progression from in vitro cell line studies toward in vivo tumor tissue screening and xenograft models has begun to provide evidence supporting the importance of NOX expression in carcinogenesis. Critical Issues: A lack of universally available, isoform-specific antibodies and animal tumor models of inducible knockout or over-expression of NOX isoforms has hindered progress toward the completion of in vivo studies. Future Directions: In vivo validation experiments and the use of large, existing gene expression data sets should help define the best model systems for studying the NOX homologues in the context of cancer. Antioxid. Redox Signal. 20, 2873–2889. PMID:24156355

  18. Hydrogen peroxide inducible clone-5 mediates reactive oxygen species signaling for hepatocellular carcinoma progression.

    PubMed

    Wu, Jia-Ru; Hu, Chi-Tan; You, Ren-In; Pan, Siou-Mei; Cheng, Chuan-Chu; Lee, Ming-Che; Wu, Chao-Chuan; Chang, Yao-Jen; Lin, Shu-Chuan; Chen, Chang-Shan; Lin, Teng-Yi; Wu, Wen-Sheng

    2015-10-20

    One of the signaling components involved in hepatocellular carcinoma (HCC) progression is the focal adhesion adaptor paxillin. Hydrogen peroxide inducible clone-5 (Hic-5), one of the paralogs of paxillin, exhibits many biological functions distinct from paxillin, but may cooperate with paxillin to trigger tumor progression. Screening of Hic-5 in 145 surgical HCCs demonstrated overexpression of Hic-5 correlated well with intra- and extra-hepatic metastasis. Hic-5 highly expressed in the patient derived HCCs with high motility such as HCC329 and HCC353 but not in the HCCs with low motility such as HCC340. Blockade of Hic-5 expression prevented constitutive migration of HCC329 and HCC353 and HGF-induced cell migration of HCC340. HCC329Hic-5(-), HCC353Hic-5(-), HCC372Hic-5(-), the HCCs stably depleted of Hic-5, exhibited reduced motility compared with each HCC expressing Scramble shRNA. Moreover, intra/extrahepatic metastasis of HCC329Hic-5(-) in SCID mice greatly decreased compared with HCC329Scramble. On the other hand, ectopic Hic-5 expression in HCC340 promoted its progression. Constitutive and HGF-induced Hic-5 expression in HCCs were suppressed by the reactive oxygen species (ROS) scavengers catalase and dithiotheritol and c-Jun N-terminal kinase (JNK) inhibitor SP600125. On the contrary, depletion of Hic-5 blocked constitutive and HGF-induced ROS generation and JNK phosphorylation in HCCs. Also, ectopic expression of Hic-5 enhanced ROS generation and JNK phosphorylation. These highlighted that Hic-5 plays a central role in the positive feedback ROS-JNK signal cascade. Finally, the Chinese herbal derived anti-HCC peptide LZ-8 suppressed constitutive Hic-5 expression and JNK phosphorylation. In conclusion, Hic-5 mediates ROS-JNK signaling and may serve as a therapeutic target for prevention of HCC progression. PMID:26416447

  19. Evidence for the generation of reactive oxygen species from hydroquinone and benzoquinone: Roles in arsenite oxidation.

    PubMed

    Qin, Wenxiu; Wang, Yujun; Fang, Guodong; Wu, Tongliang; Liu, Cun; Zhou, Dongmei

    2016-05-01

    Natural organic matter (NOM) significantly affects the fate, bioavailability, and toxicity of arsenic in the environment. In the present study, we investigated the oxidation of As(III) in the presence of hydroquinone (HQ) and benzoquinone (BQ), which were selected as model quinone moieties for NOM. It was found that As(III) was oxidized to As(V) in the presence of HQ or BQ at neutral conditions, and the oxidation efficiency of As(III) increased from 33% to 92% in HQ solutions and from 0 to 80% in BQ solutions with pH increasing from 6.5 to 8.5. The oxidation mechanism was further explored with electron spin resonance (ESR) technique. The results showed that semiquinone radicals (SQ(-)) were generated from the comproportionation reaction between BQ and HQ, which mediated the formation of superoxide anion (O2(-)), hydrogen peroxide (H2O2) and hydroxyl radical (OH). Both the SQ(-), H2O2 and OH contributed to the oxidation of As(III). The increase of pH favored the formation of SQ(-), and thus promoted the generation of reactive oxygen species (ROS) as well as As(III) oxidation. Increasing concentrations of HQ and BQ from 0.1 to 1.0 mM enhanced As(III) oxidation from 65% to 94% and from 10% to 53%, respectively. The findings of this study facilitate our understanding of the fate and transformation of As(III) in organic-rich aquatic environments and highlight quinone moieties as the potential oxidants for As(III) in the remediation of arsenic contaminated sites. PMID:26891359

  20. A role for reactive oxygen species in JAK2 V617F myeloproliferative neoplasm progression.

    PubMed

    Marty, C; Lacout, C; Droin, N; Le Couédic, J-P; Ribrag, V; Solary, E; Vainchenker, W; Villeval, J-L; Plo, I

    2013-11-01

    Although other mutations may predate the acquisition of the JAK2(V617F) mutation, the latter is sufficient to drive the disease phenotype observed in BCR-ABL-negative myeloproliferative neoplasms (MPNs). One of the consequences of JAK2(V617F) is genetic instability that could explain JAK2(V617F)-mediated MPN progression and heterogeneity. Here, we show that JAK2(V617F) induces the accumulation of reactive oxygen species (ROS) in the hematopoietic stem cell compartment of a knock-in (KI) mouse model and in patients with JAK2(V617F) MPNs. JAK2(V617F)-dependent ROS elevation was partly mediated by an AKT-induced decrease in catalase expression and was accompanied by an increased number of 8-oxo-guanines and DNA double-strand breaks (DSBs). Moreover, there was evidence for a mitotic recombination event in mice resulting in loss of heterozygosity of Jak2(V617F). Mice engrafted with 30% of Jak2(V617F) KI bone marrow (BM) cells developed a polycythemia vera-like disorder. Treatment with the anti-oxidant N-acetylcysteine (NAC) substantially restored blood parameters and reduced damages to DNA. Furthermore, NAC induced a marked decrease in splenomegaly with reduction in the frequency of the Jak2(V617F)-positive hematopoietic progenitors in BM and spleen. Altogether, overproduction of ROS is a mediator of JAK2(V617F)-induced DNA damages that promote disease progression. Targeting ROS accumulation might prevent the development of JAK2(V617F) MPNs. PMID:23558526

  1. Role of Reactive Oxygen Species in the Abrogation of Oxaliplatin Activity by Cetuximab in Colorectal Cancer

    PubMed Central

    Santoro, Valeria; Jia, Ruochen; Thompson, Hannah; Nijhuis, Anke; Jeffery, Rosemary; Kiakos, Konstantinos; Silver, Andrew R.; Hartley, John A.

    2016-01-01

    Background: The antibody cetuximab, targeting epidermal growth factor receptor (EGFR), is used to treat metastatic colorectal cancer (mCRC). Clinical trials suggest reduced benefit from the combination of cetuximab with oxaliplatin. The aim of this study was to investigate potential negative interactions between cetuximab and oxaliplatin. Methods: Thiazolyl blue tetrazolium bromide (MTT) assay and Calcusyn software were used to characterize drug interactions. Reactive oxygen species (ROS) were measured by flow cytometry and real-time polymerase chain reaction oxidative stress arrays identified genes regulating ROS production. Chromatin immunoprecipitation (ChIP) measured signal transducer and activator of transcription 1 (STAT-1) binding to dual oxidase 2 (DUOX2) promoter. SW48, DLD-1 KRAS wild-type cell lines and DLD-1 xenograft models exposed to cetuximab, oxaliplatin, or oxaliplatin + cetuximab (control [saline]; n = 3 mice per treatment group) were used. Statistical tests were two-sided. Results: Cetuximab and oxaliplatin exhibited antagonistic effects on cellular proliferation and apoptosis (caspase 3/7 activity reduced by 1.4-fold, 95% confidence interval [CI] = 0.78 to 2.11, P = .003) as opposed to synergistic effects observed with the irinotecan metabolite 7-Ethyl-10-hydroxycamptothecin (SN-38). Although both oxaliplatin and SN-38 produced ROS, only oxaliplatin-mediated apoptosis was ROS dependent. Production of ROS by oxaliplatin was secondary to STAT1-mediated transcriptional upregulation of DUOX2 (3.1-fold, 95% CI = 1.75 to 2.41, P < .001). Inhibition of DUOX2 induction and p38 activation by cetuximab reduced oxaliplatin cytotoxicity. Conclusions: Inhibition of STAT1 and DUOX2-mediated ROS generation by cetuximab impairs p38-dependent apoptosis by oxaliplatin in preclinical models and may contribute to reduced efficacy in clinical settings. Understanding the rationale for unexpected trial results will inform improved rationales for combining EGFR

  2. Alkbh8 Regulates Selenocysteine-Protein Expression to Protect against Reactive Oxygen Species Damage

    PubMed Central

    Endres, Lauren; Dziergowska, Agnieszka; Małkiewicz, Andrzej; Melendez, J. Andres; Dedon, Peter C.; Begley, Thomas J.

    2015-01-01

    Environmental and metabolic sources of reactive oxygen species (ROS) can damage DNA, proteins and lipids to promote disease. Regulation of gene expression can prevent this damage and can include increased transcription, translation and post translational modification. Cellular responses to ROS play important roles in disease prevention, with deficiencies linked to cancer, neurodegeneration and ageing. Here we detail basal and damage-induced translational regulation of a group of oxidative-stress response enzymes by the tRNA methyltransferase Alkbh8. Using a new gene targeted knockout mouse cell system, we show that Alkbh8-/- embryonic fibroblasts (MEFs) display elevated ROS levels, increased DNA and lipid damage and hallmarks of cellular stress. We demonstrate that Alkbh8 is induced in response to ROS and is required for the efficient expression of selenocysteine-containing ROS detoxification enzymes belonging to the glutathione peroxidase (Gpx1, Gpx3, Gpx6 and likely Gpx4) and thioredoxin reductase (TrxR1) families. We also show that, in response to oxidative stress, the tRNA modification 5-methoxycarbonylmethyl-2′-O-methyluridine (mcm5Um) increases in normal MEFs to drive the expression of ROS detoxification enzymes, with this damage-induced reprogramming of tRNA and stop-codon recoding corrupted in Alkbh8-/- MEFS. These studies define Alkbh8 and tRNA modifications as central regulators of cellular oxidative stress responses in mammalian systems. In addition they highlight a new animal model for use in environmental and cancer studies and link translational regulation to the prevention of DNA and lipid damage. PMID:26147969

  3. The involvement of reactive oxygen species in oral cancers of betel quid/tobacco chewers.

    PubMed

    Stich, H F; Anders, F

    1989-09-01

    Most biological reactions, including carcinogenesis, are complex processes involving thousands of compounds, their metabolites and intermediates. The separation of events which form part of a direct chain leading to neoplastic transformation from those which are mere by-products is a herculean task. In this study, we focused on the pros and cons of reactive oxygen species (ROS) being involved in the development of oral cancer among chewers of tobacco and areca nuts. The results revealed that bursts of ROS generation occur at different stages of carcinogenesis, and are caused by different mechanisms. This observation may have considerable practical implications. Different strategies will be required in the administration of chemopreventive agents in order to trap ROS formed in the alkaline (due to the addition of slaked lime) chewing mixture within the saliva of a chewer, to scavenge ROS within mucosal cells exposed to an array of tobacco- or areca nut-related carcinogens or tumour promoters, and to inhibit the action of ROS released from ROS-generating white cells during lymphocytic infiltration of the oral mucosa at a precancerous stage. The remission of oral leukoplakias following the administration of vitamin A (200,000 IU/week) or vitamin A (100,000 IU/week) plus beta-carotene (180 mg/week) for 6 months, the inhibition of new leukoplakias during this trial period, and the reduction of micronucleated oral mucosal cells in chewers treated with beta-carotene or vitamin A are indeed promising results. However, a better understanding of the role of ROS in various stages of carcinogenesis will provide the basis for selection of the proper chemopreventive agents and the design of a treatment regime which may either prevent the formation of precancerous lesions, induce their remission, or inhibit the progression of precancerous lesions into malignant cancers. PMID:2671701

  4. Reactive oxygen species modulate Anopheles gambiae immunity against bacteria and Plasmodium.

    PubMed

    Molina-Cruz, Alvaro; DeJong, Randall J; Charles, Bradley; Gupta, Lalita; Kumar, Sanjeev; Jaramillo-Gutierrez, Giovanna; Barillas-Mury, Carolina

    2008-02-01

    The involvement of reactive oxygen species (ROS) in mosquito immunity against bacteria and Plasmodium was investigated in the malaria vector Anopheles gambiae. Strains of An. gambiae with higher systemic levels of ROS survive a bacterial challenge better, whereas reduction of ROS by dietary administration of antioxidants significantly decreases survival, indicating that ROS are required to mount effective antibacterial responses. Expression of several ROS detoxification enzymes increases in the midgut and fat body after a blood meal. Furthermore, expression of several of these enzymes increases to even higher levels when mosquitoes are fed a Plasmodium berghei-infected meal, indicating that the oxidative stress after a blood meal is exacerbated by Plasmodium infection. Paradoxically, a complete lack of induction of catalase mRNA and lower catalase activity were observed in P. berghei-infected midguts. This suppression of midgut catalase expression is a specific response to ookinete midgut invasion and is expected to lead to higher local levels of hydrogen peroxide. Further reduction of catalase expression by double-stranded RNA-mediated gene silencing promoted parasite clearance by a lytic mechanism and reduced infection significantly. High mosquito mortality is often observed after P. berghei infection. Death appears to result in part from excess production of ROS, as mortality can be decreased by oral administration of uric acid, a strong antioxidant. We conclude that ROS modulate An. gambiae immunity and that the mosquito response to P. berghei involves a local reduction of detoxification of hydrogen peroxide in the midgut that contributes to limit Plasmodium infection through a lytic mechanism. PMID:18065421

  5. Influence of dissolved organic matter on photogenerated reactive oxygen species and metal-oxide nanoparticle toxicity.

    PubMed

    Li, Yang; Niu, Junfeng; Shang, Enxiang; Crittenden, John Charles

    2016-07-01

    The effect of humic acid (HA) or fulvic acid (FA) on reactive oxygen species (ROS) generation by six metal-oxide nanoparticles (NPs) and their toxicities toward Escherichia coli was investigated under UV irradiation. Dissolved organic matter (DOM) decreased OH generation by TiO2, ZnO, and Fe2O3, with FA inhibiting OH generation more than HA. The generated OH in NPs/DOM mixtures was higher than the measured concentrations because DOM consumes OH faster than its molecular probe. None of NPs/FA mixtures produced O2(-). The generated O2(-) concentrations in NPs/HA mixtures (except Fe2O3/HA) were higher than the sum of O2(-) concentrations that produced as NPs and HA were presented by themselves. Synergistic O2(-) generation in NPs/HA mixtures resulted from O2 reduction by electron transferred from photoionized HA to NPs. DOM increased (1)O2 generation by TiO2, CuO, CeO2, and SiO2, and FA promoted (1)O2 generation more than HA. Enhanced (1)O2 generation resulted from DOM sensitization of NPs. HA did not increase (1)O2 generation by ZnO and Fe2O3 primarily because released ions quenched (1)O2 precursor ((3)HA*). Linear correlation was developed between total ROS concentrations generated by NPs/DOM mixtures and bacterial survival rates (R(2) ≥ 0.80). The results implied the necessity of considering DOM when investigating the photoreactivity of NPs. PMID:27064207

  6. Glucose modulation induces reactive oxygen species and increases P-glycoprotein-mediated multidrug resistance to chemotherapeutics

    PubMed Central

    Seebacher, N A; Richardson, D R; Jansson, P J

    2015-01-01

    Background and Purpose Cancer cells develop resistance to stress induced by chemotherapy. In tumours, a considerable glucose gradient exists, resulting in stress. Notably, hypoxia-inducible factor-1 (HIF-1) is a redox-sensitive transcription factor that regulates P-glycoprotein (Pgp), a crucial drug-efflux transporter involved in multidrug resistance (MDR). Here, we investigated how glucose levels regulate Pgp-mediated drug transport and resistance. Experimental Approach Human tumour cells (KB31, KBV1, A549 and DMS-53) were incubated under glucose starvation to hyperglycaemic conditions. Flow cytometry assessed reactive oxygen species (ROS) generation and Pgp activity. HIF-1α, NF-κB and Pgp expression were assessed by reverse transcriptase-PCR and Western blotting. Fluorescence microscopy examined p65 distribution and a luciferase-reporter assay assessed HIF-1 promoter-binding activity. The effect of glucose-induced stress on Pgp-mediated drug resistance was examined after incubating cells with the chemotherapeutic and Pgp substrate, doxorubicin (DOX), and performing MTT assays validated by viable cell counts. Key Results Changes in glucose levels markedly enhanced cellular ROS and conferred Pgp-mediated drug resistance. Low and high glucose levels increased (i) ROS generation via NADPH oxidase 4 and mitochondrial membrane destabilization; (ii) HIF-1 activity; (iii) nuclear translocation of the NF-κB p65 subunit; and (iv) HIF-1α mRNA and protein levels. Increased HIF-1α could also be due to decreased prolyl hydroxylase protein under these conditions. The HIF-1α target, Pgp, was up-regulated at low and high glucose levels, which led to lower cellular accumulation of Pgp substrate, rhodamine123, and greater resistance to DOX. Conclusions and Implications As tumour cells become glucose-deprived or exposed to high glucose levels, this increases stress, leading to a more aggressive MDR phenotype via up-regulation of Pgp. PMID:25586174

  7. A Strategy to Promote the Electrocatalytic Activity of Spinels for Oxygen Reduction by Structure Reversal.

    PubMed

    Wu, Guangping; Wang, Jun; Ding, Wei; Nie, Yao; Li, Li; Qi, Xueqiang; Chen, Siguo; Wei, Zidong

    2016-01-22

    The electrocatalytic performance of a spinel for the oxygen reduction reaction (ORR) can be significantly promoted by reversing its crystalline structure from the normal to the inverse. As the spinel structure reversed, the activation and cleavage of O-O bonds are accelerated owing to a dissimilarity effect of the distinct metal atoms co-occupying octahedral sites. The Co(II)Fe(III)Co(III)O4 spinel with the Fe and Co co-occupying inverse structure exhibits an excellent ORR activity, which even exceeds that of the state-of-the-art commercial Pt/C by 42 mV in alkaline medium. PMID:26663768

  8. Oxygen and Air Nanobubble Water Solution Promote the Growth of Plants, Fishes, and Mice

    PubMed Central

    Ebina, Kosuke; Shi, Kenrin; Hirao, Makoto; Hashimoto, Jun; Kawato, Yoshitaka; Kaneshiro, Shoichi; Morimoto, Tokimitsu; Koizumi, Kota; Yoshikawa, Hideki

    2013-01-01

    Nanobubbles (<200 nm in diameter) have several unique properties such as long lifetime in liquid owing to its negatively charged surface, and its high gas solubility into the liquid owing to its high internal pressure. They are used in variety of fields including diagnostic aids and drug delivery, while there are no reports assessing their effects on the growth of lives. Nanobubbles of air or oxygen gas were generated using a nanobubble aerator (BUVITAS; Ligaric Company Limited, Osaka, Japan). Brassica campestris were cultured hydroponically for 4 weeks within air-nanobubble water or within normal water. Sweetfish (for 3 weeks) and rainbow trout (for 6 weeks) were kept either within air-nanobubble water or within normal water. Finally, 5 week-old male DBA1/J mice were bred with normal free-chaw and free-drinking either of oxygen-nanobubble water or of normal water for 12 weeks. Oxygen-nanobubble significantly increased the dissolved oxygen concentration of water as well as concentration/size of nanobubbles which were relatively stable for 70 days. Air-nanobubble water significantly promoted the height (19.1 vs. 16.7 cm; P<0.05), length of leaves (24.4 vs. 22.4 cm; P<0.01), and aerial fresh weight (27.3 vs. 20.3 g; P<0.01) of Brassica campestris compared to normal water. Total weight of sweetfish increased from 3.0 to 6.4 kg in normal water, whereas it increased from 3.0 to 10.2 kg in air-nanobubble water. In addition, total weight of rainbow trout increased from 50.0 to 129.5 kg in normal water, whereas it increased from 50.0 to 148.0 kg in air-nanobubble water. Free oral intake of oxygen-nanobubble water significantly promoted the weight (23.5 vs. 21.8 g; P<0.01) and the length (17.0 vs. 16.1 cm; P<0.001) of mice compared to that of normal water. We have demonstrated for the first time that oxygen and air-nanobubble water may be potentially effective tools for the growth of lives. PMID:23755221

  9. Oxygen and air nanobubble water solution promote the growth of plants, fishes, and mice.

    PubMed

    Ebina, Kosuke; Shi, Kenrin; Hirao, Makoto; Hashimoto, Jun; Kawato, Yoshitaka; Kaneshiro, Shoichi; Morimoto, Tokimitsu; Koizumi, Kota; Yoshikawa, Hideki

    2013-01-01

    Nanobubbles (<200 nm in diameter) have several unique properties such as long lifetime in liquid owing to its negatively charged surface, and its high gas solubility into the liquid owing to its high internal pressure. They are used in variety of fields including diagnostic aids and drug delivery, while there are no reports assessing their effects on the growth of lives. Nanobubbles of air or oxygen gas were generated using a nanobubble aerator (BUVITAS; Ligaric Company Limited, Osaka, Japan). Brassica campestris were cultured hydroponically for 4 weeks within air-nanobubble water or within normal water. Sweetfish (for 3 weeks) and rainbow trout (for 6 weeks) were kept either within air-nanobubble water or within normal water. Finally, 5 week-old male DBA1/J mice were bred with normal free-chaw and free-drinking either of oxygen-nanobubble water or of normal water for 12 weeks. Oxygen-nanobubble significantly increased the dissolved oxygen concentration of water as well as concentration/size of nanobubbles which were relatively stable for 70 days. Air-nanobubble water significantly promoted the height (19.1 vs. 16.7 cm; P<0.05), length of leaves (24.4 vs. 22.4 cm; P<0.01), and aerial fresh weight (27.3 vs. 20.3 g; P<0.01) of Brassica campestris compared to normal water. Total weight of sweetfish increased from 3.0 to 6.4 kg in normal water, whereas it increased from 3.0 to 10.2 kg in air-nanobubble water. In addition, total weight of rainbow trout increased from 50.0 to 129.5 kg in normal water, whereas it increased from 50.0 to 148.0 kg in air-nanobubble water. Free oral intake of oxygen-nanobubble water significantly promoted the weight (23.5 vs. 21.8 g; P<0.01) and the length (17.0 vs. 16.1 cm; P<0.001) of mice compared to that of normal water. We have demonstrated for the first time that oxygen and air-nanobubble water may be potentially effective tools for the growth of lives. PMID:23755221

  10. Significance of Oxygen Supply in Jarosite Biosynthesis Promoted by Acidithiobacillus ferrooxidans

    PubMed Central

    Liang, Jianru; Zhou, Lixiang

    2015-01-01

    Jarosite [(Na+, K+, NH4+, H3O+)Fe3(SO4)2(OH)6] is an efficient scavenger for trace metals in Fe- and SO42--rich acidic water. During the biosynthesis of jarosite promoted by Acidithiobacillus ferrooxidans, the continuous supply of high oxygen levels is a common practice that results in high costs. To evaluate the function of oxygen in jarosite production by A. ferrooxidans, three groups of batch experiments with different oxygen supply levels (i.e., loading volume percentages of FeSO4 solution of 20%, 40%, and 70% v/v in the flasks), as well as three groups of sealed flask experiments with different limiting oxygen supply conditions (i.e., the solutions were not sealed at the initial stage of the ferrous oxidation reaction by paraffin but were rather sealed at the end of the ferrous oxidation reaction at 48 h), were tested. The formed Fe-precipitates were characterized via X-ray powder diffraction and scanning electron microscope-energy dispersive spectral analysis. The results showed that the biosynthesis of jarosite by A. ferrooxidans LX5 could be achieved at a wide range of solution loading volume percentages. The rate and efficiency of the jarosite biosynthesis were poorly correlated with the concentration of dissolved oxygen in the reaction solution. Similar jarosite precipitates, expressed as KFe3 (SO4) 2(OH)6 with Fe/S molar ratios between 1.61 and 1.68, were uniformly formed in unsealed and 48 h sealed flasks. These experimental results suggested that the supply of O2 was only essential in the period of the oxidation of ferrous iron to ferric but was not required in the period of ferric precipitation. PMID:25807372

  11. Palladium-Based Nanomaterials: A Platform to Produce Reactive Oxygen Species for Catalyzing Oxidation Reactions.

    PubMed

    Long, Ran; Huang, Hao; Li, Yaping; Song, Li; Xiong, Yujie

    2015-11-25

    Oxidation reactions by molecular oxygen (O2 ) over palladium (Pd)-based nanomaterials are a series of processes crucial to the synthesis of fine chemicals. In the past decades, investigations of related catalytic materials have mainly been focused on the synthesis of Pd-based nanomaterials from the angle of tailoring their surface structures, compositions and supporting materials, in efforts to improve their activities in organic reactions. From the perspective of rational materials design, it is imperative to address the fundamental issues associated with catalyst performance, one of which should be oxygen activation by Pd-based nanomaterials. Here, the fundamentals that account for the transformation from O2 to reactive oxygen species over Pd, with a focus on singlet O2 and its analogue, are introduced. Methods for detecting and differentiating species are also presented to facilitate future fundamental research. Key factors for tuning the oxygen activation efficiencies of catalytic materials are then outlined, and recent developments in Pd-catalyzed oxygen-related organic reactions are summarized in alignment with each key factor. To close, we discuss the challenges and opportunities for photocatalysis research at this unique intersection as well as the potential impact on other research fields. PMID:26422795

  12. Oxygen stress reduces zoospore survival of Phytophthora species in a simulated aquatic system

    PubMed Central

    2014-01-01

    Background The genus Phytophthora includes a group of agriculturally important pathogens and they are commonly regarded as water molds. They produce motile zoospores that can move via water currents and on their own locomotion in aquatic environments. However, zoosporic response to dissolved oxygen, an important water quality parameter, is not known. Like other water quality parameters, dissolved oxygen concentration in irrigation reservoirs fluctuates dramatically over time. The aim of this study was to determine whether and how zoospore survival may be affected by elevated and low concentrations of dissolved oxygen in water to better understand the aquatic biology of these pathogens in irrigation reservoirs. Results Zoospores of P. megasperma, P. nicotianae, P. pini and P. tropicalis were assessed for survival in 10% Hoagland’s solution at a range of dissolved concentrations from 0.9 to 20.1 mg L-1 for up to seven exposure times from 0 to 72 h. Zoospore survival was measured by resultant colony counts per ml. Zoospores of these species survived the best in control Hoagland’s solution at dissolved oxygen concentrations of 5.3 to 5.6 mg L-1. Zoospore survival rates decreased with increasing and decreasing concentration of dissolved oxygen, depending upon Phytophthora species and exposure time. Overall, P. megasperma and P. pini are less sensitive than P. nicotianae and P. tropicalis to hyperoxia and hypoxia conditions. Conclusion Zoospores in the control solution declined over time and this natural decline process was enhanced under hyperoxia and hypoxia conditions. These findings suggest that dramatic fluctuations of dissolved oxygen in irrigation reservoirs contribute to the population decline of Phytophthora species along the water path in the same reservoirs. These findings advanced our understanding of the aquatic ecology of these pathogens in irrigation reservoirs. They also provided a basis for pathogen risk mitigation by prolonging the turnover

  13. In situ surface-enhanced Raman scattering spectroelectrochemistry of oxygen species.

    PubMed

    Itoh, Takashi; Maeda, Toshiteru; Kasuya, Atsuo

    2006-01-01

    In situ surface-enhanced Raman scattering (SERS) combined with electrochemical analysis is applied to the determination of oxygen species on silver electrodes in alkaline hydroxide aqueous solution at room temperature and gold electrodes in carbonate melts at high temperature. This technique, referred to as SERS spectroelectrochemistry, reveals Raman spectral lines in the 500-1100 cm(-1) range under electrode potential scanning, assignable to superoxide ions (O2-) and peroxide ions (O2(2-)) on the electrode surface. These lines for oxygen molecule species have potential dependence with changing potential. In the alkaline hydroxide aqueous solution, the Raman peaks due to oxygen molecules are observed at potentials between 0.2 V and -0.8 V (vs. Ag/AgCl) only in the cathodic scan. This irreversible behavior in cyclic voltammograms indicates the existence of an intermediate stage in the oxygen reduction process, in which oxygen is released from the AgO films on the electrode at potentials corresponding to the onset of the last current peak in the voltammogram. This liberated oxygen molecule remains in solution at the interface until hydroxyls or water molecules are formed when the potential reaches the potential zero charge (PZC). In the high-temperature carbonate melts, Raman lines at 1047, 1080, and 800 cm(-1) are apparent for the eutectic (62 + 38) mol% (Li + K)CO3 melt at 923 K, and at 735 cm(-1) for the Li2CO3 melt at 1123 K. These results suggest that oxygen reduction in the Li2CO3 melt involves only peroxide ions, while that in (62 + 38) mol% (Li + K)CO3 involves both peroxide and superoxide ions at the three-phase boundary interface. PMID:16833110

  14. Procyanidins from Nelumbo nucifera Gaertn. Seedpod induce autophagy mediated by reactive oxygen species generation in human hepatoma G2 cells.

    PubMed

    Duan, Yuqing; Xu, Hui; Luo, Xiaoping; Zhang, Haihui; He, Yuanqing; Sun, Guibo; Sun, Xiaobo

    2016-04-01

    In this study, autophagic effect of procyanidins from lotus (Nelumbo nucifera Gaertn.) seedpod (LSPCs) on human hepatoma G2 (HepG2) cells, and the inherent correlation between autophagic levels and reactive oxygen species (ROS) generation were investigated. The results showed that LSPCs increased monodansylcadaverine (MDC) fluorescence intensity and LC3-I/LC3-II conversion in HepG2 cells. In addition, the typically autophagic characteristics (autophagosomes and autolysosomes) were observed in LSPCs-treated cells, but not found in the cells treated with autophagy inhibitor 3-methyladenine (3-MA). Furthermore, the elevated ROS level was in line with the increasing of autophagy activation caused by LSPCs, however, both 3-MA and the ROS scavenger N-acetylcyteine (NAC) inhibitors effectively suppressed the autophagy and ROS generation triggered by LSPCs. As a result, these results indicated that LSPCs induced HepG2 cell autophagy in a time- and dose-dependent manner, and promoted reactive oxygen species (ROS) generation on HepG2 cells. Moreover, we found that LSPCs caused DNA damage, S phase arrest and the decrement of mitochondria membrane potential (MMP) which were associated with ROS generation. In summary, our findings demonstrated that the LSPCs-induced autophagy and autophagic cell death were triggered by the ROS generation in HepG2 cells, which might be associated with ROS generation through the mitochondria-dependent signaling way. PMID:27044822

  15. Mutagenicity of arsenic in mammalian cells: role of reactive oxygen species

    NASA Technical Reports Server (NTRS)

    Hei, T. K.; Liu, S. X.; Waldren, C.

    1998-01-01

    Arsenite, the trivalent form of arsenic present in the environment, is a known human carcinogen that lacked mutagenic activity in bacterial and standard mammalian cell mutation assays. We show herein that when evaluated in an assay (AL cell assay), in which both intragenic and multilocus mutations are detectable, that arsenite is in fact a strong dose-dependent mutagen and that it induces mostly large deletion mutations. Cotreatment of cells with the oxygen radical scavenger dimethyl sulfoxide significantly reduces the mutagenicity of arsenite. Thus, the carcinogenicity of arsenite can be explained at least in part by it being a mutagen that depends on reactive oxygen species for its activity.

  16. Promoted oxidation of phenol in aqueous solution using molecular oxygen at mild conditions

    SciTech Connect

    Vogel, F.; Harf, J.; Hug, A.; Rohr, P.R. von

    1999-05-01

    Wet oxidation with molecular oxygen at mild conditions (temperature < 200 C, pressure {le} 2 MPa) is an economically attractive pretreatment step for non-biodegradable aqueous waste streams. In order to overcome the low reactivity of molecular oxygen towards organic molecules at these mild process conditions, an initiator was used in combination with ferrous ions in the acidic range. The promoted oxidation of phenol in aqueous solution was investigated in a 4 liters stirred autoclave. It was possible to degrade the phenol at temperatures as low as 100 C without observing an induction time. The remaining solution contained mainly acetic and formic acid and was well biodegradable. The oxidative behavior of the oxygen/phenol system could be explained using the well-known autoxidation mechanism for aliphatic molecules. 4-hydroperoxy-phenol is suggested as a key intermediate. Measured products are p-benzoquinone, hydroquinone, catechol, maleic, oxalic, pyruvic, formic, and acetic acid. Dimers could also be identified in sample extracts. A global pathway including all identified products is presented.

  17. Hyperbaric oxygen preconditioning promotes neovascularization of transplanted skin flaps in rats

    PubMed Central

    Liu, Xuehua; Yang, Jing; Li, Zhuo; Yang, Lin; Wang, Cong; Gao, Chunjin; Liang, Fang

    2014-01-01

    To determine whether Hyperbaric oxygen preconditioning (HBO-PC) promotes neovascularization by increasing Stromal cell derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) in transplanted skin flaps of rats. The epigastric pedicle skin flap was established in a rat model. Rats were randomly assigned to the following five groups: 1) sham-operated group (SH); 2) ischemia followed by reperfusion 3 days postoperatively group (IR3d); 3) ischemia followed by reperfusion 5 days postoperatively group (IR5d); 4) hyperbaric oxygen preconditioning and ischemia followed by reperfusion 3 days postoperatively group (HBO-PC3d); and 5) hyperbaric oxygen preconditioning and ischemia followed by reperfusion 5 days postoperatively group(HBO-PC5d). For the groups receiving HBO-PC, animals underwent 1 hour of HBO at 2.0 ATA in 100% O2 twice per day for 3 days consecutively prior to surgery. After perfusion, Laser Doppler perfusion imaging (LDPI) was performed, and skin flap tissue samples were harvested for histological evaluation and western blot analysis. Perfusion was significantly improved in the HBO-PC groups compared with the IR groups on postoperative 3 and 5. Microvessel density (MVD) was significantly increased by HBO-PC compared with IR groups postoperatively. Western blot analysis revealed that SDF-1 and CXCR4 expression in the HBO-PC groups was significantly increased compared with IR groups. HBO-PC promoted neovascularization via increasing expression levels of SDF-1 and CXCR4 in transplanted skin flaps of rats. PMID:25197344

  18. Antioxidant effects of the sarsaparilla via scavenging of reactive oxygen species and induction of antioxidant enzymes in human dermal fibroblasts.

    PubMed

    Park, Gunhyuk; Kim, Tae-mi; Kim, Jeong Hee; Oh, Myung Sook

    2014-07-01

    Ultraviolet (UV) radiation from sunlight causes distinct changes in collagenous skin tissues as a result of the breakdown of collagen, a major component of the extracellular matrix. UV irradiation downregulates reactive oxygen species (ROS)-elimination pathways, thereby promoting the production of ROS, which are implicated in skin aging. Smilax glabra Roxb (sarsaparilla) has been used in folk medicine because of its many effects. However, no study on the protective effects of sarsaparilla root (SR) on human dermal fibroblasts has been reported previously. Here, we investigated the protective effect of SR against oxidative stress in dermal fibroblasts. SR significantly inhibited oxidative damage and skin-aging factor via mitogen-activated protein kinase signaling pathways. Also, SR decreased Ca(2+) and ROS, mitochondrial membrane potential, dysfunction, and increased glutathione, NAD(P)H dehydrogenase and heme oxygenase-1. These results demonstrate that SR can protect dermal fibroblasts against UVB-induced skin aging via antioxidant effects. PMID:25022355

  19. Prooxidant action of knipholone anthrone: copper dependent reactive oxygen species generation and DNA damage.

    PubMed

    Habtemariam, S; Dagne, E

    2009-07-01

    Knipholone (KP) and knipholone anthrone (KA) are natural 4-phenylanthraquinone structural analogues with established differential biological activities including in vitro antioxidant and cytotoxic properties. By using DNA damage as an experimental model, the comparative Cu(II)-dependent prooxidant action of these two compounds were studied. In the presence of Cu(II) ions, the antioxidant KA (3.1-200 microM) but not KP (6-384 microM) caused a concentration-dependent pBR322 plasmid DNA strand scission. The DNA damage induced by KA could be abolished by reactive oxygen species scavengers, glutathione and catalase as well as EDTA and a specific Cu(I) chelator bathocuproine disulfonic acid. In addition to Cu(II) chelating activity, KA readily reduces Cu(II) to Cu(I). Copper-dependent generation of reactive oxygen species and the subsequent macromolecular damage may be involved in the antimicrobial and cytotoxic activity of KA. PMID:19345716

  20. Regulation of signal transduction by reactive oxygen species in the cardiovascular system

    PubMed Central

    Brown, David I.; Griendling, Kathy K.

    2015-01-01

    Oxidative stress has long been implicated in cardiovascular disease, but more recently, the role of reactive oxygen species in normal physiological signaling has been elucidated. Signaling pathways modulated by reactive oxygen species (ROS) are complex and compartmentalized, and we are only beginning to identify the molecular modifications of specific targets. Here we review the current literature regarding ROS signaling in the cardiovascular system, focusing on the role of ROS in normal physiology and how dysregulation of signaling circuits contributes to cardiovascular diseases including atherosclerosis, ischemia-reperfusion injury, cardiomyopathy and heart failure. In particular, we consider how ROS modulate signaling pathways related to phenotypic modulation, migration and adhesion, contractility, proliferation and hypertrophy, angiogenesis, endoplasmic reticulum stress, apoptosis and senescence. Understanding the specific targets of ROS may guide the development of the next generation of ROS-modifying therapies to reduce morbidity and mortality associated with oxidative stress. PMID:25634975

  1. Biochemical changes in rat testis induced in vitro by reactive oxygen species.

    PubMed

    Nechifor, Marina Tamara; Constantin, Carolina; Manda, Gina; Neagu, Monica; Dinu, Diana

    2006-01-01

    We report the effects of reactive oxygen species generated by ultraviolet-A radiation on some biochemical parameters specific for oxidative stress, in rat testis homogenates. Results show an increase in lipid peroxidation products under ultraviolet-A exposure, and suggest that the involved mechanism is typical for a radical-mediated chain reaction. The amount of SH groups also increases during irradiation, probably as a consequence of conformational changes in proteins. Electrophoresis results revealed protein pattern changes mainly in the low molecular weight domain. The catalytic activities of alkaline phosphatase and gamma-glutamil transpeptidase are modified under the oxidative conditions generated by reactive oxygen species. The changes of the enzymatic activities are UVA exposure time-dependent, suggesting that conformational modifications are responsible for enzymatic activities enhancement. PMID:18389730

  2. Stabilization of thylakoid membranes in isoprene-emitting plants reduces formation of reactive oxygen species.

    PubMed

    Velikova, Violeta; Sharkey, Thomas D; Loreto, Francesco

    2012-01-01

    Isoprene is emitted by a significant fraction of the world's vegetation. Isoprene makes leaves more thermotolerant, yet we do not fully understand how. We have recently shown that isoprene stabilizes thylakoid membranes under heat stress. Here we show that heat-stressed, isoprene-emitting transgenic Arabidopsis plants also produce a lower pool of reactive oxygen and reactive nitrogen species, and that this was especially due to a lower accumulation of H2O2 in isoprene emitting plants. It remains difficult to disentangle whether in heat stressed plants isoprene also directly reacts with and quenches reactive oxygen species (ROS), or reduces ROS formation by stabilizing thylakoids. We present considerations that make the latter a more likely mechanism, under our experimental circumstances. PMID:22301981

  3. The role of reactive oxygen species on Plasmodium melanotic encapsulation in Anopheles gambiae

    PubMed Central

    Kumar, Sanjeev; Christophides, George K.; Cantera, Rafael; Charles, Bradley; Han, Yeon Soo; Meister, Stephan; Dimopoulos, George; Kafatos, Fotis C.; Barillas-Mury, Carolina

    2003-01-01

    Malaria transmission depends on the competence of some Anopheles mosquitoes to sustain Plasmodium development (susceptibility). A genetically selected refractory strain of Anopheles gambiae blocks Plasmodium development, melanizing, and encapsulating the parasite in a reaction that begins with tyrosine oxidation, and involves three quantitative trait loci. Morphological and microarray mRNA expression analysis suggest that the refractory and susceptible strains have broad physiological differences, which are related to the production and detoxification of reactive oxygen species. Physiological studies corroborate that the refractory strain is in a chronic state of oxidative stress, which is exacerbated by blood feeding, resulting in increased steady-state levels of reactive oxygen species, which favor melanization of parasites as well as Sephadex beads. PMID:14623973

  4. The role of reactive oxygen species on Plasmodium melanotic encapsulation in Anopheles gambiae.

    PubMed

    Kumar, Sanjeev; Christophides, George K; Cantera, Rafael; Charles, Bradley; Han, Yeon Soo; Meister, Stephan; Dimopoulos, George; Kafatos, Fotis C; Barillas-Mury, Carolina

    2003-11-25

    Malaria transmission depends on the competence of some Anopheles mosquitoes to sustain Plasmodium development (susceptibility). A genetically selected refractory strain of Anopheles gambiae blocks Plasmodium development, melanizing, and encapsulating the parasite in a reaction that begins with tyrosine oxidation, and involves three quantitative trait loci. Morphological and microarray mRNA expression analysis suggest that the refractory and susceptible strains have broad physiological differences, which are related to the production and detoxification of reactive oxygen species. Physiological studies corroborate that the refractory strain is in a chronic state of oxidative stress, which is exacerbated by blood feeding, resulting in increased steady-state levels of reactive oxygen species, which favor melanization of parasites as well as Sephadex beads. PMID:14623973

  5. Identification of different oxygen species in oxide nanostructures with (17)O solid-state NMR spectroscopy.

    PubMed

    Wang, Meng; Wu, Xin-Ping; Zheng, Sujuan; Zhao, Li; Li, Lei; Shen, Li; Gao, Yuxian; Xue, Nianhua; Guo, Xuefeng; Huang, Weixin; Gan, Zhehong; Blanc, Frédéric; Yu, Zhiwu; Ke, Xiaokang; Ding, Weiping; Gong, Xue-Qing; Grey, Clare P; Peng, Luming

    2015-02-01

    Nanostructured oxides find multiple uses in a diverse range of applications including catalysis, energy storage, and environmental management, their higher surface areas, and, in some cases, electronic properties resulting in different physical properties from their bulk counterparts. Developing structure-property relations for these materials requires a determination of surface and subsurface structure. Although microscopy plays a critical role owing to the fact that the volumes sampled by such techniques may not be representative of the whole sample, complementary characterization methods are urgently required. We develop a simple nuclear magnetic resonance (NMR) strategy to detect the first few layers of a nanomaterial, demonstrating the approach with technologically relevant ceria nanoparticles. We show that the (17)O resonances arising from the first to third surface layer oxygen ions, hydroxyl sites, and oxygen species near vacancies can be distinguished from the oxygen ions in the bulk, with higher-frequency (17)O chemical shifts being observed for the lower coordinated surface sites. H2 (17)O can be used to selectively enrich surface sites, allowing only these particular active sites to be monitored in a chemical process. (17)O NMR spectra of thermally treated nanosized ceria clearly show how different oxygen species interconvert at elevated temperature. Density functional theory calculations confirm the assignments and reveal a strong dependence of chemical shift on the nature of the surface. These results open up new strategies for characterizing nanostructured oxides and their applications. PMID:26601133

  6. Reactive oxygen species produced upon photoexcitation of sunscreens containing titanium dioxide (an EPR study).

    PubMed

    Brezová, Vlasta; Gabcová, Sona; Dvoranová, Dana; Stasko, Andrej

    2005-05-13

    Commercial sunscreen products containing titanium dioxide were irradiated with lambda>300 nm and the formation of oxygen- (.OH, O2.-/.OOH) and carbon-centered radicals was monitored by EPR spectroscopy and spin trapping technique using 5,5-dimethyl-1-pyrroline N-oxide, alpha-phenyl-N-tert-butylnitrone (PBN), alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone as spin traps, and free nitroxide radical 4-hydroxy-2,2,6,6-tetramethylpiperidine N-oxyl. The photoinduced production of singlet oxygen was shown by 4-hydroxy-2,2,6,6-piperidine. The generation of reactive oxygen radical species upon irradiation of sunscreens significantly depends on their composition, as the additives present (antioxidants, radical-scavengers, solvents) can transform the reactive radicals formed to less harmful products. The continuous in situ irradiation of titanium dioxide powder, recommended for cosmetic application, investigated in different solvents (water, dimethyl sulfoxide, isopropyl myristate) resulted in the generation of oxygen-centered reactive radical species (superoxide anion radical, hydroxyl and alkoxyl radicals). PMID:15878117

  7. Identification of different oxygen species in oxide nanostructures with 17O solid-state NMR spectroscopy

    PubMed Central

    Wang, Meng; Wu, Xin-Ping; Zheng, Sujuan; Zhao, Li; Li, Lei; Shen, Li; Gao, Yuxian; Xue, Nianhua; Guo, Xuefeng; Huang, Weixin; Gan, Zhehong; Blanc, Frédéric; Yu, Zhiwu; Ke, Xiaokang; Ding, Weiping; Gong, Xue-Qing; Grey, Clare P.; Peng, Luming

    2015-01-01

    Nanostructured oxides find multiple uses in a diverse range of applications including catalysis, energy storage, and environmental management, their higher surface areas, and, in some cases, electronic properties resulting in different physical properties from their bulk counterparts. Developing structure-property relations for these materials requires a determination of surface and subsurface structure. Although microscopy plays a critical role owing to the fact that the volumes sampled by such techniques may not be representative of the whole sample, complementary characterization methods are urgently required. We develop a simple nuclear magnetic resonance (NMR) strategy to detect the first few layers of a nanomaterial, demonstrating the approach with technologically relevant ceria nanoparticles. We show that the 17O resonances arising from the first to third surface layer oxygen ions, hydroxyl sites, and oxygen species near vacancies can be distinguished from the oxygen ions in the bulk, with higher-frequency 17O chemical shifts being observed for the lower coordinated surface sites. H217O can be used to selectively enrich surface sites, allowing only these particular active sites to be monitored in a chemical process. 17O NMR spectra of thermally treated nanosized ceria clearly show how different oxygen species interconvert at elevated temperature. Density functional theory calculations confirm the assignments and reveal a strong dependence of chemical shift on the nature of the surface. These results open up new strategies for characterizing nanostructured oxides and their applications. PMID:26601133

  8. Extracorporeal membrane oxygenation promotes long chain fatty acid oxidation in the immature swine heart in vivo

    SciTech Connect

    Kajimoto, Masaki; O'Kelly-Priddy, Colleen M.; Ledee, Dolena R.; Xu, Chun; Isern, Nancy G.; Olson, Aaron; Portman, Michael A.

    2013-09-01

    Extracorporeal membrane oxygenation (ECMO) supports infants and children with severe cardiopulmonary compromise. Nutritional support for these children includes provision of medium- and long-chain fatty acids (FAs). However, ECMO induces a stress response, which could limit the capacity for FA oxidation. Metabolic impairment could induce new or exacerbate existing myocardial dysfunction. Using a clinically relevant piglet model, we tested the hypothesis that ECMO maintains the myocardial capacity for FA oxidation and preserves myocardial energy state. Provision of 13-Carbon labeled medium-chain FA (octanoate), longchain free FAs (LCFAs), and lactate into systemic circulation showed that ECMO promoted relative increases in myocardial LCFA oxidation while inhibiting lactate oxidation. Loading of these labeled substrates at high dose into the left coronary artery demonstrated metabolic flexibility as the heart preferentially oxidized octanoate. ECMO preserved this octanoate metabolic response, but also promoted LCFA oxidation and inhibited lactate utilization. Rapid upregulation of pyruvate dehydrogenase kinase-4 (PDK4) protein appeared to participate in this metabolic shift during ECMO. ECMO also increased relative flux from lactate to alanine further supporting the role for pyruvate dehydrogenase inhibition by PDK4. High dose substrate loading during ECMO also elevated the myocardial energy state indexed by phosphocreatine to ATP ratio. ECMO promotes LCFA oxidation in immature hearts, while maintaining myocardial energy state. These data support the appropriateness of FA provision during ECMO support for the immature heart.

  9. Mitochondrial Reactive Oxygen Species at the Heart of the Matter: New Therapeutic Approaches for Cardiovascular Diseases

    PubMed Central

    Kornfeld, Opher S.; Hwang, Sunhee; Disatnik, Marie-Hélène; Chen, Che-Hong; Qvit, Nir; Mochly-Rosen, Daria

    2015-01-01

    Reactive oxygen species (ROS) have been implicated in a variety of age-related diseases including multiple cardiovascular disorders. However, translation of ROS scavengers (anti-oxidants) into the clinic has not been successful. These anti-oxidants grossly reduce total levels of cellular ROS including ROS that participate in physiological signaling. In this review, we challenge the traditional anti-oxidant therapeutic approach that targets ROS directly with novel approaches that improve mitochondrial functions to more effectively treat cardiovascular diseases. PMID:25999419

  10. Stability and characterization of oxygen species in alkali molten carbonated: A thermodynamic and electrochemical approach

    SciTech Connect

    Cassir, M.; Moutiers, G.; Devynck, J. . Lab d'Electrochimie)

    1993-11-01

    The study of the chemical and electrochemical properties of molten carbonate has been widely discussed in the last 20 years because of the necessity for optimizing molten carbonate fuel cell (MCFC) performance. The stability and electrochemical behavior of reduced oxygen species were investigated in several alkali molten carbonates at different oxoacidity levels and temperatures. Theoretical predictions and experimental results were in good agreement and show that, in Na-K, Li-Na, Li-K, and Li-Na-K melts, peroxide species can only be stabilized in basic media. Superoxide species, unstable in lithium-containing carbonate, can be stabilized in Na-K under slightly basic conditions. Peroxide/oxide and superoxide/oxide redox systems were characterized by voltammetric and convolution potential sweep techniques. It was shown that CO[sub 2] does not participate in the rate-determining reduction mechanisms of both superoxide and peroxide species. Electrochemical parameters relative to the cited systems (D, [delta], E[sup 0], E[sub 1/2]), as well as the solubility of reduced oxygen species were determined.

  11. Hydrogen peroxide is the most toxic oxygen species for Onchocerca cervicalis microfilariae.

    PubMed

    Callahan, H L; Crouch, R K; James, E R

    1990-06-01

    The toxicity of the active oxygen species hydrogen peroxide, superoxide radical, hydroxyl radical and singlet oxygen to microfilariae (mf) has been studied in vitro, using active oxygen-generating systems and scavengers/inhibitors. Mf viability was monitored by uptake of the radiolabel, [3H]2-deoxy-D-glucose. Hydrogen peroxide and singlet oxygen, but not superoxide radical or hydroxyl radical, are toxic for mf. Hydrogen peroxide was toxic for mf within 2 h at concentrations as low as 5 microM, an amount eosinophils have been shown to release in vitro (Weiss et al. 1986). Catalase and thiourea, but not inactivated catalase, superoxide dismutase (SOD), singlet oxygen scavengers, or hydroxyl radical scavengers, protected mf. Mf have relatively high levels of endogenous SOD but no measurable glutathione peroxidase and low levels of catalase when compared with other parasites (Callahan, Crouch & James, 1988). The low levels of hydrogen peroxide-scavenging enzymes correlate well with mf sensitivity to hydrogen peroxide and the protective effect of exogenous catalase. PMID:2163503

  12. Reactive oxygen species in chick hair cells after gentamicin exposure in vitro.

    PubMed

    Hirose, K; Hockenbery, D M; Rubel, E W

    1997-02-01

    Reactive oxygen species have been invoked as a causative agent of cell death in many different developmental and pathological states. The presence of free radicals and their importance of hair cell death due to aminoglycosides is suggested by a number of studies that have demonstrated a protective effect of antioxidants. By using dichlorofluorescin (DCFH) a fluorescent compound that is a reporter of reactive oxygen species, we have shown that free radicals are rapidly produced by avian hair cells in vitro after exposure to gentamicin. In addition, free radical scavengers, catalase and glutathione, were tested with DCFH fluorescent imaging for their ability to quench the production of reactive oxygen species in hair cells after drug exposure. Both free radical scavengers were very effective in suppressing drug-induced production of free radicals. Next, we investigated the ability of these antioxidants to preserve the structural integrity of hair cells after exposure to gentamicin. We were not able to detect any attenuation of the hair cell loss using antioxidants in conjunction with gentamicin. This result must be qualified by the fact that the antioxidants used were not effective over long-term gentamicin exposure. Therefore, methodological constraints prevented adequately testing possible protective effects of the free radical scavengers in this model system. PMID:9119753

  13. Generation of reactive oxygen species and radiation response in lymphocytes and tumor cells.

    PubMed

    Shankar, Bhavani; Kumar, S Santosh; Sainis, K B

    2003-10-01

    Several types of lymphoid and myeloid tumor cells are known to be relatively resistant to radiation-induced apoptosis compared to normal lymphocytes. The intracellular generation of reactive oxygen species was measured in irradiated spleen cells from C57BL/6 and BALB/c mice and murine tumor cells (EL-4 and P388) by flow cytometry using dichlorodihydrofluoresceindiacetate and dihydrorhodamine 123 as fluorescent probes. The amount of reactive oxygen species generated per cell was low in the tumor cells compared to spleen cells exposed to 1 to 10 Gy of gamma radiation. This could be due to the higher total antioxidant levels in tumor cells compared to normal cells. Further, the changes in mitochondrial membrane potential and cytoplasmic Ca2+ content were appreciable in lymphocytes even at a dose of 1 Gy. In EL-4 cells, no such changes were observed at any of the doses used. About 65% of spleen cells underwent apoptosis 24 h after 1 Gy irradiation. However, under the same conditions, EL-4 and P388 cells failed to undergo apoptosis, but they accumulated in G2/M phase. Thus the intrinsic radioresistance of tumor cells may be due to a decreased generation of reactive oxygen species after irradiation and down-regulation of the subsequent events leading to apoptosis. PMID:12968927

  14. Reactive oxygen species (ROS) mediates non-freezing cold injury of rat sciatic nerve

    PubMed Central

    Geng, Zhiwei; Tong, Xiaoyan; Jia, Hongjuan

    2015-01-01

    Non-freezing cold injury is an injury characterized by neuropathy, developing when patients expose to cold environments. Reactive oxygen species (ROS) has been shown as a contributing factor for the non-freezing cold nerve injury. However, the detailed connections between non-freezing cold nerve injury and ROS have not been described. In order to investigate the relationship between non-freezing cold nerve injury and reactive oxygen species, we study the effects of two cooling methods-the continuous cooling and the intermittent cooling with warming intervals-on rat sciatic nerves. Specifically, we assess the morphological changes and ROS production of the sciatic nerves underwent different cooling treatments. Our data shows both types of cooling methods cause nerve injury and ROS production. However, despite of identical cooling degree and duration, the sciatic nerves processed by intermittent cooling with warming intervals present more ROS production, severer reperfusion injury and pathological destructions than the sciatic nerves processed by continuous cooling. This result indicates reactive oxygen species, as a product of reperfusion, facilitates non-freezing cold nerve injury. PMID:26629065

  15. Tissue injury by reactive oxygen species and the protective effects of flavonoids.

    PubMed

    de Groot, H; Rauen, U

    1998-01-01

    Reactive oxygen species contribute decisively to a great variety of diseases. Flavonoids are benzo-gamma-pyrone derivatives of plant origin found in various fruits and vegetables but also in tea and in red wine. Some of the flavonoids, such as quercetin and silibinin, can effectively protect cells and tissues against the deleterious effects of reactive oxygen species. Their antioxidant activity results from scavenging of free radicals and other oxidizing intermediates, from the chelation of iron or copper ions and from inhibition of oxidases. For their free radical scavenging properties, scavenging of lipid- and protein-derived radicals is presumably of special importance. A non-radical reactive oxygen species effectively trapped by flavonoids is hypochlorous acid. In general, the antioxidative properties of flavonoids are favoured by a high degree of OH substitution. On the other hand, inhibition of enzymatic functions other than oxidases, e.g., inhibition of lipoxygenase and thus prevention of the formation of leukotrienes, may also participate in the cell and tissue protective properties of flavonoids. PMID:9646056

  16. Selective decreased de novo synthesis of glomerular proteoglycans under the influence of reactive oxygen species.

    PubMed Central

    Kashihara, N; Watanabe, Y; Makino, H; Wallner, E I; Kanwar, Y S

    1992-01-01

    The effect of reactive oxygen species on de novo synthesis of heparan sulfate proteoglycans (HSPGs) of the renal glomerulus was investigated in an organ perfusion system. Isolated kidneys were perfused for 7 hr with a medium containing [35S]sulfate to label sulfated proteoglycans or [35S]methionine to label total glomerular glycoproteins. For the generation of reactive oxygen species, xanthine and xanthine oxidase were included in the perfusion medium, and catalase and superoxide dismutase were used as scavenging agents. Proteoglycans were characterized by Sepharose CL-6B and DEAE-Sephacel chromatographies and SDS/PAGE analysis. The labeled glycoproteins were immunoprecipitated with anti-HSPG, anti-type IV collagen, and anti-laminin, and their specific radioactivities were determined. With exposure to reactive oxygen species, a drastic dose-dependent decrease in de novo synthesis of proteoglycans was seen, and that effect was reversible by catalase treatment. No alterations in the biochemical characteristics of proteoglycans were noted. Immunoprecipitation studies revealed a 16-fold decrease in the synthesis of nascent core peptide of HSPGs, while at comparable concentrations of xanthine and xanthine oxidase, synthesis of type IV collagen and laminin slightly decreased (approximately 15%). Morphologic studies revealed a 14-fold decrease in [35S]sulfate-associated autoradiographic grains overlying the glomerular basement membrane, a critical component of the ultrafiltration apparatus. Relevance of the selective decreased de novo synthesis of HSPGs of the glomerular basement membrane is discussed in terms of increased glomerular permeability to plasma proteins. Images PMID:1631123

  17. Neuroprotection of taurine against reactive oxygen species is associated with inhibiting NADPH oxidases.

    PubMed

    Han, Zhou; Gao, Li-Yan; Lin, Yu-Hui; Chang, Lei; Wu, Hai-Yin; Luo, Chun-Xia; Zhu, Dong-Ya

    2016-04-15

    It is well established that taurine shows potent protection against glutamate-induced injury to neurons in stroke. The neuroprotection may result from multiple mechanisms. Increasing evidences suggest that NADPH oxidases (Nox), the primary source of superoxide induced by N-methyl-d-aspartate (NMDA) receptor activation, are involved in the process of oxidative stress. We found that 100μM NMDA induced oxidative stress by increasing the reactive oxygen species level, which contributed to the cell death, in vitro. Neuron cultures pretreated with 25mM taurine showed lower percentage of death cells and declined reactive oxygen species level. Moreover, taurine attenuated Nox2/Nox4 protein expression and enzyme activity and declined intracellular calcium intensity during NMDA-induced neuron injury. Additionally, taurine also showed neuroprotection against H2O2-induced injury, accompanying with Nox inhibition. So, we suppose that protection of taurine against reactive oxygen species during NMDA-induced neuron injury is associated with Nox inhibition, probably in a calcium-dependent manner. PMID:26945820

  18. The aryl hydrocarbon receptor promotes aging phenotypes across species

    PubMed Central

    Eckers, Anna; Jakob, Sascha; Heiss, Christian; Haarmann-Stemmann, Thomas; Goy, Christine; Brinkmann, Vanessa; Cortese-Krott, Miriam M.; Sansone, Roberto; Esser, Charlotte; Ale-Agha, Niloofar; Altschmied, Joachim; Ventura, Natascia; Haendeler, Judith

    2016-01-01

    The ubiquitously expressed aryl hydrocarbon receptor (AhR) induces drug metabolizing enzymes as well as regulators of cell growth, differentiation and apoptosis. Certain AhR ligands promote atherosclerosis, an age-associated vascular disease. Therefore, we investigated the role of AhR in vascular functionality and aging. We report a lower pulse wave velocity in young and old AhR-deficient mice, indicative of enhanced vessel elasticity. Moreover, endothelial nitric oxide synthase (eNOS) showed increased activity in the aortas of these animals, which was reflected in increased NO production. Ex vivo, AhR activation reduced the migratory capacity of primary human endothelial cells. AhR overexpression as well as treatment with a receptor ligand, impaired eNOS activation and reduced S-NO content. All three are signs of endothelial dysfunction. Furthermore, AhR expression in blood cells of healthy human volunteers positively correlated with vessel stiffness. In the aging model Caenorhabditis elegans, AhR-deficiency resulted in increased mean life span, motility, pharynx pumping and heat shock resistance, suggesting healthier aging. Thus, AhR seems to have a negative impact on vascular and organismal aging. Finally, our data from human subjects suggest that AhR expression levels could serve as an additional, new predictor of vessel aging. PMID:26790370

  19. Targeting mitochondrial reactive oxygen species to modulate hypoxia-induced pulmonary hypertension.

    PubMed

    Adesina, Sherry E; Kang, Bum-Yong; Bijli, Kaiser M; Ma, Jing; Cheng, Juan; Murphy, Tamara C; Michael Hart, C; Sutliff, Roy L

    2015-10-01

    Pulmonary hypertension (PH) is characterized by increased pulmonary vascular remodeling, resistance, and pressures. Reactive oxygen species (ROS) contribute to PH-associated vascular dysfunction. NADPH oxidases (Nox) and mitochondria are major sources of superoxide (O(2)(•-)) and hydrogen peroxide (H(2)O(2)) in pulmonary vascular cells. Hypoxia, a common stimulus of PH, increases Nox expression and mitochondrial ROS (mtROS) production. The interactions between these two sources of ROS generation continue to be defined. We hypothesized that mitochondria-derived O(2)(•-) (mtO(2)(•-)) and H(2)O(2) (mtH(2)O(2)) increase Nox expression to promote PH pathogenesis and that mitochondria-targeted antioxidants can reduce mtROS, Nox expression, and hypoxia-induced PH. Exposure of human pulmonary artery endothelial cells to hypoxia for 72 h increased mtO(2)(•-) and mtH(2)O(2). To assess the contribution of mtO(2)(•-) and mtH(2)O(2) to hypoxia-induced PH, mice that overexpress superoxide dismutase 2 (Tg(hSOD2)) or mitochondria-targeted catalase (MCAT) were exposed to normoxia (21% O(2)) or hypoxia (10% O(2)) for three weeks. Compared with hypoxic control mice, MCAT mice developed smaller hypoxia-induced increases in RVSP, α-SMA staining, extracellular H(2)O(2) (Amplex Red), Nox2 and Nox4 (qRT-PCR and Western blot), or cyclinD1 and PCNA (Western blot). In contrast, Tg(hSOD2) mice experienced exacerbated responses to hypoxia. These studies demonstrate that hypoxia increases mtO(2)(•-) and mtH(2)O(2). Targeting mtH(2)O(2) attenuates PH pathogenesis, whereas targeting mtO(2)(•-) exacerbates PH. These differences in PH pathogenesis were mirrored by RVSP, vessel muscularization, levels of Nox2 and Nox4, proliferation, and H(2)O(2) release. These studies suggest that targeted reductions in mtH(2)O(2) generation may be particularly effective in preventing hypoxia-induced PH. PMID:26073127

  20. Apogossypolone targets mitochondria and light enhances its anticancer activity by stimulating generation of singlet oxygen and reactive oxygen species

    PubMed Central

    Hu, Zhe-Yu; Wang, Jing; Cheng, Gang; Zhu, Xiao-Feng; Huang, Peng; Yang, Dajun; Zeng, Yi-Xin

    2011-01-01

    Apogossypolone (ApoG2), a novel derivative of gossypol, has been shown to be a potent inhibitor of antiapoptotic Bcl-2 family proteins and to have antitumor activity in multiple types of cancer cells. Recent reports suggest that gossypol stimulates the generation of cellular reactive oxygen species (ROS) in leukemia and colorectal carcinoma cells; however, gossypol-mediated cell death in leukemia cells was reported to be ROS-independent. This study was conducted to clarify the effect of ApoG2-induced ROS on mitochondria and cell viability, and to further evaluate its utility as a treatment for nasopharyngeal carcinoma (NPC). We tested the photocytotoxicity of ApoG2 to the poorly differentiated NPC cell line CNE-2 using the ROS-generating TL/10 illumination system. The rapid ApoG2-induced cell death was partially reversed by the antioxidant N-acetyl-L-cysteine (NAC), but the ApoG2-induced reduction of mitochondrial membrane potential (MMP) was not reversed by NAC. In the presence of TL/10 illumination, ApoG2 generated massive amounts of singlet oxygen and was more effective in inhibiting cell growth than in the absence of illumination. We also determined the influence of light on the anti-proliferative activity of ApoG2 using a CNE-2–xenograft mouse model. ApoG2 under TL/10 illumination healed tumor wounds and suppressed tumor growth more effectively than ApoG2 treatment alone. These results indicate that the ApoG2-induced CNE-2 cell death is partly ROS-dependent. ApoG2 may be used with photodynamic therapy (PDT) to treat NPC. PMID:21192843

  1. Optimizing Pulse Waveforms in Plasma Jets for Reactive Oxygen Species (ROS) Production

    NASA Astrophysics Data System (ADS)

    Norberg, Seth; Babaeva, Natalia Yu.; Kushner, Mark J.

    2012-10-01

    Reactive oxygen species (ROS) are desired in numerous applications from the destruction of harmful proteins and bacteria for sterilization in the medical field to taking advantage of the metastable characteristics of O2(^1δ) to transfer energy to other species. Advances in atmospheric pressure plasma jets in recent years show the possibility of using this application as a source of reactive oxygen species. In this paper, we report on results from a computational investigation of atmospheric pressure plasma jets in a dielectric barrier discharge (DBD) configuration. The computer model used in this study, nonPDPSIM, solves transport equations for charged and neutral species, Poisson's equation for the electric potential, the electron energy conservation equation for the electron temperature, and Navier-Stokes equations for the neutral gas flow. A Monte Carlo simulation is used to track sheath accelerated secondary electrons emitted from surfaces and the energy of ions incident onto surfaces. Rate coefficients and transport coefficients for the bulk plasma are obtained from local solutions of Boltzmann's equation for the electron energy distribution. Radiation transport is addressed using a Green's function approach. Various waveforms for the voltage source were examined in analogy to spiker-sustainer systems used at lower gas pressures.

  2. Myocardial Reloading after Extracorporeal Membrane Oxygenation Alters Substrate Metabolism While Promoting Protein Synthesis

    SciTech Connect

    Kajimoto, Masaki; Priddy, Colleen M.; Ledee, Dolena; Xu, Chun; Isern, Nancy G.; Olson, Aaron; Des Rosiers, Christine; Portman, Michael A.

    2013-08-19

    Extracorporeal membrane oxygenation (ECMO) unloads the heart providing a bridge to recovery in children after myocardial stunning. Mortality after ECMO remains high.Cardiac substrate and amino acid requirements upon weaning are unknown and may impact recovery. We assessed the hypothesis that ventricular reloading modulates both substrate entry into the citric acid cycle (CAC) and myocardial protein synthesis. Fourteen immature piglets (7.8-15.6 kg) were separated into 2 groups based on ventricular loading status: 8 hour-ECMO (UNLOAD) and post-wean from ECMO (RELOAD). We infused [2-13C]-pyruvate as an oxidative substrate and [13C6]-L-leucine, as a tracer of amino acid oxidation and protein synthesis into the coronary artery. RELOAD showed marked elevations in myocardial oxygen consumption above baseline and UNLOAD. Pyruvate uptake was markedly increased though RELOAD decreased pyruvate contribution to oxidative CAC metabolism.RELOAD also increased absolute concentrations of all CAC intermediates, while maintaining or increasing 13C-molar percent enrichment. RELOAD also significantly increased cardiac fractional protein synthesis rates by >70% over UNLOAD. Conclusions: RELOAD produced high energy metabolic requirement and rebound protein synthesis. Relative pyruvate decarboxylation decreased with RELOAD while promoting anaplerotic pyruvate carboxylation and amino acid incorporation into protein rather than to the CAC for oxidation. These perturbations may serve as therapeutic targets to improve contractile function after ECMO.

  3. Dynamics of localized charges in dopamine-modified TiO{sub 2} and their effect on the formation of reactive oxygen species.

    SciTech Connect

    Dimitrijevic, N.; Rozhkova, E.; Rajh, T.

    2009-03-04

    Modification of TiO{sub 2} nanoparticles with dopamine enables harvesting of visible light and promotes spatial separation of charges. The formation of reactive oxygen species (OH, {sup 1}O{sub 2}, O{sub 2}{sup -}, HO{sub 2}, H{sub 2}O{sub 2}) upon illumination of TiO{sub 2}/dopamine was studied using complementary spin-trap EPR and radical-induced fluorescence techniques. The localization of holes on dopamine suppresses oxidation of adsorbed water molecules at the surface of nanoparticles, and thus formation of OH radicals. At the same time, dopamine does not affect electronic properties of photogenerated electrons and their reaction with dissolved oxygen to produce superoxide anions. Superoxide anions are proposed to generate singlet oxygen through dismutation reaction, resulting in a low yield of {sup 1}O{sub 2} detected.

  4. A three species model to simulate application of Hyperbaric Oxygen Therapy to chronic wounds.

    PubMed

    Flegg, Jennifer A; McElwain, Donald L S; Byrne, Helen M; Turner, Ian W

    2009-07-01

    Chronic wounds are a significant socioeconomic problem for governments worldwide. Approximately 15% of people who suffer from diabetes will experience a lower-limb ulcer at some stage of their lives, and 24% of these wounds will ultimately result in amputation of the lower limb. Hyperbaric Oxygen Therapy (HBOT) has been shown to aid the healing of chronic wounds; however, the causal reasons for the improved healing remain unclear and hence current HBOT protocols remain empirical. Here we develop a three-species mathematical model of wound healing that is used to simulate the application of hyperbaric oxygen therapy in the treatment of wounds. Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds. Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective. We provide constraints that depend on the model parameters for the range of HBOT protocols that will stimulate healing. More specifically, we predict that patients with a poor arterial supply of oxygen, high consumption of oxygen by the wound tissue, chronically hypoxic wounds, and/or a dysfunctional endothelial cell response to oxygen are at risk of nonresponsiveness to HBOT. The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the cost-effectiveness of this therapy. PMID:19649306

  5. A Three Species Model to Simulate Application of Hyperbaric Oxygen Therapy to Chronic Wounds

    PubMed Central

    Flegg, Jennifer A.; McElwain, Donald L. S.; Byrne, Helen M.; Turner, Ian W.

    2009-01-01

    Chronic wounds are a significant socioeconomic problem for governments worldwide. Approximately 15% of people who suffer from diabetes will experience a lower-limb ulcer at some stage of their lives, and 24% of these wounds will ultimately result in amputation of the lower limb. Hyperbaric Oxygen Therapy (HBOT) has been shown to aid the healing of chronic wounds; however, the causal reasons for the improved healing remain unclear and hence current HBOT protocols remain empirical. Here we develop a three-species mathematical model of wound healing that is used to simulate the application of hyperbaric oxygen therapy in the treatment of wounds. Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds. Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective. We provide constraints that depend on the model parameters for the range of HBOT protocols that will stimulate healing. More specifically, we predict that patients with a poor arterial supply of oxygen, high consumption of oxygen by the wound tissue, chronically hypoxic wounds, and/or a dysfunctional endothelial cell response to oxygen are at risk of nonresponsiveness to HBOT. The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the cost-effectiveness of this therapy. PMID:19649306

  6. Role of reactive oxygen and nitrogen species in the vascular responses to inflammation

    PubMed Central

    Kvietys, Peter R.; Granger, D. Neil

    2012-01-01

    Inflammation is a complex and potentially life-threatening condition that involves the participation of a variety of chemical mediators, signaling pathways, and cell types. The microcirculation, which is critical for the initiation and perpetuation of an inflammatory response, exhibits several characteristic functional and structural changes in response to inflammation. These include vasomotor dysfunction (impaired vessel dilation and constriction), the adhesion and transendothelial migration of leukocytes, endothelial barrier dysfunction (increased vascular permeability), blood vessel proliferation (angiogenesis), and enhanced thrombus formation. These diverse responses of the microvasculature largely reflect the endothelial cell dysfunction that accompanies inflammation and the central role of these cells in modulating processes as varied as blood flow regulation, angiogenesis, and thrombogenesis. The importance of endothelial cells in inflammation-induced vascular dysfunction is also predicated on the ability of these cells to produce and respond to reactive oxygen and nitrogen species. Inflammation seems to upset the balance between nitric oxide and superoxide within (and surrounding) endothelial cells, which is necessary for normal vessel function. This review is focused on defining the molecular targets in the vessel wall that interact with reactive oxygen species and nitric oxide to produce the characteristic functional and structural changes that occur in response to inflammation. This analysis of the literature is consistent with the view that reactive oxygen and nitrogen species contribute significantly to the diverse vascular responses in inflammation and supports efforts that are directed at targeting these highly reactive species to maintain normal vascular health in pathological conditions that are associated with acute or chronic inflammation. PMID:22154653

  7. Sphingosine-1-phosphate promotes erythrocyte glycolysis and oxygen release for adaptation to high-altitude hypoxia.

    PubMed

    Sun, Kaiqi; Zhang, Yujin; D'Alessandro, Angelo; Nemkov, Travis; Song, Anren; Wu, Hongyu; Liu, Hong; Adebiyi, Morayo; Huang, Aji; Wen, Yuan E; Bogdanov, Mikhail V; Vila, Alejandro; O'Brien, John; Kellems, Rodney E; Dowhan, William; Subudhi, Andrew W; Jameson-Van Houten, Sonja; Julian, Colleen G; Lovering, Andrew T; Safo, Martin; Hansen, Kirk C; Roach, Robert C; Xia, Yang

    2016-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive signalling lipid highly enriched in mature erythrocytes, with unknown functions pertaining to erythrocyte physiology. Here by employing nonbiased high-throughput metabolomic profiling, we show that erythrocyte S1P levels rapidly increase in 21 healthy lowland volunteers at 5,260 m altitude on day 1 and continue increasing to 16 days with concurrently elevated erythrocyte sphingonisne kinase 1 (Sphk1) activity and haemoglobin (Hb) oxygen (O2) release capacity. Mouse genetic studies show that elevated erythrocyte Sphk1-induced S1P protects against tissue hypoxia by inducing O2 release. Mechanistically, we show that intracellular S1P promotes deoxygenated Hb anchoring to the membrane, enhances the release of membrane-bound glycolytic enzymes to the cytosol, induces glycolysis and thus the production of 2,3-bisphosphoglycerate (2,3-BPG), an erythrocyte-specific glycolytic intermediate, which facilitates O2 release. Altogether, we reveal S1P as an intracellular hypoxia-responsive biolipid promoting erythrocyte glycolysis, O2 delivery and thus new therapeutic opportunities to counteract tissue hypoxia. PMID:27417539

  8. Sphingosine-1-phosphate promotes erythrocyte glycolysis and oxygen release for adaptation to high-altitude hypoxia

    PubMed Central

    Sun, Kaiqi; Zhang, Yujin; D'Alessandro, Angelo; Nemkov, Travis; Song, Anren; Wu, Hongyu; Liu, Hong; Adebiyi, Morayo; Huang, Aji; Wen, Yuan E.; Bogdanov, Mikhail V.; Vila, Alejandro; O'Brien, John; Kellems, Rodney E.; Dowhan, William; Subudhi, Andrew W.; Jameson-Van Houten, Sonja; Julian, Colleen G.; Lovering, Andrew T.; Safo, Martin; Hansen, Kirk C.; Roach, Robert C.; Xia, Yang

    2016-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive signalling lipid highly enriched in mature erythrocytes, with unknown functions pertaining to erythrocyte physiology. Here by employing nonbiased high-throughput metabolomic profiling, we show that erythrocyte S1P levels rapidly increase in 21 healthy lowland volunteers at 5,260 m altitude on day 1 and continue increasing to 16 days with concurrently elevated erythrocyte sphingonisne kinase 1 (Sphk1) activity and haemoglobin (Hb) oxygen (O2) release capacity. Mouse genetic studies show that elevated erythrocyte Sphk1-induced S1P protects against tissue hypoxia by inducing O2 release. Mechanistically, we show that intracellular S1P promotes deoxygenated Hb anchoring to the membrane, enhances the release of membrane-bound glycolytic enzymes to the cytosol, induces glycolysis and thus the production of 2,3-bisphosphoglycerate (2,3-BPG), an erythrocyte-specific glycolytic intermediate, which facilitates O2 release. Altogether, we reveal S1P as an intracellular hypoxia-responsive biolipid promoting erythrocyte glycolysis, O2 delivery and thus new therapeutic opportunities to counteract tissue hypoxia. PMID:27417539

  9. Cytotoxicity of InP/ZnS quantum dots related to reactive oxygen species generation.

    SciTech Connect

    Chibli, H.; Carlini, L.; Park, S.; Dimitrijevic, N. M.; Nadeau, J. L.

    2011-01-01

    Indium phosphide (InP) quantum dots (QDs) have emerged as a presumably less hazardous alternative to cadmium-based particles, but their cytotoxicity has not been well examined. Although their constituent elements are of very low toxicity to cells in culture, they nonetheless exhibit phototoxicity related to generation of reactive oxygen species by excited electrons and/or holes interacting with water and molecular oxygen. Using spin-trap electron paramagnetic resonance (EPR) spectroscopy and reporter assays, we find a considerable amount of superoxide and a small amount of hydroxyl radical formed under visible illumination of biocompatible InP QDs with a single ZnS shell, comparable to what is seen with CdTe. A double thickness shell reduces the reactive oxygen species concentration approximately two-fold. Survival assays in five cell lines correspondingly indicate a distinct reduction in toxicity with the double-shell InP QDs. Toxicity varies significantly across cell lines according to the efficiency of uptake, being overall significantly less than what is seen with CdTe or CdSe/ZnS. This indicates that InP QDs are a useful alternative to cadmium-containing QDs, while remaining capable of electron-transfer processes that may be undesirable or which may be exploited for photosensitization applications.

  10. Antioxidants protect against reactive oxygen species associated with adriamycin-treated cardiomyocytes.

    PubMed

    DeAtley, S M; Aksenov, M Y; Aksenova, M V; Harris, B; Hadley, R; Cole Harper, P; Carney, J M; Butterfield, D A

    1999-02-01

    Adriamycin (ADM) is a broad-spectrum antineoplastic antibiotic used to treat cancer patients. However, the usefulness of this drug is presently limited by the development of a dose-dependent cardiotoxicity. A current hypothesis for the ADM-induced cardiotoxicity is the production of reactive oxygen radicals by the drug. We utilized the fluorescent indicator 2',7'-dichlorodihydrofluorescein diacetate (DCFH/DA), in which fluorescence appears if reactive oxygen species (ROS) are present, to investigate the ability of ADM to generate reactive oxygen species and the potential protective effect of antioxidants in a cultured cardiomyocyte model. All three of the antioxidants (alpha-phenyl-tert-butyl nitrone (PBN), trolox, and 5-aminosalicylic acid (5-ASA)) tested in our ADM-treated myocytes provided protection against the oxidative stress induced by the drug. These findings suggest that antioxidants modulate ADM-induced oxidative stress, and they are discussed in terms of a possible therapeutic strategy in the prevention of cardiotoxicity resulting from ADM administration. PMID:10211937

  11. Antimicrobial strategies centered around reactive oxygen species - bactericidal antibiotics, photodynamic therapy and beyond

    PubMed Central

    Vatansever, Fatma; de Melo, Wanessa C.M.A.; Avci, Pinar; Vecchio, Daniela; Sadasivam, Magesh; Gupta, Asheesh; Chandran, Rakkiyappan; Karimi, Mahdi; Parizotto, Nivaldo A; Yin, Rui; Tegos, George P; Hamblin, Michael R

    2013-01-01

    Reactive oxygen species (ROS) can attack a diverse range of targets to exert antimicrobial activity, which accounts for their versatility in mediating host defense against a broad range of pathogens. Most ROS are formed by the partial reduction of molecular oxygen. Four major ROS are recognized comprising: superoxide (O2•−), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and singlet oxygen (1O2), but they display very different kinetics and levels of activity. The effects of O2•− and H2O2 are less acute than those of •OH and 1O2, since the former are much less reactive and can be detoxified by endogenous antioxidants (both enzymatic and non-enzymatic) that are induced by oxidative stress. In contrast, no enzyme can detoxify •OH or 1O2, making them extremely toxic and acutely lethal. The present review will highlight the various methods of ROS formation and their mechanism of action. Antioxidant defenses against ROS in microbial cells and the use of ROS by antimicrobial host defense systems are covered. Antimicrobial approaches primarily utilizing ROS comprise both bactericidal antibiotics, and non-pharmacological methods such as photodynamic therapy, titanium dioxide photocatalysis, cold plasma and medicinal honey. A brief final section covers, reactive nitrogen species, and related therapeutics, such as acidified nitrite and nitric oxide releasing nanoparticles. PMID:23802986

  12. Production of Energetic Active-Oxygen Species at Atmospheric Pressure by Linear Microplasma Arrays

    NASA Astrophysics Data System (ADS)

    Rawlins, Wilson; Galbally-Kinney, Kristin; Davis, Steven; Hoskinson, Alan; Hopwood, Jeffrey

    2014-10-01

    Linear arrays of stripline resonators operated at microwave frequencies and low powers provide spatially and temporally continuous micro-discharges with high E/N at atmospheric pressure. When implemented in a discharge-flow reactor, these microplasmas excite metastable singlet molecular oxygen and dissociate oxygen molecules to produce atomic oxygen, with efficiencies comparable to conventional microwave resonant cavities at low pressures. At elevated pressure, production of atomic oxygen leads to prompt formation of ozone immediately downstream of the discharge exit. We have observed and quantified the production of O2(a 1 Δ) metastables and O3 in the effluent of linear microplasma arrays for O2/He, O2/Ar, O2/N2/He,andO2/N2/Ar mixtures as functions of pressure, gas flow rate, and species mixing ratio. We compare results for single-array microplasmas, where the discharge products are formed in a small volume and entrained into the bulk flow, and overlapping dual-array microplasmas which process larger gas flow volumes. Supported by the Air Force Research Laboratory and Department of Energy.

  13. Photochemistry of Dissolved Black Carbon Released from Biochar: Reactive Oxygen Species Generation and Phototransformation.

    PubMed

    Fu, Heyun; Liu, Huiting; Mao, Jingdong; Chu, Wenying; Li, Qilin; Alvarez, Pedro J J; Qu, Xiaolei; Zhu, Dongqiang

    2016-02-01

    Dissolved black carbon (BC) released from biochar can be one of the more photoactive components in the dissolved organic matter (DOM) pool. Dissolved BC was mainly composed of aliphatics and aromatics substituted by aromatic C-O and carboxyl/ester/quinone moieties as determined by solid-state nuclear magnetic resonance. It underwent 56% loss of absorbance at 254 nm, almost complete loss of fluorescence, and 30% mineralization during a 169 h simulated sunlight exposure. Photoreactions preferentially targeted aromatic and methyl moieties, generating CH2/CH/C and carboxyl/ester/quinone functional groups. During irradiation, dissolved BC generated reactive oxygen species (ROS) including singlet oxygen and superoxide. The apparent quantum yield of singlet oxygen was 4.07 ± 0.19%, 2-3 fold higher than many well-studied DOM. Carbonyl-containing structures other than aromatic ketones were involved in the singlet oxygen sensitization. The generation of superoxide apparently depended on electron transfer reactions mediated by silica minerals in dissolved BC, in which phenolic structures served as electron donors. Self-generated ROS played an important role in the phototransformation. Photobleaching of dissolved BC decreased its ability to further generate ROS due to lower light absorption. These findings have significant implications on the environmental fate of dissolved BC and that of priority pollutants. PMID:26717492

  14. A Role for Reactive Oxygen Species Produced by NADPH Oxidases in the Embryo and Aleurone Cells in Barley Seed Germination

    PubMed Central

    Ishibashi, Yushi; Kasa, Shinsuke; Sakamoto, Masatsugu; Aoki, Nozomi; Kai, Kyohei; Yuasa, Takashi; Hanada, Atsushi; Yamaguchi, Shinjiro; Iwaya-Inoue, Mari

    2015-01-01

    Reactive oxygen species (ROS) promote the germination of several seeds, and antioxidants suppress it. However, questions remain regarding the role and production mechanism of ROS in seed germination. Here, we focused on NADPH oxidases, which produce ROS. After imbibition, NADPH oxidase mRNAs were expressed in the embryo and in aleurone cells of barley seed; these expression sites were consistent with the sites of ROS production in the seed after imbibition. To clarify the role of NADPH oxidases in barley seed germination, we examined gibberellic acid (GA) / abscisic acid (ABA) metabolism and signaling in barley seeds treated with diphenylene iodonium chloride (DPI), an NADPH oxidase inhibitor. DPI significantly suppressed germination, and suppressed GA biosynthesis and ABA catabolism in embryos. GA, but not ABA, induced NADPH oxidase activity in aleurone cells. Additionally, DPI suppressed the early induction of α-amylase by GA in aleurone cells. These results suggest that ROS produced by NADPH oxidases promote GA biosynthesis in embryos, that GA induces and activates NADPH oxidases in aleurone cells, and that ROS produced by NADPH oxidases induce α-amylase in aleurone cells. We conclude that the ROS generated by NADPH oxidases regulate barley seed germination through GA / ABA metabolism and signaling in embryo and aleurone cells. PMID:26579718

  15. A Role for Reactive Oxygen Species Produced by NADPH Oxidases in the Embryo and Aleurone Cells in Barley Seed Germination.

    PubMed

    Ishibashi, Yushi; Kasa, Shinsuke; Sakamoto, Masatsugu; Aoki, Nozomi; Kai, Kyohei; Yuasa, Takashi; Hanada, Atsushi; Yamaguchi, Shinjiro; Iwaya-Inoue, Mari

    2015-01-01

    Reactive oxygen species (ROS) promote the germination of several seeds, and antioxidants suppress it. However, questions remain regarding the role and production mechanism of ROS in seed germination. Here, we focused on NADPH oxidases, which produce ROS. After imbibition, NADPH oxidase mRNAs were expressed in the embryo and in aleurone cells of barley seed; these expression sites were consistent with the sites of ROS production in the seed after imbibition. To clarify the role of NADPH oxidases in barley seed germination, we examined gibberellic acid (GA) / abscisic acid (ABA) metabolism and signaling in barley seeds treated with diphenylene iodonium chloride (DPI), an NADPH oxidase inhibitor. DPI significantly suppressed germination, and suppressed GA biosynthesis and ABA catabolism in embryos. GA, but not ABA, induced NADPH oxidase activity in aleurone cells. Additionally, DPI suppressed the early induction of α-amylase by GA in aleurone cells. These results suggest that ROS produced by NADPH oxidases promote GA biosynthesis in embryos, that GA induces and activates NADPH oxidases in aleurone cells, and that ROS produced by NADPH oxidases induce α-amylase in aleurone cells. We conclude that the ROS generated by NADPH oxidases regulate barley seed germination through GA / ABA metabolism and signaling in embryo and aleurone cells. PMID:26579718

  16. Newly synthesized bis-benzimidazole compound 8 induces apoptosis, autophagy and reactive oxygen species generation in HeLa cells.

    PubMed

    Chu, Naying; Yao, Guodong; Liu, Yuan; Cheng, Maosheng; Ikejima, Takashi

    2016-09-01

    Compound 8 (C8) is a newly synthesized bis-benzimidazole derivative and exerts significant anti-tumor activity in vitro. Previous studies demonstrated that C8 induced apoptosis and autophagy in human promyelocytic leukemia HL60 cells. However, cytotoxicity study on human peripheral blood mononuclear cells (hPBMC) showed that C8 exhibited less toxicity in normal cells. In this study, the molecular mechanism of C8 on human cervical carcinoma HeLa cells was investigated. The results showed that C8 inhibited the growth of HeLa cells and triggered both apoptotic and autophagic cell death. Subsequent experiment also indicated that reactive oxygen species (ROS) generation was induced in C8-treated HeLa cells. Since ROS scavenger decreased the ratio of apoptotic and autophagic cells, ROS generation contributed to C8-induced apoptosis and autophagy. Furthermore, inhibitors of apoptosis and autophagy also reduced ROS generation, respectively. Autophagy inhibition increased cell growth compared to C8-treated group and attenuated apoptotic cell death, indicating that C8-induced autophagy promoted apoptosis for cell death. However, the percentage of autophagic cells was enhanced when limiting apoptosis process. Taken together, C8 induced ROS-mediated apoptosis and autophagy in HeLa cells, autophagy promoted apoptosis but the former was antagonized by the latter. The data also gave us a new perspective on the anti-tumor effect of C8. PMID:27497983

  17. Reactive oxygen species mediate pollen tube rupture to release sperm for fertilization in Arabidopsis

    NASA Astrophysics Data System (ADS)

    Duan, Qiaohong; Kita, Daniel; Johnson, Eric A.; Aggarwal, Mini; Gates, Laura; Wu, Hen-Ming; Cheung, Alice Y.

    2014-01-01

    In flowering plants, sperm are transported inside pollen tubes to the female gametophyte for fertilization. The female gametophyte induces rupture of the penetrating pollen tube, resulting in sperm release and rendering them available for fertilization. Here we utilize the Arabidopsis FERONIA (FER) receptor kinase mutants, whose female gametophytes fail to induce pollen tube rupture, to decipher the molecular mechanism of this critical male-female interactive step. We show that FER controls the production of high levels of reactive oxygen species at the entrance to the female gametophyte to induce pollen tube rupture and sperm release. Pollen tube growth assays in vitro and in the pistil demonstrate that hydroxyl free radicals are likely the most reactive oxygen molecules, and they induce pollen tube rupture in a Ca2+-dependent process involving Ca2+ channel activation. Our results provide evidence for a RHO GTPase-based signalling mechanism to mediate sperm release for fertilization in plants.

  18. Communication: CO oxidation by silver and gold cluster cations: Identification of different active oxygen species

    SciTech Connect

    Popolan, Denisia M.; Bernhardt, Thorsten M.

    2011-03-07

    The oxidation of carbon monoxide with nitrous oxide on mass-selected Au{sub 3}{sup +} and Ag{sub 3}{sup +} clusters has been investigated under multicollision conditions in an octopole ion trap experiment. The comparative study reveals that for both gold and silver cations carbon dioxide is formed on the clusters. However, whereas in the case of Au{sub 3}{sup +} the cluster itself acts as reactive species that facilitates the formation of CO{sub 2} from N{sub 2}O and CO, for silver the oxidized clusters Ag{sub 3}O{sub x}{sup +} (n= 1-3) are identified as active in the CO oxidation reaction. Thus, in the case of the silver cluster cations N{sub 2}O is dissociated and one oxygen atom is suggested to directly react with CO, whereas a second kind of oxygen strongly bound to silver is acting as a substrate for the reaction.

  19. Reaction of Paprika Carotenoids, Capsanthin and Capsorubin, with Reactive Oxygen Species.

    PubMed

    Nishino, Azusa; Yasui, Hiroyuki; Maoka, Takashi

    2016-06-15

    The reaction of paprika carotenoids, capsanthin and capsorubin, with reactive oxygen species (ROS), such as superoxide anion radical (·O2(-)), hydroxyl radical (·OH), and singlet oxygen ((1)O2), was analyzed by LC/PDA ESI-MS and ESR spectrometry. Capsanthin formed both the 5,6-epoxide and 5,8-epoxide by reaction with ·O2(-) and ·OH. Furthermore, capsanthin also formed 5,6- and 5,8-endoperoxide on reaction with (1)O2. The same results were obtained in the case of capsanthin diacetate. On the other hand, capsorubin showed higher stability against these ROS. Capsorubin formed 7,8-epoxide on reaction with ·O2(-) and ·OH and 7,8-endoperoxide on reaction with (1)O2. PMID:27229653

  20. Sexual Preferences in Nutrient Utilization Regulate Oxygen Consumption and Reactive Oxygen Species Generation in Schistosoma mansoni: Potential Implications for Parasite Redox Biology

    PubMed Central

    Oliveira, Matheus P.; Correa Soares, Juliana B. R.; Oliveira, Marcus F.

    2016-01-01

    Schistosoma mansoni, one of the causative agents of human schistosomiasis, has a unique antioxidant network that is key to parasite survival and a valuable chemotherapeutic target. The ability to detoxify and tolerate reactive oxygen species increases along S. mansoni development in the vertebrate host, suggesting that adult parasites are more exposed to redox challenges than young stages. Indeed, adult parasites are exposed to multiple redox insults generated from blood digestion, activated immune cells, and, potentially, from their own parasitic aerobic metabolism. However, it remains unknown how reactive oxygen species are produced by S. mansoni metabolism, as well as their biological effects on adult worms. Here, we assessed the contribution of nutrients and parasite gender to oxygen utilization pathways, and reactive oxygen species generation in whole unpaired adult S. mansoni worms. We also determined the susceptibilities of both parasite sexes to a pro-oxidant challenge. We observed that glutamine and serum importantly contribute to both respiratory and non-respiratory oxygen utilization in adult worms, but with different proportions among parasite sexes. Analyses of oxygen utilization pathways revealed that respiratory rates were high in male worms, which contrast with high non-respiratory rates in females, regardless nutritional sources. Interestingly, mitochondrial complex I-III activity was higher than complex IV specifically in females. We also observed sexual preferences in substrate utilization to sustain hydrogen peroxide production towards glucose in females, and glutamine in male worms. Despite strikingly high oxidant levels and hydrogen peroxide production rates, female worms were more resistant to a pro-oxidant challenge than male parasites. The data presented here indicate that sexual preferences in nutrient metabolism in adult S. mansoni worms regulate oxygen utilization and reactive oxygen species production, which may differently contribute

  1. Sexual Preferences in Nutrient Utilization Regulate Oxygen Consumption and Reactive Oxygen Species Generation in Schistosoma mansoni: Potential Implications for Parasite Redox Biology.

    PubMed

    Oliveira, Matheus P; Correa Soares, Juliana B R; Oliveira, Marcus F

    2016-01-01

    Schistosoma mansoni, one of the causative agents of human schistosomiasis, has a unique antioxidant network that is key to parasite survival and a valuable chemotherapeutic target. The ability to detoxify and tolerate reactive oxygen species increases along S. mansoni development in the vertebrate host, suggesting that adult parasites are more exposed to redox challenges than young stages. Indeed, adult parasites are exposed to multiple redox insults generated from blood digestion, activated immune cells, and, potentially, from their own parasitic aerobic metabolism. However, it remains unknown how reactive oxygen species are produced by S. mansoni metabolism, as well as their biological effects on adult worms. Here, we assessed the contribution of nutrients and parasite gender to oxygen utilization pathways, and reactive oxygen species generation in whole unpaired adult S. mansoni worms. We also determined the susceptibilities of both parasite sexes to a pro-oxidant challenge. We observed that glutamine and serum importantly contribute to both respiratory and non-respiratory oxygen utilization in adult worms, but with different proportions among parasite sexes. Analyses of oxygen utilization pathways revealed that respiratory rates were high in male worms, which contrast with high non-respiratory rates in females, regardless nutritional sources. Interestingly, mitochondrial complex I-III activity was higher than complex IV specifically in females. We also observed sexual preferences in substrate utilization to sustain hydrogen peroxide production towards glucose in females, and glutamine in male worms. Despite strikingly high oxidant levels and hydrogen peroxide production rates, female worms were more resistant to a pro-oxidant challenge than male parasites. The data presented here indicate that sexual preferences in nutrient metabolism in adult S. mansoni worms regulate oxygen utilization and reactive oxygen species production, which may differently contribute

  2. Role of reactive oxygen and nitrogen species in etiopathogenesis of rheumatoid arthritis.

    PubMed

    Bauerová, K; Bezek, A

    1999-10-01

    Rheumatoid arthritis (RA) is a chronic disease affecting up to 3% of the population in most countries. The causes of RA have not been completely elucidated. This paper aims to review the role of reactive oxygen and nitrogen species in the etiopathogenesis of RA. Reactive oxygen species (ROS), such as superoxide radical, hydrogen peroxide, hydroxyl radical and hypochlorous acid, as well as reactive nitrogen species (RNS), such as nitric oxide and peroxynitrite, contribute significantly to tissue injury in RA. Several mechanisms are involved in the generation and action of ROS and RNS. Superoxide radical, hydrogen peroxide and nitric oxide do not directly damage the majority of biological molecules. They are however converted into the highly reactive hydroxyl radical, which reacts with almost all molecules in living cells. The resulting chronic inflammation process can be reduced with antioxidant therapy. To date, scavenging, preventive, and enzyme antioxidants are available. The most important mode is scavenging of the hydroxyl radical and of hypochlorous acid. Another important way is to inhibit production of RNS and ROS by neutrophils, monocytes, and macrophages. The control of inflammation in arthritic patients by natural as well as synthetic antioxidants could become a relevant component of antirheumatic prevention and therapy. PMID:10703714

  3. Reactive Oxygen Species Generation by Lunar Simulants in Simulated Lung Fluid

    NASA Astrophysics Data System (ADS)

    Schoonen, M. A.; Kaur, J.; Rickman, D.

    2015-12-01

    The current interest in human exploration of the Moon and other airless planetary bodies has rekindled research into the harmful effects of Lunar dust on human health. Our team has evaluated the spontaneous formation of Reactive Oxygen Species (ROS; hydroxyl radicals, superoxide, and hydrogen peroxide) of a suite of lunar simulants when dispersed in deionized water. Of these species, hydroxyl radical reacts almost immediately with any biomolecule leading to oxidative damage. Sustained production of OH radical as a result of mineral exposure can initiate or enhance disease. The results in deionized water indicate that mechanical stress and the absence of molecular oxygen and water, important environmental characteristics of the lunar environment, can lead to enhanced production of ROS in general. On the basis of the results with deionized water, a few of the simulants were selected for additional studies to evaluate the formation of hydrogen peroxide, a precursor of hydroxyl radical in Simulated Lung Fluid. These simulants dispersed in deionized water typically produce a maximum in H2O2 within 10 to 40 minutes. However, experiments in SLF show a slow steady increase in H2O2 concentration that has been documented to continue for as long as 7 hours. Control experiments with one simulant demonstrate that the rise in H2O2 depends on the availability of dissolved O2. We speculate that this continuous rise in oxygenated SLF might be a result of metal ion-mediated oxidation of organic components, such as glycine in SLF. Ion-mediated oxidation essentially allows dissolved molecular oxygen to react with dissolved organic compounds by forming a metal-organic complex. Results of separate experiments with dissolved Fe, Ni, and Cu and speciation calculations support this notion.

  4. Rule-based knowledge acquisition method for promoter prediction in human and Drosophila species.

    PubMed

    Huang, Wen-Lin; Tung, Chun-Wei; Liaw, Chyn; Huang, Hui-Ling; Ho, Shinn-Ying

    2014-01-01

    The rapid and reliable identification of promoter regions is important when the number of genomes to be sequenced is increasing very speedily. Various methods have been developed but few methods investigate the effectiveness of sequence-based features in promoter prediction. This study proposes a knowledge acquisition method (named PromHD) based on if-then rules for promoter prediction in human and Drosophila species. PromHD utilizes an effective feature-mining algorithm and a reference feature set of 167 DNA sequence descriptors (DNASDs), comprising three descriptors of physicochemical properties (absorption maxima, molecular weight, and molar absorption coefficient), 128 top-ranked descriptors of 4-mer motifs, and 36 global sequence descriptors. PromHD identifies two feature subsets with 99 and 74 DNASDs and yields test accuracies of 96.4% and 97.5% in human and Drosophila species, respectively. Based on the 99- and 74-dimensional feature vectors, PromHD generates several if-then rules by using the decision tree mechanism for promoter prediction. The top-ranked informative rules with high certainty grades reveal that the global sequence descriptor, the length of nucleotide A at the first position of the sequence, and two physicochemical properties, absorption maxima and molecular weight, are effective in distinguishing promoters from non-promoters in human and Drosophila species, respectively. PMID:24955394

  5. Iron-induced tissue damage and cancer: the role of reactive oxygen species-free radicals.

    PubMed

    Okada, S

    1996-05-01

    Oxygen is poisonous, but we cannot live without it. The high oxidizing potential of oxygen molecules (dioxygen) is a valuable source of energy for the organism and its reactivity is low; that is, spin forbidden. However, the dioxygen itself is a 'free radical' and, especially in the presence of transition metals, it is a major promoter of radical reactions in the cell. Humans survive only by virtue of their elaborate defense mechanisms against oxygen toxicity. Iron is the most abundant transition metal in the human body. Because iron shows wide variation in redox potential with different co-ordination ligands, it may be used as a redox intermediate in many biological mechanism. However, it is precisely this redox activeness that makes iron a key participant in free radical production. The current research on the relationship between iron and cancer is briefly reviewed. Research results are reported here which indicate that iron, when bound to certain ligands, can cause free-radical mediated tissue damage and become carcinogenic. The present study also suggests that iron may also have a significant role in spontaneous human cancer. PMID:8809878

  6. Serratia Secondary Metabolite Prodigiosin Inhibits Pseudomonas aeruginosa Biofilm Development by Producing Reactive Oxygen Species that Damage Biological Molecules

    PubMed Central

    Kimyon, Önder; Das, Theerthankar; Ibugo, Amaye I.; Kutty, Samuel K.; Ho, Kitty K.; Tebben, Jan; Kumar, Naresh; Manefield, Mike

    2016-01-01

    Prodigiosin is a heterocyclic bacterial secondary metabolite belonging to the class of tripyrrole compounds, synthesized by various types of bacteria including Serratia species. Prodigiosin has been the subject of intense research over the last decade for its ability to induce apoptosis in several cancer cell lines. Reports suggest that prodigiosin promotes oxidative damage to double-stranded DNA (dsDNA) in the presence of copper ions and consequently leads to inhibition of cell-cycle progression and cell death. However, prodigiosin has not been previously implicated in biofilm inhibition. In this study, the link between prodigiosin and biofilm inhibition through the production of redox active metabolites is presented. Our study showed that prodigiosin (500 μM) (extracted from Serratia marcescens culture) and a prodigiosin/copper(II) (100 μM each) complex have strong RNA and dsDNA cleaving properties while they have no pronounced effect on protein. Results support a role for oxidative damage to biomolecules by H2O2 and hydroxyl radical generation. Further, it was demonstrated that reactive oxygen species scavengers significantly reduced the DNA and RNA cleaving property of prodigiosin. P. aeruginosa cell surface hydrophobicity and biofilm integrity were significantly altered due to the cleavage of nucleic acids by prodigiosin or the prodigiosin/copper(II) complex. In addition, prodigiosin also facilitated the bactericidal activity. The ability of prodigiosinto cause nucleic acid degradation offers novel opportunities to interfere with extracellular DNA dependent bacterial biofilms. PMID:27446013

  7. Serratia Secondary Metabolite Prodigiosin Inhibits Pseudomonas aeruginosa Biofilm Development by Producing Reactive Oxygen Species that Damage Biological Molecules.

    PubMed

    Kimyon, Önder; Das, Theerthankar; Ibugo, Amaye I; Kutty, Samuel K; Ho, Kitty K; Tebben, Jan; Kumar, Naresh; Manefield, Mike

    2016-01-01

    Prodigiosin is a heterocyclic bacterial secondary metabolite belonging to the class of tripyrrole compounds, synthesized by various types of bacteria including Serratia species. Prodigiosin has been the subject of intense research over the last decade for its ability to induce apoptosis in several cancer cell lines. Reports suggest that prodigiosin promotes oxidative damage to double-stranded DNA (dsDNA) in the presence of copper ions and consequently leads to inhibition of cell-cycle progression and cell death. However, prodigiosin has not been previously implicated in biofilm inhibition. In this study, the link between prodigiosin and biofilm inhibition through the production of redox active metabolites is presented. Our study showed that prodigiosin (500 μM) (extracted from Serratia marcescens culture) and a prodigiosin/copper(II) (100 μM each) complex have strong RNA and dsDNA cleaving properties while they have no pronounced effect on protein. Results support a role for oxidative damage to biomolecules by H2O2 and hydroxyl radical generation. Further, it was demonstrated that reactive oxygen species scavengers significantly reduced the DNA and RNA cleaving property of prodigiosin. P. aeruginosa cell surface hydrophobicity and biofilm integrity were significantly altered due to the cleavage of nucleic acids by prodigiosin or the prodigiosin/copper(II) complex. In addition, prodigiosin also facilitated the bactericidal activity. The ability of prodigiosinto cause nucleic acid degradation offers novel opportunities to interfere with extracellular DNA dependent bacterial biofilms. PMID:27446013

  8. The roles of polycarboxylates in Cr(VI)/sulfite reaction system: Involvement of reactive oxygen species and intramolecular electron transfer.

    PubMed

    Jiang, Bo; Wang, Xianli; Liu, Yukun; Wang, Zhaohui; Zheng, Jingtang; Wu, Mingbo

    2016-03-01

    In this study, the effects of polycarboxylates on both Cr(VI) reduction and S(IV) consumption in Cr(VI)/S(IV) system was investigated in acidic solution. Under aerobic condition, the productions of reactive oxygen species (ROS), i.e., SO4(-) and OH, have been confirmed in S(IV) reducing Cr(VI) process by using electron spin resonance and fluorescence spectrum techniques, leading to the excess consumption of S(IV). However, when polycarboxylates (oxalic, citric, malic and tartaric acid) were present in Cr(VI)/S(IV) system, the affinity of polycarboxylates to CrSO6(2-) can greatly promote the reduction of Cr(VI) via expanding the coordination of Cr(VI) species from tetrahedron to hexahedron. Besides, as alternatives to S(IV), these polycarboxylates can also act as electron donors for Cr(VI) reduction via intramolecular electron transfer reaction, which is dependent on the energies of the highest occupied molecular orbital of these polycarboxylates. Notably, the variant electron donating capacity of these polycarboxylates resulted in different yield of ROS and therefore the oxidation efficiencies of other pollutants, e.g., rhodamine B and As(III). Generally, this study does not only shed light on the mechanism of S(IV) reducing Cr(VI) process mediated by polycarboxylates, but also provides an escalated, cost-effective and green strategy for the remediation of Cr(VI) using sulfite as a reductant. PMID:26610099

  9. Biological Activities of Reactive Oxygen and Nitrogen Species: Oxidative Stress versus Signal Transduction

    PubMed Central

    Weidinger, Adelheid; Kozlov, Andrey V.

    2015-01-01

    In the past, reactive oxygen and nitrogen species (RONS) were shown to cause oxidative damage to biomolecules, contributing to the development of a variety of diseases. However, recent evidence has suggested that intracellular RONS are an important component of intracellular signaling cascades. The aim of this review was to consolidate old and new ideas on the chemical, physiological and pathological role of RONS for a better understanding of their properties and specific activities. Critical consideration of the literature reveals that deleterious effects do not appear if only one primary species (superoxide radical, nitric oxide) is present in a biological system, even at high concentrations. The prerequisite of deleterious effects is the formation of highly reactive secondary species (hydroxyl radical, peroxynitrite), emerging exclusively upon reaction with another primary species or a transition metal. The secondary species are toxic, not well controlled, causing irreversible damage to all classes of biomolecules. In contrast, primary RONS are well controlled (superoxide dismutase, catalase), and their reactions with biomolecules are reversible, making them ideal for physiological/pathophysiological intracellular signaling. We assume that whether RONS have a signal transducing or damaging effect is primarily defined by their quality, being primary or secondary RONS, and only secondly by their quantity. PMID:25884116

  10. Generation of reactive oxygen species by interaction between antioxidants used as food additive and metal ions.

    PubMed

    Iwasaki, Yusuke; Oda, Momoko; Tsukuda, Yuri; Nagamori, Yuki; Nakazawa, Hiroyuki; Ito, Rie; Saito, Koichi

    2014-01-01

    Food additives, such as preservatives, sweeteners, coloring agents, and flavoring agents, are widely used in food manufacturing. However, their combined effects on the human body are not known. The purpose of this study was to examine whether combinations of antioxidants and metal ions generate reactive oxygen species (ROS) under in vitro conditions using electron spin resonance (ESR). Among the metal ions examined, only iron and copper generated ROS in the presence of antioxidants. Moreover, certain phenolic antioxidants having pro-oxidant activity induced DNA oxidation and degradation via the generation of high levels of ROS in the presence of copper ion, resulting in complete degradation of DNA in vitro. PMID:25212818

  11. Superparamagnetic iron oxide nanoparticles as radiosensitizer via enhanced reactive oxygen species formation.

    PubMed

    Klein, Stefanie; Sommer, Anja; Distel, Luitpold V R; Neuhuber, Winfried; Kryschi, Carola

    2012-08-24

    Internalization of citrate-coated and uncoated superparamagnetic iron oxide nanoparticles by human breast cancer (MCF-7) cells was verified by transmission electron microscopy imaging. Cytotoxicity studies employing metabolic and trypan blue assays manifested their excellent biocompatibility. The production of reactive oxygen species in iron oxide nanoparticle loaded MCF-7 cells was explained to originate from both, the release of iron ions and their catalytically active surfaces. Both initiate the Fenton and Haber-Weiss reaction. Additional oxidative stress caused by X-ray irradiation of MCF-7 cells was attributed to the increase of catalytically active iron oxide nanoparticle surfaces. PMID:22842461

  12. Reactive oxygen species and nitric oxide mediate plasticity of neuronal calcium signaling

    PubMed Central

    Yermolaieva, Olena; Brot, Nathan; Weissbach, Herbert; Heinemann, Stefan H.; Hoshi, Toshinori

    2000-01-01

    Reactive oxygen species (ROS) and nitric oxide (NO) are important participants in signal transduction that could provide the cellular basis for activity-dependent regulation of neuronal excitability. In young rat cortical brain slices and undifferentiated PC12 cells, paired application of depolarization/agonist stimulation and oxidation induces long-lasting potentiation of subsequent Ca2+ signaling that is reversed by hypoxia. This potentiation critically depends on NO production and involves cellular ROS utilization. The ability to develop the Ca2+ signal potentiation is regulated by the developmental stage of nerve tissue, decreasing markedly in adult rat cortical neurons and differentiated PC12 cells. PMID:10618438

  13. Induced reactive oxygen species improve enzyme production from Aspergillus niger cultivation.

    PubMed

    Sahoo, Susmita; Rao, K Krishnamurthy; Suraishkumar, G K

    2003-05-01

    Intracellular reactive oxygen species (iROS) induction by HOCl was used as a novel strategy to improve enzyme productivities in Aspergillus niger growing in a bioreactor. With induced iROS, the specific intracellular activities of alpha-amylase, protease, catalase, and glucose oxidase were increased by about 170%, 250%, 320%, and 260%, respectively. The optimum specific iROS level for achieving maximum cell concentration and enzyme production was about 15 mmol g cell-1. The type of iROS inducing the enzyme production was identified to be a derivative of the superoxide radical. PMID:12882014

  14. Role of reactive oxygen species and TRP channels in the cough reflex.

    PubMed

    Taylor-Clark, Thomas E

    2016-09-01

    The cough reflex is evoked by noxious stimuli in the airways. Although this reflex is essential for health, it can be triggered chronically in inflammatory and infectious airway disease. Neuronal transient receptor potential (TRP) channels such as ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) are polymodal receptors expressed on airway nociceptive afferent nerves. Reactive oxygen species (ROS) and other reactive compounds are associated with inflammation, from either NADPH oxidase or mitochondria. These reactive compounds cause activation and hyperexcitability of nociceptive afferents innervating the airways, and evidence suggests key contributions of TRPA1 and TRPV1. PMID:27016063

  15. Mechanism of artemisinin phytotoxicity action: induction of reactive oxygen species and cell death in lettuce seedlings.

    PubMed

    Yan, Zhi-Qiang; Wang, Dan-Dan; Ding, Lan; Cui, Hai-Yan; Jin, Hui; Yang, Xiao-Yan; Yang, Jian-She; Qin, Bo

    2015-03-01

    Artemisinin has been recognized as an allelochemical that inhibits growth of several plant species. However, its mode of action is not well clarified. In this study, the mechanism of artemisinin phytotoxicity on lettuce seedlings was investigated. Root and shoot elongation of lettuce seedlings were inhibited by artemisinin in a concentration-dependent manner. The compound effectively arrested cell division and caused loss of cell viability in root tips of lettuce. Overproduction of reactive oxygen species (ROS) was induced by artemisinin. Lipid peroxidation, proline overproduction and reduction of chlorophyll content in lettuce seedlings were found after treatments. These results suggested that artemisinin could induce ROS overproduction, which caused membrane lipids peroxidation and cell death, and impacted mitosis and physiological processes, resulting in growth inhibition of receptor plants. PMID:25658194

  16. Exceedingly Fast Oxygen Atom Transfer to Olefins via a Catalytically Competent Nonheme Iron Species.

    PubMed

    Serrano-Plana, Joan; Aguinaco, Almudena; Belda, Raquel; García-España, Enrique; Basallote, Manuel G; Company, Anna; Costas, Miquel

    2016-05-17

    The reaction of [Fe(CF3 SO3 )2 (PyNMe3 )] with excess peracetic acid at -40 °C leads to the accumulation of a metastable compound that exists as a pair of electromeric species, [Fe(III) (OOAc)(PyNMe3 )](2+) and [Fe(V) (O)(OAc)(PyNMe3 )](2+) , in fast equilibrium. Stopped-flow UV/Vis analysis confirmed that oxygen atom transfer (OAT) from these electromeric species to olefinic substrates is exceedingly fast, forming epoxides with stereoretention. The impact of the electronic and steric properties of the substrate on the reaction rate could be elucidated, and the relative reactivities determined for the catalytic oxidations could be reproduced by kinetic studies. The observed fast reaction rates and high selectivities demonstrate that this metastable compound is a truly competent OAT intermediate of relevance for nonheme iron catalyzed epoxidations. PMID:27071372

  17. Trait adaptation promotes species coexistence in diverse predator and prey communities.

    PubMed

    Klauschies, Toni; Vasseur, David A; Gaedke, Ursula

    2016-06-01

    Species can adjust their traits in response to selection which may strongly influence species coexistence. Nevertheless, current theory mainly assumes distinct and time-invariant trait values. We examined the combined effects of the range and the speed of trait adaptation on species coexistence using an innovative multispecies predator-prey model. It allows for temporal trait changes of all predator and prey species and thus simultaneous coadaptation within and among trophic levels. We show that very small or slow trait adaptation did not facilitate coexistence because the stabilizing niche differences were not sufficient to offset the fitness differences. In contrast, sufficiently large and fast trait adaptation jointly promoted stable or neutrally stable species coexistence. Continuous trait adjustments in response to selection enabled a temporally variable convergence and divergence of species traits; that is, species became temporally more similar (neutral theory) or dissimilar (niche theory) depending on the selection pressure, resulting over time in a balance between niche differences stabilizing coexistence and fitness differences promoting competitive exclusion. Furthermore, coadaptation allowed prey and predator species to cluster into different functional groups. This equalized the fitness of similar species while maintaining sufficient niche differences among functionally different species delaying or preventing competitive exclusion. In contrast to previous studies, the emergent feedback between biomass and trait dynamics enabled supersaturated coexistence for a broad range of potential trait adaptation and parameters. We conclude that accounting for trait adaptation may explain stable and supersaturated species coexistence for a broad range of environmental conditions in natural systems when the absence of such adaptive changes would preclude it. Small trait changes, coincident with those that may occur within many natural populations, greatly enlarged

  18. Macrophages promote vasculogenesis of retinal neovascularization in an oxygen-induced retinopathy model in mice.

    PubMed

    Gao, Xiang; Wang, Yu-Sheng; Li, Xiao-Qin; Hou, Hui-Yuan; Su, Jing-Bo; Yao, Li-Bo; Zhang, Jian

    2016-06-01

    To investigate the role of macrophages in oxygen-induced retinal neovascularization (NV) in mice, particularly the involvement of bone marrow-derived cells (BMCs) and the underlying mechanisms, BMCs from green fluorescent protein (GFP) transgenic mice were transplanted into postnatal day (P) 1 mice after irradiation. The mice were exposed to 75 % oxygen from P7 to P12 to initiate oxygen-induced retinopathy (OIR). The macrophages were depleted by injection of clodronate-liposomes (lip) intraperitoneally. The eyes were collected at P12 and P17. Retinal flatmounts and histopathological cross-sections were performed to analyze the severity of retinal NV and BMC recruitment. BMCs immunopositive for CD31 (PECAM-1; endothelial cell marker) and α-SMA (smooth muscle cell marker) antigens were detected using a confocal microscope. Expression of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1) mRNA was detected by RT-PCR. The VEGF, SDF-1, CXCR4 and CD45 protein expression was detected by western blot examination. The retinal avascular area in OIR mice at P12 was unaffected after macrophage depletion carried out twice (38.27 ± 1.92 % reduction) using clodronate-lip. The retinal avascular area and the NV area at P17 were reduced after macrophage depletion four times (79.53 ± 1.02 % reduction); these findings were supported by retinal flatmounts and histopathological cross-sections. Macrophage depletion led to significant inhibition of BMC recruitment into the NV tufts at P17, with decreased expression of retinal VEGF, SDF-1, CXCR4 and CD45. The recruited BMCs differentiated primarily into CD31-positive endothelial cells (ECs) and α-SMA-positive smooth muscle cells (SMCs). This study suggested that macrophages promoted the vasculogenesis of retinal NV, particularly the contribution of BMCs in the mouse OIR model, which might be triggered by VEGF and SDF-1 production. PMID:26841878

  19. Copper elevated embryonic hemoglobin through reactive oxygen species during zebrafish erythrogenesis.

    PubMed

    Zhou, Xin-Ying; Zhang, Ting; Ren, Long; Wu, Jun-Jie; Wang, Weimin; Liu, Jing-Xia

    2016-06-01

    Copper, as an essential trace mineral, can cause diseases such as childhood leukemia at excess levels, but has been applied in anemia therapy for a long time. However, few reports have studied its role during hematopoiesis at the molecular level in an animal model. In this study, by microarray, qRT-PCR, whole-mount in situ hybridization and O-dianisidine staining detections, we revealed the increased expression of hemoglobin in copper-exposed embryos. Secondly, we found that copper-exposed embryos exhibited high levels of reactive oxygen species (ROS), and genes in oxygen binding and oxygen transporting were up-regulated in the embryos. Finally, we found that ROS scavengers NAC, GSH, and DMTU not only inhibited in vivo ROS levels induced by copper, but also significantly decreased high expression of hemoglobin back to almost normal levels in copper exposed embryos, and also helped with copper elimination from the embryos. Our data first demonstrated that ROS mediated copper induced hemoglobin expression in vertebrates, partly revealing the underlying molecular mechanism of copper therapy for anemia. Moreover, we revealed that copper homeostasis was broken by its induced ROS and ROS helped with copper overloading in the body, which could be applied as a novel therapy target for copper-caused diseases. PMID:26991749

  20. Redox and Reactive Oxygen Species Regulation of Mitochondrial Cytochrome c Oxidase Biogenesis

    PubMed Central

    Bourens, Myriam; Fontanesi, Flavia; Soto, Iliana C.; Liu, Jingjing

    2013-01-01

    Abstract Significance: Cytochrome c oxidase (COX), the last enzyme of the mitochondrial respiratory chain, is the major oxygen consumer enzyme in the cell. COX biogenesis involves several redox-regulated steps. The process is highly regulated to prevent the formation of pro-oxidant intermediates. Recent Advances: Regulation of COX assembly involves several reactive oxygen species and redox-regulated steps. These include: (i) Intricate redox-controlled machineries coordinate the expression of COX isoenzymes depending on the environmental oxygen concentration. (ii) COX is a heme A-copper metalloenzyme. COX copper metallation involves the copper chaperone Cox17 and several other recently described cysteine-rich proteins, which are oxidatively folded in the mitochondrial intermembrane space. Copper transfer to COX subunits 1 and 2 requires concomitant transfer of redox power. (iii) To avoid the accumulation of reactive assembly intermediates, COX is regulated at the translational level to minimize synthesis of the heme A-containing Cox1 subunit when assembly is impaired. Critical Issues: An increasing number of regulatory pathways converge to facilitate efficient COX assembly, thus preventing oxidative stress. Future Directions: Here we will review on the redox-regulated COX biogenesis steps and will discuss their physiological relevance. Forthcoming insights into the precise regulation of mitochondrial COX biogenesis in normal and stress conditions will likely open future perspectives for understanding mitochondrial redox regulation and prevention of oxidative stress. Antioxid. Redox Signal. 19, 1940–1952. PMID:22937827

  1. Investigation of a sterilization system using active oxygen species generated by ultraviolet irradiation.

    PubMed

    Yoshino, Kiyoshi; Matsumoto, Hiroyuki; Iwasaki, Tatsuyuki; Kinoshita, Shinobu; Noda, Kazutoshi; Oya, Kei; Iwamori, Satoru

    2015-01-01

    We have been investigating an advanced sterilization system that employs active oxygen species (AOS). We designed the sterilization equipment, including an evacuation system, which generates AOS from pure oxygen gas using ultraviolet irradiation, in order to study the conditions necessary for sterilization in the system's chamber. Using Geobachillus stearothermophilus spores (10(6) CFU) in a sterile bag as a biological indicator (BI) in the chamber of the AOS sterilization apparatus, we examined the viability of the BI as a function of exposure time, assessing the role of the decompression level in the sterilization performance. We found that the survival curves showed exponential reduction, and that the decompression level did not exert a significant influence on the survival curve. Subsequently, we investigated the sterilization effect as influenced by the spatial and environmental temperature variation throughout the chamber, and found that the sterilization effect varied with position, due to the varying environmental temperature in the respective areas. We confirmed that temperature is one of the most important factors influencing sterilization in the chamber, and estimated the temperature effect on the distribution of atomic oxygen concentration, using the quartz crystal microbalance (QCM) method with fluorocarbon thin film prepared by radio frequency sputtering. PMID:25817808

  2. Inhibitory activities of soluble and bound millet seed phenolics on free radicals and reactive oxygen species.

    PubMed

    Chandrasekara, Anoma; Shahidi, Fereidoon

    2011-01-12

    Oxidative stress, caused by reactive oxygen species (ROS), is responsible for modulating several pathological conditions and aging. Soluble and bound phenolic extracts of commonly consumed millets, namely, kodo, finger (Ravi), finger (local), foxtail, proso, little, and pearl, were investigated for their phenolic content and inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and ROS, namely, hydroxyl radical, peroxyl radical, hydrogen peroxide (H(2)O(2)), hypochlorous acid (HOCl), and singlet oxygen ((1)O(2)). Inhibition of DPPH and hydroxyl radicals was detrmined using electron paramagnetic resonance (EPR) spectroscopy. The peroxyl radical inhibitory activity was measured using the oxygen radical absorbance capacity (ORAC) assay. The scavenging of H(2)O(2), HOCl, and (1)O(2) was evaluated using colorimetric methods. The results were expressed as micromoles of ferulic acid equivalents (FAE) per gram of grain on a dry weight basis. In addition, major hydroxycinnamic acids were identified and quantified using high-performance liquid chromatography (HPLC) and HPLC-mass spectrometry (MS). All millet varieties displayed effective radical and ROS inhibition activities, which generally positively correlated with phenolic contents, except for hydroxyl radical. HPLC analysis revealed the presence of ferulic and p-coumaric acids as major hydroxycinnamic acids in phenolic extract and responsible for the observed effects. Bound extracts of millet contributed 38-99% to ROS scavenging, depending on the variety and the test system employed. Hence, bound phenolics must be included in the evaluation of the antioxidant activity of millets and other cereals. PMID:21133411

  3. Light-responsive polymer nanoreactors: a source of reactive oxygen species on demand

    NASA Astrophysics Data System (ADS)

    Baumann, Patric; Balasubramanian, Vimalkumar; Onaca-Fischer, Ozana; Sienkiewicz, Andrzej; Palivan, Cornelia G.

    2012-12-01

    Various domains present the challenges of responding to stimuli in a specific manner, with the desired sensitivity or functionality, and only when required. Stimuli-responsive systems that are appropriately designed can effectively meet these challenges. Here, we introduce nanoreactors that encapsulate photosensitizer-protein conjugates in polymer vesicles as a source of ``on demand'' reactive oxygen species. Vesicles made of poly(2-methyloxazoline)-poly(dimethylsiloxane)-poly(2-methyloxazoline) successfully encapsulated the photosensitizer Rose Bengal-bovine serum albumin conjugate (RB-BSA) during a self-assembly process, as demonstrated by UV-Vis spectroscopy. A combination of light scattering and transmission electron microscopy indicated that the nanoreactors are stable over time. They serve a dual role: protecting the photosensitizer in the inner cavity and producing in situ reactive oxygen species (ROS) upon irradiation with appropriate electromagnetic radiation. Illumination with appropriate wavelength light allows us to switch on/off and to control the production of ROS. Because of the oxygen-permeable nature of the polymer membrane of vesicles, ROS escape into the environment around vesicles, as established by electron paramagnetic resonance. The light-sensitive nanoreactor is taken up by HeLa cells in a Trojan horse fashion: it is nontoxic and, when irradiated with the appropriate laser light, produces ROS that induce cell death in a precise area corresponding to the irradiation zone. These nanoreactors can be used in theranostic approaches because they can be detected via the fluorescent photosensitizer signal and simultaneously produce ROS efficiently ``on demand''.Various domains present the challenges of responding to stimuli in a specific manner, with the desired sensitivity or functionality, and only when required. Stimuli-responsive systems that are appropriately designed can effectively meet these challenges. Here, we introduce nanoreactors that

  4. Overexpression of stanniocalcin-1 inhibits reactive oxygen species and renal ischemia/reperfusion injury in mice.

    PubMed

    Huang, Luping; Belousova, Tatiana; Chen, Minyi; DiMattia, Gabriel; Liu, Dajun; Sheikh-Hamad, David

    2012-10-01

    Reactive oxygen species, endothelial dysfunction, inflammation, and mitogen-activated protein kinases have important roles in the pathogenesis of ischemia/reperfusion kidney injury. Stanniocalcin-1 (STC1) suppresses superoxide generation in many systems through the induction of mitochondrial uncoupling proteins and blocks the cytokine-induced rise in endothelial permeability. Here we tested whether transgenic overexpression of STC1 protects from bilateral ischemia/reperfusion kidney injury. This injury in wild-type mice caused a halving of the creatinine clearance; severe tubular vacuolization and cast formation; increased infiltration of macrophages and T cells; higher vascular permeability; greater production of superoxide and hydrogen peroxide; and higher ratio of activated extracellular regulated kinase/activated Jun-N-terminal kinase and p38, all compared to sham-treated controls. Mice transgenic for human STC1 expression, however, had resistance to equivalent ischemia/reperfusion injury indicated as no significant change from controls in any of these parameters. Tubular epithelial cells in transgenic mice expressed higher mitochondrial uncoupling protein 2 and lower superoxide generation. Pre-treatment of transgenic mice with paraquat, a generator of reactive oxygen species, before injury restored the susceptibility to ischemia/reperfusion kidney injury, suggesting that STC1 protects by an anti-oxidant mechanism. Thus, STC1 may be a therapeutic target for ischemia/reperfusion kidney injury. PMID:22695329

  5. Nitric oxide and reactive oxygen species are required for systemic acquired resistance in plants

    PubMed Central

    El-Shetehy, Mohamed; Wang, Caixia; Shine, M B; Yu, Keshun; Kachroo, Aardra; Kachroo, Pradeep

    2015-01-01

    Systemic acquired resistance (SAR) is a form of broad-spectrum disease resistance that is induced in response to primary infection and that protects uninfected portions of the plant against secondary infections by related or unrelated pathogens. SAR is associated with an increase in chemical signals that operate in a collective manner to confer protection against secondary infections. These include, the phytohormone salicylic acid (SA), glycerol-3-phosphate (G3P), azelaic acid (AzA) and more recently identified signals nitric oxide (NO) and reactive oxygen species (ROS). NO, ROS, AzA and G3P function in the same branch of the SAR pathway, and in parallel to the SA-regulated branch. NO and ROS function upstream of AzA/G3P and different reactive oxygen species functions in an additive manner to mediate chemical cleavage of the C9 double bond on C18 unsaturated fatty acids to generate AzA. The parallel and additive functioning of various chemical signals provides important new insights in the overlapping pathways leading to SAR. PMID:26375184

  6. Extensive Dark Biological Production of Reactive Oxygen Species in Brackish and Freshwater Ponds.

    PubMed

    Zhang, Tong; Hansel, Colleen M; Voelker, Bettina M; Lamborg, Carl H

    2016-03-15

    Within natural waters, photodependent processes are generally considered the predominant source of reactive oxygen species (ROS), a suite of biogeochemically important molecules. However, recent discoveries of dark particle-associated ROS production in aquatic environments and extracellular ROS production by various microorganisms point to biological activity as a significant source of ROS in the absence of light. Thus, the objective of this study was to explore the occurrence of dark biological production of the ROS superoxide (O2(-)) and hydrogen peroxide (H2O2) in brackish and freshwater ponds. Here we show that the ROS superoxide and hydrogen peroxide were present in dark waters at comparable concentrations as in sunlit waters. This suggests that, at least for the short-lived superoxide species, light-independent processes were an important control on ROS levels in these natural waters. Indeed, we demonstrated that dark biological production of ROS extensively occurred in brackish and freshwater environments, with greater dark ROS production rates generally observed in the aphotic relative to the photic zone. Filtering and formaldehyde inhibition confirmed the biological nature of a majority of this dark ROS production, which likely involved phytoplankton, particle-associated heterotrophic bacteria, and NADH-oxidizing enzymes. We conclude that biological ROS production is widespread, including regions devoid of light, thereby expanding the relevance of these reactive molecules to all regions of our oxygenated global habit. PMID:26854358

  7. The role of reactive oxygen species in mesenchymal stem cell adipogenic and osteogenic differentiation: a review.

    PubMed

    Atashi, Fatemeh; Modarressi, Ali; Pepper, Michael S

    2015-05-15

    Mesenchymal stromal cells (MSCs) are promising candidates for tissue engineering and regenerative medicine. The multipotent stem cell component of MSC isolates is able to differentiate into derivatives of the mesodermal lineage including adipocytes, osteocytes, chondrocytes, and myocytes. Many common pathways have been described in the regulation of adipogenesis and osteogenesis. However, stimulation of osteogenesis appears to suppress adipogenesis and vice-versa. Increasing evidence implicates a tight regulation of these processes by reactive oxygen species (ROS). ROS are short-lived oxygen-containing molecules that display high chemical reactivity toward DNA, RNA, proteins, and lipids. Mitochondrial complexes I and III, and the NADPH oxidase isoform NOX4 are major sources of ROS production during MSC differentiation. ROS are thought to interact with several pathways that affect the transcription machinery required for MSC differentiation including the Wnt, Hedgehog, and FOXO signaling cascades. On the other hand, elevated levels of ROS, defined as oxidative stress, lead to arrest of the MSC cell cycle and apoptosis. Tightly regulated levels of ROS are therefore critical for MSC terminal differentiation, although the precise sources, localization, levels and the exact species of ROS implicated remain to be determined. This review provides a detailed overview of the influence of ROS on adipogenic and osteogenic differentiation in MSCs. PMID:25603196

  8. Borrelia burgdorferi membranes are the primary targets of reactive oxygen species

    PubMed Central

    Boylan, Julie A; Lawrence, Kevin A; Downey, Jennifer S; Gherardini, Frank C

    2008-01-01

    Spirochetes living in an oxygen-rich environment or when challenged by host immune cells are exposed to reactive oxygen species (ROS). These species can harm/destroy cysteinyl residues, iron-sulphur clusters, DNA and polyunsaturated lipids, leading to inhibition of growth or cell death. Because Borrelia burgdorferi contains no intracellular iron, DNA is most likely not a major target for ROS via Fenton reaction. In support of this, growth of B. burgdorferi in the presence of 5 mM H2O2 had no effect on the DNA mutation rate (spontaneous coumermycin A1 resistance), and cells treated with 10 mM t-butyl hydroperoxide or 10 mM H2O2 show no increase in DNA damage. Unlike most bacteria, B. burgdorferi incorporates ROS-susceptible polyunsaturated fatty acids from the environment into their membranes. Analysis of lipoxidase-treated B. burgdorferi cells by Electron Microscopy showed significant irregularities indicative of membrane damage. Fatty acid analysis of cells treated with lipoxidase indicated that host-derived linoleic acid had been dramatically reduced (50-fold) in these cells, with a corresponding increase in the levels of malondialdehyde by-product (fourfold). These data suggest that B. burgdorferi membrane lipids are targets for attack by ROS encountered in the various stages of the infective cycle. PMID:18373524

  9. Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation

    SciTech Connect

    Meeran, Syed M.; Katiyar, Suchitra; Katiyar, Santosh K.

    2008-05-15

    Phytochemicals show promise as potential chemopreventive or chemotherapeutic agents against various cancers. Here we report the chemotherapeutic effects of berberine, a phytochemical, on human prostate cancer cells. The treatment of human prostate cancer cells (PC-3) with berberine induced dose-dependent apoptosis but this effect of berberine was not seen in non-neoplastic human prostate epithelial cells (PWR-1E). Berberine-induced apoptosis was associated with the disruption of the mitochondrial membrane potential, release of apoptogenic molecules (cytochrome c and Smac/DIABLO) from mitochondria and cleavage of caspase-9,-3 and PARP proteins. This effect of berberine on prostate cancer cells was initiated by the generation of reactive oxygen species (ROS) irrespective of their androgen responsiveness, and the generation of ROS was through the increased induction of xanthine oxidase. Treatment of cells with allopurinol, an inhibitor of xanthine oxidase, inhibited berberine-induced oxidative stress in cancer cells. Berberine-induced apoptosis was blocked in the presence of antioxidant, N-acetylcysteine, through the prevention of disruption of mitochondrial membrane potential and subsequently release of cytochrome c and Smac/DIABLO. In conclusion, the present study reveals that the berberine-mediated cell death of human prostate cancer cells is regulated by reactive oxygen species, and therefore suggests that berberine may be considered for further studies as a promising therapeutic candidate for prostate cancer.

  10. The Role of Reactive Oxygen Species in Mesenchymal Stem Cell Adipogenic and Osteogenic Differentiation: A Review

    PubMed Central

    Atashi, Fatemeh; Modarressi, Ali

    2015-01-01

    Mesenchymal stromal cells (MSCs) are promising candidates for tissue engineering and regenerative medicine. The multipotent stem cell component of MSC isolates is able to differentiate into derivatives of the mesodermal lineage including adipocytes, osteocytes, chondrocytes, and myocytes. Many common pathways have been described in the regulation of adipogenesis and osteogenesis. However, stimulation of osteogenesis appears to suppress adipogenesis and vice-versa. Increasing evidence implicates a tight regulation of these processes by reactive oxygen species (ROS). ROS are short-lived oxygen-containing molecules that display high chemical reactivity toward DNA, RNA, proteins, and lipids. Mitochondrial complexes I and III, and the NADPH oxidase isoform NOX4 are major sources of ROS production during MSC differentiation. ROS are thought to interact with several pathways that affect the transcription machinery required for MSC differentiation including the Wnt, Hedgehog, and FOXO signaling cascades. On the other hand, elevated levels of ROS, defined as oxidative stress, lead to arrest of the MSC cell cycle and apoptosis. Tightly regulated levels of ROS are therefore critical for MSC terminal differentiation, although the precise sources, localization, levels and the exact species of ROS implicated remain to be determined. This review provides a detailed overview of the influence of ROS on adipogenic and osteogenic differentiation in MSCs. PMID:25603196

  11. Promoting Engagement: Using Species Action Plans to Bring Together Students and Conservation Professionals

    ERIC Educational Resources Information Center

    Scott, Graham W.; Turnbull, Shona; Spencer, James

    2008-01-01

    We describe an exercise, the production of a species action plan, which utilises components of both transmission mode and experiential learning. This exercise brings together students and a professional role model to promote a stronger engagement with aspects of local biodiversity management. We outline perceived benefits and outcomes of the…

  12. Richness of lichen species, especially of threatened ones, is promoted by management methods furthering stand continuity.

    PubMed

    Boch, Steffen; Prati, Daniel; Hessenmöller, Dominik; Schulze, Ernst-Detlef; Fischer, Markus

    2013-01-01

    Lichens are a key component of forest biodiversity. However, a comprehensive study analyzing lichen species richness in relation to several management types, extending over different regions and forest stages and including information on site conditions is missing for temperate European forests. In three German regions (Schwäbische Alb, Hainich-Dün, Schorfheide-Chorin), the so-called Biodiversity Exploratories, we studied lichen species richness in 631 forest plots of 400 m(2) comprising different management types (unmanaged, selection cutting, deciduous and coniferous age-class forests resulting from clear cutting or shelterwood logging), various stand ages, and site conditions, typical for large parts of temperate Europe. We analyzed how lichen species richness responds to management and habitat variables (standing biomass, cover of deadwood, cover of rocks). We found strong regional differences with highest lichen species richness in the Schwäbische Alb, probably driven by regional differences in former air pollution, and in precipitation and habitat variables. Overall, unmanaged forests harbored 22% more threatened lichen species than managed age-class forests. In general, total, corticolous, and threatened lichen species richness did not differ among management types of deciduous forests. However, in the Schwäbische-Alb region, deciduous forests had 61% more lichen species than coniferous forests and they had 279% more threatened and 76% more corticolous lichen species. Old deciduous age classes were richer in corticolous lichen species than young ones, while old coniferous age-classes were poorer than young ones. Overall, our findings highlight the importance of stand continuity for conservation. To increase total and threatened lichen species richness we suggest (1) conserving unmanaged forests, (2) promoting silvicultural methods assuring stand continuity, (3) conserving old trees in managed forests, (4) promoting stands of native deciduous tree species

  13. Production characteristics of reactive oxygen/nitrogen species in water using atmospheric pressure discharge plasmas

    NASA Astrophysics Data System (ADS)

    Takahashi, Kazuhiro; Satoh, Kohki; Itoh, Hidenori; Kawaguchi, Hideki; Timoshkin, Igor; Given, Martin; MacGregor, Scott

    2016-07-01

    A pulsed discharge, a DC corona discharge, and a plasma jet are separately generated above a water surface, and reactive oxygen species and reactive nitrogen species (ROS/RNS) in the water are investigated. ROS/RNS in water after the sparging of the off-gas of a packed-bed dielectric barrier discharge (PB-DBD) are also investigated. H2O2, NO2 ‑, and NO3 ‑ are detected after plasma exposure and only NO3 ‑ after off-gas sparging. Short-lifetime species in plasma are found to play an important role in H2O2 and NO2 ‑ production and long-lifetime species in NO3 ‑ production. NO x may inhibit H2O2 production through OH consumption to produce HNO2 and HNO3. O3 does not contribute to ROS/RNS production. The pulsed plasma exposure is found to be effective for the production of H2O2 and NO2 ‑, and the off-gas sparging of the PB-DBD for the production of NO3 ‑.

  14. Oxygen consumption and thermoregulatory responses in three species of South American marsupials.

    PubMed

    Ribeiro, Marcel Cintra Pereira; Bicudo, José Eduardo Pereira Wilken

    2007-07-01

    Oxygen consumption (VO(2)), body temperature (T(b)) and wet thermal conductance (C(wet)), under resting conditions, exposure to low ambient temperature (T(a)) and during sustained exercise (treadmill running) were measured in three phylogenetic related (same family; Didelphidae) South American marsupials possessing similar body masses: Caluromys philander (arboreal/fruit and insect eating), Philander opossum (terrestrial and arboreal/omnivore), and Metachirus nudicaudatus (terrestrial/omnivore). Our measurements of VO(2) and C(wet) under resting conditions agree with those previously reported for other marsupials. We expected that C. philander would show a lower maximal sustained VO(2), compared to the other two species, based on its more reduced skeletal muscle mass. However, the values obtained for C. philander were not statistically different (ANOVA) from those obtained for the other two species. When exposed to low ambient temperature (12 degrees C), differences among the three species were detected, i.e., M. nudicaudatus did not survive, while the other two species were able to reduce their T(b) under such conditions. C. philander gradually decreases its T(b) when cold exposed, and P. opossum shows a more pronounced T(b) drop only when exposure to low ambient temperatures occurs for a more prolonged period of time. PMID:17020814

  15. Parkin Protects against Oxygen-Glucose Deprivation/Reperfusion Insult by Promoting Drp1 Degradation.

    PubMed

    Tang, Jiayu; Hu, Zhiping; Tan, Jieqiong; Yang, Sonlin; Zeng, Liuwang

    2016-01-01

    Ischemic stroke results in severe brain damage and remains one of the leading causes of death and disability worldwide. Effective neuroprotective therapies are needed to reduce brain damage resulting from ischemic stroke. Mitochondria are crucial for cellular energy production and homeostasis. Modulation of mitochondrial function mediates neuroprotection against ischemic brain damage. Dynamin-related protein 1 (Drp1) and parkin play a key role in regulating mitochondrial dynamics. They are potential therapeutic targets for neuroprotection in ischemic stroke. Protective effects of parkin-Drp1 pathway on mitochondria were assessed in a cellular ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces mitochondrial fragmentation. The expression of Drp1 protein is increased after OGDR insult, while the parkin protein level is decreased. The altered protein level of Drp1 after OGDR injury is mediated by parkin through ubiquitin proteasome system (UPS). Drp1 depletion protects against OGDR induced mitochondrial damage and apoptosis. Meanwhile, parkin overexpression protects against OGDR induced apoptosis and mitochondrial dysfunction, which is attenuated by increased expression of Drp1. Our data demonstrate that parkin protects against OGDR insult through promoting degradation of Drp1. This neuroprotective potential of parkin-Drp1 pathway against OGDR insult will pave the way for developing novel neuroprotective agents for cerebral ischemia-reperfusion related disorders. PMID:27597885

  16. Parkin Protects against Oxygen-Glucose Deprivation/Reperfusion Insult by Promoting Drp1 Degradation

    PubMed Central

    Tang, Jiayu; Hu, Zhiping; Tan, Jieqiong; Yang, Sonlin

    2016-01-01

    Ischemic stroke results in severe brain damage and remains one of the leading causes of death and disability worldwide. Effective neuroprotective therapies are needed to reduce brain damage resulting from ischemic stroke. Mitochondria are crucial for cellular energy production and homeostasis. Modulation of mitochondrial function mediates neuroprotection against ischemic brain damage. Dynamin-related protein 1 (Drp1) and parkin play a key role in regulating mitochondrial dynamics. They are potential therapeutic targets for neuroprotection in ischemic stroke. Protective effects of parkin-Drp1 pathway on mitochondria were assessed in a cellular ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces mitochondrial fragmentation. The expression of Drp1 protein is increased after OGDR insult, while the parkin protein level is decreased. The altered protein level of Drp1 after OGDR injury is mediated by parkin through ubiquitin proteasome system (UPS). Drp1 depletion protects against OGDR induced mitochondrial damage and apoptosis. Meanwhile, parkin overexpression protects against OGDR induced apoptosis and mitochondrial dysfunction, which is attenuated by increased expression of Drp1. Our data demonstrate that parkin protects against OGDR insult through promoting degradation of Drp1. This neuroprotective potential of parkin-Drp1 pathway against OGDR insult will pave the way for developing novel neuroprotective agents for cerebral ischemia-reperfusion related disorders. PMID:27597885

  17. Detection of irradiation induced reactive oxygen species production in live cells

    NASA Astrophysics Data System (ADS)

    Gao, Bo; Zhu, Debin

    2006-09-01

    Reactive oxygen species (ROS) is thought to play an important role in cell signaling of apoptosis, necrosis, and proliferation. Light irradiation increases mitochondrial reactive oxygen species (ROS) production and mediates its intracellular signaling by adjusting the redox potential in tumor cells. Mitochondria are the main source of ROS in the living cell. Superoxide anions (0 II - are likely the first ROS generated in the mitochondria following radiation damage, and then convert to hydrogen peroxide (H II0 II), hydroxyl radical (•OH), and singlet oxygen (10 II), etc. Conventional methods for research ROS production in mitochondria mostly use isolated mitochondria rather than mitochondria in living cells. In this study, a highly selective probe to detect mitochondrial 0 II - in live cells, MitoSOX TM Red, was applied to quantify the mitochondrial ROS production in human lung adenocarcinoma cells (ASTC-a-1) with laser scanning microscope (LSM) after ultraviolet C (UVC) and He-Ne laser irradiation. Dichiorodihydrofluoresein diacetate (DCFHDA), a common used fluorescent probe for ROS detection without specificity, were used as a comparison to image the ROS production. The fluorescent image of MItoSOX TM Red counterstained with MitoTracker Deep Red 633, a mitochondria selective probe, shows that the mitochondrial ROS production increases distinctly after UVC and He-Ne laser irradiation. DCFH-DA diffuses labeling throughout the cell though its fluorescence increases markedly too. In conclusion, the fluorescent method with MitoSOX TM Red reagent is proved to be a promising technique to research the role of ROS in radiation induced apoptosis.

  18. Warm acclimation and oxygen depletion induce species-specific responses in salmonids.

    PubMed

    Anttila, Katja; Lewis, Mario; Prokkola, Jenni M; Kanerva, Mirella; Seppänen, Eila; Kolari, Irma; Nikinmaa, Mikko

    2015-05-15

    Anthropogenic activities are greatly altering the habitats of animals, whereby fish are already encountering several stressors simultaneously. The purpose of the current study was to investigate the capacity of fish to respond to two different environmental stressors (high temperature and overnight hypoxia) separately and together. We found that acclimation to increased temperature (from 7.7±0.02°C to 14.9±0.05°C) and overnight hypoxia (daily changes from normoxia to 63-67% oxygen saturation), simulating climate change and eutrophication, had both antagonistic and synergistic effects on the capacity of fish to tolerate these stressors. The thermal tolerance of Arctic char (Salvelinus alpinus) and landlocked salmon (Salmo salar m. sebago) increased with warm acclimation by 1.3 and 2.2°C, respectively, but decreased when warm temperature was combined with overnight hypoxia (by 0.2 and 0.4°C, respectively). In contrast, the combination of the stressors more than doubled hypoxia tolerance in salmon and also increased hypoxia tolerance in char by 22%. Salmon had 1.2°C higher thermal tolerance than char, but char tolerated much lower oxygen levels than salmon at a given temperature. The changes in hypoxia tolerance were connected to the responses of the oxygen supply and delivery system. The relative ventricle mass was higher in cold- than in warm-acclimated salmon but the thickness of the compact layer of the ventricle increased with the combination of warm and hypoxia acclimation in both species. Char had also significantly larger hearts and thicker compact layers than salmon. The results illustrate that while fish can have protective responses when encountering a single environmental stressor, the combination of stressors can have unexpected species-specific effects that will influence their survival capacity. PMID:25827840

  19. Reactive Oxygen Species and Induction of Lignin Peroxidase in Phanerochaete chrysosporium

    PubMed Central

    Belinky, Paula A.; Flikshtein, Nufar; Lechenko, Sergey; Gepstein, Shimon; Dosoretz, Carlos G.

    2003-01-01

    We studied oxidative stress in lignin peroxidase (LIP)-producing cultures (cultures flushed with pure O2) of Phanerochaete chrysosporium by comparing levels of reactive oxygen species (ROS), cumulative oxidative damage, and antioxidant enzymes with those found in non-LIP-producing cultures (cultures grown with free exchange of atmospheric air [control cultures]). A significant increase in the intracellular peroxide concentration and the degree of oxidative damage to macromolecules, e.g., DNA, lipids, and proteins, was observed when the fungus was exposed to pure O2 gas. The specific activities of manganese superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase and the consumption of glutathione were all higher in cultures exposed to pure O2 (oxygenated cultures) than in cultures grown with atmospheric air. Significantly higher gene expression of the LIP-H2 isozyme occurred in the oxygenated cultures. A hydroxyl radical scavenger, dimethyl sulfoxide (50 mM), added to the culture every 12 h, completely abolished LIP expression at the mRNA and protein levels. This effect was confirmed by in situ generation of hydroxyl radicals via the Fenton reaction, which significantly enhanced LIP expression. The level of intracellular cyclic AMP (cAMP) was correlated with the starvation conditions regardless of the oxygenation regimen applied, and similar cAMP levels were obtained at high O2 concentrations and in cultures grown with atmospheric air. These results suggest that even though cAMP is a prerequisite for LIP expression, high levels of ROS, preferentially hydroxyl radicals, are required to trigger LIP synthesis. Thus, the induction of LIP expression by O2 is at least partially mediated by the intracellular ROS. PMID:14602606

  20. Contrasted resistance of stone-dwelling Geodermatophilaceae species to stresses known to give rise to reactive oxygen species.

    PubMed

    Gtari, Maher; Essoussi, Imen; Maaoui, Radhi; Sghaier, Haïtham; Boujmil, Rabeb; Gury, Jérôme; Pujic, Petar; Brusetti, Lorenzo; Chouaia, Bessem; Crotti, Elena; Daffonchio, Daniele; Boudabous, Abdellatif; Normand, Philippe

    2012-06-01

    Stones in arid environments are inhabited by actinobacteria of the family Geodermatophilaceae like the genera Blastococcus and Modestobacter frequently isolated from altered calcarenites. Their habitat requires adaptation to light-induced and other stresses that generate reactive oxygen species. Here, we show that representative members of the species Blastococcus saxobsidens, Geodermatophilus obscurus, and Modestobacter multiseptatus are differentially adapted to stresses associated with arid environments. Whereas B. saxobsidens was found to be sensitive to gamma radiation (D(10)  = 900 Gy; 10% survival at 900 Gy), M. multiseptatus was moderately (D(10)  = 6000 Gy) and G. obscurus was highly tolerant (D(10)  = 9000 Gy). A difference in resistance to high-frequency (λ value = 254 nm) UV was shown by B. saxobsidens, M. multiseptatus, and G. obscurus, being sensitive, tolerant, and highly tolerant (D(10) of 6, 900, and > 3500 kJ m(-2) , respectively). Tolerance to desiccation, mitomycin C and hydrogen peroxide correlated with the ionizing radiation and UV resistance profiles of the three species and were correlated with the pigments synthesized. Resistance to heavy metals/metalloids did not follow the same pattern, with resistance to Ag(2+) and Pb(2+) being similar for B. saxobsidens, M. multiseptatus, and G. obscurus, whereas resistance to AsO4 3-, Cr(2+) , or Cu(2+) was greater for B. saxobsidens than for the other two species. The stress resistance profiles of M. multiseptatus and B. saxobsidens were reflected in different calcarenite colonization patterns. While M. multiseptatus was predominantly isolated from the first two millimeters of stone surface, B. saxobsidens was predominantly isolated from the deeper part of the stone where it is better protected from sun irradiation, suggesting that the response to light- and desiccation-induced oxidative stress is an important driver for niche colonization in the stone biotope. PMID:22296311

  1. Oxygen-assisted reduction of Au species on Au/SiO2 catalyst in room temperature CO oxidation

    SciTech Connect

    Wu, Zili; Zhou, Shenghu; Zhu, Haoguo; Dai, Sheng; Overbury, Steven {Steve} H

    2008-01-01

    An unexpected oxygen-assisted reduction of cationic Au species by CO was found on a Au/SiO2 catalyst at room temperature; CO oxidation activity increases simultaneously with the reduction of Au species, suggesting the key role of metallic Au played in CO oxidation on Au/SiO2.

  2. Differential accumulation of reactive oxygen and nitrogen species in maize lines with contrasting drought tolerance and aflatoxin resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Abiotic stresses such as drought stress can exacerbate aflatoxin contamination of maize kernels. Previous studies showed that maize lines resistance to aflatoxin contamination tend to exhibit enhanced drought tolerance and accumulate lower levels of reactive oxygen species (ROS) and nitrogen species...

  3. Identification and quantification of oxygen species adsorbed on Pt(111) single-crystal and polycrystalline Pt electrodes by photoelectron spectroscopy.

    PubMed

    Wakisaka, Mitsuru; Suzuki, Hirokazu; Mitsui, Satoshi; Uchida, Hiroyuki; Watanabe, Masahiro

    2009-02-17

    We have positively identified oxygen species on Pt(111) single-crystal and polycrystalline Pt electrodes in N2-purged 0.1 M HF solution by X-ray photoelectron spectroscopy combined with an electrochemical cell. Four oxygen species (Oad, OHad, and two types of water molecules) were distinguished. The binding energies of each species were nearly constant over the whole potential region and independent of the single- or polycrystalline electrodes. The coverages, however, varied considerably and were dependent on the electrode potential. We have for the first time demonstrated clear differences in the surface oxidation processes for Pt(111) and polycrystalline Pt electrodes. PMID:19152331

  4. The role of molecular oxygen in the iron(III)-promoted oxidative dehydrogenation of amines.

    PubMed

    Saucedo-Vázquez, Juan Pablo; Kroneck, Peter M H; Sosa-Torres, Martha Elena

    2015-03-28

    A mechanistic study is presented of the oxidative dehydrogenation of the iron(III) complex [Fe(III)L(3)](3+), 1, (L(3) = 1,9-bis(2'-pyridyl)-5-[(ethoxy-2''-pyridyl)methyl]-2,5,8-triazanonane) in ethanol in the presence of molecular oxygen. The product of the reaction was identified by NMR spectroscopy and X-ray crystallography as the identical monoimine complex [Fe(II)L(4)](2+), 2, (L(4) = 1,9-bis(2'-pyridyl)-5-[(ethoxy-2''-pyridyl)methyl]-2,5,8-triazanon-1-ene) also formed under an inert nitrogen atmosphere. Molecular oxygen is an active player in the oxidative dehydrogenation of iron(III) complex 1. Reduced oxygen species, e.g., superoxide, (O2˙(-)) and peroxide (O2(2-)), are formed and undergo single electron transfer reactions with ligand-based radical intermediates. The experimental rate law can be described by the third order rate equation, -d[(Fe(III)L(3))(3+)]/dt = kOD[(Fe(III)L(3))(3+)][EtO(-)][O2], with kOD = 3.80 ± 0.09 × 10(7) M(-2) s(-1) (60 °C, μ = 0.01 M). The reduction O2 → O2˙(-) represents the rate determining step, with superoxide becoming further reduced to peroxide as shown by a coupled heme catalase assay. In an independent study, with H2O2, replacing O2 as the oxidant, the experimental rate law depended on [H2O2]: -d[(Fe(III)L(3))(3+)]/dt = kH2O2[(Fe(III)L(3))(3+)][H2O2]), with kH2O2 = 6.25 ± 0.02 × 10(-3) M(-1) s(-1). In contrast to the reaction performed under N2, no kinetic isotope effect (KIE) or general base catalysis was found for the reaction of iron(III) complex 1 with O2. Under N2, two consecutive one-electron oxidation steps of the ligand coupled to proton removal produced the iron(II)-monoimine complex [Fe(II)L(4)](2+) and the iron(II)-amine complex [Fe(II)L(3)](2+) in a 1 : 1 ratio (disproportionation), with the amine deprotonation being the rate determining step. Notably, the reaction is almost one order of magnitude faster in the presence of O2, with kEtO(-) = 3.02 ± 0.09 × 10(5) M(-1) s(-1) (O2) compared to k

  5. Evaluation of multistep derivatization methods for identification and quantification of oxygenated species in organic aerosol.

    PubMed

    Flores, Rosa M; Doskey, Paul V

    2015-10-30

    Two, 3-step methods for derivatizing mono- and multi-functional species with carbonyl (CO), carboxylic acid (-COOH), and alcohol (-OH) moieties were compared and optimized. In Method 1, the CO, -COOH, and -OH moieties were converted (1) to methyloximes (R-CN-OCH3) with O-methylhydroxylamine hydrochloride (MHA), (2) to methyl esters (OC-R-OCH3) with (trimethylsilyl)diazomethane in methanol (TMSD/MeOH), and (3) to trimethylsilyl ethers [R-OSi(CH3)3] with N,O-bis(trimethylsilyl)-trifluoroacetamide (BSTFA) containing 1% trimethylchlorosilane (TMCS), respectively. Steps 1 and 3 of both methods were identical; however, in Step 2 of Method 2, -COOH moieties were derivatized with 10% (v/v) boron trifluoride (BF3) in MeOH or n-butanol (n-BuOH). The BF3/MeOH and BF3/n-BuOH were ineffective at converting species with more than 2-OH moieties. Average standard deviations for derivatization of 36 model compounds by the 3-step methods using TMSD/MeOH and BF3/(MeOH) were 7.4 and 14.8%, respectively. Average derivatization efficiencies for Methods 1 and 2 were 88.0 and 114%, respectively. Despite the lower average derivatization efficiency of Method 1, distinct advantages included a greater certainty of derivatization yield for the entire suite of mono- and multi-functional species and fewer processing steps for sequential derivatization. Detection limits for Method 1 using GC×GC-ToF-MS were 0.3-54pgm(-3). Approximately 100 oxygenated organic species were identified and quantified in aerosol filtered from 39m(3) of air in an urban location. Levels of species were 0.013-17ngm(-3) and were nearly all above the Method 1 limit of detection. PMID:26427323

  6. Metabolism of reactive oxygen species and reactive nitrogen species in pepper (Capsicum annuum L.) plants under low temperature stress.

    PubMed

    Airaki, Morad; Leterrier, Marina; Mateos, Rosa M; Valderrama, Raquel; Chaki, Mounira; Barroso, Juan B; Del Río, Luis A; Palma, José M; Corpas, Francisco J

    2012-02-01

    Low temperature is an environmental stress that affects crop production and quality and regulates the expression of many genes, and the level of a number of proteins and metabolites. Using leaves from pepper (Capsicum annum L.) plants exposed to low temperature (8 °C) for different time periods (1 to 3 d), several key components of the metabolism of reactive nitrogen and oxygen species (RNS and ROS, respectively) were analysed. After 24 h of exposure at 8 °C, pepper plants exhibited visible symptoms characterized by flaccidity of stems and leaves. This was accompanied by significant changes in the metabolism of RNS and ROS with an increase of both protein tyrosine nitration (NO(2) -Tyr) and lipid peroxidation, indicating that low temperature induces nitrosative and oxidative stress. During the second and third days at low temperature, pepper plants underwent cold acclimation by adjusting their antioxidant metabolism and reverting the observed nitrosative and oxidative stress. In this process, the levels of the soluble non-enzymatic antioxidants ascorbate and glutathione, and the activity of the main NADPH-generating dehydrogenases were significantly induced. This suggests that ascorbate, glutathione and the NADPH-generating dehydrogenases have a role in the process of cold acclimation through their effect on the redox state of the cell. PMID:21414013

  7. Promoting species establishment in a phragmites-dominated great lakes coastal wetland

    USGS Publications Warehouse

    Carlson, M.L.; Kowalski, K.P.; Wilcox, D.A.

    2009-01-01

    This study examined efforts to promote species establishment and maintain diversity in a Phragmites-dominated wetland where primary control measures were underway. A treatment experiment was performed at Crane Creek, a drowned-river-mouth wetland in Ottawa National Wildlife Refuge along the shore of western Lake Erie. Following initial aerial spraying of Phragmites with glyphosate, this study tested combinations of cutting, raking, and additional hand spraying of Phragmites with glyphosate as methods to promote growth of other wetland species and increase plant diversity. Percent-cover vegetation data were collected in permanent plots before and after treatments, and follow-up sampling was performed the following year. Increased species richness, species emergence, and relative dominance of non-Phragmites taxa were used as measures of treatment success. We also examined treatment effects on Phragmites cover. Dimensionality of seedbank and soil properties was reduced using principal component analysis. With the exception of nitrogen, soil nutrients affected species establishment, non-Phragmites taxa dominance, and Phragmites cover. A more viable seedbank led to greater species emergence. Treatments had differential effects on diversity depending on elevation and resulting degree of hydrologic inundation. Whereas raking to remove dead Phragmites biomass was central to promoting species establishment in dry areas, spraying had a greater impact in continually inundated areas. For treatment success across elevations into the year following treatments, spraying in combination with cutting and raking had the greatest effect. The results of this study suggest that secondary treatments can produce a short-term benefit to the plant community in areas treated for Phragmites.

  8. A novel biointerface that suppresses cell morphological changes by scavenging excess reactive oxygen species.

    PubMed

    Ikeda, Yutaka; Yoshinari, Tomoki; Nagasaki, Yukio

    2015-09-01

    During cell cultivation on conventional culture dishes, various events results in strong stresses that lead to the production of bioactive species such as reactive oxygen species (ROS) and nitric oxide. These reactive species cause variable damage to cells and stimulate cellular responses. Here, we report the design of a novel biocompatible surface that decreases stress by not only morphologically modifying the dish surface by using poly(ethylene glycol) tethered chains, but also actively scavenging oxidative stress by using our novel nitroxide radical-containing polymer. A block copolymer, poly(ethylene glycol)-b-poly[(2,2,6,6-tetramethylpiperidine-N-oxyl)aminomethylstyrene] (PEG-b-PMNT) was used to coat the surface of a dish. Differentiation of undifferentiated human leukemia (HL-60) cells was found to be suppressed on the polymer-coated dish. Notably, HL-60 cell cultivation caused apoptosis under high-density conditions, while spontaneous apoptosis was suppressed in cells plated on the PEG-b-PMNT-modified surface, because a healthy mitochondrial membrane potential was maintained. In contrast, low molecular weight antioxidants did not have apparent effects on the maintenance of mitochondria. We attribute this to the lack of cellular internalization of our immobilized polymer and selective scavenging of excessive ROS generated outside of cells. These results demonstrate the utility of our novel biocompatible material for actively scavenging ROS and thus maintaining cellular morphology. PMID:25691268

  9. Relationship between Active Oxygen Species, Lipid Peroxidation, Necrosis, and Phytoalexin Production Induced by Elicitins in Nicotiana.

    PubMed Central

    Rusterucci, C.; Stallaert, V.; Milat, M. L.; Pugin, A.; Ricci, P.; Blein, J. P.

    1996-01-01

    Excised leaves of Nicotiana tabacum var Xanthi and Nicotiana rustica were treated with cryptogein and capsicein, basic and acidic elicitins, respectively. Both compounds induced leaf necrosis, the intensity of which depended on concentration and duration of treatment. N. tabacum var Xanthi was the most sensitive species and cryptogein was the most active elicitin. Lipid peroxidation in elicitin-treated Nicotiana leaves was closely correlated with the appearance of necrosis. Elicitin treatments induced a rapid and transient burst of active oxygen species (AOS) in cell cultures of both Nicotiana species, with the production by Xanthi cells being 6-fold greater than that by N. rustica. Similar maximum AOS production levels were observed with both elicitins, but capsicein required 10-fold higher concentrations than those of cryptogein. Phytoalexin production was lower in response to both elicitins in N. tabacum var Xanthi cells than in N. rustica cells, and capsicein was the most efficient elicitor of this response. In cryptogein-treated cell suspensions, phytoalexin synthesis was unaffected by diphenyleneiodonium, which inhibited AOS generation, nor was it affected by tiron or catalase, which suppressed AOS accumulation in the extracellular medium. These results suggest that AOS production, lipid peroxidation, and necrosis are directly related, whereas phytoalexin production depends on neither the presence nor the intensity of these responses. PMID:12226334

  10. Oxidative DNA Adducts Following Cu2+-Mediated Activation of Dihydroxy PCBs: Role of Reactive Oxygen Species1

    PubMed Central

    Spencer, Wendy A.; Lehmler, Hans-Joachim; Robertson, Larry W.; Gupta, Ramesh C.

    2009-01-01

    Polychlorinated biphenyls (PCBs) are toxic industrial chemicals, complete carcinogens and efficacious tumor promoters. However, the mechanism(s) of PCB-mediated carcinogenicity remains largely undefined. One likely pathway by which these agents may play a role in carcinogenesis is the generation of oxidative DNA damage by redox cycling of dihydroxylated PCB metabolites. We have now employed a new 32P-postlabeling system to examine novel oxidative DNA lesions induced by Cu2+-mediated activation of PCB metabolites. 32P-Postlabeling of DNA incubated with various PCB metabolites resulted in over a dozen novel polar oxidative DNA adducts that were chromatographically similar for all active agents. The most potent metabolites tested were the hydroquinones (hydroxyl groups arranged para to each other) yielding polar oxidative adduct levels ranging from 55 to 142 adducts/106 nucleotides. PCB catechols, or ortho-dihydroxy metabolites, were up to 40% less active than their corresponding hydroquinone congeners while mono hydroxylated and quinone metabolites did not produce detectable oxidative damage over that of vehicle. With the exception of 2,4,5-Cl-2′,5′-dihydroxybiphenyl, this oxidative DNA damage appeared to be inversely related to chlorine content: no chlorine ≈ mono- > di- > tri-chlorinated metabolites. Importantly, copper, but not iron, was essential for activation of the PCB metabolites to these polar oxidative DNA adducts since in its absence or in the presence of the Cu+-specific scavenger, bathocuproine, no adducts were detected. Intervention studies with known reactive oxygen species (ROS) modifiers suggested that H2O2, singlet oxygen, hydroxyl radical and superoxide may also be involved in this PCB-mediated oxidative DNA damage. These data indicate a mechanistic role of several ROS, in addition to copper, in PCB-induced DNA damage and provide further support for oxidative DNA damage in PCB-mediated carcinogenesis. PMID:19233261

  11. Do specialized flowers promote reproductive isolation? Realized pollination accuracy of three sympatric Pedicularis species

    PubMed Central

    Armbruster, W. Scott; Shi, Xiao-Qing; Huang, Shuang-Quan

    2014-01-01

    Background and Aims Interest in pollinator-mediated evolutionary divergence of flower phenotype and speciation in plants has been at the core of plant evolutionary studies since Darwin. Specialized pollination is predicted to lead to reproductive isolation and promote speciation among sympatric species by promoting partitioning of (1) the species of pollinators used, (2) when pollinators are used, or (3) the sites of pollen placement. Here this last mechanism is investigated by observing the pollination accuracy of sympatric Pedicularis species (Orobanchacae). Methods Pollinator behaviour was observed on three species of Pedicularis (P. densispica, P. tricolor and P. dichotoma) in the Hengduan Mountains, south-west China. Using fluorescent powder and dyed pollen, the accuracy was assessed of stigma contact with, and pollen deposition on, pollinating bumble-bees, respectively. Key Results All three species of Pedicularis were pollinated by bumble-bees. It was found that the adaptive accuracy of female function was much higher than that of male function in all three flower species. Although peak pollen deposition corresponded to the optimal location on the pollinator (i.e. the site of stigma contact) for each species, substantial amounts of pollen were scattered over much of the bees' bodies. Conclusions The Pedicularis species studied in the eastern Himalayan region did not conform with Grant's ‘Pedicularis Model’ of mechanical reproductive isolation. The specialized flowers of this diverse group of plants seem unlikely to have increased the potential for reproductive isolation or influenced rates of speciation. It is suggested instead that the extreme species richness of the Pedicularis clade was generated in other ways and that specialized flowers and substantial pollination accuracy evolved as a response to selection generated by the diversity of co-occurring congeners. PMID:24047714

  12. Oxygen species on the silver surface oxidized by MW-discharge: Study by photoelectron spectroscopy and DFT model calculations

    NASA Astrophysics Data System (ADS)

    Kibis, Lidiya S.; Avdeev, Vasilii I.; Koscheev, Sergei V.; Boronin, Andrei I.

    2010-07-01

    A polycrystalline silver surface has been studied by synchrotron radiation photoelectron spectroscopy after deep oxidation by microwave discharge in an O 2 atmosphere. Oxidized structures with high oxygen content, AgO x with x > 1, have been found on the silver surface after oxidation at 300-400 K. The line shapes observed in the O1s spectra were decomposed into five components and indicated that complex oxidized species were formed. An analysis of the oxidized structures with binding energies, Еb(O1s), greater than 530 eV pointed to the presence of both Ag-O and O-O bonds. We have carried out a detailed experimental study of the valence band spectra in a wide spectral range (up to 35 eV), which has allowed us to register the multicomponent structure of spectra below Ag4d band. These features were assigned to the formation of Ag-O and O-O bonds composed of molecular (associative) oxygen species. DFT model calculations showed that saturation of the defect oxidized silver surface with oxygen leads to the formation of associative oxygen species, such as superoxides, with electrophilic properties and covalent bonding. The high stability of oxygen-rich silver structures, AgO x, can be explained by the formation of small silver particles during the intensive MW oxidation, which can stabilize such oxygen species.

  13. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo

    PubMed Central

    Wu, Liying; Huang, Xin; Wu, Kuiwu; Xu, Lun; Li, Dahu; Liu, Shuhong; Zhao, Yongqi; Fan, Ming; Zhu, Lingling

    2015-01-01

    Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ) of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCs)in vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr) and DG (approximately 10 Torr) were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr). Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain. PMID:26466323

  14. Diffusion of a multi-species component and its role in oxygen and water transport in silicates

    NASA Technical Reports Server (NTRS)

    Zhang, Youxue; Stolper, E. M.; Wasserburg, G. J.

    1991-01-01

    The diffusion of a multispecies component is complicated by the different diffusion coefficient of each species and the interconversion reactions among the species. A diffusion equation is derived that incorporates the diffusive fluxes of all species contributing to the component's concentration. The effect of speciation on diffusion is investigated experimentally by measuring concentration profiles of all species developed during diffusion experiments. Data on water diffusion in rhyolitic glasses indicate that H2O molecules predominate over OH groups as the diffusing species at very low to high water concentrations. A simple theoretical relationship is drawn between the effective total oxygen diffusion coefficient and the total water concentration of silicates at low water content.

  15. Plasma-Induced Oxygen Vacancies in Ultrathin Hematite Nanoflakes Promoting Photoelectrochemical Water Oxidation.

    PubMed

    Zhu, Changqing; Li, Changli; Zheng, Maojun; Delaunay, Jean-Jacques

    2015-10-14

    The incorporation of oxygen vacancies in hematite has been investigated as a promising route to improve oxygen evolution reaction activity of hematite photoanodes used in photoelectrochemical water oxidation. However, introducing oxygen vacancies intentionally in α-Fe2O3 for active solar water splitting through facile and effective methods remains a challenge. Herein, air plasma treatment is shown to produce oxygen vacancies in α-Fe2O3, and ultrathin α-Fe2O3 nanoflakes are used to investigate the effect of oxygen vacancies on the performance of photoelectrochemical oxygen oxidation. Increasing the plasma treatment duration and power is found to increase the density of oxygen vacancies and leads to a significant enhancement of the photocurrent response. The nanoflake photoanode with the optimized plasma treatment yields an incident photo-to-current conversion efficiency of 35.4% at 350 nm under 1.6 V vs RHE without resorting to any other cocatalysts, an efficiency far exceeding that of the pristine α-Fe2O3 nanoflakes (∼2.2%). Evidence for the presence of high density of oxygen vacancies confined in nanoflakes is clarified by X-ray photoelectron spectroscopy. The increased number of oxygen vacancies after plasma treatment resulting in an increased carrier density is interpreted as the main cause for the enhanced oxygen evolution reaction activity. PMID:26400020

  16. Redox-inactive metal ions promoted the catalytic reactivity of non-heme manganese complexes towards oxygen atom transfer.

    PubMed

    Choe, Cholho; Yang, Ling; Lv, Zhanao; Mo, Wanling; Chen, Zhuqi; Li, Guangxin; Yin, Guochuan

    2015-05-21

    Redox-inactive metal ions can modulate the reactivity of redox-active metal ions in a variety of biological and chemical oxidations. Many synthetic models have been developed to help address the elusive roles of these redox-inactive metal ions. Using a non-heme manganese(II) complex as the model, the influence of redox-inactive metal ions as a Lewis acid on its catalytic efficiency in oxygen atom transfer was investigated. In the absence of redox-inactive metal ions, the manganese(II) catalyst is very sluggish, for example, in cyclooctene epoxidation, providing only 9.9% conversion with 4.1% yield of epoxide. However, addition of 2 equiv. of Al(3+) to the manganese(II) catalyst sharply improves the epoxidation, providing up to 97.8% conversion with 91.4% yield of epoxide. EPR studies of the manganese(II) catalyst in the presence of an oxidant reveal a 16-line hyperfine structure centered at g = 2.0, clearly indicating the formation of a mixed valent di-μ-oxo-bridged diamond core, Mn(III)-(μ-O)2-Mn(IV). The presence of a Lewis acid like Al(3+) causes the dissociation of this diamond Mn(III)-(μ-O)2-Mn(IV) core to form monomeric manganese(iv) species which is responsible for improved epoxidation efficiency. This promotional effect has also been observed in other manganese complexes bearing various non-heme ligands. The findings presented here have provided a promising strategy to explore the catalytic reactivity of some di-μ-oxo-bridged complexes by adding non-redox metal ions to in situ dissociate those dimeric cores and may also provide clues to understand the mechanism of methane monooxygenase which has a similar diiron diamond core as the intermediate. PMID:25904197

  17. Reperfusion injury and reactive oxygen species: The evolution of a concept☆

    PubMed Central

    Granger, D. Neil; Kvietys, Peter R.

    2015-01-01

    Reperfusion injury, the paradoxical tissue response that is manifested by blood flow-deprived and oxygen-starved organs following the restoration of blood flow and tissue oxygenation, has been a focus of basic and clinical research for over 4-decades. While a variety of molecular mechanisms have been proposed to explain this phenomenon, excess production of reactive oxygen species (ROS) continues to receive much attention as a critical factor in the genesis of reperfusion injury. As a consequence, considerable effort has been devoted to identifying the dominant cellular and enzymatic sources of excess ROS production following ischemia-reperfusion (I/R). Of the potential ROS sources described to date, xanthine oxidase, NADPH oxidase (Nox), mitochondria, and uncoupled nitric oxide synthase have gained a status as the most likely contributors to reperfusion-induced oxidative stress and represent priority targets for therapeutic intervention against reperfusion-induced organ dysfunction and tissue damage. Although all four enzymatic sources are present in most tissues and are likely to play some role in reperfusion injury, priority and emphasis has been given to specific ROS sources that are enriched in certain tissues, such as xanthine oxidase in the gastrointestinal tract and mitochondria in the metabolically active heart and brain. The possibility that multiple ROS sources contribute to reperfusion injury in most tissues is supported by evidence demonstrating that redox-signaling enables ROS produced by one enzymatic source (e.g., Nox) to activate and enhance ROS production by a second source (e.g., mitochondria). This review provides a synopsis of the evidence implicating ROS in reperfusion injury, the clinical implications of this phenomenon, and summarizes current understanding of the four most frequently invoked enzymatic sources of ROS production in post-ischemic tissue. PMID:26484802

  18. Reactive Oxygen Species Production by Potato Tuber Mitochondria Is Modulated by Mitochondrially Bound Hexokinase Activity1

    PubMed Central

    Camacho-Pereira, Juliana; Meyer, Laudiene Evangelista; Machado, Lilia Bender; Oliveira, Marcus Fernandes; Galina, Antonio

    2009-01-01

    Potato tuber (Solanum tuberosum) mitochondria (PTM) have a mitochondrially bound hexokinase (HK) activity that exhibits a pronounced sensitivity to ADP inhibition. Here we investigated the role of mitochondrial HK activity in PTM reactive oxygen species generation. Mitochondrial HK has a 10-fold higher affinity for glucose (Glc) than for fructose (KMGlc = 140 μm versus KMFrc = 1,375 μm). Activation of PTM respiration by succinate led to an increase in hydrogen peroxide (H2O2) release that was abrogated by mitochondrial HK activation. Mitochondrial HK activity caused a decrease in the mitochondrial membrane potential and an increase in oxygen consumption by PTM. Inhibition of Glc phosphorylation by mannoheptulose or GlcNAc induced a rapid increase in H2O2 release. The blockage of H2O2 release sustained by Glc was reverted by oligomycin and atractyloside, indicating that ADP recycles through the adenine nucleotide translocator and F0F1ATP synthase is operative during the mitochondrial HK reaction. Inhibition of mitochondrial HK activity by 60% to 70% caused an increase of 50% in the maximal rate of H2O2 release. Inhibition in H2O2 release by mitochondrial HK activity was comparable to, or even more potent, than that observed for StUCP (S. tuberosum uncoupling protein) activity. The inhibition of H2O2 release in PTM was two orders of magnitude more selective for the ADP produced from the mitochondrial HK reaction than for that derived from soluble yeast (Saccharomyces cerevisiae) HK. Modulation of H2O2 release and oxygen consumption by Glc and mitochondrial HK inhibitors in potato tuber slices shows that hexoses and mitochondrial HK may act as a potent preventive antioxidant mechanism in potato tubers. PMID:19109413

  19. Mitochondrial Respiration Deficits Driven by Reactive Oxygen Species in Experimental Temporal Lobe Epilepsy

    PubMed Central

    Rowley, Shane; Liang, Li-Ping; Fulton, Ruth; Shimizu, Takahiko; Day, Brian; Patel, Manisha

    2015-01-01

    Metabolic alterations have been implicated in the etiology of temporal lobe epilepsy (TLE), but whether or not they have a functional impact on cellular energy producing pathways (glycolysis and/or oxidative phosphorylation) is unknown. The goal of this study was to determine if alterations in cellular bioenergetics occur using real-time analysis of mitochondrial oxygen consumption and glycolytic rates in an animal model of TLE. We hypothesized that increased steady-state levels of reactive oxygen species (ROS) initiated by epileptogenic injury result in impaired mitochondrial respiration. We established methodology for assessment of bioenergetic parameters in isolated synaptosomes from the hippocampus of Sprague-Dawley rats at various times in the kainate (KA) model of TLE. Deficits in indices of mitochondrial respiration were observed at time points corresponding with the acute and chronic phases of epileptogenesis. We asked if mitochondrial bioenergetic dysfunction occurred as a result of increased mitochondrial ROS and if it could be attenuated in the KA model by pharmacologically scavenging ROS. Increased steady-state ROS in mice with forebrain-specific conditional deletion of manganese superoxide dismutase (Sod2fl/flNEXCre/Cre) in mice resulted in profound deficits in mitochondrial oxygen consumption. Pharmacological scavenging of ROS with a catalytic antioxidant restored mitochondrial respiration deficits in the KA model of TLE. Together, these results demonstrate that mitochondrial respiration deficits occur in experimental TLE and ROS mechanistically contribute to these deficits. Furthermore, this study provides novel methodology for assessing cellular metabolism during the entire time course of disease development. PMID:25600213

  20. Individuals with higher metabolic rates have lower levels of reactive oxygen species in vivo

    PubMed Central

    Salin, Karine; Auer, Sonya K.; Rudolf, Agata M.; Anderson, Graeme J.; Cairns, Andrew G.; Mullen, William; Hartley, Richard C.; Selman, Colin; Metcalfe, Neil B.

    2015-01-01

    There is increasing interest in the effect of energy metabolism on oxidative stress, but much ambiguity over the relationship between the rate of oxygen consumption and the generation of reactive oxygen species (ROS). Production of ROS (such as hydrogen peroxide, H2O2) in the mitochondria is primarily inferred indirectly from measurements in vitro, which may not reflect actual ROS production in living animals. Here, we measured in vivo H2O2 content using the recently developed MitoB probe that becomes concentrated in the mitochondria of living organisms, where it is converted by H2O2 into an alternative form termed MitoP; the ratio of MitoP/MitoB indicates the level of mitochondrial H2O2 in vivo. Using the brown trout Salmo trutta, we tested whether this measurement of in vivo H2O2 content over a 24 h-period was related to interindividual variation in standard metabolic rate (SMR). We showed that the H2O2 content varied up to 26-fold among fish of the same age and under identical environmental conditions and nutritional states. Interindividual variation in H2O2 content was unrelated to mitochondrial density but was significantly associated with SMR: fish with a higher mass-independent SMR had a lower level of H2O2. The mechanism underlying this observed relationship between SMR and in vivo H2O2 content requires further investigation, but may implicate mitochondrial uncoupling which can simultaneously increase SMR but reduce ROS production. To our knowledge, this is the first study in living organisms to show that individuals with higher oxygen consumption rates can actually have lower levels of H2O2. PMID:26382073

  1. Individuals with higher metabolic rates have lower levels of reactive oxygen species in vivo.

    PubMed

    Salin, Karine; Auer, Sonya K; Rudolf, Agata M; Anderson, Graeme J; Cairns, Andrew G; Mullen, William; Hartley, Richard C; Selman, Colin; Metcalfe, Neil B

    2015-09-01

    There is increasing interest in the effect of energy metabolism on oxidative stress, but much ambiguity over the relationship between the rate of oxygen consumption and the generation of reactive oxygen species (ROS). Production of ROS (such as hydrogen peroxide, H2O2) in the mitochondria is primarily inferred indirectly from measurements in vitro, which may not reflect actual ROS production in living animals. Here, we measured in vivo H2O2 content using the recently developed MitoB probe that becomes concentrated in the mitochondria of living organisms, where it is converted by H2O2 into an alternative form termed MitoP; the ratio of MitoP/MitoB indicates the level of mitochondrial H2O2 in vivo. Using the brown trout Salmo trutta, we tested whether this measurement of in vivo H2O2 content over a 24 h-period was related to interindividual variation in standard metabolic rate (SMR). We showed that the H2O2 content varied up to 26-fold among fish of the same age and under identical environmental conditions and nutritional states. Interindividual variation in H2O2 content was unrelated to mitochondrial density but was significantly associated with SMR: fish with a higher mass-independent SMR had a lower level of H2O2. The mechanism underlying this observed relationship between SMR and in vivo H2O2 content requires further investigation, but may implicate mitochondrial uncoupling which can simultaneously increase SMR but reduce ROS production. To our knowledge, this is the first study in living organisms to show that individuals with higher oxygen consumption rates can actually have lower levels of H2O2. PMID:26382073

  2. Photoirradiation of dehydropyrrolizidine alkaloids--formation of reactive oxygen species and induction of lipid peroxidation.

    PubMed

    Zhao, Yuewei; Xia, Qingsu; Yin, Jun Jie; Lin, Ge; Fu, Peter P

    2011-09-10

    Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and human. PAs require metabolic activation to generate pyrrolic metabolites (dehydro-PAs) that bind cellular protein and DNA, leading to hepatotoxicity and genotoxicity, including tumorigenicity. In this study we report that UVA photoirradiation of a series of dehydro-PAs, e.g., dehydromonocrotaline, dehydroriddelliine, dehydroretrorsine, dehydrosenecionine, dehydroseneciphylline, dehydrolasiocarpine, dehydroheliotrine, and dehydroretronecine (DHR) at 0-70 J/cm2 in the presence of a lipid, methyl linoleate, resulted in lipid peroxidation in a light dose-responsive manner. When irradiated in the presence of sodium azide, the level of lipid peroxidation decreased; lipid peroxidation was enhanced when methanol was replaced by deuterated methanol. These results suggest that singlet oxygen is a photo-induced product. When irradiated in the presence of superoxide dismutase, the level of lipid peroxidation decreased, indicating that lipid peroxidation is also mediated by superoxide. Electron spin resonance (ESR) spin trapping studies confirmed that both singlet oxygen and superoxide anion radical were formed during photoirradiation. These results indicate that UVA photoirradiation of dehydro-PAs generates reactive oxygen species (ROS) that mediated the initiation of lipid peroxidation. UVA irradiation of the parent PAs and other PA metabolites, including PA N-oxides, under similar experimental conditions did not produce lipid peroxidation. It is known that PAs induce skin cancer and are secondary (hepatogenous) photosensitization agents. Our results suggest that dehydro-PAs are the active metabolites responsible for skin cancer formation and PA-induced secondary photosensitization. PMID:21723383

  3. LIPOXIN A4 MEDIATES AORTIC CONTRACTION VIA RHOA/RHO KINASE, ENDOTHELIAL DYSFUNCTION AND REACTIVE OXYGEN SPECIES

    PubMed Central

    Wenceslau, Camilla Ferreira; McCarthy, Cameron G.; Szasz, Theodora; Webb, R. Clinton

    2015-01-01

    Background Lipoxin A4 (LXA4) is a biologically active product generated from arachidonic acid by lipoxygenase action. The production of lipoxins is enhanced by aspirin through acetylation of cyclooxygenase-2, via a mechanism known as “aspirin-triggered lipoxin”. LXA4 has both anti-inflammatory and proinflammatory actions, the latter being related with reocclusion and restenosis after coronary angioplasty in patients treated with aspirin. However, little is known of the actions of LXA4 on the vasculature. We hypothesized that LXA4 promotes contractile responses and contributes to endothelial dysfunction. Methods We used aorta from Wistar rats to assess vascular function. Reactive oxygen species (ROS) production and contractile and regulatory proteins were investigated. Results LXA4 induced concentration-dependent contractions via formyl peptide receptor-2 activation and both RhoA/Rho kinase inhibitor and ROS scavenger decreased this contraction. Also, endothelium removal, and COX-2 and NAD(P)H oxidase inhibitors attenuate the LXA4-induced contraction. LXA4 potentiated phenylephrine-induced contraction and inhibited acetylcholine-induced relaxation. In the presence of LXA4, ROS production was increased and protein expression of RhoA, phospho-myosin light chain, COX-2 and p67phox was higher. Conclusion LXA4 has a functional role in the vasculature and may contribute to further vascular damage in conditions where its production is exacerbated, such as in angioplasty-associated complications treated with aspirin. PMID:25612650

  4. Salinomycin simultaneously induces apoptosis and autophagy through generation of reactive oxygen species in osteosarcoma U2OS cells.

    PubMed

    Kim, Sang-Hun; Choi, Young-Jun; Kim, Kwang-Youn; Yu, Sun-Nyoung; Seo, Young-Kyo; Chun, Sung-Sik; Noh, Kyung-Tae; Suh, Jeung-Tak; Ahn, Soon-Cheol

    2016-04-29

    Salinomycin, a polyether antibiotic, acts as a highly selective potassium ionophore. It was reported to anticancer activity on various cancer cell lines. In this study, salinomycin was examined on apoptosis and autophagy through generation of reactive oxygen species (ROS) in osteosarcoma U2OS cells. Apoptosis, autophagy, mitochondrial membrane potential (MMP) and ROS were analyzed using flow cytometry. Also, expressions of apoptosis- and autophagy-related proteins were determined by western blotting. As a result, salinomycin triggered apoptosis of U2OS cells, which was accompanied by change of MMP and cleavage of caspases-3 and poly (ADP-ribose) polymerase. And salinomycin increased the expression of autophagy-related protein and accumulation of acidic vesicular organelles (AVO). Salinomycin-induced ROS production promotes both apoptosis and autophagy, as evidenced by the result that treatment of N-acetyl-l-cysteine (NAC), a ROS scavenger, attenuated both apoptosis and autophagy. In addition, inhibition of autophagy by 3-methyladenine (3 MA) enhanced the salinoymcin-induced apoptosis. Taken together, these results suggested that salinomycin-induced autophagy, as a survival mechanism, might be a potential strategy through ROS regulation in cancer therapy. PMID:27033598

  5. Hop proanthocyanidins induce apoptosis, protein carbonylation, and cytoskeleton disorganization in human colorectal adenocarcinoma cells via reactive oxygen species

    PubMed Central

    Chung, Woon-Gye; Miranda, Cristobal L.; Stevens, Jan F.; Maier, Claudia S.

    2009-01-01

    Proanthocyanidins (PCs) have been shown to suppress the growth of diverse human cancer cells and are considered as promising additions to the arsenal of chemopreventive phytochemicals. An oligomeric mixture of PCs from hops (Humulus lupulus) significantly decreased cell viability of human colon cancer HT-29 cells in a dose-dependent manner. Hop PCs, at 50 or 100 μg/ml, exhibited apoptosis-inducing properties as shown by the increase in caspase-3 activity. Increased levels of intracellular reactive oxygen species (ROS) was accompanied by an augmented accumulation of protein carbonyls. Mass spectrometry-based proteomic analysis in combination with 2-alkenal-specific immunochemical detection identified β-actin and protein disulfide isomerase as major putative targets of acrolein adduction. Incubation of HT-29 cells with hop PCs resulted in morphological changes that indicated disruption of the actin cytoskeleton. PC-mediated hydrogen peroxide (H2O2) formation in the cell culture media was also quantified; but, the measured H2O2 levels would not explain the observed changes in the oxidative modifications of actin. These findings suggest new modes of action for proanthocyandins as antitumorgenic agents in human colon cancer cells, namely, promotion of protein oxidative modifications and cytoskeleton derangement. PMID:19271284

  6. An atmospheric-pressure cold plasma leads to apoptosis in Saccharomyces cerevisiae by accumulating intracellular reactive oxygen species and calcium

    NASA Astrophysics Data System (ADS)

    Ma, R. N.; Feng, H. Q.; Liang, Y. D.; Zhang, Q.; Tian, Y.; Su, B.; Zhang, J.; Fang, J.

    2013-07-01

    A non-thermal plasma is known to induce apoptosis of various cells but the mechanism is not yet clear. A eukaryotic model organism Saccharomyces cerevisiaewas used to investigate the cellular and biochemical regulations of cell apoptosis and cell cycle after an atmospheric-pressure cold plasma treatment. More importantly, intracellular calcium (Ca2+) was first involved in monitoring the process of plasma-induced apoptosis in this study. We analysed the cell apoptosis and cell cycle by flow cytometry and observed the changes in intracellular reactive oxygen species (ROS) and Ca2+ concentration, cell mitochondrial membrane potential (Δψm) as well as nuclear DNA morphology via fluorescence staining assay. All experimental results indicated that plasma-generated ROS leads to the accumulation of intracellular ROS and Ca2+ that ultimately contribute to apoptosis associated with cell cycle arrest at G1 phase through depolarization of Δψm and fragmenting nuclear DNA. This work provides a novel insight into the physical and biological mechanism of apoptosis induced by a plasma which could benefit for promoting the development of plasmas applied to cancer therapy.

  7. Cell Permeability, Migration, and Reactive Oxygen Species Induced by Multi-Walled Carbon Nanotubes in Human Microvascular Endothelial Cells

    PubMed Central

    Pacurari, M; Qian, Y; Fu, W; Schwegler-Berry, D; Ding, M; Castranova, V; Guo, NL

    2011-01-01

    Multi-walled carbon nanotubes (MWCNT) have elicited great interest in biomedical applications due to their extraordinary physical, chemical, and optical properties. Intravenous administration of MWCNT-based medical imaging agents and drugs in animal models was utilized. However, the potential harmful health effects of MWCNT administration in humans have not yet been elucidated. Furthermore, to date, there are no apparent reports regarding the precise mechanisms of translocation of MWCNT into target tissues and organs from blood circulation. This study demonstrates that exposure to MWCNT leads to an increase in cell permeability in human microvascular endothelial cells (HMVEC). The results obtained from this study also showed that the MWCNT-induced rise in endothelial permeability is mediated by reactive oxygen species (ROS) production and actin filament remodeling. In addition, it was found that MWCNT promoted cell migration in HMVEC. Mechanistically, MWCNT exposure elevated the levels of monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule 1 (ICAM-1) in HMVEC. Taken together, these results provide new insights into the bioreactivity of MWCNT, which may have implications in the biomedical application of MWCNT in vascular targeting, imaging, and drug delivery. The results generated from this study also elucidate the potential adverse effects of MWCNT exposure on humans at the cellular level. PMID:22129238

  8. Epoxyeicosatrienoic acids attenuate reactive oxygen species level, mitochondrial dysfunction, caspase activation, and apoptosis in carcinoma cells treated with arsenic trioxide.

    PubMed

    Liu, Liu; Chen, Chen; Gong, Wei; Li, Yuanjing; Edin, Matthew L; Zeldin, Darryl C; Wang, Dao Wen

    2011-11-01

    Epoxyeicosatrienoic acids (EETs) and the cytochrome P450 epoxygenase CYP2J2 promote tumorogenesis in vivo and in vitro via direct stimulation of tumor cell growth and inhibition of tumor cell apoptosis. Herein, we describe a novel mechanism of inhibition of tumor cell apoptosis by EETs. In Tca-8113 cancer cells, the antileukemia drug arsenic trioxide (ATO) led to the generation of reactive oxygen species (ROS), impaired mitochondrial function, and induced apoptosis. 11,12-EET pretreatment increased expression of the antioxidant enzymes superoxide dismutase and catalase and inhibited ATO-induced apoptosis. 11,12-EET also prevented the ATO-induced activation of p38 mitogen-activated protein kinase, c-Jun NH(2)-terminal kinase, caspase-3, and caspase-9. Therefore, 11,12-EET-pretreatment attenuated the ROS generation, loss of mitochondrial function, and caspase activation observed after ATO treatment. Moreover, the CYP2J2-specific inhibitor compound 26 enhanced arsenic cytotoxicity to a clinically relevant concentration of ATO (1-2 μM). Both the thiol-containing antioxidant, N-acetyl-cysteine, and 11,12-EET reversed the synergistic effect of the two agents. Taken together, these data indicate that 11,12-EET inhibits apoptosis induced by ATO through a mechanism that involves induction of antioxidant proteins and attenuation of ROS-mediated mitochondrial dysfunction. PMID:21846841

  9. Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice.

    PubMed

    Han, Byung Hee; Zhou, Meng-Liang; Johnson, Andrew W; Singh, Itender; Liao, Fan; Vellimana, Ananth K; Nelson, James W; Milner, Eric; Cirrito, John R; Basak, Jacob; Yoo, Min; Dietrich, Hans H; Holtzman, David M; Zipfel, Gregory Joseph

    2015-02-24

    Cerebral amyloid angiopathy (CAA) is characterized by deposition of amyloid β peptide (Aβ) within walls of cerebral arteries and is an important cause of intracerebral hemorrhage, ischemic stroke, and cognitive dysfunction in elderly patients with and without Alzheimer's Disease (AD). NADPH oxidase-derived oxidative stress plays a key role in soluble Aβ-induced vessel dysfunction, but the mechanisms by which insoluble Aβ in the form of CAA causes cerebrovascular (CV) dysfunction are not clear. Here, we demonstrate evidence that reactive oxygen species (ROS) and, in particular, NADPH oxidase-derived ROS are a key mediator of CAA-induced CV deficits. First, the NADPH oxidase inhibitor, apocynin, and the nonspecific ROS scavenger, tempol, are shown to reduce oxidative stress and improve CV reactivity in aged Tg2576 mice. Second, the observed improvement in CV function is attributed both to a reduction in CAA formation and a decrease in CAA-induced vasomotor impairment. Third, anti-ROS therapy attenuates CAA-related microhemorrhage. A potential mechanism by which ROS contribute to CAA pathogenesis is also identified because apocynin substantially reduces expression levels of ApoE-a factor known to promote CAA formation. In total, these data indicate that ROS are a key contributor to CAA formation, CAA-induced vessel dysfunction, and CAA-related microhemorrhage. Thus, ROS and, in particular, NADPH oxidase-derived ROS are a promising therapeutic target for patients with CAA and AD. PMID:25675483

  10. GGsTOP increases migration of human periodontal ligament cells in vitro via reactive oxygen species pathway.

    PubMed

    Jiang, Ying; Wang, Xiang; Li, Ying; Mu, Sen; Zhou, Shuang; Liu, Yi; Zhang, Bin

    2016-05-01

    GGsTOP is a novel and selective inhibitor of gamma-glutamyl transferase (GGT), a cell-surface enzyme that has a key role in glutathione homeostasis and the maintenance of cellular reactive oxygen species (ROS). ROS are essential for wound healing. However, little is known about the molecular mechanisms underlying the inhibition of GGT by GGsTOP in human periodontal ligament cells (hPLCs). The present study assessed GGT expression in mouse periodontal ligament tissues, GGT activity in hPLCs, and the potential physiological effect of GGsTOP on hPLC migration. Immunohistochemical analysis confirmed that GGT was widely expressed in mouse periodontal ligament tissue. Treatment with GGsTOP was associated with greater proliferation and migration of hPLCs, and higher levels of cellular ROS compared with untreated hPLCs. However, the increase in intracellular ROS was attenuated in hPLCs co‑cultured with the anti‑oxidant N‑acetylcysteine (NAC), a precursor of glutathione. The higher ROS levels associated with GGsTOP treatment were in parallel with increases in the levels of type I collagen and alpha smooth muscle actin, which was inhibited in hPLCs co‑cultured with NAC. Thus, GGsTOP may promote hPLC migration and participate in the maintenance of the periodontal ligament apparatus via the ROS pathway. PMID:27035100

  11. The role of reactive oxygen species and nitric oxide in programmed cell death associated with self-incompatibility.

    PubMed

    Serrano, Irene; Romero-Puertas, María C; Sandalio, Luisa M; Olmedilla, Adela

    2015-05-01

    Successful sexual reproduction often relies on the ability of plants to recognize self- or genetically-related pollen and prevent pollen tube growth soon after germination in order to avoid self-fertilization. Angiosperms have developed different reproductive barriers, one of the most extended being self-incompatibility (SI). With SI, pistils are able to reject self or genetically-related pollen thus promoting genetic variability. There are basically two distinct systems of SI: gametophytic (GSI) and sporophytic (SSI) based on their different molecular and genetic control mechanisms. In both types of SI, programmed cell death (PCD) has been found to play an important role in the rejection of self-incompatible pollen. Although reactive oxygen species (ROS) were initially recognized as toxic metabolic products, in recent years, a new role for ROS has become apparent: the control and regulation of biological processes such as growth, development, response to biotic and abiotic environmental stimuli, and PCD. Together with ROS, nitric oxide (NO) has become recognized as a key regulator of PCD. PCD is an important mechanism for the controlled elimination of targeted cells in both animals and plants. The major focus of this review is to discuss how ROS and NO control male-female cross-talk during fertilization in order to trigger PCD in self-incompatible pollen, providing a highly effective way to prevent self-fertilization. PMID:25750430

  12. Stop the Flow: A Paradigm for Cell Signaling Mediated by Reactive Oxygen Species in the Pulmonary Endothelium

    PubMed Central

    Browning, Elizabeth A.; Chatterjee, Shampa; Fisher, Aron B.

    2015-01-01

    The lung endothelium is exposed to mechanical stimuli through shear stress arising from blood flow and responds to altered shear by activation of NADPH (NOX2) to generate reactive oxygen species (ROS). This review describes the pathway for NOX2 activation and the downstream ROS-mediated signaling events on the basis of studies of isolated lungs and flow-adapted endothelial cells in vitro that are subjected to acute flow cessation (ischemia). Altered mechanical stress is detected by a cell-associated complex involving caveolae and other membrane proteins that results in endothelial cell membrane depolarization and then the activation of specific kinases that lead to the assembly of NOX2 components. ROS generated by this enzyme amplify the mechanosignal within the endothelial cell to regulate activation and/or synthesis of proteins that participate in cell growth, proliferation, differentiation, apoptosis, and vascular remodeling. These responses indicate an important role for NOX2-derived ROS associated with mechanotransduction in promoting vascular homeostasis. PMID:22077215

  13. Phenethyl isothiocyanate inhibits growth of human chronic myeloid leukemia K562 cells via reactive oxygen species generation and caspases.

    PubMed

    Wang, Yating; Wei, Sixi; Wang, Jishi; Fang, Qin; Chai, Qixiang

    2014-07-01

    Phenethyl isothiocyanate (PEITC), a potential cancer chemopreventive constituent of cruciferous vegetables, including watercress, has been reported to inhibit cancer cell growth by arresting the cell cycle and inducing apoptosis in various human cancer cell models. However, the role of PEITC in the inhibition of human chronic myeloid leukemia (CML) K562 cell growth and its underlying mechanisms have yet to be elucidated. In the present study, PEITC was found to induce cell death through the induction of reactive oxygen species (ROS) stress and oxidative damage. Heme oxygenase‑1 (HO‑1), which participates in the development of numerous tumors and the sensitivity of these tumors to chemotherapeutic drugs, plays a protective role by modulating oxidative injury. Therefore, the present study assessed the inhibitory effect of PEITC on K562 cells and whether HO‑1 facilitated cell apoptosis and ROS generation. PEITC was found to suppress cell growth and cause apoptosis by promoting Fas and Fas ligand expression, increasing ROS generation and by the successive release of cytochrome c as well as the activation of caspase‑9 and caspase‑3. PEITC was also combined with the HO‑1 inhibitor zinc protoporphyrin IX and the inducer hemin to assess whether HO‑1 determines cell survival and ROS generation. The results of the present study suggest that PEITC may be a potential anti‑tumor compound for CML therapy, and that HO‑1 has a critical function in PEITC‑induced apoptosis and ROS generation. PMID:24788892

  14. Pyocyanin, a virulence factor produced by Pseudomonas aeruginosa, alters root development through reactive oxygen species and ethylene signaling in Arabidopsis.

    PubMed

    Ortiz-Castro, Randy; Pelagio-Flores, Ramón; Méndez-Bravo, Alfonso; Ruiz-Herrera, León Francisco; Campos-García, Jesús; López-Bucio, José

    2014-04-01

    Pyocyanin acts as a virulence factor in Pseudomonas aeruginosa, a plant and animal pathogen. In this study, we evaluated the effect of pyocyanin on growth and development of Arabidopsis seedlings. Root inoculation with P. aeruginosa PAO1 strain inhibited primary root growth in wild-type (WT) Arabidopsis seedlings. In contrast, single lasI- and double rhlI-/lasI- mutants of P. aeruginosa defective in pyocyanin production showed decreased root growth inhibition concomitant with an increased phytostimulation. Treatment with pyocyanin modulates root system architecture, inhibiting primary root growth and promoting lateral root and root hair formation without affecting meristem viability or causing cell death. These effects correlated with altered proportions of hydrogen peroxide and superoxide in root tips and with an inhibition of cell division and elongation. Mutant analyses showed that pyocyanin modulation of root growth was likely independent of auxin, cytokinin, and abscisic acid but required ethylene signaling because the Arabidopsis etr1-1, ein2-1, and ein3-1 ethylene-related mutants were less sensitive to pyocyanin-induced root stoppage and reactive oxygen species (ROS) distribution. Our findings suggest that pyocyanin is an important factor modulating the interplay between ROS production and root system architecture by an ethylene-dependent signaling. PMID:24224532

  15. Treadmill Exercise Induces Neutrophil Recruitment into Muscle Tissue in a Reactive Oxygen Species-Dependent Manner. An Intravital Microscopy Study

    PubMed Central

    Nunes-Silva, Albená; Bernardes, Priscila T. T.; Rezende, Bárbara M.; Lopes, Fernando; Gomes, Elisa C.; Marques, Pedro E.; Lima, Paulo M. A.; Coimbra, Cândido C.; Menezes, Gustavo B.; Teixeira, Mauro M.; Pinho, Vanessa

    2014-01-01

    Intense exercise is a physiological stress capable of inducing the interaction of neutrophils with muscle endothelial cells and their transmigration into tissue. Mechanisms driving this physiological inflammatory response are not known. Here, we investigate whether production of reactive oxygen species is relevant for neutrophil interaction with endothelial cells and recruitment into the quadriceps muscle in mice subjected to the treadmill fatiguing exercise protocol. Mice exercised until fatigue by running for 56.3±6.8 min on an electric treadmill. Skeletal muscle was evaluated by intravital microscopy at different time points after exercise, and then removed to assess local oxidative stress and histopathological analysis. We observed an increase in plasma lactate and creatine kinase (CK) concentrations after exercise. The numbers of monocytes, neutrophils, and lymphocytes in blood increased 12 and 24 hours after the exercise. Numbers of rolling and adherent leukocytes increased 3, 6, 12, and 24 hours post-exercise, as assessed by intravital microscopy. Using LysM-eGFP mice and confocal intravital microscopy technology, we show that the number of transmigrating neutrophils increased 12 hours post-exercise. Mutant gp91phox-/- (non-functional NADPH oxidase) mice and mice treated with apocynin showed diminished neutrophil recruitment. SOD treatment promoted further adhesion and transmigration of leukocytes 12 hours after the exercise. These findings confirm our hypothesis that treadmill exercise increases the recruitment of leukocytes to the postcapillary venules, and NADPH oxidase-induced ROS plays an important role in this process. PMID:24798414

  16. Gefitinib-mediated reactive oxygen specie (ROS) instigates mitochondrial dysfunction and drug resistance in lung cancer cells.

    PubMed

    Okon, Imoh S; Coughlan, Kathleen A; Zhang, Miao; Wang, Qiongxin; Zou, Ming-Hui

    2015-04-01

    Therapeutic benefits offered by tyrosine kinase inhibitors (TKIs), such as gefitinib (Iressa) and erlotinib (Tarceva), are limited due to the development of resistance, which contributes to treatment failure and cancer-related mortality. The aim of this study was to elucidate mechanistic insight into cellular perturbations that accompany acquired gefitinib resistance in lung cancer cells. Several lung adenocarcinoma (LAD) cell lines were screened to characterize epidermal growth factor receptor (EGFR) expression and mutation profile. To circumvent intrinsic variations between cell lines with respect to response to drug treatments, we generated gefitinib-resistant H1650 clone by long-term, chronic culture under gefitinib selection of parental cell line. Isogenic cells were analyzed by microarray, Western blot, flow cytometry, and confocal and transmission electron microscope. We observed that although chronic gefitinib treatment provided effective action against its primary target (aberrant EGFR activity), secondary effects resulted in increased cellular reactive oxygen species (ROS). Gefitinib-mediated ROS correlated with epithelial-mesenchymal transition, as well as striking perturbation of mitochondrial morphology and function. However, gefitinib treatment in the presence of ROS scavenger provided a partial rescue of mitochondrial aberrations. Furthermore, withdrawal of gefitinib from previously resistant clones correlated with normalized expression of epithelial-mesenchymal transition genes. These findings demonstrate that chronic gefitinib treatment promotes ROS and mitochondrial dysfunction in lung cancer cells. Antioxidants may alleviate ROS-mediated resistance. PMID:25681445

  17. Reactive oxygen species mediate oxaliplatin-induced epithelial-mesenchymal transition and invasive potential in colon cancer.

    PubMed

    Jiao, Lin; Li, Dan-Dan; Yang, Chen-Lu; Peng, Rui-Qing; Guo, Yi-Qun; Zhang, Xiao-Shi; Zhu, Xiao-Feng

    2016-06-01

    Therapeutic benefits offered by common chemotherapy drugs, such as oxaliplatin, are limited due to the development of resistance, which contributes to treatment failure and metastasis. The epithelial-mesenchymal transition (EMT) is a key event contributing to the development of resistance to chemotherapeutics. Although the relationship between oxaliplatin and chemotherapy resistance has been described for decades, the molecular mechanisms have remained elusive. The aim of the present study was to investigate the underlying mechanisms of oxaliplatin-mediated metastasis. Here, we identify reactive oxygen species (ROS) as mediators that promote the oxaliplatin-induced EMT. Following oxaliplatin treatment, the messenger RNA (mRNA) levels of most peroxiredoxin family genes, except for peroxiredoxin 1 (prdx1) gene, were constant or even decreased, resulting in ROS abundance. And the antioxidant guardian Nrf2 was unconspicuously raised both transcriptionally and translationally with oxaliplatin treatment as compared to those induced by topotecan treatment, which has been proved with no induced metastasis. In addition, the study evaluated high levels of ROS leading to EMT via activation of the known oncogenes Akt and Snail. Using the Akt inhibitor LY294002 or knocking down Snail expression via RNA interference (RNAi) reversed the effects of oxaliplatin on the EMT and metastasis. Our studies establish a role for the ROS-Akt-Snail axis as a mechanism by which chemotherapeutics induce EMT and cancer metastasis. PMID:26733168

  18. Macrophages as target cells for Mayaro virus infection: involvement of reactive oxygen species in the inflammatory response during virus replication.

    PubMed

    Cavalheiro, Mariana G; Costa, Leandro Silva DA; Campos, Holmes S; Alves, Letícia S; Assunção-Miranda, Iranaia; Poian, Andrea T DA

    2016-09-01

    Alphaviruses among the viruses that cause arthritis, consisting in a public health problem worldwide by causing localized outbreaks, as well as large epidemics in humans. Interestingly, while the Old World alphaviruses are arthritogenic, the New World alphaviruses cause encephalitis. One exception is Mayaro virus (MAYV), which circulates exclusively in South America but causes arthralgia and is phylogenetically related to the Old World alphaviruses. Although MAYV-induced arthritis in humans is well documented, the molecular and cellular factors that contribute to its pathogenesis are completely unknown. In this study, we demonstrated for the first time that macrophages, key players in arthritis development, are target cells for MAYV infection, which leads to cell death through apoptosis. We showed that MAYV replication in macrophage induced the expression of TNF, a cytokine that would contribute to pathogenesis of MAYV fever, since TNF promotes an inflammatory profile characteristic of arthritis. We also found a significant increase in the production of reactive oxygen species (ROS) at early times of infection, which coincides with the peak of virus replication and precedes TNF secretion. Treatment of the cells with antioxidant agents just after infection completely abolished TNF secretion, indicating an involvement of ROS in inflammation induced during MAYV infection. PMID:27627069

  19. GGsTOP increases migration of human periodontal ligament cells in vitro via reactive oxygen species pathway

    PubMed Central

    JIANG, YING; WANG, XIANG; LI, YING; MU, SEN; ZHOU, SHUANG; LIU, YI; ZHANG, BIN

    2016-01-01

    GGsTOP is a novel and selective inhibitor of gamma-glutamyl transferase (GGT), a cell-surface enzyme that has a key role in glutathione homeostasis and the maintenance of cellular reactive oxygen species (ROS). ROS are essential for wound healing. However, little is known about the molecular mechanisms underlying the inhibition of GGT by GGsTOP in human periodontal ligament cells (hPLCs). The present study assessed GGT expression in mouse periodontal ligament tissues, GGT activity in hPLCs, and the potential physiological effect of GGsTOP on hPLC migration. Immunohistochemical analysis confirmed that GGT was widely expressed in mouse periodontal ligament tissue. Treatment with GGsTOP was associated with greater proliferation and migration of hPLCs, and higher levels of cellular ROS compared with untreated hPLCs. However, the increase in intracellular ROS was attenuated in hPLCs co-cultured with the anti-oxidant N-acetylcysteine (NAC), a precursor of glutathione. The higher ROS levels associated with GGsTOP treatment were in parallel with increases in the levels of type I collagen and alpha smooth muscle actin, which was inhibited in hPLCs co-cultured with NAC. Thus, GGsTOP may promote hPLC migration and participate in the maintenance of the periodontal ligament apparatus via the ROS pathway. PMID:27035100

  20. Development of Superoxide Dismutase Mimetic Surfaces to Reduce Accumulation of Reactive Oxygen Species for Neural Interfacing Applications

    PubMed Central

    Potter-Baker, Kelsey A.; Nguyen, Jessica K.; Kovach, Kyle M.; Gitomer, Martin M.; Srail, Tyler W.; Stewart, Wade G.; Skousen, John L.; Capadona, Jeffrey R.

    2014-01-01

    Despite successful initial recording, neuroinflammatory-mediated oxidative stress products can contribute to microelectrode failure by a variety of mechanisms including: inducing microelectrode corrosion, degrading insulating/passivating materials, promoting blood-brain barrier breakdown, and directly damaging surrounding neurons. We have shown that a variety of anti-oxidant treatments can reduce intracortical microelectrode-mediated oxidative stress, and preserve neuronal viability. Unfortunately, short-term soluble delivery of anti-oxidant therapies may be unable to provide sustained therapeutic benefits due to low bio-availability and fast clearance rates. In order to develop a system to provide sustained neuroprotection, we investigated modifying the microelectrode surface with an anti-oxidative coating. For initial proof of concept, we chose the superoxide dismutase (SOD) mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP). Our system utilizes a composite coating of adsorbed and immobilized MnTBAP designed to provide an initial release followed by continued presentation of an immobilized layer of the antioxidant. Surface modification was confirmed by XPS and QCMB-D analysis. Antioxidant activity of composite surfaces was determined using a Riboflavin/NitroBlue Tetrazolium (RF/NBT) assay. Our results indicate that the hybrid modified surfaces provide several days of anti-oxidative activity. Additionally, in vitro studies with BV-2 microglia cells indicated a significant reduction of intracellular and extracellular reactive oxygen species when cultured on composite MnTBAP surfaces. PMID:25132966

  1. Tks5-dependent, Nox-mediated Generation of Reactive Oxygen Species is Necessary for Invadopodia Formation*

    PubMed Central

    Diaz, Begoña; Shani, Gidon; Pass, Ian; Anderson, Diana; Quintavalle, Manuela; Courtneidge, Sara A.

    2009-01-01

    Invadopodia are actin-rich membrane protrusions of cancer cells which facilitate pericellular proteolysis and invasive behavior. We show here that reactive oxygen species (ROS) generated by the NADPH oxidase (Nox) system are necessary for invadopodia formation and function. The invadopodia protein Tks5 is structurally related to p47phox, a Nox component in phagocytic cells. Knockdown of Tks5 reduces total ROS levels in cancer cells. Furthermore, Tks5 and p22phox can associate with each other, suggesting that Tks5 is part of the Nox complex. Tyrosine phosphorylation of Tks5 and Tks4, but not other Src substrates, is reduced by Nox inhibition. We propose that Tks5 facilitates the production of ROS necessary for invadopodia formation, and that in turn ROS modulates Tks5 tyrosine phosphorylation in a positive feedback loop. PMID:19755709

  2. Ionized gas (plasma) delivery of reactive oxygen species (ROS) into artificial cells

    NASA Astrophysics Data System (ADS)

    Hong, Sung-Ha; Szili, Endre J.; Jenkins, A. Toby A.; Short, Robert D.

    2014-09-01

    This study was designed to enhance our understanding of how reactive oxygen species (ROS), generated ex situ by ionized gas (plasma), can affect the regulation of signalling processes within cells. A model system, comprising of a suspension of phospholipid vesicles (cell mimics) encapsulating a ROS reporter, was developed to study the plasma delivery of ROS into cells. For the first time it was shown that plasma unequivocally delivers ROS into cells over a sustained period and without compromising cell membrane integrity. An important consideration in cell and biological assays is the presence of serum, which significantly reduced the transfer efficiency of ROS into the vesicles. These results are key to understanding how plasma treatments can be tailored for specific medical or biotechnology applications. Further, the phospholipid vesicle ROS reporter system may find use in other studies involving the application of free radicals in biology and medicine.

  3. Oxygen-derived species: their relation to human disease and environmental stress.

    PubMed Central

    Halliwell, B; Cross, C E

    1994-01-01

    Free radicals and other reactive oxygen species (ROS) are constantly formed in the human body, often for useful metabolic purposes. Antioxidant defenses protect against them, but these defenses are not completely adequate, and systems that repair damage by ROS are also necessary. Mild oxidative stress often induces antioxidant defense enzymes, but severe stress can cause oxidative damage to lipids, proteins, and DNA within cells, leading to such events as DNA strand breakage and disruption of calcium ion metabolism. Oxidative stress can result from exposure to toxic agents, and by the process of tissue injury itself. Ozone, oxides of nitrogen, and cigarette smoke can cause oxidative damage; but the molecular targets that they damage may not be the same. PMID:7705305

  4. Reactive Oxygen Species Modulate the Differentiation of Neurons in Clonal Cortical Cultures.

    PubMed Central

    Tsatmali, Marina; Walcott, Elisabeth C.; Makarenkova, Helen; Crossin, Kathryn L.

    2007-01-01

    Reactive oxygen species (ROS) are important regulators of intracellular signaling. We examined the expression of ROS during rat brain development and explored their role in differentiation using cortical cultures. High levels of ROS were found in newborn neurons. Neurons produced ROS, not connected with cell death, throughout embryogenesis and postnatal stages. By P20, ROS-producing cells were found only in neurogenic regions. Cells with low levels of ROS, isolated from E15 brains by FACS, differentiated into neurons, oligodendrocytes, and astrocytes in clonal cultures. Neurons produced high ROS early in culture and later differentiated into two types: large pyramidal-like neurons that fired no or only a single action potential and smaller neurons that expressed nuclear calretinin and fired repeated action potentials. Antioxidant treatment did not alter neuron number but increased the ratio of small to large neurons. These findings suggest that modulation of ROS levels influences multiple aspects of neuronal differentiation. PMID:17000118

  5. Reactive Oxygen Species and Autophagy Modulation in Non-Marine Drugs and Marine Drugs

    PubMed Central

    Farooqi, Ammad Ahmad; Fayyaz, Sundas; Hou, Ming-Feng; Li, Kun-Tzu; Tang, Jen-Yang; Chang, Hsueh-Wei

    2014-01-01

    It is becoming more understandable that an existing challenge for translational research is the development of pharmaceuticals that appropriately target reactive oxygen species (ROS)-mediated molecular networks in cancer cells. In line with this approach, there is an overwhelmingly increasing list of many non-marine drugs and marine drugs reported to be involved in inhibiting and suppressing cancer progression through ROS-mediated cell death. In this review, we describe the strategy of oxidative stress-based therapy and connect the ROS modulating effect to the regulation of apoptosis and autophagy. Finally, we focus on exploring the function and mechanism of cancer therapy by the autophagy modulators including inhibitors and inducers from non-marine drugs and marine drugs. PMID:25402829

  6. UVB dependence of quantum dot reactive oxygen species generation in common skin cell models

    PubMed Central

    MORTENSEN, LUKE J.; FAULKNOR, RENEA; RAVICHANDRAN, SUPRIYA; ZHENG, HONG; DELOUISE, LISA A.

    2015-01-01

    Studies have shown that UVB can slightly increase the penetration of nanoparticles through skin and significantly alter skin cell biology, thus it is important to understand if and how UVB may impact subsequent nanoparticle skin cell interactions. The research presented herein evaluates the effect of UVB on quantum dot (QD) uptake and reactive oxygen species (ROS) generation in primary keratinocytes, primary melanocytes, and related cell lines. QD exposure induced cell type dependent ROS responses increased by pre-exposing cells to UVB and correlated with the level of QD uptake. Our results suggest that keratinocytes may be at greater risk for QD induced ROS generation than melanocytes, and raise awareness about the differential cellular effects that topically applied nanomaterials may have on UVB exposed skin. PMID:26485933

  7. The Role of Heme and Reactive Oxygen Species in Proliferation and Survival of Trypanosoma cruzi

    PubMed Central

    Paes, Marcia Cristina; Cosentino-Gomes, Daniela; de Souza, Cíntia Fernandes; Nogueira, Natália Pereira de Almeida; Meyer-Fernandes, José Roberto

    2011-01-01

    Trypanosoma cruzi, the protozoan responsible for Chagas disease, has a complex life cycle comprehending two distinct hosts and a series of morphological and functional transformations. Hemoglobin degradation inside the insect vector releases high amounts of heme, and this molecule is known to exert a number of physiological functions. Moreover, the absence of its complete biosynthetic pathway in T. cruzi indicates heme as an essential molecule for this trypanosomatid survival. Within the hosts, T. cruzi has to cope with sudden environmental changes especially in the redox status and heme is able to increase the basal production of reactive oxygen species (ROS) which can be also produced as byproducts of the parasite aerobic metabolism. In this regard, ROS sensing is likely to be an important mechanism for the adaptation and interaction of these organisms with their hosts. In this paper we discuss the main features of heme and ROS susceptibility in T. cruzi biology. PMID:22007287

  8. Hyaluronan coated cerium oxide nanoparticles modulate CD44 and reactive oxygen species expression in human fibroblasts.

    PubMed

    Lord, Megan S; Farrugia, Brooke L; Yan, Claudia M Y; Vassie, James A; Whitelock, John M

    2016-07-01

    Cerium oxide nanoparticles are being widely explored for cell therapies. In this study, nanoceria was functionalized with hyaluronan (HA) using the organosilane linker, 3-aminopropyltriethoxysilane. HA-nanoceria was found to be cytocompatible and to reduce intracellular reactive oxygen species in human fibroblasts. The HA-nanoceria was found to colocalize with CD44 on the surface of the cells and once internalized traffic to the lysosomes, be degraded and induce markers of autophagy. These particles were also effective in reducing the cell surface expression of CD44. Together these data suggest that HA-nanoceria is a promising drug delivery material to target CD44-expressing cells through a variety of mechanisms. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1736-1746, 2016. PMID:26946213

  9. Fast, Ultrasensitive Detection of Reactive Oxygen Species Using a Carbon Nanotube Based-Electrocatalytic Intracellular Sensor.

    PubMed

    Rawson, Frankie J; Hicks, Jacqueline; Dodd, Nicholas; Abate, Wondwossen; Garrett, David J; Yip, Nga; Fejer, Gyorgy; Downard, Alison J; Baronian, Kim H R; Jackson, Simon K; Mendes, Paula M

    2015-10-28

    Herein, we report a highly sensitive electrocatalytic sensor-cell construct that can electrochemically communicate with the internal environment of immune cells (e.g., macrophages) via the selective monitoring of a particular reactive oxygen species (ROS), hydrogen peroxide. The sensor, which is based on vertically aligned single-walled carbon nanotubes functionalized with an osmium electrocatalyst, enabled the unprecedented detection of a local intracellular "pulse" of ROS on a short second time scale in response to bacterial endotoxin (lipopolysaccharide-LPS) stimulation. Our studies have shown that this initial pulse of ROS is dependent on NADPH oxidase (NOX) and toll like receptor 4 (TLR4). The results suggest that bacteria can induce a rapid intracellular pulse of ROS in macrophages that initiates the classical innate immune response of these cells to infection. PMID:26438964

  10. Reactive oxygen species production in single cells following laser irradiation (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Duquette, Michelle L.; Kim, Justine; Shi, Linda Z.; Berns, Michael W.

    2015-08-01

    Region specific DNA breaks can be created in single cells using laser light that damages DNA but does not directly generate reactive oxygen species (ROS). We have examined the cellular response to directly generated DNA breaks in single cells. Using a combination of ROS specific dyes and oxidase inhibitors we have found that the oxidase and chromatin remodeling protein Lysine demethylase I (LSD1) generates detectable ROS as a byproduct of its chromatin remodeling activity during the initial DNA damage response. ROS is produced at detectable amounts primarily within the first 3 minutes post irradiation. LSD1 activity has been previously associated with transcriptional regulation therefore these findings have implications for regulation of gene expression following DNA damage particularly in cells with altered redox states.

  11. Development of a Sensitive Bioluminogenic Probe for Imaging Highly Reactive Oxygen Species in Living Rats.

    PubMed

    Kojima, Ryosuke; Takakura, Hideo; Kamiya, Mako; Kobayashi, Eiji; Komatsu, Toru; Ueno, Tasuku; Terai, Takuya; Hanaoka, Kenjiro; Nagano, Tetsuo; Urano, Yasuteru

    2015-12-01

    A sensitive bioluminogenic probe for highly reactive oxygen species (hROS), SO3 H-APL, was developed based on the concept of dual control of bioluminescence emission by means of bioluminescent enzyme-induced electron transfer (BioLeT) and modulation of cell-membrane permeability. This probe enables non-invasive visualization of physiologically relevant amounts of hROS generated deep inside the body of living rats for the first time. It is expected to serve as a practical analytical tool for investigating a wide range of biological functions of hROS in vivo. The design concept should be applicable to other in vivo bioluminogenic probes. PMID:26474404

  12. [Comparative antioxidant action on the level of reactive oxygen species in normal and transformed fibroblasts].

    PubMed

    Liublinskaia, O G; Kirpichnikova, K M; Gamaleĭ, I A

    2013-01-01

    We studied the changes in the level of reactive oxygen species (ROS) in normal (3T3) and transformed (3T3-SV40) murine fibroblasts under the antioxidant action for 15 min using fluorescent probe carbo- xy-H2DCFDA. We have shown that N-acetylcysteine (NAC) decreased ROS level in both cellular types. Another antioxidant, alpha-lipoic acid (ALA), and its reduced form, dihydrolipoic acid (DHLA), caused the prooxidant effects. Both ALA and DHLA in the concentration range of 0.1-1.25 mM increased ROS level in dose dependent manner in both cellular types. The ability of ALA and DHLA to activate hydrogen peroxide production is discussed. PMID:25509127

  13. Polyglutamine expansion inhibits respiration by increasing reactive oxygen species in isolated mitochondria

    SciTech Connect

    Puranam, Kasturi L.; Wu, Guanghong; Strittmatter, Warren J.; Burke, James R. . E-mail: james.burke@duke.edu

    2006-03-10

    Huntington's disease results from expansion of the polyglutamine (PolyQ) domain in the huntingtin protein. Although the cellular mechanism by which pathologic-length PolyQ protein causes neurodegeneration is unclear, mitochondria appear central in pathogenesis. We demonstrate in isolated mitochondria that pathologic-length PolyQ protein directly inhibits ADP-dependent (state 3) mitochondrial respiration. Inhibition of mitochondrial respiration by PolyQ protein is not due to reduction in the activities of electron transport chain complexes, mitochondrial ATP synthase, or the adenine nucleotide translocase. We show that pathologic-length PolyQ protein increases the production of reactive oxygen species in isolated mitochondria. Impairment of state 3 mitochondrial respiration by PolyQ protein is reversed by addition of the antioxidants N-acetyl-L-cysteine or cytochrome c. We propose a model in which pathologic-length PolyQ protein directly inhibits mitochondrial function by inducing oxidative stress.

  14. Early Increase of Reactive Oxygen Species in Pea Seedling Roots Under Hypergravity

    NASA Astrophysics Data System (ADS)

    Jadko, Sergiy; Syvash, Alexander; Klymchuk, Dmytro

    Early increase of intensity of peroxidation and formation of reactive oxygen species (ROS) in plant cells take place under various impacts. The ROS can act as second messengers in mechanism of cell responses (Mittler et al 2006; Jadko et al 2007). Early stages of ROS content (chemiluminescence, ChL) in pea root cells under 3, 5, 10 and 15g during centrifugation have been investigated. After 30 min of centrifugation, especially under 10 and 15g, the intensity of ChL increased and was higher on 40-50% comparing to controls. Than the ChL slowly decreased and reached the controls in 1 hour. The changes of the ChL depend on both the dose and the duration of centrifugation. The role of ROS in mechanism of cell response to hypergravity is discussed.

  15. Evidence for photochemical production of reactive oxygen species in desert soils.

    PubMed

    Georgiou, Christos D; Sun, Henry J; McKay, Christopher P; Grintzalis, Konstantinos; Papapostolou, Ioannis; Zisimopoulos, Dimitrios; Panagiotidis, Konstantinos; Zhang, Gaosen; Koutsopoulou, Eleni; Christidis, George E; Margiolaki, Irene

    2015-01-01

    The combination of intense solar radiation and soil desiccation creates a short circuit in the biogeochemical carbon cycle, where soils release significant amounts of CO2 and reactive nitrogen oxides by abiotic oxidation. Here we show that desert soils accumulate metal superoxides and peroxides at higher levels than non-desert soils. We also show the photogeneration of equimolar superoxide and hydroxyl radical in desiccated and aqueous soils, respectively, by a photo-induced electron transfer mechanism supported by their mineralogical composition. Reactivity of desert soils is further supported by the generation of hydroxyl radical via aqueous extracts in the dark. Our findings extend to desert soils the photogeneration of reactive oxygen species by certain mineral oxides and also explain previous studies on desert soil organic oxidant chemistry and microbiology. Similar processes driven by ultraviolet radiation may be operating in the surface soils on Mars. PMID:25960012

  16. Reactive oxygen species production and antioxidant enzyme activity during epididymal sperm maturation in Corynorhinus mexicanus bats.

    PubMed

    Arenas-Ríos, Edith; Rosado García, Adolfo; Cortés-Barberena, Edith; Königsberg, Mina; Arteaga-Silva, Marcela; Rodríguez-Tobón, Ahiezer; Fuentes-Mascorro, Gisela; León-Galván, Miguel Angel

    2016-03-01

    Prolonged sperm storage in the epididymis of Corynorhinus mexicanus bats after testicular regression has been associated with epididymal sperm maturation in the caudal region, although the precise factors linked with this phenomenon are unknown. The aim of this work is to determine the role of reactive oxygen species (ROS) and changes in antioxidant enzymatic activity occurring in the spermatozoa and epididymal fluid over time, in sperm maturation and storage in the caput, corpus and cauda of the bat epididymis. Our data showed that an increment in ROS production coincided with an increase in superoxide dismutase (SOD) activity in epididymal fluid and with a decrease in glutathione peroxidase (GPX) activity in the spermatozoa in at different time points and epididymal regions. The increase in ROS production was not associated with oxidative damage measured by lipid peroxidation. The results of the current study suggest the existence of a shift in the redox balance, which might be associated with sperm maturation and storage. PMID:26952757

  17. Inactivation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species.

    PubMed

    Hurd, Thomas R; Collins, Yvonne; Abakumova, Irina; Chouchani, Edward T; Baranowski, Bartlomiej; Fearnley, Ian M; Prime, Tracy A; Murphy, Michael P; James, Andrew M

    2012-10-12

    Reactive oxygen species are byproducts of mitochondrial respiration and thus potential regulators of mitochondrial function. Pyruvate dehydrogenase kinase 2 (PDHK2) inhibits the pyruvate dehydrogenase complex, thereby regulating entry of carbohydrates into the tricarboxylic acid (TCA) cycle. Here we show that PDHK2 activity is inhibited by low levels of hydrogen peroxide (H(2)O(2)) generated by the respiratory chain. This occurs via reversible oxidation of cysteine residues 45 and 392 on PDHK2 and results in increased pyruvate dehydrogenase complex activity. H(2)O(2) derives from superoxide (O(2)(.)), and we show that conditions that inhibit PDHK2 also inactivate the TCA cycle enzyme, aconitase. These findings suggest that under conditions of high mitochondrial O(2)(.) production, such as may occur under nutrient excess and low ATP demand, the increase in O(2)() and H(2)O(2) may provide feedback signals to modulate mitochondrial metabolism. PMID:22910903

  18. Genetic damage in CHO cells exposed to enzymically generated active oxygen species.

    PubMed

    Phillips, B J; James, T E; Anderson, D

    1984-05-01

    The genetic toxicity of active oxygen species produced during the enzymic oxidation of xanthine has been investigated using Chinese hamster ovary (CHO) cells. Incubation of cells with xanthine plus xanthine oxidase resulted in extensive chromosome breakage and sister-chromatid exchange and gave a small increase in frequency of thioguanine-resistant cells (HGPRT test). Inclusion of superoxide dismutase or catalase in the xanthine/xanthine oxidase system inhibited chromosome breakage, whereas only catalase prevented SCE and mutant induction. It is concluded that hydrogen peroxide is responsible for most of the genetic effects observed in CHO cells exposed to xanthine/xanthine oxidase but that superoxide plays a key role in chromosome breakage. PMID:6325900

  19. Inactivation of Pyruvate Dehydrogenase Kinase 2 by Mitochondrial Reactive Oxygen Species*

    PubMed Central

    Hurd, Thomas R.; Collins, Yvonne; Abakumova, Irina; Chouchani, Edward T.; Baranowski, Bartlomiej; Fearnley, Ian M.; Prime, Tracy A.; Murphy, Michael P.; James, Andrew M.

    2012-01-01

    Reactive oxygen species are byproducts of mitochondrial respiration and thus potential regulators of mitochondrial function. Pyruvate dehydrogenase kinase 2 (PDHK2) inhibits the pyruvate dehydrogenase complex, thereby regulating entry of carbohydrates into the tricarboxylic acid (TCA) cycle. Here we show that PDHK2 activity is inhibited by low levels of hydrogen peroxide (H2O2) generated by the respiratory chain. This occurs via reversible oxidation of cysteine residues 45 and 392 on PDHK2 and results in increased pyruvate dehydrogenase complex activity. H2O2 derives from superoxide (O2˙̄), and we show that conditions that inhibit PDHK2 also inactivate the TCA cycle enzyme, aconitase. These findings suggest that under conditions of high mitochondrial O2˙̄ production, such as may occur under nutrient excess and low ATP demand, the increase in O2˙̄ and H2O2 may provide feedback signals to modulate mitochondrial metabolism. PMID:22910903

  20. The Injury and Therapy of Reactive Oxygen Species in Intracerebral Hemorrhage Looking at Mitochondria

    PubMed Central

    Qu, Jie; Chen, Weixiang; Hu, Rong; Feng, Hua

    2016-01-01

    Intracerebral hemorrhage is an emerging major health problem often resulting in death or disability. Reactive oxygen species (ROS) have been identified as one of the major damaging factors in ischemic stroke. However, there is less discussion about ROS in hemorrhage stroke. Metabolic products of hemoglobin, excitatory amino acids, and inflammatory cells are all sources of ROS, and ROS harm the central nervous system through cell death and structural damage, especially disruption of the blood-brain barrier. We have considered the antioxidant system of the CNS itself and the drugs aiming to decrease ROS after ICH, and we find that mitochondria are key players in all of these aspects. Moreover, when the mitochondrial permeability transition pore opens, ROS-induced ROS release, which leads to extensive liberation of ROS and mitochondrial failure, occurs. Therefore, the mitochondrion may be a significant target for elucidating the problem of ROS in ICH; however, additional experimental support is required. PMID:27293511

  1. Symbiotic lactobacilli stimulate gut epithelial proliferation via Nox-mediated generation of reactive oxygen species

    PubMed Central

    Jones, Rheinallt M; Luo, Liping; Ardita, Courtney S; Richardson, Arena N; Kwon, Young Man; Mercante, Jeffrey W; Alam, Ashfaqul; Gates, Cymone L; Wu, Huixia; Swanson, Phillip A; Lambeth, J David; Denning, Patricia W; Neish, Andrew S

    2013-01-01

    The resident prokaryotic microbiota of the metazoan gut elicits profound effects on the growth and development of the intestine. However, the molecular mechanisms of symbiotic prokaryotic–eukaryotic cross-talk in the gut are largely unknown. It is increasingly recognized that physiologically generated reactive oxygen species (ROS) function as signalling secondary messengers that influence cellular proliferation and differentiation in a variety of biological systems. Here, we report that commensal bacteria, particularly members of the genus Lactobacillus, can stimulate NADPH oxidase 1 (Nox1)-dependent ROS generation and consequent cellular proliferation in intestinal stem cells upon initial ingestion into the murine or Drosophila intestine. Our data identify and highlight a highly conserved mechanism that symbiotic microorganisms utilize in eukaryotic growth and development. Additionally, the work suggests that specific redox-mediated functions may be assigned to specific bacterial taxa and may contribute to the identification of microbes with probiotic potential. PMID:24141879

  2. Evidence that reactive oxygen species do not mediate NF-κB activation

    PubMed Central

    Hayakawa, Makio; Miyashita, Hiroshi; Sakamoto, Isao; Kitagawa, Masatoshi; Tanaka, Hirofumi; Yasuda, Hideyo; Karin, Michael; Kikugawa, Kiyomi

    2003-01-01

    It has been postulated that reactive oxygen species (ROS) may act as second messengers leading to nuclear factor (NF)-κB activation. This hypothesis is mainly based on the findings that N-acetyl-l-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC), compounds recognized as potential antioxidants, can inhibit NF-κB activation in a wide variety of cell types. Here we reveal that both NAC and PDTC inhibit NF-κB activation independently of antioxidative function. NAC selectively blocks tumor necrosis factor (TNF)-induced signaling by lowering the affinity of receptor to TNF. PDTC inhibits the IκB–ubiquitin ligase activity in the cell-free system where extracellular stimuli-regulated ROS production does not occur. Furthermore, we present evidence that endogenous ROS produced through Rac/NADPH oxidase do not mediate NF-κB signaling, but instead lower the magnitude of its activation. PMID:12839997

  3. Reciprocal regulation of TGF-β and reactive oxygen species: A perverse cycle for fibrosis

    PubMed Central

    Liu, Rui-Ming; Desai, Leena P.

    2015-01-01

    Transforming growth factor beta (TGF-β) is the most potent pro-fibrogenic cytokine and its expression is increased in almost all of fibrotic diseases. Although signaling through Smad pathway is believed to play a central role in TGF-β's fibrogenesis, emerging evidence indicates that reactive oxygen species (ROS) modulate TGF-β's signaling through different pathways including Smad pathway. TGF-β1 increases ROS production and suppresses antioxidant enzymes, leading to a redox imbalance. ROS, in turn, induce/activate TGF-β1 and mediate many of TGF-β's fibrogenic effects, forming a vicious cycle (see graphic flow chart on the right). Here, we review the current knowledge on the feed-forward mechanisms between TGF-β1 and ROS in the development of fibrosis. Therapeutics targeting TGF-β-induced and ROS-dependent cellular signaling represents a novel approach in the treatment of fibrotic disorders. PMID:26496488

  4. Endothelial GRK2 regulates vascular homeostasis through the control of free radical oxygen species

    PubMed Central

    Ciccarelli, Michele; Sorriento, Daniela; Franco, Antonietta; Fusco, Anna; Giudice, Carmine Del; Annunziata, Roberto; Cipolletta, Ersilia; Monti, Maria Gaia; Dorn, Gerald W; Trimarco, Bruno; Iaccarino, Guido

    2014-01-01

    Objective The role of endothelial GRK2 was investigated in mice with selective deletion of the kinase in the endothelium (Tie2-CRE/GRK2fl/fl). Approach and Results Aortas from Tie2-CRE/GRK2fl/fl presented functional and structural alterations as compared to control GRK2fl/fl mice. In particular, vasoconstriction was blunted to different agonists, and collagen and elastic rearrangement and macrophage infiltration were observed. In primary cultured endothelial cells deficient for GRK2, mitochondrial reactive oxygen species (ROS) was increased, leading to expression of cytokines. Chronic treatment with a ROS scavenger in mice corrected the vascular phenotype by recovering vasoconstriction, structural abnormalities and reducing macrophage infiltration. Conclusions These results demonstrate that GRK2 removal compromises vascular phenotype and integrity by increasing endothelial ROS production. PMID:23950144

  5. Fast, Ultrasensitive Detection of Reactive Oxygen Species Using a Carbon Nanotube Based-Electrocatalytic Intracellular Sensor

    PubMed Central

    2015-01-01

    Herein, we report a highly sensitive electrocatalytic sensor-cell construct that can electrochemically communicate with the internal environment of immune cells (e.g., macrophages) via the selective monitoring of a particular reactive oxygen species (ROS), hydrogen peroxide. The sensor, which is based on vertically aligned single-walled carbon nanotubes functionalized with an osmium electrocatalyst, enabled the unprecedented detection of a local intracellular “pulse” of ROS on a short second time scale in response to bacterial endotoxin (lipopolysaccharide-LPS) stimulation. Our studies have shown that this initial pulse of ROS is dependent on NADPH oxidase (NOX) and toll like receptor 4 (TLR4). The results suggest that bacteria can induce a rapid intracellular pulse of ROS in macrophages that initiates the classical innate immune response of these cells to infection. PMID:26438964

  6. Using consensus bayesian network to model the reactive oxygen species regulatory pathway.

    PubMed

    Hu, Liangdong; Wang, Limin

    2013-01-01

    Bayesian network is one of the most successful graph models for representing the reactive oxygen species regulatory pathway. With the increasing number of microarray measurements, it is possible to construct the bayesian network from microarray data directly. Although large numbers of bayesian network learning algorithms have been developed, when applying them to learn bayesian networks from microarray data, the accuracies are low due to that the databases they used to learn bayesian networks contain too few microarray data. In this paper, we propose a consensus bayesian network which is constructed by combining bayesian networks from relevant literatures and bayesian networks learned from microarray data. It would have a higher accuracy than the bayesian networks learned from one database. In the experiment, we validated the bayesian network combination algorithm on several classic machine learning databases and used the consensus bayesian network to model the Escherichia coli's ROS pathway. PMID:23457624

  7. Mechanisms that Regulate Production of Reactive Oxygen Species by Cytochrome P450

    SciTech Connect

    Zangar, Richard C.; Davydov, Dmitri R.; Verma, Seema

    2004-09-15

    Mammalian cytochromes P450 (P450) are a family of heme-thiolate enzymes involved in the oxidative metabolism of a variety of endogenous and exogenous lipophilic compounds. Poor coupling of the P450 catalytic cycle results in continuous production of reactive oxygen species (ROS), which affect signaling pathways and other cellular functions. P450 generation of ROS is tightly controlled by regulation of gene transcription, as well as by modulation of interactions between protein constituents of the monooxygenase that affects its activity, coupling and stability. Malfunction of these mechanisms may result in a burst of ROS production, which can cause lipid peroxidation and oxidative stress. In turn, oxidative stress downregulates P450 levels by a variety of feedback mechanisms. This review provides an overview of recent advances in our understanding of these feedback mechanisms that serve to limit P450 production of ROS. Some of the more likely physiological and cellular effects of P450 generation of ROS are also discussed.

  8. High osmotic pressure increases reactive oxygen species generation in rabbit corneal epithelial cells by endoplasmic reticulum

    PubMed Central

    Wang, Peng; Sheng, Minjie; Li, Bing; Jiang, Yaping; Chen, Yihui

    2016-01-01

    Tear high osmotic pressure (HOP) has been recognized as the core mechanism underlying ocular surface inflammation, injury and symptoms and is closely associated with many ocular surface diseases, especially dry eye. The endoplasmic reticulum (ER) is a multi-functional organelle responsible for protein synthesis, folding and transport, biological synthesis of lipids, vesicle transport and intracellular calcium storage. Accumulation of unfolded proteins and imbalance of calcium ion in the ER would induce ER stress and protective unfolded protein response (UPR). Many studies have demonstrated that ER stress can induce cell apoptosis. However, the association between tear HOP and ER stress has not been studied systematically. In the present study, rabbit corneal epithelial cells were treated with HOP and results showed that the production of reactive oxygen species increased markedly, which further activated the ER signaling pathway and ultimately induced cell apoptosis. These findings shed new lights on the pathogenesis and clinical treatment of dry eye and other ocular surface diseases. PMID:27158374

  9. Signaling Networks Involving Reactive Oxygen Species and Ca2+ in Plants

    NASA Astrophysics Data System (ADS)

    Kuchitsu, Kazuyuki

    2013-01-01

    Although plants never evolved central information processing organs such as brains, plants have evolved distributed information processing systems and are able to sense various environmental changes and reorganize their body plan coordinately without moving. Recent molecular biological studies revealed molecular bases for elementary processes of signal transduction in plants. Though reactive oxygen species (ROS) are highly toxic substances produced through aerobic respiration and photosynthesis, plants possess ROS-producing enzymes whose activity is highly regulated by binding of Ca2+. In turn, Ca2+- permeable channel proteins activated by ROS are shown to be localized to the cell membrane. These two components are proposed to constitute a positive feedback loop to amplify cellular signals. Such molecular physiological studies should be important steps to understand information processing systems in plants and future application for technology related to environmental, energy and food sciences.

  10. Juglone induces cell death of Acanthamoeba through increased production of reactive oxygen species.

    PubMed

    Jha, Bijay Kumar; Jung, Hui-Jung; Seo, Incheol; Suh, Seong-Il; Suh, Min-Ho; Baek, Won-Ki

    2015-12-01

    Juglone (5-hydroxy-1,4-naphthoquinone) is a major chemical constituent of Juglans mandshruica Maxim. Recent studies have demonstrated that juglone exhibits anti-cancer, anti-bacterial, anti-viral, and anti-parasitic properties. However, its effect against Acanthamoeba has not been defined yet. The aim of this study was to investigate the effect of juglone on Acanthamoeba. We demonstrate that juglone significantly inhibits the growth of Acanthamoeba castellanii at 3-5 μM concentrations. Juglone increased the production of reactive oxygen species (ROS) and caused cell death of A. castellanii. Inhibition of ROS by antioxidant N-acetyl-l-cysteine (NAC) restored the cell viability. Furthermore, our results show that juglone increased the uptake of mitochondrial specific dye. Collectively, these results indicate that ROS played a significant role in the juglone-induced cell death of Acanthamoeba. PMID:26358271

  11. Reactive oxygen species-mediated neurodegeneration is independent of the ryanodine receptor in Caernorhabditis elegans

    PubMed Central

    Young, Lyndsay EA; Williams, Daniel C.

    2016-01-01

    Despite the significant impacts on human health caused by neurodegeneration, our understanding of the degeneration process is incomplete. The nematode Caenorhabditis elegans is emerging as a genetic model organism well suited for identification of conserved cellular mechanisms and molecular pathways of neurodegeneration. Studies in the worm have identified factors that contribute to neurodegeneration, including excitotoxicity and stress due to reactive oxygen species (ROS). Disruption of the gene unc-68, which encodes the ryanodine receptor, abolishes excitotoxic cell death, indicating a role for calcium (Ca2+) signaling in neurodegeneration. We tested the requirement for unc-68 in ROS-mediated neurodegeneration using the genetically encoded photosensitizer KillerRed. Upon illumination of KillerRed expressing animals to produce ROS, we observed similar levels of degeneration in wild-type and unc-68 mutant strains. Our results indicate that ROS-mediated cell death is independent of unc-68 and suggest multiple molecular pathways of neurodegeneration.

  12. PGC-1α and reactive oxygen species regulate human embryonic stem cell-derived cardiomyocyte function.

    PubMed

    Birket, Matthew J; Casini, Simona; Kosmidis, Georgios; Elliott, David A; Gerencser, Akos A; Baartscheer, Antonius; Schumacher, Cees; Mastroberardino, Pier G; Elefanty, Andrew G; Stanley, Ed G; Mummery, Christine L

    2013-01-01

    Diminished mitochondrial function is causally related to some heart diseases. Here, we developed a human disease model based on cardiomyocytes from human embryonic stem cells (hESCs), in which an important pathway of mitochondrial gene expression was inactivated. Repression of PGC-1α, which is normally induced during development of cardiomyocytes, decreased mitochondrial content and activity and decreased the capacity for coping with energetic stress. Yet, concurrently, reactive oxygen species (ROS) levels were lowered, and the amplitude of the action potential and the maximum amplitude of the calcium transient were in fact increased. Importantly, in control cardiomyocytes, lowering ROS levels emulated this beneficial effect of PGC-1α knockdown and similarly increased the calcium transient amplitude. Our results suggest that controlling ROS levels may be of key physiological importance for recapitulating mature cardiomyocyte phenotypes, and the combination of bioassays used in this study may have broad application in the analysis of cardiac physiology pertaining to disease. PMID:24371810

  13. PGC-1α and Reactive Oxygen Species Regulate Human Embryonic Stem Cell-Derived Cardiomyocyte Function

    PubMed Central

    Birket, Matthew J.; Casini, Simona; Kosmidis, Georgios; Elliott, David A.; Gerencser, Akos A.; Baartscheer, Antonius; Schumacher, Cees; Mastroberardino, Pier G.; Elefanty, Andrew G.; Stanley, Ed G.; Mummery, Christine L.

    2013-01-01

    Summary Diminished mitochondrial function is causally related to some heart diseases. Here, we developed a human disease model based on cardiomyocytes from human embryonic stem cells (hESCs), in which an important pathway of mitochondrial gene expression was inactivated. Repression of PGC-1α, which is normally induced during development of cardiomyocytes, decreased mitochondrial content and activity and decreased the capacity for coping with energetic stress. Yet, concurrently, reactive oxygen species (ROS) levels were lowered, and the amplitude of the action potential and the maximum amplitude of the calcium transient were in fact increased. Importantly, in control cardiomyocytes, lowering ROS levels emulated this beneficial effect of PGC-1α knockdown and similarly increased the calcium transient amplitude. Our results suggest that controlling ROS levels may be of key physiological importance for recapitulating mature cardiomyocyte phenotypes, and the combination of bioassays used in this study may have broad application in the analysis of cardiac physiology pertaining to disease. PMID:24371810

  14. Protection of neuronal cells against reactive oxygen species by carnosine and related compounds.

    PubMed

    Boldyrev, Alexander; Bulygina, Elena; Leinsoo, Toomas; Petrushanko, Irina; Tsubone, Shiori; Abe, Hiroki

    2004-01-01

    Carnosine and related compounds were compared in terms of their abilities to decrease the levels of reactive oxygen species (ROS) in suspensions of isolated neurons activated by N-methyl-D-aspartic acid (NMDA) using both stationary fluorescence measurements and flow cytometry. Carnosine was found to suppress the fluorescent signal induced by ROS production and decreased the proportion of highly fluorescent neurons, while histidine showed opposite effects. N-Acetylated derivatives of both carnosine and histidine demonstrated weak (statistically indistinguishable) suppressive effects on the ROS signal. N-Methylated derivatives of carnosine suppressed intracellular ROS generation to the same extent as carnosine. This rank of effectiveness is distinct from that previously obtained for the anti-radical ability of CRCs (anserine>carnosine>ophidine). These differences suggest that the similar ability of carnosine and its N-methylated derivatives to protect neuronal cells against the excitotoxic effect of NMDA is not solely related to the antioxidant properties of these compounds. PMID:14698913

  15. Reactive oxygen species (ROS)-induced actin glutathionylation controls actin dynamics in neutrophils

    PubMed Central

    Sakai, Jiro; Li, Jingyu; Subramanian, Kulandayan K.; Mondal, Subhanjan; Bajrami, Besnik; Hattori, Hidenori; Jia, Yonghui; Dickinson, Bryan C.; Zhong, Jia; Ye, Keqiang; Chang, Christopher J; Ho, Ye-Shih; Zhou, Jun; Luo, Hongbo R.

    2012-01-01

    Summary The regulation of actin dynamics is pivotal for cellular processes such as cell adhesion, migration, and phagocytosis, and thus is crucial for neutrophils to fulfill their roles in innate immunity. Many factors have been implicated in signal-induced actin polymerization, however the essential nature of the potential negative modulators are still poorly understood. Here we report that NADPH oxidase-dependent physiologically generated reactive oxygen species (ROS) negatively regulate actin polymerization in stimulated neutrophils via driving reversible actin glutathionylation. Disruption of glutaredoxin 1 (Grx1), an enzyme that catalyzes actin deglutathionylation, increased actin glutathionylation, attenuated actin polymerization, and consequently impaired neutrophil polarization, chemotaxis, adhesion, and phagocytosis. Consistently, Grx1-deficient murine neutrophils showed impaired in vivo recruitment to sites of inflammation and reduced bactericidal capability. Together, these results present a physiological role for glutaredoxin and ROS- induced reversible actin glutathionylation in regulation of actin dynamics in neutrophils. PMID:23159440

  16. Generation of singlet oxygen and other radical species by quantum dot and carbon dot nanosensitizers

    NASA Astrophysics Data System (ADS)

    Generalov, Roman; Christensen, Ingeborg L.; Chen, Wei; Sun, Ya-Ping; Kristensen, Solveig; Juzenas, Petras

    2009-06-01

    Medicinal applications of luminescent semiconductor quantum dots are of growing interest. In spite of the fact that their fabrication and imaging applications have been extensively investigated for the last decade, very little is documented on photodynamic action of quantum dots. In this study we demonstrate generation of singlet oxygen and other radical species upon exposure of quantum dots to blue light and therapeutic red light. Extent of radical production can be readily modified by antioxidants. Lay and scientific communities are two sites concerning potential hazards and enthusiastic applications of nanotechnology. Synthesis of quantum dots composed of less toxic materials is of great interest. A new candidate is a ubiquitous element carbon, which on nanoscale exhibits strong photoluminescence.

  17. Reactive Oxygen Species in the Regulation of Stomatal Movements1[OPEN

    PubMed Central

    Sierla, Maija; Waszczak, Cezary; Vahisalu, Triin

    2016-01-01

    Guard cells form stomatal pores that optimize photosynthetic carbon dioxide uptake with minimal water loss. Stomatal movements are controlled by complex signaling networks that respond to environmental and endogenous signals. Regulation of stomatal aperture requires coordinated activity of reactive oxygen species (ROS)-generating enzymes, signaling proteins, and downstream executors such as ion pumps, transporters, and plasma membrane channels that control guard cell turgor pressure. Accumulation of ROS in the apoplast and chloroplasts is among the earliest hallmarks of stomatal closure. Subsequent increase in cytoplasmic Ca2+ concentration governs the activity of multiple kinases that regulate the activity of ROS-producing enzymes and ion channels. In parallel, ROS directly regulate the activity of multiple proteins via oxidative posttranslational modifications to fine-tune guard cell signaling. In this review, we summarize recent advances in the role of ROS in stomatal closure and discuss the importance of ROS in regulation of signal amplification and specificity in guard cells. PMID:27208297

  18. Modulation of macrophage-mediated cytotoxicity by kerosene soot: Possible role of reactive oxygen species

    SciTech Connect

    Arif, J.M.; Khan, S.G.; Ashquin, M.; Rahman, Q. )

    1993-05-01

    The involvement of reactive oxygen species (ROS) in the cytotoxicity of soot on rat alveolar macrophages has been postulated. A single intratracheal injection of soot (5 mg) in corn oil significantly induced the macrophage population, hydrogen peroxide (H[sub 2]O[sub 2]) generation, thiobarbituric acid (TBA)-reactive substanced of lipid peroxidation, and the activities of extracellular acid phosphatase (AP) and lactate dehydrogenase (LDH) at 1, 4, 8, and 16 days of postinoculation. The activities of glutathione peroxidase (GPX) and catalase (CAT) were significantly inhibited at all the stages, while glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) showed a different pattern. These results show that soot is cytotoxic to alveolar macrophages and suggest that ROS may play a primary role in the cytotoxic process. 28 refs., 4 figs., 1 tab.

  19. Electrocatalytic performances of N-doped graphene with anchored iridium species in oxygen reduction reaction

    NASA Astrophysics Data System (ADS)

    Choi, Kwangrok; Lee, Seungjun; Shim, Yeonjun; Oh, Junghoon; Kim, Sujin; Park, Sungjin

    2015-09-01

    Development of new systems with high catalytic performances in the oxygen reduction reaction (ORR) for practical applications in fuel cells and metal-air batteries is a challenge. We develop a one-pot solution method for producing a novel hybrid material consisting of Ir species anchored on N-doped graphene. The hybrid is synthesized by reacting graphene oxide with IrCl3 · xH2O in dimethylformamide under reflux. Chemical and structural analyses confirm the attachment of Ir atoms to the N and O atoms of the N-doped graphene-based materials. The hybrid shows a good electrocatalytic performance for the ORR in alkaline media, with an onset potential of 0.88 V (versus the reversible hydrogen electrode), high long-term durability, and good tolerance for methanol poisoning.

  20. Reactive oxygen species, redox signaling and neuroinflammation in Alzheimer's disease: the NF-κB connection.

    PubMed

    Kaur, Upinder; Banerjee, Priyanjalee; Bir, Aritri; Sinha, Maitrayee; Biswas, Atanu; Chakrabarti, Sasanka

    2015-01-01

    Oxidative stress and inflammatory response are important elements of Alzheimer's disease (AD) pathogenesis, but the role of redox signaling cascade and its cross-talk with inflammatory mediators have not been elucidated in details in this disorder. The review summarizes the facts about redox-signaling cascade in the cells operating through an array of kinases, phosphatases and transcription factors and their downstream components. The biology of NF-κB and its activation by reactive oxygen species (ROS) and proinflammatory cytokines in the pathogenesis of AD have been specially highlighted citing evidence both from post-mortem studies in AD brain and experimental research in animal or cell-based models of AD. The possibility of identifying new disease-modifying drugs for AD targeting NF-κBsignaling cascade has been discussed in the end. PMID:25620241

  1. Modulation of Crassostrea virginica hemocyte reactive oxygen species production by Listonella anguillarum.

    PubMed

    Bramble, L; Anderson, R S

    1997-01-01

    Luminol- and lucigenin-augmented chemiluminescence (CL) were used to evaluate the ability of Listonella (formerly Vibrio) anguillarum to stimulate the production of reactive oxygen species (ROS) by Crassostrea virginica hemocytes. Whereas heat-killed L. anguillarum stimulated hemocyte CL in the lucigenin system, viable L. anguillarum did not. Neither viable nor heat-killed bacteria stimulated hemocyte production of luminol CL. Metabolically active L. anguillarum generated ROS, as indicated by luminol and lucigenin CL. It is proposed that bacterial catalase suppressed hemocyte-derived luminol CL. L. anguillarum, which possesses the antioxidant enzyme catalase, suppressed luminol CL generated by zymosan-stimulated hemocytes. Conversely, the catalase negative bacterium Carnobacterium piscicola had no effect on hemocyte-derived luminol CL elicited by zymosan. The inability of viable L. anguillarum to stimulate hemocyte ROS production, as measured by CL, does not support the proposed role for ROS in hemocyte-mediated bactericidal activity. PMID:9303272

  2. Role of Reactive Oxygen Species in Pathogenesis of Radiocontrast-Induced Nephropathy

    PubMed Central

    Pisani, Antonio; Faga, Teresa; Ashour, Michael; Di Nuzzi, Antonella; Mancini, Aldo

    2013-01-01

    In vitro and in vivo studies have demonstrated enhanced hypoxia and formation of reactive oxygen species (ROS) in the kidney following the administration of iodinated contrast media, which play a relevant role in the development of contrast media-induced nephropathy. Many studies indeed support this possibility, suggesting a protective effect of ROS scavenging or reduced ROS formation with the administration of N-acetylcysteine and bicarbonate infusion, respectively. Furthermore, most risk factors, predisposing to contrast-induced nephropathy, are prone to enhanced renal parenchymal hypoxia and ROS formation. In this review, the association of renal hypoxia and ROS-mediated injury is outlined. Generated during contrast-induced renal parenchymal hypoxia, ROS may exert direct tubular and vascular endothelial injury and might further intensify renal parenchymal hypoxia by virtue of endothelial dysfunction and dysregulation of tubular transport. Preventive strategies conceivably should include inhibition of ROS generation or ROS scavenging. PMID:24459673

  3. Zinc Induces Apoptosis of Human Melanoma Cells, Increasing Reactive Oxygen Species, p53 and FAS Ligand.

    PubMed

    Provinciali, Mauro; Pierpaoli, Elisa; Bartozzi, Beatrice; Bernardini, Giovanni

    2015-10-01

    The aim of this study was to examine the in vitro effect of zinc on the apoptosis of human melanoma cells, by studying the zinc-dependent modulation of intracellular levels of reactive oxygen species (ROS) and of p53 and FAS ligand proteins. We showed that zinc concentrations ranging from 33.7 μM to 75 μM Zn(2+) induced apoptosis in the human melanoma cell line WM 266-4. This apoptosis was associated with an increased production of intracellular ROS, and of p53 and FAS ligand protein. Treatment of tumor cells with the antioxidant N-acetylcysteine was able to prevent Zn(2+)-induced apoptosis, as well as the increase of p53 and FAS ligand protein induced by zinc. Zinc induces apoptosis in melanoma cells by increasing ROS and this effect may be mediated by the ROS-dependent induction of p53 and FAS/FAS ligand. PMID:26408691

  4. 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. PMID:27566079

  5. The Roles of Mitochondrial Reactive Oxygen Species in Cellular Signaling and Stress Response in Plants.

    PubMed

    Huang, Shaobai; Van Aken, Olivier; Schwarzländer, Markus; Belt, Katharina; Millar, A Harvey

    2016-07-01

    Mitochondria produce ATP via respiratory oxidation of organic acids and transfer of electrons to O2 via the mitochondrial electron transport chain. This process produces reactive oxygen species (ROS) at various rates that can impact respiratory and cellular function, affecting a variety of signaling processes in the cell. Roles in redox signaling, retrograde signaling, plant hormone action, programmed cell death, and defense against pathogens have been attributed to ROS generated in plant mitochondria (mtROS). The shortcomings of the black box-idea of mtROS are discussed in the context of mechanistic considerations and the measurement of mtROS The overall aim of this update is to better define our current understanding of mtROS and appraise their potential influence on cellular function in plants. Furthermore, directions for future research are provided, along with suggestions to increase reliability of mtROS measurements. PMID:27021189

  6. UVB Dependence of Quantum Dot Reactive Oxygen Species Generation in Common Skin Cell Models.

    PubMed

    Mortensen, Luke J; Faulknor, Renea; Ravichandran, Supriya; Zheng, Hong; DeLouise, Lisa A

    2015-09-01

    Studies have shown that UVB can slightly increase the penetration of nanoparticles through skin and significantly alter skin cell biology, thus it is important to understand if and how UVB may impact subsequent nanoparticle skin cell interactions. The research presented herein evaluates the effect of UVB on quantum dot (QD) uptake and reactive oxygen species (ROS) generation in primary keratinocytes, primary melanocytes, and related cell lines. QD exposure induced cell type dependent ROS responses increased by pre-exposing cells to UVB and correlated with the level of QD uptake. Our results suggest that keratinocytes may be at greater risk for QD induced ROS generation than melanocytes, and raise awareness about the differential cellular effects that topically applied nanomaterials may have on UVB exposed skin. PMID:26485933

  7. Chlamydia Infection Across Host Species Boundaries Promotes Distinct Sets of Transcribed Anti-Apoptotic Factors

    PubMed Central

    Messinger, Joshua E.; Nelton, Emmalin; Feeney, Colleen; Gondek, David C.

    2015-01-01

    Chlamydiae, obligate intracellular bacteria, cause significant human and veterinary associated diseases. Having emerged an estimated 700-million years ago, these bacteria have twice adapted to humans as a host species, causing sexually transmitted infection (C. trachomatis) and respiratory associated disease (C. pneumoniae). The principle mechanism of host cell defense against these intracellular bacteria is the induction of cell death via apoptosis. However, in the “arms race” of co-evolution, Chlamydiae have developed mechanisms to promote cell viability and inhibit cell death. Herein we examine the impact of Chlamydiae infection across multiple host species on transcription of anti-apoptotic genes. We found mostly distinct patterns of gene expression (Mcl1 and cIAPs) elicited by each pathogen-host pair indicating Chlamydiae infection across host species boundaries does not induce a universally shared host response. Understanding species specific host-pathogen interactions is paramount to deciphering how potential pathogens become emerging diseases. PMID:26779446

  8. Endogenous and endobiotic induced reactive oxygen species formation by isolated hepatocytes.

    PubMed

    Siraki, Arno G; Pourahmad, Jalal; Chan, Tom S; Khan, Sumsullah; O'Brien, Peter J

    2002-01-01

    The rat hepatocyte catalyzed oxidation of 2',7'-dichlorofluorescin to form the fluorescent 2,7'-dichlorofluorescein was used to measure endogenous and xenobiotic-induced reactive oxygen species (ROS) formation by intact isolated rat hepatocytes. Various oxidase substrates and inhibitors were then used to identify the intracellular oxidases responsible. Endogenous ROS formation was markedly increased in catalase-inhibited or GSH-depleted hepatocytes, and was inhibited by ROS scavengers or desferoxamine. Endogenous ROS formation was also inhibited by cytochrome P450 inhibitors, but was not affected by oxypurinol, a xanthine oxidase inhibitor, or phenelzine, a monoamine oxidase inhibitor. Mitochondrial respiratory chain inhibitors or hypoxia, on the other hand, markedly increased ROS formation before cytotoxicity ensued. Furthermore, uncouplers of oxidative phosphorylation inhibited endogenous ROS formation. This suggests endogenous ROS formation can largely be attributed to oxygen reduction by reduced mitochondrial electron transport components and reduced cytochrome P450 isozymes. Addition of monoamine oxidase substrates increased antimycin A-resistant respiration and ROS formation before cytotoxicity ensued. Addition of peroxisomal substrates also increased antimycin A-resistant respiration but they were less effective at inducing ROS formation and were not cytotoxic. However, peroxisomal substrates readily induced ROS formation and were cytotoxic towards catalase-inhibited hepatocytes, which suggests that peroxisomal catalase removes endogenous H(2)O(2) formed in the peroxisomes. Hepatocyte catalyzed dichlorofluorescin oxidation induced by oxidase substrates, e.g., benzylamine, was correlated with the cytotoxicity induced in catalase-inhibited hepatocytes. PMID:11755311

  9. Oxidative Stress in the Developing Rat Brain due to Production of Reactive Oxygen and Nitrogen Species

    PubMed Central

    Wilhelm, Jiří; Vytášek, Richard; Uhlík, Jiří; Vajner, Luděk

    2016-01-01

    Oxidative stress after birth led us to localize reactive oxygen and nitrogen species (RONS) production in the developing rat brain. Brains were assessed a day prenatally and on postnatal days 1, 2, 4, 8, 14, 30, and 60. Oxidation of dihydroethidium detected superoxide; 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate revealed hydrogen peroxide; immunohistochemical proof of nitrotyrosine and carboxyethyllysine detected peroxynitrite formation and lipid peroxidation, respectively. Blue autofluorescence detected protein oxidation. The foetuses showed moderate RONS production, which changed cyclically during further development. The periods and sites of peak production of individual RONS differed, suggesting independent generation. On day 1, neuronal/glial RONS production decreased indicating that increased oxygen concentration after birth did not cause oxidative stress. Dramatic changes in the amount and the sites of RONS production occurred on day 4. Nitrotyrosine detection reached its maximum. Day 14 represented other vast alterations in RONS generation. Superoxide production in arachnoidal membrane reached its peak. From this day on, the internal elastic laminae of blood vessels revealed the blue autofluorescence. The adult animals produced moderate levels of superoxide; all other markers reached their minimum. There was a strong correlation between detection of nitrotyrosine and carboxyethyllysine probably caused by lipid peroxidation initiated with RONS. PMID:27190574

  10. Reactive Oxygen Species in the Regulation of Synaptic Plasticity and Memory

    PubMed Central

    Klann, Eric

    2011-01-01

    Abstract The brain is a metabolically active organ exhibiting high oxygen consumption and robust production of reactive oxygen species (ROS). The large amounts of ROS are kept in check by an elaborate network of antioxidants, which sometimes fail and lead to neuronal oxidative stress. Thus, ROS are typically categorized as neurotoxic molecules and typically exert their detrimental effects via oxidation of essential macromolecules such as enzymes and cytoskeletal proteins. Most importantly, excessive ROS are associated with decreased performance in cognitive function. However, at physiological concentrations, ROS are involved in functional changes necessary for synaptic plasticity and hence, for normal cognitive function. The fine line of role reversal of ROS from good molecules to bad molecules is far from being fully understood. This review focuses on identifying the multiple sources of ROS in the mammalian nervous system and on presenting evidence for the critical and essential role of ROS in synaptic plasticity and memory. The review also shows that the inability to restrain either age- or pathology-related increases in ROS levels leads to opposite, detrimental effects that are involved in impairments in synaptic plasticity and memory function. Antioxid. Redox Signal. 14, 2013–2054. PMID:20649473

  11. Effect of ectomycorrhizal colonization and drought on reactive oxygen species metabolism of Nothofagus dombeyi roots.

    PubMed

    Alvarez, Maricel; Huygens, Dries; Fernandez, Carlos; Gacitúa, Yessy; Olivares, Erick; Saavedra, Isabel; Alberdi, Miren; Valenzuela, Eduardo

    2009-08-01

    Infection with ectomycorrhizal fungi can increase the ability of plants to resist drought stress through morphophysiological and biochemical mechanisms. However, the metabolism of antioxidative enzyme activities in the ectomycorrhizal symbiosis remains poorly understood. This study investigated biomass production, reactive oxygen metabolism (hydrogen peroxide and malondialdehyde concentration) and antioxidant enzyme activity (superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase) in pure cultures of the ectomycorrhizal fungi Descolea antartica Sing. and Pisolithus tinctorius (Pers.) Coker & Couch, and non-mycorrhizal and mycorrhizal roots of Nothofagus dombeyi (Mirb.) roots under well-watered conditions and drought conditions (DC). The studied ectomycorrhizal fungi regulated their antioxidative enzyme metabolism differentially in response to drought, resulting in cellular damage in D. antartica but not in P. tinctorius. Ectomycorrhizal inoculation and water treatment had a significant effect on all parameters studied, including relative water content of the plant. As such, N. dombeyi plants in symbiosis experienced a lower oxidative stress effect than non-mycorrhizal plants under DC. Additionally, ectomycorrhizal N. dombeyi roots showed a greater antioxidant enzyme activity relative to non-mycorrhizal roots, an effect which was further expressed under DC. The association between the non-specific P. tinctorius and N. dombeyi had a more effective reactive oxygen species (ROS) metabolism than the specific D. antartica-N. dombeyi symbiosis. We conclude that the combination of effective ROS prevention and ROS detoxification by ectomycorrhizal plants resulted in reduced cellular damage and increased plant growth relative to non-mycorrhizal plants under drought. PMID:19483186

  12. Reactive oxygen species mediate cognitive deficits in experimental temporal lobe epilepsy.

    PubMed

    Pearson, Jennifer N; Rowley, Shane; Liang, Li-Ping; White, Andrew M; Day, Brian J; Patel, Manisha

    2015-10-01

    Cognitive dysfunction is an important comorbidity of temporal lobe epilepsy (TLE). However, no targeted therapies are available and the mechanisms underlying cognitive impairment, specifically deficits in learning and memory associated with TLE remain unknown. Oxidative stress is known to occur in the pathogenesis of TLE but its functional role remains to be determined. Here, we demonstrate that oxidative stress and resultant processes contribute to cognitive decline associated with epileptogenesis. Using a synthetic catalytic antioxidant, we show that pharmacological removal of reactive oxygen species (ROS) prevents 1) oxidative stress, 2) deficits in mitochondrial oxygen consumption rates, 3) hippocampal neuronal loss and 4) cognitive dysfunction without altering the intensity of the initial status epilepticus (SE) or epilepsy development in a rat model of SE-induced TLE. Moreover, the effects of the catalytic antioxidant on cognition persisted beyond the treatment period suggestive of disease-modification. The data implicate oxidative stress as a novel mechanism by which cognitive dysfunction can arise during epileptogenesis and suggest a potential disease-modifying therapeutic approach to target it. PMID:26184893

  13. Reactive oxygen species: physiological roles in the regulation of vascular cells.

    PubMed

    Vara, D; Pula, G

    2014-01-01

    Reactive oxygen species (ROS) are now appreciated to play several important roles in a number of biological processes and regulate cell physiology and function. ROS are a heterogeneous chemical class that includes radicals, such as superoxide ion (O2(•-)), hydroxyl radical (OH(•)) and nitric oxide (NO(•)), and non-radicals, such as hydrogen peroxide (H2O2), singlet oxygen ((1)O2), hypochlorous acid (HOCl), and peroxynitrite (NO3 (-)). In the cardiovascular system, besides playing a critical role in the development and progression of vasculopathies and other important pathologies such as congestive heart failure, atherosclerosis and thrombosis, ROS also regulate physiological processes. Evidence from a wealth of cardiovascular research studies suggests that ROS act as second messengers and play an essential role in vascular homeostasis by influencing discrete signal transduction pathways in various systems and cell types. They are produced throughout the vascular system, regulate differentiation and contractility of vascular smooth muscle cells, control vascular endothelial cell proliferation and migration, mediate platelet activation and haemostasis, and significantly contribute to the immune response. Our understanding of ROS chemistry and cell biology has evolved to the point of realizing that different ROS have distinct and important roles in cardiovascular physiology. This review will outline sources, functions and molecular mechanisms of action of different ROS in the cardiovascular system and will describe their emerging role in healthy cardiovascular physiology and homeostasis. PMID:24894168

  14. Nitric Oxide and Reactive Oxygen Species in the Pathogenesis of Preeclampsia

    PubMed Central

    Matsubara, Keiichi; Higaki, Takashi; Matsubara, Yuko; Nawa, Akihiro

    2015-01-01

    Preeclampsia (PE) is characterized by disturbed extravillous trophoblast migration toward uterine spiral arteries leading to increased uteroplacental vascular resistance and by vascular dysfunction resulting in reduced systemic vasodilatory properties. Its pathogenesis is mediated by an altered bioavailability of nitric oxide (NO) and tissue damage caused by increased levels of reactive oxygen species (ROS). Furthermore, superoxide (O2−) rapidly inactivates NO and forms peroxynitrite (ONOO−). It is known that ONOO− accumulates in the placental tissues and injures the placental function in PE. In addition, ROS could stimulate platelet adhesion and aggregation leading to intravascular coagulopathy. ROS-induced coagulopathy causes placental infarction and impairs the uteroplacental blood flow in PE. The disorders could lead to the reduction of oxygen and nutrients required for normal fetal development resulting in fetal growth restriction. On the other hand, several antioxidants scavenge ROS and protect tissues against oxidative damage. Placental antioxidants including catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) protect the vasculature from ROS and maintain the vascular function. However, placental ischemia in PE decreases the antioxidant activity resulting in further elevated oxidative stress, which leads to the appearance of the pathological conditions of PE including hypertension and proteinuria. Oxidative stress is defined as an imbalance between ROS and antioxidant activity. This review provides new insights about roles of oxidative stress in the pathophysiology of PE. PMID:25739077

  15. Reactive oxygen species and the bacteriostatic and bactericidal effects of isoconazole nitrate.

    PubMed

    Czaika, Viktor A; Siebenbrock, Jan; Czekalla, Frank; Zuberbier, Torsten; Sieber, Martin A

    2013-05-01

    Bacterial superinfections often occur in dermatomycoses, resulting in greatly inflamed or eczematous skin. The objective of this study was to evaluate the antibacterial efficacy of isoconazole nitrate (ISN), a broad-spectrum antimicrobial imidazole, commonly used to treat dermatomycoses. Several gram-positive bacteria minimal inhibitory concentrations (MICs) for ISN (ISN solution or ISN-containing creams: Travogen or corticosteroid-containing Travocort) and ampicillin were obtained using the broth-dilution method. Speed of onset of the bactericidal effect was determined with bacterial killing curves. Reactive oxygen species (ROS) were visualised by staining cells with singlet oxygen detector stain. Compared with ampicillin MICs, ISN MICs for Bacillus cereus, Staphylococcus haemolyticus and Staphylococcus hominis were lower and ISN MICs for Corynebacterium tuberculostearicum and Streptococcus salivarius were similar. Incubation with ISN led to a 50% kill rate for Staphylococcus aureus and methicillin-resistant strains (MRSA). Post-ISN incubation, 36% (30 min) and 90% (60 min) of S. aureus cells were positive for ROS. Isoconazole nitrate has a broad bacteriostatic and bactericidal action, also against a MRSA strain that was not reduced by the corticosteroid in the Travocort cream. Data suggest that the antibacterial effect of ISN may be ROS dependent. An antifungal agent with robust antibacterial activity can provide a therapeutic advantage in treating dermatomycoses with suspected bacterial superinfections. PMID:23574020

  16. Prussian Blue Nanoparticles as Multienzyme Mimetics and Reactive Oxygen Species Scavengers.

    PubMed

    Zhang, Wei; Hu, Sunling; Yin, Jun-Jie; He, Weiwei; Lu, Wei; Ma, Ming; Gu, Ning; Zhang, Yu

    2016-05-11

    The generation of reactive oxygen species (ROS) is an important mechanism of nanomaterial toxicity. We found that Prussian blue nanoparticles (PBNPs) can effectively scavenge ROS via multienzyme-like activity including peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) activity. Instead of producing hydroxyl radicals (•OH) through the Fenton reaction, PBNPs were shown to be POD mimetics that can inhibit •OH generation. We theorized for the first time that the multienzyme-like activities of PBNPs were likely caused by the abundant redox potentials of their different forms, making them efficient electron transporters. To study the ROS scavenging ability of PBNPs, a series of in vitro ROS-generating models was established using chemicals, UV irradiation, oxidized low-density lipoprotein, high glucose contents, and oxygen glucose deprivation and reperfusion. To demonstrate the ROS scavenging ability of PBNPs, an in vivo inflammation model was established using lipoproteins in Institute for Cancer Research (ICR) mice. The results indicated that PBNPs hold great potential for inhibiting or relieving injury induced by ROS in these pathological processes. PMID:26918394

  17. Reactive oxygen species differentially affect T cell receptor-signaling pathways.

    PubMed

    Cemerski, Saso; Cantagrel, Alain; Van Meerwijk, Joost P M; Romagnoli, Paola

    2002-05-31

    Oxidative stress plays an important role in the induction of T lymphocyte hyporesponsiveness observed in several human pathologies including cancer, rheumatoid arthritis, leprosy, and AIDS. To investigate the molecular basis of oxidative stress-induced T cell hyporesponsiveness, we have developed an in vitro system in which T lymphocytes are rendered hyporesponsive by co-culture with oxygen radical-producing activated neutrophils. We have observed a direct correlation between the level of T cell hyporesponsiveness induced and the concentration of reactive oxygen species produced. Moreover, induction of T cell hyporesponsiveness is blocked by addition of N-acetyl cysteine, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, and catalase, confirming the critical role of oxidative stress in this system. The pattern of tyrosine-phosphorylated proteins was profoundly altered in hyporesponsive as compared with normal T cells. In hyporesponsive T cells, T cell receptor (TCR) ligation no longer induced phospholipase C-gamma1 activation and caused reduced Ca(2+) flux. In contrast, despite increased levels of ERK1/2 phosphorylation, TCR-dependent activation of mitogen-activated protein kinase ERK1/2 was unaltered in hyporesponsive T lymphocytes. A late TCR-signaling event such as caspase 3 activation was as well unaffected in hyporesponsive T lymphocytes. Our data indicate that TCR-signaling pathways are differentially affected by physiological levels of oxidative stress and would suggest that although "hyporesponsive" T cells have lost certain effector functions, they may have maintained or gained others. PMID:11916964

  18. Detecting, Visualizing and Quantitating the Generation of Reactive Oxygen Species in an Amoeba Model System

    PubMed Central

    Zhang, Xuezhi; Soldati, Thierry

    2013-01-01

    Reactive oxygen species (ROS) comprise a range of reactive and short-lived, oxygen-containing molecules, which are dynamically interconverted or eliminated either catalytically or spontaneously. Due to the short life spans of most ROS and the diversity of their sources and subcellular localizations, a complete picture can be obtained only by careful measurements using a combination of protocols. Here, we present a set of three different protocols using OxyBurst Green (OBG)-coated beads, or dihydroethidium (DHE) and Amplex UltraRed (AUR), to monitor qualitatively and quantitatively various ROS in professional phagocytes such as Dictyostelium. We optimised the beads coating procedures and used OBG-coated beads and live microscopy to dynamically visualize intraphagosomal ROS generation at the single cell level. We identified lipopolysaccharide (LPS) from E. coli as a potent stimulator for ROS generation in Dictyostelium. In addition, we developed real time, medium-throughput assays using DHE and AUR to quantitatively measure intracellular superoxide and extracellular H2O2 production, respectively. PMID:24300479

  19. Peroxiredoxin-5 targeted to the mitochondrial intermembrane space attenuates hypoxia-induced reactive oxygen species signalling.

    PubMed

    Sabharwal, Simran S; Waypa, Gregory B; Marks, Jeremy D; Schumacker, Paul T

    2013-12-15

    The ability to adapt to acute and chronic hypoxia is critical for cellular survival. Two established functional responses to hypoxia include the regulation of gene transcription by HIF (hypoxia-inducible factor), and the constriction of pulmonary arteries in response to alveolar hypoxia. The mechanism of O2 sensing in these responses is not established, but some studies implicate hypoxia-induced mitochondrial ROS (reactive oxygen species) signalling. To further test this hypothesis, we expressed PRDX5 (peroxiredoxin-5), a H2O2 scavenger, in the IMS (mitochondrial intermembrane space), reasoning that the scavenging of ROS in that compartment should abrogate cellular responses triggered by the release of mitochondrial oxidants to the cytosol. Using adenoviral expression of IMS-PRDX5 (IMS-targeted PRDX5) in PASMCs (pulmonary artery smooth muscle cells) we show that IMS-PRDX5 inhibits hypoxia-induced oxidant signalling in the IMS and cytosol. It also inhibits HIF-1α stabilization and HIF activity in a dose-dependent manner without disrupting cellular oxygen consumption. IMS-PRDX5 expression also attenuates the increase in cytosolic [Ca(2+)] in PASMCs during hypoxia. These results extend previous work by demonstrating the importance of IMS-derived ROS signalling in both the HIF and lung vascular responses to hypoxia. PMID:24044889

  20. Development of micellar reactive oxygen species assay for photosafety evaluation of poorly water-soluble chemicals.

    PubMed

    Seto, Yoshiki; Kato, Masashi; Yamada, Shizuo; Onoue, Satomi

    2013-09-01

    A reactive oxygen species (ROS) assay was previously developed for photosafety assessment; however, the phototoxic potential of some chemicals cannot be evaluated because of their limited aqueous solubility. The present study was undertaken to develop a new micellar ROS (mROS) assay system for poorly water-soluble chemicals using a micellar solution of 0.5% (v/v) Tween 20 for solubility enhancement. In repeated mROS assay, intra- and inter-day precisions (coefficient of variation) were found to be below 11%, and the Z'-factors for singlet oxygen and superoxide suggested a large separation band between positive and negative standards. The ROS and mROS assays were applied to 65 phototoxins and 18 non-phototoxic compounds for comparative purposes. Of all 83 chemicals, 25 were unevaluable in the ROS assay due to poor solubility, but only 2 were in the mROS assay. Upon mROS assay on these model chemicals, the individual specificity was 76.5%, and the positive and negative predictivities were found to be 93.9% and 86.7%, respectively. The mROS assay provided 2 false negative predictions, although negative predictivity for the ROS assay was found to be 100%. Considering the pros and cons of these assays, strategic combined use of the ROS and mROS assays might be efficacious for reliable photosafety assessment with high applicability and predictivity. PMID:23727251

  1. Action of reactive oxygen species in the antifungal mechanism of gemini-pyridinium salts against yeast.

    PubMed

    Shirai, Akihiro; Ueta, Shouko; Maseda, Hideaki; Kourai, Hiroki; Omasa, Takeshi

    2012-06-01

    We previously found that the gemini quaternary salt (gemini-QUAT) containing two pyridinium residues per molecule, 3,3'- (2,7-dioxaoctane) bis (1-decylpyridinium bromide) (3DOBP-4,10) , exerted fungicidal activity against Saccharomyces cerevisiae and caused respiration inhibition and the cytoplasmic leakage of ATP, magnesium, and potassium ions. Here, we investigated how the gemini-QUAT, 3DOBP-4,10, exerts more powerful antimicrobial activity than the mono-QUAT N-cetylpyridinium chloride (CPC) and examined the association between reactive oxygen species (ROS) and the antimicrobial mechanism. Antifungal assays showed that the activity of 3DOBP-4,10 against two yeasts, S. cerevisiae and Candida albicans, was significantly elevated under aerobic conditions, and largely reduced under anaerobic conditions (nitrogen atmosphere) . Adding radical scavengers such as superoxide dismutase, catalase and potassium iodide (KI) also decreased the fungicidal activity of 3DOBP-4,10 but negligibly affected that of CPC. We measured survival under static conditions and found that the rapid fungicidal profile of 3DOBP-4,10 was lost, whereas that of CPC was slightly affected in the presence of KI. Our results suggest that 3DOBP-4,10 exerts powerful antimicrobial activity by penetrating the cell wall and membrane, which then allows oxygen to enter the cells, where it participates in the generation of intracellular ROS. The activity could thus be attributable to a synergic antimicrobial combination of the disruption of organelle membranes by the QUAT and oxidative stress imposed by ROS. PMID:22790843

  2. Scavenging of reactive oxygen species as the mechanism of drug action.

    PubMed

    Robak, J; Marcinkiewicz, E

    1995-01-01

    Reactive oxygen species (ROS) are generated when oxygen is supplied in excess and/or its reduction is insufficient. The best explored ROS are superoxide anions, hydroxyl radicals and hydrogen peroxide. The first two are free radicals. ROS are harmful for the living cells and are implicated in a variety of pathological processes and diseases. Drugs used in the treatment of these states are either stimulators of endogenous defense mechanisms against ROS or inhibitors of ROS formation. Six groups of anti-ROS substances have been described in this paper. 1) Antioxidant substances used in substitutive therapy such as enzymes (e.g. superoxide dismutase), substances containing thiol groups and vitamins (A, E, P, C). 2) Chelating agents (e.g. desferoxamine), which lower the level of prooxidative transition metal ions. 3) Inhibitors of superoxide ions generation by stimulated cells or xanthine oxidase. Such mechanism of action was described for xanthine oxidase inhibitor-allopurinol. 4) Superoxide scavengers. Many known drugs were investigated for this activity, but the best documentation was presented for flavonoids. 5) Substances which eliminate hydrogen peroxide, mainly glutathione and its precursors. 6) Scavengers of hydroxyl radicals. Studies of the above activity were conducted mainly using an unspecific method--estimation of malondialdehyde generated during the action of hydroxyl radicals on lipids or on desoxyribose. Inhibition of malondialdehyde formation was described for many drugs of plant and synthetic origin. PMID:8688896

  3. Hypoxia-Dependent Reactive Oxygen Species Signaling in the Pulmonary Circulation: Focus on Ion Channels

    PubMed Central

    Veit, Florian; Pak, Oleg; Brandes, Ralf P.

    2015-01-01

    Abstract Significance: An acute lack of oxygen in the lung causes hypoxic pulmonary vasoconstriction, which optimizes gas exchange. In contrast, chronic hypoxia triggers a pathological vascular remodeling causing pulmonary hypertension, and ischemia can cause vascular damage culminating in lung edema. Recent Advances: Regulation of ion channel expression and gating by cellular redox state is a widely accepted mechanism; however, it remains a matter of debate whether an increase or a decrease in reactive oxygen species (ROS) occurs under hypoxic conditions. Ion channel redox regulation has been described in detail for some ion channels, such as Kv channels or TRPC6. However, in general, information on ion channel redox regulation remains scant. Critical Issues and Future Directions: In addition to the debate of increased versus decreased ROS production during hypoxia, we aim here at describing and deciphering why different oxidants, under different conditions, can cause both activation and inhibition of channel activity. While the upstream pathways affecting channel gating are often well described, we need a better understanding of redox protein modifications to be able to determine the complexity of ion channel redox regulation. Against this background, we summarize the current knowledge on hypoxia-induced ROS-mediated ion channel signaling in the pulmonary circulation. Antioxid. Redox Signal. 22, 537–552 PMID:25545236

  4. Nitric Oxide and Reactive Oxygen Species Coordinately Regulate the Germination of Puccinia striiformis f. sp. tritici Urediniospores

    PubMed Central

    Yin, Shuining; Gao, Zhijuan; Wang, Chenfang; Huang, Lili; Kang, Zhensheng; Zhang, Hongchang

    2016-01-01

    Nitric oxide (NO) and reactive oxygen species (ROS) function as signaling molecules in a number of critical signal transduction pathways in plants, including plant biotic interactions. In addition to the role of plant-derived NO and ROS in plant resistance, which has been well documented, pathogen-produced NO and ROS have recently emerged as important players in fungal development and pathogenesis. However, the effects of pathogenic fungi-derived NO and ROS on signaling pathways during fungal pre-infection development remain unknown. Here, using a combination of pharmacological approaches and confocal microscopy, we investigated the roles of NO and ROS during the germination of Puccinia striiformis Westend f. sp. tritici (Pst) the wheat stripe rust pathogen. Both NO and ROS have a crucial role in uredinial germination. The scavengers of NO and ROS delayed spore germination and decreased the lengths of germ tubes. A similar phenotype was produced after treatment with the promoter. However, the spores germinated and grew normally when the levels of NO and ROS were simultaneously elevated by the application of a promoter of NO and a donor of ROS. Confocal laser microscopy indicated that both NO and ROS preferentially localized at the germ pores and apexes of growing germ tubes when the ROS/NO ratio in the spores was maintained in a specific range. We concluded that both NO and ROS are critical signaling molecules in the pre-infection development of Pst and that the polar growth of the germ tube is coordinately regulated by NO and ROS. PMID:26941716

  5. Nitric Oxide and Reactive Oxygen Species Coordinately Regulate the Germination of Puccinia striiformis f. sp. tritici Urediniospores.

    PubMed

    Yin, Shuining; Gao, Zhijuan; Wang, Chenfang; Huang, Lili; Kang, Zhensheng; Zhang, Hongchang

    2016-01-01

    Nitric oxide (NO) and reactive oxygen species (ROS) function as signaling molecules in a number of critical signal transduction pathways in plants, including plant biotic interactions. In addition to the role of plant-derived NO and ROS in plant resistance, which has been well documented, pathogen-produced NO and ROS have recently emerged as important players in fungal development and pathogenesis. However, the effects of pathogenic fungi-derived NO and ROS on signaling pathways during fungal pre-infection development remain unknown. Here, using a combination of pharmacological approaches and confocal microscopy, we investigated the roles of NO and ROS during the germination of Puccinia striiformis Westend f. sp. tritici (Pst) the wheat stripe rust pathogen. Both NO and ROS have a crucial role in uredinial germination. The scavengers of NO and ROS delayed spore germination and decreased the lengths of germ tubes. A similar phenotype was produced after treatment with the promoter. However, the spores germinated and grew normally when the levels of NO and ROS were simultaneously elevated by the application of a promoter of NO and a donor of ROS. Confocal laser microscopy indicated that both NO and ROS preferentially localized at the germ pores and apexes of growing germ tubes when the ROS/NO ratio in the spores was maintained in a specific range. We concluded that both NO and ROS are critical signaling molecules in the pre-infection development of Pst and that the polar growth of the germ tube is coordinately regulated by NO and ROS. PMID:26941716

  6. Interconnection of reactive oxygen species chemistry across the interfaces of atmospheric, environmental, and biological processes.

    PubMed

    Anglada, Josep M; Martins-Costa, Marilia; Francisco, Joseph S; Ruiz-López, Manuel F

    2015-03-17

    Oxidation reactions are ubiquitous and play key roles in the chemistry of the atmosphere, in water treatment processes, and in aerobic organisms. Ozone (O3), hydrogen peroxide (H2O2), hydrogen polyoxides (H2Ox, x > 2), associated hydroxyl and hydroperoxyl radicals (HOx = OH and HO2), and superoxide and ozonide anions (O2(-) and O3(-), respectively) are the primary oxidants in these systems. They are commonly classified as reactive oxygen species (ROS). Atmospheric chemistry is driven by a complex system of chain reactions of species, including nitrogen oxides, hydroxyl and hydroperoxide radicals, alkoxy and peroxy radicals, and ozone. HOx radicals contribute to keeping air clean, but in polluted areas, the ozone concentration increases and creates a negative impact on plants and animals. Indeed, ozone concentration is used to assess air quality worldwide. Clouds have a direct effect on the chemical composition of the atmosphere. On one hand, cloud droplets absorb many trace atmospheric gases, which can be scavenged by rain and fog. On the other hand, ionic species can form in this medium, which makes the chemistry of the atmosphere richer and more complex. Furthermore, recent studies have suggested that air-cloud interfaces might have a significant impact on the overall chemistry of the troposphere. Despite the large differences in molecular composition, concentration, and thermodynamic conditions among atmospheric, environmental, and biological systems, the underlying chemistry involving ROS has many similarities. In this Account, we examine ROS and discuss the chemical characteristics common to all of these systems. In water treatment, ROS are key components of an important subset of advanced oxidation processes. Ozonation, peroxone chemistry, and Fenton reactions play important roles in generating sufficient amounts of hydroxyl radicals to purify wastewater. Biochemical processes within living organisms also involve ROS. These species can come from pollutants in

  7. Mitochondrial reactive oxygen species in mice lacking superoxide dismutase 2: attenuation via antioxidant treatment.

    PubMed

    Morten, Karl J; Ackrell, Brian A C; Melov, Simon

    2006-02-10

    Mice that lack the mitochondrial form of superoxide dismutase (SOD2) incur severe pathologies and mitochondrial deficiencies, including major depletion of complex II, as a consequence of buildup of endogenous reactive oxygen species (Melov, S., Coskun, P., Patel, M., Tuinstra, R., Cottrell, B., Jun, A. S., Zastawny, T. H., Dizdaroglu, M., Goodman, S. I., Huang, T. T., Miziorko, H., Epstein, C. J., and Wallace, D. C. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 846-851 and Li, Y., Huang, T. T., Carlson, E. J., Melov, S., Ursell, P. C., Olson, J. L., Noble, L. J., Yoshimura, M. P., Berger, C., Chan, P. H., Wallace, D. C., and Epstein, C. J. (1995) Nat. Genet. 11, 376-381). These problems can be greatly attenuated or rescued by synthetic antioxidant treatment, such as with the catalytic antioxidant EUK189 (Hinerfeld, D., Traini, M. D., Weinberger, R. P., Cochran, B., Doctrow, S. R., Harry, J., and Melov, S. (2004) J. Neurochem. 88, 657-667). We have used heart mitochondria from sod2 null mice to better understand mitochondrial reactive oxygen species production both in the absence of SOD2 and following in vivo antioxidant treatment. Isolated heart mitochondria from 5-day-old sod2 null animals respiring on the complex II substrate succinate exhibited statistically significant higher levels of mitochondrial O2* (157%, p < 0.01) but significantly less H2O2 (33%, p < 0.001) than wild type littermates. Treatment of sod2 nullizygous mice with EUK189 proportionately increased the levels of complex II and H2O2. Increased production of O2* resulting from complex II normalization had no effect on steady state levels due to the rapid conversion to H2O2, a process presumably aided by the presence of the EUK189, an SOD mimetic. PMID:16326710

  8. Protective effects of myricitrin against osteoporosis via reducing reactive oxygen species and bone-resorbing cytokines

    SciTech Connect

    Huang, Qiang; Gao, Bo; Wang, Long; Hu, Ya-Qian; Lu, Wei-Guang; Yang, Liu; Luo, Zhuo-Jing; Liu, Jian

    2014-11-01

    Oxidative stress is a crucial pathogenic factor in the development of osteoporosis. Myricitrin, isolated from Myrica cerifera, is a potent antioxidant. We hypothesized that myricitrin possessed protective effects against osteoporosis by partially reducing reactive oxygen species (ROS) and bone-resorbing cytokines in osteoblastic MC3T3-E1 cells and human bone marrow stromal cells (hBMSCs). We investigated myricitrin on osteogenic differentiation under oxidative stress. Hydrogen peroxide (H{sub 2}O{sub 2}) was used to establish an oxidative cell injury model. Our results revealed that myricitrin significantly improved some osteogenic markers in these cells. Myricitrin decreased lipid production and reduced peroxisome proliferator-activated receptor gamma-2 (PPARγ2) expression in hBMSCs. Moreover, myricitrin reduced the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 and partially suppressed ROS production. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our results demonstrated that myricitrin supplementation reduced serum malondialdehyde (MDA) activity and increased reduced glutathione (GSH) activity. Importantly, it ameliorated the micro-architecture of trabecular bones in the 4th lumbar vertebrae (L4) and distal femur. Taken together, these results indicated that the protective effects of myricitrin against osteoporosis are linked to a reduction in ROS and bone-resorbing cytokines, suggesting that myricitrin may be useful in bone metabolism diseases, particularly osteoporosis. - Highlights: • Myricitrin protects MC3T3-E1 cells and hBMSCs from oxidative stress. • It is accompanied by a decrease in oxidative stress and bone-resorbing cytokines. • Myricitrin decreases serum reactive oxygen species to some degree. • Myricitrin partly reverses ovariectomy effects in vivo. • Myricitrin may represent a beneficial anti-osteoporosis treatment method.

  9. Exendin-4 Protects Mitochondria from Reactive Oxygen Species Induced Apoptosis in Pancreatic Beta Cells

    PubMed Central

    Li, Zhen; Zhou, Zhiguang; Huang, Gan; Hu, Fang; Xiang, Yufei; He, Lining

    2013-01-01

    Objective Mitochondrial oxidative stress is the basis for pancreatic β-cell apoptosis and a common pathway for numerous types of damage, including glucotoxicity and lipotoxicity. We cultivated mice pancreatic β-cell tumor Min6 cell lines in vitro and observed pancreatic β-cell apoptosis and changes in mitochondrial function before and after the addition of Exendin-4. Based on these observations, we discuss the protective role of Exendin-4 against mitochondrial oxidative damage and its relationship with Ca2+-independent phospholipase A2. Methods We established a pancreatic β-cell oxidative stress damage model using Min6 cell lines cultured in vitro with tert-buty1 hydroperoxide and hydrogen peroxide. We then added Exendin-4 to observe changes in the rate of cell apoptosis (Annexin-V-FITC-PI staining flow cytometry and DNA ladder). We detected the activity of the caspase 3 and 8 apoptotic factors, measured the mitochondrial membrane potential losses and reactive oxygen species production levels, and detected the expression of cytochrome c and Smac/DLAMO in the cytosol and mitochondria, mitochondrial Ca2-independent phospholipase A2 and Ca2+-independent phospholipase A2 mRNA. Results The time-concentration curve showed that different percentages of apoptosis occurred at different time-concentrations in tert-buty1 hydroperoxide- and hydrogen peroxide-induced Min6 cells. Incubation with 100 µmol/l of Exendin-4 for 48 hours reduced the Min6 cell apoptosis rate (p<0.05). The mitochondrial membrane potential loss and total reactive oxygen species levels decreased (p<0.05), and the release of cytochrome c and Smac/DLAMO from the mitochondria was reduced. The study also showed that Ca2+-independent phospholipase A2 activity was positively related to Exendin-4 activity. Conclusion Exendin-4 reduces Min6 cell oxidative damage and the cell apoptosis rate, which may be related to Ca2-independent phospholipase A2. PMID:24204601

  10. Saliva promotes survival and even proliferation of Candida species in tap water.

    PubMed

    Barbot, Vanessa; Migeot, Virginie; Rodier, Marie-Hélène; Deborde, Marie; Imbert, Christine

    2011-11-01

    Candida yeasts colonize the human oral cavity as commensals or opportunistic pathogens. They may be isolated from water circulating in dental unit waterlines mixed with traces of saliva mainly because of the dysfunction of antiretraction valves. This study deals with the growth ability of Candida albicans, Candida glabrata and Candida parapsilosis in tap water with saliva (0-20% v/v). Results show that C. glabrata is the most susceptible species in tap water. Furthermore, saliva promotes both survival and proliferation of the three studied Candida species in tap water. PMID:22092759

  11. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence.

    PubMed

    Reiter, R J; Tan, D X; Manchester, L C; Qi, W

    2001-01-01

    Melatonin (N-acetyl-5-methoxytryptamine), an endogenously produced indole found throughout the animal kingdom, was recently reported, using a variety of techniques, to be a scavenger of a number of reactive oxygen and reactive nitrogen species both in vitro and in vivo. Initially, melatonin was discovered to directly scavenge the high toxic hydroxyl radical (*OH). The methods used to prove the interaction of melatonin with the *OH included the generation of the radical using Fenton reagents or the ultraviolet photolysis of hydrogen peroxide (H202) with the use of spin-trapping agents, followed by electron spin resonance (ESR) spectroscopy, pulse radiolysis followed by ESR, and several spectrofluorometric and chemical (salicylate trapping in vivo) methodologies. One product of the reaction of melatonin with the *OH was identified as cyclic 3-hydroxymelatonin (3-OHM) using high-performance liquid chromatography with electrochemical (HPLC-EC) detection, electron ionization mass spectrometry (EIMS), proton nuclear magnetic resonance (1H NMR) and COSY 1H NMR. Cyclic 3-OHM appears in the urine of humans and other mammals and in rat urine its concentration increases when melatonin is given exogenously or after an imposed oxidative stress (exposure to ionizing radiation). Urinary cyclic 3-OHM levels are believed to be a biomarker (footprint molecule) of in vivo *OH production and its scavenging by melatonin. Although the data are less complete, besides the *OH, melatonin in cell-free systems has been shown to directly scavenge H2O2, singlet oxygen (1O2) and nitric oxide (NO*), with little or no ability to scavenge the superoxide anion radical (O2*-) In vitro, melatonin also directly detoxifies the peroxynitrite anion (ONOO-) and/or peroxynitrous acid (ONOOH), or the activated form of this molecule, ONOOH*; the product of the latter interaction is proposed to be 6-OHM. How these in vitro findings relate to the in vivo antioxidant actions of melatonin remains to be

  12. Oxygen isotopes in tree rings show good coherence between species and sites in Bolivia

    NASA Astrophysics Data System (ADS)

    Baker, Jessica C. A.; Hunt, Sarah F. P.; Clerici, Santiago J.; Newton, Robert J.; Bottrell, Simon H.; Leng, Melanie J.; Heaton, Timothy H. E.; Helle, Gerhard; Argollo, Jaime; Gloor, Manuel; Brienen, Roel J. W.

    2015-10-01

    A tree ring oxygen isotope (δ18OTR) chronology developed from one species (Cedrela odorata) growing in a single site has been shown to be a sensitive proxy for rainfall over the Amazon Basin, thus allowing reconstructions of precipitation in a region where meteorological records are short and scarce. Although these results suggest that there should be large-scale (> 100 km) spatial coherence of δ18OTR records in the Amazon, this has not been tested. Furthermore, it is of interest to investigate whether other, possibly longer-lived, species similarly record interannual variation of Amazon precipitation, and can be used to develop climate sensitive isotope chronologies. In this study, we measured δ18O in tree rings from seven lowland and one highland tree species from Bolivia. We found that cross-dating with δ18OTR gave more accurate tree ring dates than using ring width. Our "isotope cross-dating approach" is confirmed with radiocarbon "bomb-peak" dates, and has the potential to greatly facilitate development of δ18OTR records in the tropics, identify dating errors, and check annual ring formation in tropical trees. Six of the seven lowland species correlated significantly with C. odorata, showing that variation in δ18OTR has a coherent imprint across very different species, most likely arising from a dominant influence of source water δ18O on δ18OTR. In addition we show that δ18OTR series cohere over large distances, within and between species. Comparison of two C. odorata δ18OTR chronologies from sites several hundreds of kilometres apart showed a very strong correlation (r = 0.80, p < 0.001, 1901-2001), and a significant (but weaker) relationship was found between lowland C. odorata trees and a Polylepis tarapacana tree growing in the distant Altiplano (r = 0.39, p < 0.01, 1931-2001). This large-scale coherence of δ18OTR records is probably triggered by a strong spatial coherence in precipitation δ18O due to large-scale controls. These results

  13. Cranberry proanthocyanidins modulate reactive oxygen species in Barrett’s and esophageal adenocarcinoma cell lines

    PubMed Central

    Weh, Katherine M.; Aiyer, Harini S.; Howell, Amy B.; Kresty, Laura A.

    2016-01-01

    BACKGROUND We recently reported that a cranberry proanthocyanidin rich extract (C-PAC) induces autophagic cell death in apoptotic resistant esophageal adenocarcinoma (EAC) cells and necrosis in autophagy resistant cells. EAC is characterized by high morbidity and mortality rates supporting development of improved preventive interventions. OBJECTIVE The current investigation sought to investigate the role of reactive oxygen species (ROS) in the context of C-PAC induced cell death. METHODS A panel of human esophageal cell lines of EAC or BE (Barrett’s esophagus) origin were treated with C-PAC and assessed for ROS modulation using CellROX® Green reagent and the Amplex Red assay to specifically measure hydrogen peroxide levels. RESULTS C-PAC significantly increased ROS levels in EAC cells, but significantly reduced ROS levels in CP-C BE cells. Increased hydrogen peroxide levels were also detected in C-PAC treated EAC cells and supernatant; however, hydrogen peroxide levels were significantly increased in medium alone, without cells, suggesting that C-PAC interferes or directly acts on the substrate. Hydrogen peroxide levels did not change in C-PAC treated CP-C BE cells. CONCLUSION These experiments provide additional mechanistic insight regarding C-PAC induced cancer cell death through modulation of ROS. Additional research is warranted to identify specific ROS species associated with C-PAC exposure.

  14. Spreading the news: subcellular and organellar reactive oxygen species production and signalling.

    PubMed

    Mignolet-Spruyt, Lorin; Xu, Enjun; Idänheimo, Niina; Hoeberichts, Frank A; Mühlenbock, Per; Brosché, Mikael; Van Breusegem, Frank; Kangasjärvi, Jaakko

    2016-06-01

    As plants are sessile organisms that have to attune their physiology and morphology continuously to varying environmental challenges in order to survive and reproduce, they have evolved complex and integrated environment-cell, cell-cell, and cell-organelle signalling circuits that regulate and trigger the required adjustments (such as alteration of gene expression). Although reactive oxygen species (ROS) are essential components of this network, their pathways are not yet completely unravelled. In addition to the intrinsic chemical properties that define the array of interaction partners, mobility, and stability, ROS signalling specificity is obtained via the spatiotemporal control of production and scavenging at different organellar and subcellular locations (e.g. chloroplasts, mitochondria, peroxisomes, and apoplast). Furthermore, these cellular compartments may crosstalk to relay and further fine-tune the ROS message. Hence, plant cells might locally and systemically react upon environmental or developmental challenges by generating spatiotemporally controlled dosages of certain ROS types, each with specific chemical properties and interaction targets, that are influenced by interorganellar communication and by the subcellular location and distribution of the involved organelles, to trigger the suitable acclimation responses in association with other well-established cellular signalling components (e.g. reactive nitrogen species, phytohormones, and calcium ions). Further characterization of this comprehensive ROS signalling matrix may result in the identification of new targets and key regulators of ROS signalling, which might be excellent candidates for engineering or breeding stress-tolerant plants. PMID:26976816

  15. Characterization of springtime airborne particulate matter-bound reactive oxygen species in Beijing.

    PubMed

    Liu, Qingyang; Zhang, Yuanxun; Liu, Yanju; Zhang, Meigen

    2014-01-01

    Epidemiologic studies have suggested that particulate matter (PM)-associated adverse health effects are related to particle composition. To study the toxicological characteristics of dust storm, airborne PM10 was collected at two sites in Beijing from March to May 2012. The production of reactive oxygen species (ROS), quantified by dithiothreitol (DTT), was used to measure the PM-induced oxidative potential. Two dust storm (DS) samples were monitored during the sampling period: one happened on March 28th (DS1) and the other one was on April 28th (DS2). The backward trajectory results showed that both events originated from Inner Mongolia and Mongolia, respectively. The increased trends of ROS activities during the dust storm episode in PM10 were observed for all the dust storms owing to a higher concentration of water-soluble components for all the PM10 samples compared to nondust storm ones. Interestingly, the correlations between DTT consumption with water-soluble species yield interesting results about the spatial variability of redox activity between sites. In particular, a tracer of soil suspension, namely Fe, contributed the most fraction to ROS variability in the urban background site. Water-soluble organic carbon (WSOC) made the highest contribution to ROS variability, suggesting that vehicle emission might be important driving factors of the PM-induced oxidative stress in the urban site. PMID:24728573

  16. Moscatilin inhibits lung cancer cell motility and invasion via suppression of endogenous reactive oxygen species.

    PubMed

    Kowitdamrong, Akkarawut; Chanvorachote, Pithi; Sritularak, Boonchoo; Pongrakhananon, Varisa

    2013-01-01

    Lung cancer is the leading cause of death among cancer patients worldwide, and most of them have died from metastasis. Migration and invasion are prerequisite processes associated with high metastasis potential in cancers. Moscatilin, a bibenzyl derivative isolated from the Thai orchid Dendrobium pulchellum, has been shown to have anticancer effect against numerous cancer cell lines. However, little is known regarding the effect of moscatilin on cancer cell migration and invasion. The present study demonstrates that nontoxic concentrations of moscatilin were able to inhibit human nonsmall cell lung cancer H23 cell migration and invasion. The inhibitory effect of moscatilin was associated with an attenuation of endogenous reactive oxygen species (ROS), in which hydroxyl radical (OH(∙)) was identified as a dominant species in the suppression of filopodia formation. Western blot analysis also revealed that moscatilin downregulated activated focal adhesion kinase (phosphorylated FAK, Tyr 397) and activated ATP-dependent tyrosine kinase (phosphorylated Akt, Ser 473), whereas their parental counterparts were not detectable changed. In conclusion, our results indicate the novel molecular basis of moscalitin-inhibiting lung cancer cell motility and invasion and demonstrate a promising antimetastatic potential of such an agent for lung cancer therapy. PMID:23738332

  17. Moscatilin Inhibits Lung Cancer Cell Motility and Invasion via Suppression of Endogenous Reactive Oxygen Species

    PubMed Central

    Kowitdamrong, Akkarawut; Chanvorachote, Pithi; Sritularak, Boonchoo

    2013-01-01

    Lung cancer is the leading cause of death among cancer patients worldwide, and most of them have died from metastasis. Migration and invasion are prerequisite processes associated with high metastasis potential in cancers. Moscatilin, a bibenzyl derivative isolated from the Thai orchid Dendrobium pulchellum, has been shown to have anticancer effect against numerous cancer cell lines. However, little is known regarding the effect of moscatilin on cancer cell migration and invasion. The present study demonstrates that nontoxic concentrations of moscatilin were able to inhibit human nonsmall cell lung cancer H23 cell migration and invasion. The inhibitory effect of moscatilin was associated with an attenuation of endogenous reactive oxygen species (ROS), in which hydroxyl radical (OH∙) was identified as a dominant species in the suppression of filopodia formation. Western blot analysis also revealed that moscatilin downregulated activated focal adhesion kinase (phosphorylated FAK, Tyr 397) and activated ATP-dependent tyrosine kinase (phosphorylated Akt, Ser 473), whereas their parental counterparts were not detectable changed. In conclusion, our results indicate the novel molecular basis of moscalitin-inhibiting lung cancer cell motility and invasion and demonstrate a promising antimetastatic potential of such an agent for lung cancer therapy. PMID:23738332

  18. The chemical kinetics and thermodynamics of sodium species in oxygen-rich hydrogen flames

    NASA Technical Reports Server (NTRS)

    Hynes, A. J.; Steinberg, M.; Schofield, K.

    1984-01-01

    Results are presented which, it is claimed, lead to a correction of previous misconceptions over the relative importance and kinetics of NaO2. It is shown that its rapid conversion to NaO and NaOH is such that it can severely perturb the NaOH/Na ratio and produce significant concentration overshoots over that predicted from the balance of the reaction of Na with H2O. This becomes increasingly the case in flames of large O2 concentrations and temperatures below 2500 K; and the corresponding large rate constants for the termolecular formation of the other alkali peroxides imply that similar considerations will be necessary for them. Depending on the rate constants for the exothermic conversions of MO2 to MO or MOH, the steady-state concentrations of MO2 could be more or less significant than for sodium. Owing to numerous reactions that produce these conversions, the MOH species will probably be the dominant species in all cases in oxygen-rich hydrogen or hydrocarbon flames, with MO concentrations at not greater than 1 percent of the bound metal.

  19. Reactive oxygen species in signalling the transcriptional activation of WIPK expression in tobacco.

    PubMed

    Xu, Juan; Yang, Kwang-Yeol; Yoo, Seung Jin; Liu, Yidong; Ren, Dongtao; Zhang, Shuqun

    2014-07-01

    Plant mitogen-activated protein kinases represented by tobacco WIPK (wounding-induced protein kinase) and its orthologs in other species are unique in their regulation at transcriptional level in response to stress and pathogen infection. We previously demonstrated that transcriptional activation of WIPK is essential for induced WIPK activity, and activation of salicylic acid-induced protein kinase (SIPK) by the constitutively active NtMEK2(DD) is sufficient to induce WIPK gene expression. Here, we report that the effect of SIPK on WIPK gene expression is mediated by reactive oxygen species (ROS). Using a combination of pharmacological and gain-of-function transgenic approaches, we studied the relationship among SIPK activation, WIPK gene activation in response to fungal cryptogein, light-dependent ROS generation in chloroplasts, and ROS generated via NADPH oxidase. In the conditional gain-of-function GVG-NtMEK2(DD) transgenic tobacco, induction of WIPK expression is dependent on the ROS generation in chloroplasts. Consistently, methyl viologen, an inducer of ROS generation in chloroplasts, highly activated WIPK expression. In addition to chloroplast-originated ROS, H(2)O(2) generated from the cell-surface NADPH oxidase could also activate WIPK gene expression, and inhibition of cryptogein-induced ROS generation also abolished WIPK gene activation. Our data demonstrate that WIPK gene activation is mediated by ROS, which provides a mechanism by which ROS influence cellular signalling processes in plant stress/defence response. PMID:24392654

  20. Species-specificity of growth-promoting effects of prolactin during rat embryogenesis

    PubMed Central

    KARABULUT, AHMET KAGAN; PRATTEN, MARGARET K.

    1998-01-01

    In the early stages of embryonic development, many growth-promoting molecules must be provided by the maternal system. The molecules involved in growth processes may be either hormones or growth factors, or molecules that interact with such factors. The pregnancy related hormone, prolactin (PRL, MW 23 kDa) has been implicated in the control of embryonic growth. The growth-promoting potential of PRL and its species-specificity was investigated by culturing 9.5 d rat embryos in vitro for 48 h in depleted serum in the presence and absence of PRL from 3 different species. The growth-supporting capacity of the serum was reduced by removal of low molecular weight molecules by prolonged filtration of the serum using filters with a molecular weight exclusion of 30 kDa. This method provided a ‘semidefined’ medium (retenate) in which embryonic growth and development was significantly reduced, demonstrating that the low molecular weight fraction of serum may contain some growth-promoting factors. Addition of PRL (0.4–25.6 ng/ml) from different species (human, sheep and rat) to retenate significantly improved embryonic growth and development, suggesting that the developing embryo may utilise PRL. Amongst PRLs, rat PRL was found to be active at much lower concentrations than either of the other molecules, and human PRL had more effect in low concentrations than sheep PRL suggesting a species-specificity for this hormone. It may be that the PRL receptors of the rat embryos have greater affinity for the rat hormone as different responses for hormones from different species have been shown. These findings suggest that embryos may be able to utilise maternally derived PRL during organogenesis. PMID:9568556

  1. Titan's photochemical model: Further update, oxygen species, and comparison with Triton and Pluto

    NASA Astrophysics Data System (ADS)

    Krasnopolsky, V. A.

    2012-12-01

    The photochemical model for Titan's atmosphere and ionosphere is improved using the Troe approximation for termolecular reactions and inclusion of four radiative association reactions from those calculated by Vuitton et al. (2012). Proper fitting of eddy diffusion results in a reduction of the mean difference between 63 observed mixing ratios and their calculated values from a factor of 5 in our previous Titan's models to a factor of 3 in the current model. Oxygen chemistry on Titan is initiated by influxes of H2O from meteorites and O+ from magnetospheric interactions with the Saturn rings and Enceladus. Two versions of the model were calculated, with and without the O+ flux. Balances of CO, CO2, H2O, and H2CO are discussed in detail for both versions. The calculated model with the O+ flux agrees with the observations of CO, CO2, and H2O, including recent H2O CIRS limb observations and measurements by the Herschel Space Observatory. Major observational data and photochemical models for Triton and Pluto are briefly discussed. While the basic atmospheric species N2, CH4, and CO are similar on Triton and Pluto, properties of their atmospheres are very different with dominating atomic species and ions in Triton's upper atmosphere and ionosphere opposed to the molecular composition on Pluto. Calculations favor a transition between two types of photochemistry at the CH4 mixing ratio of ~5×10-4. Therefore the current Triton's photochemistry is still similar to that at the Voyager flyby despite the observed increase in N2 and CH4. The meteorite H2O results in precipitation of CO on Triton and CO2 on Pluto near perihelion. Main oxygen species on Titan: observations and the model. Solid lines show the model with both meteorite influx of H2O and magnetospheric flux of O+. Thin lines show the model without flux of O+. Observations: (1) CIRS (de Kok et al. 2007), (2) CIRS at 5°N (Vinatier et al. 2010), (3) ISO (Coustenis et al. 1998), (4) INMS (Cui et al., 2009), (5) CIRS

  2. Which values regarding nature and other species are we promoting in the Australian science curriculum?

    NASA Astrophysics Data System (ADS)

    Castano Rodriguez, Carolina

    2015-08-01

    Through a critical textual analysis of the content and structure of the new Australian science curriculum, in this paper I identify the values it encourages and those that are absent. I investigate whether the Australian science curriculum is likely to promote the attitudes needed to educate generations of children who act more responsibly with other species and the environment. Over the past decades, there has been an increasing awareness of the human impact on the environment and other species. Consistently, there is a growing awareness of the role of education in encouraging children to act in a more ethical, responsible, and caring way. However, it is still unclear as to whether national curricula can (or will aspire to) accomplish this. In Australia, a national science curriculum has been implemented. In this paper I argue that the Australian science curriculum is likely to miss the opportunity to cultivate values of care for nature and other species. Instead, it is likely to reinforce anthropocentric attitudes toward our natural environment. The importance of explicitly promoting values that encourage care and respect for all species and challenges anthropocentric views of other animals and nature are discussed.

  3. Nested species interactions promote feasibility over stability during the assembly of a pollinator community.

    PubMed

    Saavedra, Serguei; Rohr, Rudolf P; Olesen, Jens M; Bascompte, Jordi

    2016-02-01

    The foundational concepts behind the persistence of ecological communities have been based on two ecological properties: dynamical stability and feasibility. The former is typically regarded as the capacity of a community to return to an original equilibrium state after a perturbation in species abundances and is usually linked to the strength of interspecific interactions. The latter is the capacity to sustain positive abundances on all its constituent species and is linked to both interspecific interactions and species demographic characteristics. Over the last 40 years, theoretical research in ecology has emphasized the search for conditions leading to the dynamical stability of ecological communities, while the conditions leading to feasibility have been overlooked. However, thus far, we have no evidence of whether species interactions are more conditioned by the community's need to be stable or feasible. Here, we introduce novel quantitative methods and use empirical data to investigate the consequences of species interactions on the dynamical stability and feasibility of mutualistic communities. First, we demonstrate that the more nested the species interactions in a community are, the lower the mutualistic strength that the community can tolerate without losing dynamical stability. Second, we show that high feasibility in a community can be reached either with high mutualistic strength or with highly nested species interactions. Third, we find that during the assembly process of a seasonal pollinator community located at The Zackenberg Research Station (northeastern Greenland), a high feasibility is reached through the nested species interactions established between newcomer and resident species. Our findings imply that nested mutualistic communities promote feasibility over stability, which may suggest that the former can be key for community persistence. PMID:26941941

  4. Determination of reactive oxygen species from ZnO micro-nano structures with shape-dependent photocatalytic activity

    SciTech Connect

    He, Weiwei; Zhao, Hongxiao; Jia, Huimin; Yin, Jun-Jie; Zheng, Zhi

    2014-05-01

    Graphical abstract: ZnO micro/nano structures with shape dependent photocatalytic activity were prepared by hydrothermal reaction. The generations of hydroxyl radical, superoxide and singlet oxygen from irradiated ZnO were identified precisely by electron spin resonance spectroscopy. The type of reactive oxygen species was determined by band gap structure of ZnO. - Highlights: • ZnO micro/nano structures with different morphologies were prepared by solvothermal reaction. • Multi-pod like ZnO structures exhibited superior photocatalytic activity. • The generations of hydroxyl radical, superoxide and singlet oxygen from irradiated ZnO were characterized precisely by electron spin resonance spectroscopy. • The type of reactive oxygen species was determined by band gap structure of ZnO. - Abstract: ZnO micro/nano structures with different morphologies have been prepared by the changing solvents used during their synthesis by solvothermal reaction. Three typical shapes of ZnO structures including hexagonal, bell bottom like and multi-pod formed and were characterized by scanning electron microscopy and X-ray diffraction. Multi pod like ZnO structures exhibited the highest photocatalytic activity toward degradation of methyl orange. Using electron spin resonance spectroscopy coupled with spin trapping techniques, we demonstrate an effective way to identify precisely the generation of hydroxyl radicals, superoxide and singlet oxygen from the irradiated ZnO multi pod structures. The type of reactive oxygen species formed was predictable from the band gap structure of ZnO. These results indicate that the shape of micro-nano structures significantly affects the photocatalytic activity of ZnO, and demonstrate the value of electron spin resonance spectroscopy for characterizing the type of reactive oxygen species formed during photoexcitation of semiconductors.

  5. Coronary endothelial dysfunction and mitochondrial reactive oxygen species in type 2 diabetic mice

    PubMed Central

    Cho, Young-Eun; Basu, Aninda; Dai, Anzhi; Heldak, Michael

    2013-01-01

    Endothelial cell (EC) dysfunction is implicated in cardiovascular diseases, including diabetes. The decrease in nitric oxide (NO) bioavailability is the hallmark of endothelial dysfunction, and it leads to attenuated vascular relaxation and atherosclerosis followed by a decrease in blood flow. In the heart, decreased coronary blood flow is responsible for insufficient oxygen supply to cardiomyocytes and, subsequently, increases the incidence of cardiac ischemia. In this study we investigate whether and how reactive oxygen species (ROS) in mitochondria contribute to coronary endothelial dysfunction in type 2 diabetic (T2D) mice. T2D was induced in mice by a high-fat diet combined with a single injection of low-dose streptozotocin. ACh-induced vascular relaxation was significantly attenuated in coronary arteries (CAs) from T2D mice compared with controls. The pharmacological approach reveals that NO-dependent, but not hyperpolarization- or prostacyclin-dependent, relaxation was decreased in CAs from T2D mice. Attenuated ACh-induced relaxation in CAs from T2D mice was restored toward control level by treatment with mitoTempol (a mitochondria-specific O2− scavenger). Coronary ECs isolated from T2D mice exhibited a significant increase in mitochondrial ROS concentration and decrease in SOD2 protein expression compared with coronary ECs isolated from control mice. Furthermore, protein ubiquitination of SOD2 was significantly increased in coronary ECs isolated from T2D mice. These results suggest that augmented SOD2 ubiquitination leads to the increase in mitochondrial ROS concentration in coronary ECs from T2D mice and attenuates coronary vascular relaxation in T2D mice. PMID:23986204

  6. Pyrite-driven reactive oxygen species formation in simulated lung fluid: implications for coal workers' pneumoconiosis.

    PubMed

    Harrington, Andrea D; Hylton, Shavonne; Schoonen, Martin A A

    2012-08-01

    The origin of coal worker's pneumoconiosis (CWP) has been long debated. A recent epidemiological study shows a correlation between what is essentially the concentration of pyrite within coal and the prevalence of CWP in miners. Hydrogen peroxide and hydroxyl radical, both reactive oxygen species (ROS), form as byproducts of pyrite oxidative dissolution in air-saturated water. Motivated by the possible importance of ROS in the pathogenesis of CWP, we conducted an experimental study to evaluate if ROS form as byproducts in the oxidative dissolution of pyrite in simulated lung fluid (SLF) under biologically applicable conditions and to determine the persistence of pyrite in SLF. While the rate of pyrite oxidative dissolution in SLF is suppressed by 51% when compared to that in air-saturated water, the initial amount of hydrogen peroxide formed as a byproduct in SLF is nearly doubled. Hydroxyl radical is also formed in the experiments with SLF, but at lower concentrations than in the experiments with water. The formation of these ROS indicates that the reaction mechanism for pyrite oxidative dissolution in SLF is no different from that in water. The elevated hydrogen peroxide concentration in SLF suggests that the decomposition, via the Fenton mechanism to hydroxyl radical or with Fe(III) to form water and molecular oxygen, is initially inhibited by the presence of SLF components. On the basis of the oxidative dissolution rate of pyrite measured in this paper, it is calculated that a respirable two micron pyrite particle will take over 3 years to dissolve completely. PMID:21989857

  7. Reactive oxygen species and PI3K/Akt signaling in cancer.

    PubMed

    Jin, Seo Yeon; Lee, Hye Sun; Kim, Eun Kyoung; Ha, Jung Min; Kim, Young Whan; Bae, SunSik

    2014-10-01

    Reactive oxygen species (ROS) are chemically reactive molecules containing oxygen and associates with multiple cellular functions such as cell proliferation, differentiation, and apoptosis. In the present study, we showed that Insulin-like growth factor-1(IGF-1) modulates SKOV-3 ovarian cancer cell by regulation of generation of ROS. Akt mediates cellular signaling pathways in association with mammalian target of rapamycin complex (mTOR) and Rac small G protein. Insulin-like growth factor-1 (IGF-1)-induced generation of ROS was completely abolished by phosphatidylinositol 3-kinase (PI3K) (LY294002, 10?µM) or Akt inhibitors (SH-5, 50?µM), whereas inhibition of extracellular-regulated kinase by an ERK inhibitor (PD98059, 10?µM) or inhibition of mammalian target of rapamycin complex 1 (mTORC1) by an mTORC1 inhibitor (Rapamycin, 100?nM) did not affect IGF-1-induced generation of ROS. Inactivation of mTORC2 by silencing Rapamycin-insensitive companion of mTOR (Rictor), abolished IGF-1-induced SKOV-3 cell migration as well as activation of Akt. However, inactivation of mTORC1 by silencing of Raptor had no effect. Silencing of Akt1 but not Akt2 attenuated IGF-1-induced generation of ROS. Expression of PIP3-dependent Rac exchanger1 (P-Rex1), a Rac guanosine exchange factor and a component of the mTOR complex. Silencing of P-Rex1 abolished IGF-1-induced generation of ROS. Finally, inhibition of NADPH oxidase system completely blunted IGF-1-induced generation of ROS, whereas inhibition of xanthine oxiase,cyclooxygenase, and mitochondrial respiratory chain complex was not effective. Given these results, we suggest that IGF-1 induces ROS generation through the PI3K/Akt/ mTOR2/NADPH oxidase signaling axis. PMID:26461347