Sample records for oxygen species overproduction

  1. PKCdelta Sensitizes Neuroblastoma Cells to L-Buthionine-Sulfoximine and Etoposide Inducing Reactive Oxygen Species Overproduction and DNA Damage

    Microsoft Academic Search

    Barbara Marengo; Chiara de Ciucis; Roberta Ricciarelli; Mario Passalacqua; Mariapaola Nitti; Jean-Marc Zingg; Umberto M. Marinari; Maria A. Pronzato; Cinzia Domenicotti; Joseph Najbauer

    2011-01-01

    Neuroblastoma is a type of pediatric cancer. The sensitivity of neuroblastoma (NB) cancer cells to chemotherapy and radiation is inhibited by the presence of antioxidants, such as glutathione (GSH), which is crucial in counteracting the endogenous production of reactive oxygen species (ROS). We have previously demonstrated that cells depleted of GSH undergo apoptosis via oxidative stress and Protein kinase C

  2. Enhanced Reactive Oxygen Species Scavenging by Overproduction of Superoxide Dismutase and Catalase Delays Postharvest Physiological Deterioration of Cassava Storage Roots1[C][W][OA

    PubMed Central

    Xu, Jia; Duan, Xiaoguang; Yang, Jun; Beeching, John R.; Zhang, Peng

    2013-01-01

    Postharvest physiological deterioration (PPD) of cassava (Manihot esculenta) storage roots is the result of a rapid oxidative burst, which leads to discoloration of the vascular tissues due to the oxidation of phenolic compounds. In this study, coexpression of the reactive oxygen species (ROS)-scavenging enzymes copper/zinc superoxide dismutase (MeCu/ZnSOD) and catalase (MeCAT1) in transgenic cassava was used to explore the intrinsic relationship between ROS scavenging and PPD occurrence. Transgenic cassava plants integrated with the expression cassette p54::MeCu/ZnSOD-35S::MeCAT1 were confirmed by Southern-blot analysis. The expression of MeCu/ZnSOD and MeCAT1 was verified by quantitative reverse transcription-polymerase chain reaction and enzymatic activity analysis both in the leaves and storage roots. Under exposure to the ROS-generating reagent methyl viologen or to hydrogen peroxide (H2O2), the transgenic plants showed higher enzymatic activities of SOD and CAT than the wild-type plants. Levels of malondialdehyde, chlorophyll degradation, lipid peroxidation, and H2O2 accumulation were dramatically reduced in the transgenic lines compared with the wild type. After harvest, the storage roots of transgenic cassava lines show a delay in their PPD response of at least 10 d, accompanied by less mitochondrial oxidation and H2O2 accumulation, compared with those of the wild type. We hypothesize that this is due to the combined ectopic expression of Cu/ZnSOD and CAT leading to an improved synergistic ROS-scavenging capacity of the roots. Our study not only sheds light on the mechanism of the PPD process but also develops an effective approach for delaying the occurrence of PPD in cassava. PMID:23344905

  3. Reactive oxygen species in cancer

    PubMed Central

    Liou, Geou-Yarh; Storz, Peter

    2013-01-01

    Elevated rates of reactive oxygen species (ROS) have been detected in almost all cancers, where they promote many aspects of tumor development and progression. However, tumor cells also express increased levels of antioxidant proteins to detoxify from ROS, suggesting that a delicate balance of intracellular ROS levels is required for cancer cell function. Further, the radical generated, the location of its generation, as well as the local concentration is important for the cellular functions of ROS in cancer. A challenge for novel therapeutic strategies will be the fine tuning of intracellular ROS signaling to effectively deprive cells from ROS-induced tumor promoting events, towards tipping the balance to ROS-induced apoptotic signaling. Alternatively, therapeutic antioxidants may prevent early events in tumor development, where ROS are important. However, to effectively target cancer cells specific ROS-sensing signaling pathways that mediate the diverse stress-regulated cellular functions need to be identified. This review discusses the generation of ROS within tumor cells, their detoxification, their cellular effects, as well as the major signaling cascades they utilize, but also provides an outlook on their modulation in therapeutics. PMID:20370557

  4. Stress Signaling III: Reactive Oxygen Species (ROS)

    Microsoft Academic Search

    Mikael Brosché; Kirk Overmyer; Michael Wrzaczek; Jaakko Kangasjärvi; Saijaliisa Kangasjärvi

    \\u000a Previously regarded merely as damaging agents, reactive oxygen species (ROS) are now understood as important signal molecules\\u000a vital to normal plant growth. This tutorial review covers the emerging view of ROS signaling networks from ROS production\\u000a to specific outputs. The chemical nature of individual reactive oxygen species, their site of the production, control of ROS\\u000a accumulation via scavenging and detoxification,

  5. Contemporary evidence on the physiological role of reactive oxygen species in human sperm function.

    PubMed

    Du Plessis, Stefan S; Agarwal, Ashok; Halabi, Jacques; Tvrda, Eva

    2015-04-01

    Reactive oxygen species (ROS) play an important role in male fertility. Overproduction of reactive oxygen species (ROS) has been associated with a variety of male fertility complications, including leukocytospermia, varicocele and idiopathic infertility. The subsequent oxidative insult to spermatozoa can manifest as insufficient energy metabolism, lipid peroxidation and DNA damage, leading to loss of motility and viability. However, various studies have demonstrated that physiological amounts of ROS play important roles in the processes of spermatozoa maturation, capacitation, hyperactivation and acrosome reaction. It is therefore crucial to define and understand the delicate oxidative balance in male reproductive cells and tissues for a better understanding of both positive as well as negative impact of ROS production on the fertilizing ability. This review will discuss the specific physiological roles, mechanisms of action and effects that ROS have on the acquisition of structural integrity and physiological activity of spermatozoa. PMID:25646893

  6. 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

  7. Superoxide Dismutases and Reactive Oxygen Species

    SciTech Connect

    Cabelli, D.E.

    2011-01-01

    The 'free radical theory' of aging was introduced over a half-century ago. In this theory, much of the deleterious effects of aging were attributed to the cumulative buildup of damage from reactive oxygen species. When discussing reactive oxygen species (ROS) in aerobic systems, both superoxide radicals (O{sub 2}{sup -}) and superoxide dismutases (SODs) are considered to play prominent roles. O{sub 2}{sup -} is formed by attachment of the electron to oxygen (O{sub 2}) that is present in tens to hundreds of micromolar concentration in vivo. SODs are enzymes that serve to eliminate O{sub 2}{sup -} by rapidly converting it to O{sub 2} and hydrogen peroxide (H{sub 2}O{sub 2}). Both the radical and the enzyme will be discussed with the focus on the systems that are present in humans.

  8. Cytochemistry and reactive oxygen species: a retrospective

    Microsoft Academic Search

    Morris J. Karnovsky

    1994-01-01

    This retrospective reviews the methodology we have developed over several decades for detecting reactive oxygen species (ROS), using the activated polymorphonuclear leukocyte (PMN) as the paradigm of a cell which vigorously generates ROS through activation of NADPH oxidase. In the seventies, the sites of ROS generation by PMN were not clear from biochemical data, and we sought to develop new

  9. 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

  10. Administration of an Antioxidant Prevents Lymphoma Development in Transmitochondrial Mice Overproducing Reactive Oxygen Species

    PubMed Central

    Yamanashi, Haruka; Hashizume, Osamu; Yonekawa, Hiromichi; Nakada, Kazuto; Hayashi, Jun-Ichi

    2014-01-01

    Because of the difficulty to exclude possible involvement of nuclear DNA mutations, it has been a controversial issue whether pathogenic mutations in mitochondrial DNA (mtDNA) and the resultant respiration defects are involved in tumor development. To address this issue, our previous study generated transmitochondrial mice (mito-mice-ND613997), which possess the nuclear and mtDNA backgrounds derived from C57BL/6J (B6) strain mice except that they carry B6 mtDNA with a G13997A mutation in the mt-Nd6 gene. Because aged mito-mice-ND613997 simultaneously showed overproduction of reactive oxygen species (ROS) in bone marrow cells and high frequency of lymphoma development, current study examined the effects of administrating a ROS scavenger on the frequency of lymphoma development. We used N-acetylcysteine (NAC) as a ROS scavenger, and showed that NAC administration prevented lymphoma development. Moreover, its administration induced longevity in mito-mice-ND613997. The gene expression profiles in bone marrow cells indicated the upregulation of the Fasl gene, which can be suppressed by NAC administration. Given that natural-killer (NK) cells mediate the apoptosis of various tumor cells via enhanced expression of genes encoding apoptotic ligands including Fasl gene, its overexpression would reflect the frequent lymphoma development in bone marrow cells. These observations suggest that continuous administration of an antioxidant would be an effective therapeutics to prevent lymphoma development enhanced by ROS overproduction. PMID:25048265

  11. Optical mapping of myocardial reactive oxygen species production throughout the reperfusion of global ischemia

    NASA Astrophysics Data System (ADS)

    Lu, Long-sheng; Liu, Yen-Bin; Sun, Chia-Wei; Lin, Lung-Chun; Su, Ming-jia; Wu, Chau-Chung

    2006-03-01

    Reactive oxygen species (ROS) are short-lived, highly reactive chemical entities that play significant roles in all levels of biology. However, their measurement requires destructive preparation, thereby limiting the continuous measurement of ROS in a living tissue. We develop an optical mapping system to visualize ROS production in an isolated and perfused rat heart. By staining the heart with dihydroethidium (DHE), a 532-nm laser beam is directed to the epicardial surface, where we collect the red fluorescence (>600 nm) for semiquantitative analysis. With this system, ROS production as well as ventricular pressure and ECG in isolated perfused rat hearts are monitored throughout the reperfusion of global ischemia. Ischemia would decrease myocardial ROS production, while reperfusion would immediately result in sustained ROS overproduction. Optical mapping would provide information regarding the spatial distribution and temporal evolution of myocardial ROS production, which would enhance knowledge of the role of free radicals in cardiovascular biology.

  12. Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis

    PubMed Central

    Khan, Saeed R.

    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 at the basal side. In addition endothelial cells lining the blood vessels may also become osteogenic producing membrane vesicles. Calcification of the vesicles gives rise to RPs. The growth of the RP’s is sustained by mineralization of collagen laid down as result of inflammation and fibrosis. PMID:25383321

  13. 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...

  14. 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 ...

  15. FORUM REVIEW ARTICLE Reactive Oxygen Species in Plant Pathogenesis

    E-print Network

    Daub, Margaret

    species (ROS) play multiple roles in interactions between plants and microbes, both as host defense mechanisms and as mediators of pathogenic and symbiotic associations. One source of ROS in these interactions, 970­989. Reactive Oxygen Species in Plant­Microbe Interactions Reactive oxygen species (ROS) play

  16. Indoor particulate reactive oxygen species concentrations.

    PubMed

    Khurshid, Shahana S; Siegel, Jeffrey A; Kinney, Kerry A

    2014-07-01

    Despite the fact that precursors to reactive oxygen species (ROS) are prevalent indoors, the concentration of ROS inside buildings is unknown. ROS on PM2.5 was measured inside and outside twelve residential buildings and eleven institutional and retail buildings. The mean (± s.d.) concentration of ROS on PM2.5 inside homes (1.37 ± 1.2 nmoles/m(3)) was not significantly different from the outdoor concentration (1.41 ± 1.0 nmoles/m(3)). Similarly, the indoor and outdoor concentrations of ROS on PM2.5 at institutional buildings (1.16 ± 0.38 nmoles/m(3) indoors and 1.68 ± 1.3 nmoles/m(3) outdoors) and retail stores (1.09 ± 0.93 nmoles/m(3) indoors and 1.12 ± 1.1 nmoles/m(3) outdoors) were not significantly different and were comparable to those in residential buildings. The indoor concentration of particulate ROS cannot be predicted based on the measurement of other common indoor pollutants, indicating that it is important to separately assess the concentration of particulate ROS in air quality studies. Daytime indoor occupational and residential exposure to particulate ROS dominates daytime outdoor exposure to particulate ROS. These findings highlight the need for further study of ROS in indoor microenvironments. PMID:24742727

  17. Mitochondrial reactive oxygen species production and elimination.

    PubMed

    Nickel, Alexander; Kohlhaas, Michael; Maack, Christoph

    2014-08-01

    Reactive oxygen species (ROS) play an important role in cardiovascular diseases, and one important source for ROS are mitochondria. Emission of ROS from mitochondria is the net result of ROS production at the electron transport chain (ETC) and their elimination by antioxidative enzymes. Both of these processes are highly dependent on the mitochondrial redox state, which is dynamically altered under different physiological and pathological conditions. The concept of "redox-optimized ROS balance" integrates these aspects and implies that oxidative stress occurs when the optimal equilibrium of an intermediate redox state is disturbed towards either strong oxidation or reduction. Furthermore, mitochondria integrate ROS signals from other cellular sources, presumably through a process termed "ROS-induced ROS release" that involves mitochondrial ion channels. Here, we attempt to integrate these recent advances in our understanding of the control of mitochondrial ROS emission and develop a concept of how in heart failure, defects in ion handling can lead to mitochondrial oxidative stress. This article is part of a Special Issue entitled "Redox Signalling in the Cardiovascular System". PMID:24657720

  18. 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

  19. Reactive Oxygen Species, SUMOylation, and Endothelial Inflammation.

    PubMed

    Le, Nhat-Tu; Corsetti, James P; Dehoff-Sparks, Janet L; Sparks, Charles E; Fujiwara, Keigi; Abe, Jun-Ichi

    2012-01-01

    Although the exact mechanism through which NADPH oxidases (Nox's) generate reactive oxygen species (ROS) is still not completely understood, it is widely considered that ROS accumulation is the cause of oxidative stress in endothelial cells. Increasing pieces of evidence strongly indicate the role for ROS in endothelial inflammation and dysfunction and subsequent development of atherosclerotic plaques, which are causes of various pathological cardiac events. An overview for a causative relationship between ROS and endothelial inflammation will be provided in this review. Particularly, a crucial role for specific protein SUMOylation in endothelial inflammation will be presented. Given that SUMOylation of specific proteins leads to increased endothelial inflammation, targeting specific SUMOylated proteins may be an elegant, effective strategy to control inflammation. In addition, the involvement of ROS production in increasing the risk of recurrent coronary events in a sub-group of non-diabetic, post-infarction patients with elevated levels of HDL-cholesterol will be presented with the emphasis that elevated HDL-cholesterol under certain inflammatory conditions can lead to increased incidence of cardiovascular events. PMID:22991685

  20. Reactive Oxygen Species, SUMOylation, and Endothelial Inflammation

    PubMed Central

    Le, Nhat-Tu; Corsetti, James P.; Dehoff-Sparks, Janet L.; Sparks, Charles E.; Fujiwara, Keigi; Abe, Jun-ichi

    2012-01-01

    Although the exact mechanism through which NADPH oxidases (Nox's) generate reactive oxygen species (ROS) is still not completely understood, it is widely considered that ROS accumulation is the cause of oxidative stress in endothelial cells. Increasing pieces of evidence strongly indicate the role for ROS in endothelial inflammation and dysfunction and subsequent development of atherosclerotic plaques, which are causes of various pathological cardiac events. An overview for a causative relationship between ROS and endothelial inflammation will be provided in this review. Particularly, a crucial role for specific protein SUMOylation in endothelial inflammation will be presented. Given that SUMOylation of specific proteins leads to increased endothelial inflammation, targeting specific SUMOylated proteins may be an elegant, effective strategy to control inflammation. In addition, the involvement of ROS production in increasing the risk of recurrent coronary events in a sub-group of non-diabetic, post-infarction patients with elevated levels of HDL-cholesterol will be presented with the emphasis that elevated HDL-cholesterol under certain inflammatory conditions can lead to increased incidence of cardiovascular events. PMID:22991685

  1. Mitochondrial reactive oxygen species accelerate gastric cancer cell invasion

    PubMed Central

    Tamura, Masato; Matsui, Hirofumi; Tomita, Tsutomu; Sadakata, Hisato; Indo, Hiroko P.; Majima, Hideyuki J.; Kaneko, Tsuyoshi; Hyodo, Ichinosuke

    2014-01-01

    Tumor invasion is the most important factor to decide patient’s prognosis. The relation between reactive oxygen species and tumor invasion is mainly reported that nicotinamide adenine dinucleotide phosphate oxidase in the cell membrane is a reactive oxygen species producer for formulating an invadopodia. On the other hand, mitochondrion was known as one of the most important reactive oxygen species-producer in the cell via an energy transfer system. However, the relation between mitochondrial reactive oxygen species and the tumor invasion was not well clarified. In this study, we evaluated the relation between mitochondrial reactive oxygen species and tumor invasion using a normal gastric mucosal cell-line (RGM-1) and a cancerous mutant RGM-1 cell-line (RGK-1). Manganese superoxide dismutase-expressing RGK-1 cell-lines were used for a scavenging mitochondrial reactive oxygen species. The cells have been evaluated their movement ability as follows; cellular ruffling frequencies, wound healing assay to evaluate horizontal cellular migration, and invasion assay using matrigel to analyze vertical cellular migration. All cellular movement abilities were inhibited by scavenging mitochondrial reactive oxygen species with manganese superoxide dismutase. Therefore mitochondrial reactive oxygen species was one of factors enhancing the tumor invasion in gastric cancer. PMID:24426185

  2. 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

  3. 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

  4. 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...

  5. 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...

  6. Reactive oxygen species-induced cytotoxic effects of zinc oxide nanoparticles in rat retinal ganglion cells.

    PubMed

    Guo, Dadong; Bi, Hongsheng; Liu, Bing; Wu, Qiuxin; Wang, Daoguang; Cui, Yan

    2013-03-01

    Recent studies have proved that zinc oxide (ZnO) nanoparticles can cause toxicity in different cell lines, oxidative stress is often hypothesized to be an important factor in cytotoxicity of ZnO nanoparticles. However, the mechanisms are incompletely understood. The present study aimed to investigate the role of oxidative stress in toxicity and possible involvement of mitochondria in the production of reactive oxygen species (ROS) upon exposure of retinal ganglion cells (RGC-5) to ZnO nanoparticles. In this study, the effects of ZnO nanoparticles on mitochondrial membrane potential and ROS levels involved in hydrogen peroxide and hydroxyl radical production were investigated via inverted fluorescence microscope and hydrogen peroxide and hydroxyl radical assay kits, respectively. Furthermore, the mRNA of caspase-12 and the protein secreted into culture supernatant were also determined by means of real-time quantitative PCR and ELISA techniques. Our studies indicate that ZnO nanoparticles could apparently decrease the mitochondrial membrane potential, increase the production of ROS and lead to the overexpression of caspase-12 in RGC-5 cells, suggesting that ZnO nanoparticle-induced toxicity via ROS overproduction will trigger endoplasmic reticulum stress, lead to the RGC-5 cell damage and finally induce apoptosis/necrosis, the overexpression of caspase-12 may be involved in cell death in RGC-5 cells. PMID:23232460

  7. Reactive oxygen species and antioxidant machinery in abiotic stress tolerance in crop plants.

    PubMed

    Gill, Sarvajeet Singh; Tuteja, Narendra

    2010-12-01

    Various abiotic stresses lead to the overproduction of reactive oxygen species (ROS) in plants which are highly reactive and toxic and cause damage to proteins, lipids, carbohydrates and DNA which ultimately results in oxidative stress. The ROS comprises both free radical (O(2)(-), superoxide radicals; OH, hydroxyl radical; HO(2), perhydroxy radical and RO, alkoxy radicals) and non-radical (molecular) forms (H(2)O(2), hydrogen peroxide and (1)O(2), singlet oxygen). In chloroplasts, photosystem I and II (PSI and PSII) are the major sites for the production of (1)O(2) and O(2)(-). In mitochondria, complex I, ubiquinone and complex III of electron transport chain (ETC) are the major sites for the generation of O(2)(-). The antioxidant defense machinery protects plants against oxidative stress damages. Plants possess very efficient enzymatic (superoxide dismutase, SOD; catalase, CAT; ascorbate peroxidase, APX; glutathione reductase, GR; monodehydroascorbate reductase, MDHAR; dehydroascorbate reductase, DHAR; glutathione peroxidase, GPX; guaicol peroxidase, GOPX and glutathione-S- transferase, GST) and non-enzymatic (ascorbic acid, ASH; glutathione, GSH; phenolic compounds, alkaloids, non-protein amino acids and ?-tocopherols) antioxidant defense systems which work in concert to control the cascades of uncontrolled oxidation and protect plant cells from oxidative damage by scavenging of ROS. ROS also influence the expression of a number of genes and therefore control the many processes like growth, cell cycle, programmed cell death (PCD), abiotic stress responses, pathogen defense, systemic signaling and development. In this review, we describe the biochemistry of ROS and their production sites, and ROS scavenging antioxidant defense machinery. PMID:20870416

  8. 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.

  9. REACTIVE OXYGEN SPECIES: Metabolism, Oxidative Stress, and Signal Transduction

    Microsoft Academic Search

    Klaus Apel; Heribert Hirt

    2004-01-01

    ? Abstract Several reactive oxygen,species (ROS) are continuously,produced,in plants as byproducts,of aerobic metabolism. Depending,on the nature of the ROS species, some are highly toxic and rapidly detoxified by various cellular enzymatic and,nonenzymatic,mechanisms.,Whereas,plants are surfeited with mechanisms,to combat increased ROS levels during abiotic stress conditions, in other circumstances plants appear to purposefully,generate ROS as signaling molecules,to control various processes including pathogen

  10. Singlet Oxygen Is the Major Reactive Oxygen Species Involved in Photooxidative Damage to Plants

    Microsoft Academic Search

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

    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 ( $^{1}{\\\\rm{O}}_{2}$; type II)-mediated lipid peroxidation (LPO) signatures by using hydroxy fatty acids as specific

  11. Antioxidants and reactive oxygen species in human fertility

    Microsoft Academic Search

    Clare T. Taylor

    2001-01-01

    The cellular components of the human reproductive system are as vulnerable as other cells to the potential detrimental effects of reactive oxygen species (ROS). Antioxidant protection is thus required, though not yet fully characterized, at sites of gametogenesis, fertilization and implantation. Spermatozoa are highly susceptible to oxidative damage due to the high content of polyunsaturated fatty acids within their plasma

  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. Modulation of Vascular Smooth Muscle Signaling by Reactive Oxygen Species

    NSDL National Science Digital Library

    Alicia N. Lyle (Emory University Department of Medicine, Division of Cardiology)

    2006-08-01

    Modulation of signaling in vascular cells by reactive oxygen species (ROS) affects many aspects of cellular function, including growth, migration, and contraction. NADPH oxidases, important sources of ROS, regulate many growth-specific and migration-related signaling pathways. Identifying the precise intracellular targets of ROS enhances understanding of their role in cardiovascular physiology and pathophysiology.

  14. Antimicrobial reactive oxygen and nitrogen species: concepts and controversies

    Microsoft Academic Search

    Ferric C. Fang

    2004-01-01

    Phagocyte-derived reactive oxygen and nitrogen species are of crucial importance for host resistance to microbial pathogens. Decades of research have provided a detailed understanding of the regulation, generation and actions of these molecular mediators, as well as their roles in resisting infection. However, differences of opinion remain with regard to their host specificity, cell biology, sources and interactions with one

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

    SciTech Connect

    Qiu, S.L.; Lin, C.L.; Chen, J.; Strongin, M. (Physics Department, Brookhaven National Laboratory, Upton, NY (USA))

    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.

  16. Properties of Reactive Oxygen Species by Quantum Monte Carlo

    E-print Network

    Andrea Zen; Bernhardt L. Trout; Leonardo Guidoni

    2014-06-16

    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.

  17. Properties of reactive oxygen species by quantum Monte Carlo

    SciTech Connect

    Zen, Andrea [Dipartimento di Fisica, La Sapienza - Università di Roma, Piazzale Aldo Moro 2, 00185 Rome (Italy); Trout, Bernhardt L. [Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, Massachusetts 02139 (United States); Guidoni, Leonardo, E-mail: leonardo.guidoni@univaq.it [Dipartimento di Scienze Fisiche e Chimiche, Università degli studi de L'Aquila, Via Vetoio, 67100 Coppito, L'Aquila (Italy)

    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.

  18. Reactive Oxygen Species in Unstimulated Hemocytes of the Pacific Oyster Crassostrea gigas: A Mitochondrial Involvement

    PubMed Central

    Donaghy, Ludovic; Kraffe, Edouard; Le Goïc, Nelly; Lambert, Christophe; Volety, Aswani K.; Soudant, Philippe

    2012-01-01

    The Pacific oyster Crassostrea gigas is a sessile bivalve mollusc whose homeostasis relies, at least partially, upon cells circulating in hemolymph and referred to as hemocytes. Oyster’s hemocytes have been reported to produce reactive oxygen species (ROS), even in absence of stimulation. Although ROS production in bivalve molluscs is mostly studied for its defence involvement, ROS may also be involved in cellular and tissue homeostasis. ROS sources have not yet been described in oyster hemocytes. The objective of the present work was to characterize the ROS sources in unstimulated hemocytes. We studied the effects of chemical inhibitors on the ROS production and the mitochondrial membrane potential (??m) of hemocytes. First, this work confirmed the specificity of JC-10 probe to measure ??m in oyster hemocytes, without being affected by ?pH, as reported in mammalian cells. Second, results show that ROS production in unstimulated hemocytes does not originate from cytoplasmic NADPH-oxidase, nitric oxide synthase or myeloperoxidase, but from mitochondria. In contrast to mammalian cells, incubation of hemocytes with rotenone (complex I inhibitor) had no effect on ROS production. Incubation with antimycin A (complex III inhibitor) resulted in a dose-dependent ROS production decrease while an over-production is usually reported in vertebrates. In hemocytes of C. gigas, the production of ROS seems similarly dependent on both ??m and ?pH. These findings point out differences between mammalian models and bivalve cells, which warrant further investigation about the fine characterization of the electron transfer chain and the respective involvement of mitochondrial complexes in ROS production in hemocytes of bivalve molluscs. PMID:23056359

  19. 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

  20. Reactive oxygen species contribute to neuropathic pain and locomotor dysfunction via activation of CamKII in remote segments following spinal cord contusion injury in rats.

    PubMed

    Gwak, Young S; Hassler, Shayne E; Hulsebosch, Claire E

    2013-09-01

    In this study, we examined whether blocking spinal cord injury (SCI)-induced increases in reactive oxygen species (ROS) by a ROS scavenger would attenuate below-level central neuropathic pain and promote recovery of locomotion. Rats with T10 SCI developed mechanical allodynia in both hind paws and overproduction of ROS, as assayed by Dhet intensity, in neurons in the lumbar 4/5 dorsal horn ((?)P<0.05). To scavenge ROS, phenyl-N-tert-butylnitrone (PBN, a ROS scavenger) was administered immediately after SCI and for 7 consecutive days (early treatment) by either intrathecal (it; 1 and 3mg) or systemic (ip; 10, 50 and 100mg) injections. In addition, the high doses of it (3mg) or ip (100mg) injections were performed at 35 days (delayed treatment) after SCI. High doses of PBN (ip, 100mg, and it, 3mg) significantly attenuated mechanical allodynia in both hind paws at both early and delayed treatments, respectively ((?)P<0.05). The abnormal hyperexcitability of wide dynamic range neurons after SCI was significantly attenuated by both early and delayed PBN treatment ((?)P<0.05). Early PBN treatment (100mg, ip, and 3mg, it) attenuated overproduction of ROS in neurons in the lumbar 4/5 dorsal horn. In addition, it and ip t-BOOH (ROS donor) treatment dose-dependently produced mechanical allodynia in both hind paws ((?)P<0.05). Both SCI and t-BOOH treatment groups showed significantly increased phospho-CamKII (pCamKII) expression in neurons and KN-93 (an inhibitor of pCamKII) significantly attenuated mechanical allodynia ((?)P<0.05). In addition, high doses of PBN significantly promoted the recovery of locomotion ((?)P<0.05). In conclusion, the present data suggest that overproduction of ROS contribute to sensory and motor abnormalities in remote segments below the lesion after thoracic SCI. PMID:23707296

  1. Production of Ozone and Reactive Oxygen Species After Welding

    Microsoft Academic Search

    H. H. Liu; Y. C. Wu; H. L. Chen

    2007-01-01

    Many toxic substances including heavy metals, ozone, carbon monoxide, carbon dioxide, and nitrogen oxides are generated during\\u000a welding. Ozone (O3) is a strong oxidant that generates reactive oxygen species (ROS) in tissue, and ambient ROS exposure associated with particles\\u000a has been determined to cause DNA damage. Ozone is produced within 30 seconds during welding. However, the length of time that

  2. Mitochondrial reactive oxygen species in cell death signaling

    Microsoft Academic Search

    Christophe Fleury; Bernard Mignotte; Jean-Luc Vayssière

    2002-01-01

    During apoptosis, mitochondrial membrane permeability (MMP) increases and the release into the cytosol of pro-apoptotic factors (procaspases, caspase activators and caspase-independent factors such as apoptosis-inducing factor (AIF)) leads to the apoptotic phenotype. Apart from this pivotal role of mitochondria during the execution phase of apoptosis (documented in other reviews of this issue), it appears that reactive oxygen species (ROS) produced

  3. Reactive oxygen species in the neuropathogenesis of hypertension

    Microsoft Academic Search

    Jeffrey R. Peterson; Ram V. Sharma; Robin L. Davisson

    2006-01-01

    New evidence that has emerged during the past several years clearly demonstrates that reactive oxygen species (ROS) in the\\u000a brain play a crucial role in blood pressure regulation by serving as signaling molecules within neurons of cardiovascular\\u000a control regions. In the forebrain, midbrain, and hindbrain, a key role for oxidant stress in the pathogenesis of angiotensin\\u000a II-dependent and various other

  4. Reactive oxygen species and hematopoietic stem cell senescence

    Microsoft Academic Search

    Lijian Shao; Hongliang Li; Senthil K. Pazhanisamy; Aimin Meng; Yong Wang; Daohong Zhou

    Hematopoietic stem cells (HSCs) are responsible for sustaining hematopoietic homeostasis and regeneration after injury for\\u000a the entire lifespan of an organism through self-renewal, proliferation, differentiation, and mobilization. Their functions\\u000a can be affected by reactive oxygen species (ROS) that are produced endogenously through cellular metabolism or after exposure\\u000a to exogenous stress. At physiological levels, ROS function as signal molecules which can

  5. Reactive Oxygen Species, Oxidative Stress and Plant Ion Channels

    Microsoft Academic Search

    Vadim Demidchik

    \\u000a Reactive oxygen species (ROS) are important toxic and regulatory agents in plants. They are produced in response to a number\\u000a of stimuli, including major biotic and abiotic stresses. Disruption of respiratory and photosynthetic electron transport chains,\\u000a as well as activation of NADPH oxidases (NOXs) and peroxidases, is a major reason for ROS generation and accumulation during\\u000a stress conditions. ROS production

  6. Mitochondria and Reactive Oxygen Species: Physiology and Pathophysiology

    PubMed Central

    Bolisetty, Subhashini; Jaimes, Edgar A.

    2013-01-01

    The air that we breathe contains nearly 21% oxygen, most of which is utilized by mitochondria during respiration. While we cannot live without it, it was perceived as a bane to aerobic organisms due to the generation of reactive oxygen and nitrogen metabolites by mitochondria and other cellular compartments. However, this dogma was challenged when these species were demonstrated to modulate cellular responses through altering signaling pathways. In fact, since this discovery of a dichotomous role of reactive species in immune function and signal transduction, research in this field grew at an exponential pace and the pursuit for mechanisms involved began. Due to a significant number of review articles present on the reactive species mediated cell death, we have focused on emerging novel pathways such as autophagy, signaling and maintenance of the mitochondrial network. Despite its role in several processes, increased reactive species generation has been associated with the origin and pathogenesis of a plethora of diseases. While it is tempting to speculate that anti-oxidant therapy would protect against these disorders, growing evidence suggests that this may not be true. This further supports our belief that these reactive species play a fundamental role in maintenance of cellular and tissue homeostasis. PMID:23528859

  7. Heavy-metal-induced reactive oxygen species: phytotoxicity and physicochemical changes in plants.

    PubMed

    Shahid, Muhammad; Pourrut, Bertrand; Dumat, Camille; Nadeem, Muhammad; Aslam, Muhammad; Pinelli, Eric

    2014-01-01

    As a result of the industrial revolution, anthropogenic activities have enhanced there distribution of many toxic heavy metals from the earth's crust to different environmental compartments. Environmental pollution by toxic heavy metals is increasing worldwide, and poses a rising threat to both the environment and to human health.Plants are exposed to heavy metals from various sources: mining and refining of ores, fertilizer and pesticide applications, battery chemicals, disposal of solid wastes(including sewage sludge), irrigation with wastewater, vehicular exhaust emissions and adjacent industrial activity.Heavy metals induce various morphological, physiological, and biochemical dysfunctions in plants, either directly or indirectly, and cause various damaging effects. The most frequently documented and earliest consequence of heavy metal toxicity in plants cells is the overproduction of ROS. Unlike redox-active metals such as iron and copper, heavy metals (e.g, Pb, Cd, Ni, AI, Mn and Zn) cannot generate ROS directly by participating in biological redox reactions such as Haber Weiss/Fenton reactions. However, these metals induce ROS generation via different indirect mechanisms, such as stimulating the activity of NADPH oxidases, displacing essential cations from specific binding sites of enzymes and inhibiting enzymatic activities from their affinity for -SH groups on the enzyme.Under normal conditions, ROS play several essential roles in regulating the expression of different genes. Reactive oxygen species control numerous processes like the cell cycle, plant growth, abiotic stress responses, systemic signalling, programmed cell death, pathogen defence and development. Enhanced generation of these species from heavy metal toxicity deteriorates the intrinsic antioxidant defense system of cells, and causes oxidative stress. Cells with oxidative stress display various chemical,biological and physiological toxic symptoms as a result of the interaction between ROS and biomolecules. Heavy-metal-induced ROS cause lipid peroxidation, membrane dismantling and damage to DNA, protein and carbohydrates. Plants have very well-organized defense systems, consisting of enzymatic and non-enzymatic antioxidation processes. The primary defense mechanism for heavy metal detoxification is the reduced absorption of these metals into plants or their sequestration in root cells.Secondary heavy metal tolerance mechanisms include activation of antioxidant enzymes and the binding of heavy metals by phytochelatins, glutathione and amino acids. These defense systems work in combination to manage the cascades of oxidative stress and to defend plant cells from the toxic effects of ROS.In this review, we summarized the biochemiCal processes involved in the over production of ROS as an aftermath to heavy metal exposure. We also described the ROS scavenging process that is associated with the antioxidant defense machinery.Despite considerable progress in understanding the biochemistry of ROS overproduction and scavenging, we still lack in-depth studies on the parameters associated with heavy metal exclusion and tolerance capacity of plants. For example, data about the role of glutathione-glutaredoxin-thioredoxin system in ROS detoxification in plant cells are scarce. Moreover, how ROS mediate glutathionylation (redox signalling)is still not completely understood. Similarly, induction of glutathione and phytochelatins under oxidative stress is very well reported, but it is still unexplained that some studied compounds are not involved in the detoxification mechanisms. Moreover,although the role of metal transporters and gene expression is well established for a few metals and plants, much more research is needed. Eventually, when results for more metals and plants are available, the mechanism of the biochemical and genetic basis of heavy metal detoxification in plants will be better understood. Moreover, by using recently developed genetic and biotechnological tools it may be possible to produce plants that have traits desirable for imparting heavy meta

  8. Production of intracellular reactive oxygen species and change of cell viability induced by atmospheric pressure plasma in normal and cancer cells

    NASA Astrophysics Data System (ADS)

    Ja Kim, Sun; Min Joh, Hea; Chung, T. H.

    2013-10-01

    The effects of atmospheric pressure plasma jet on cancer cells (human lung carcinoma cells) and normal cells (embryonic kidney cells and bronchial epithelial cells) were investigated. Using a detection dye, the production of intracellular reactive oxygen species (ROS) was found to be increased in plasma-treated cells compared to non-treated and gas flow-treated cells. A significant overproduction of ROS and a reduction in cell viability were induced by plasma exposure on cancer cells. Normal cells were observed to be less affected by the plasma-mediated ROS, and cell viability was less changed. The selective effect on cancer and normal cells provides a promising prospect of cold plasma as a cancer therapy.

  9. Oxygen consumption in six species of chitons in relation to their position on the shore

    Microsoft Academic Search

    Robin C. Murdoch; Sandra E. Shumway

    1980-01-01

    Aerial and aquatic oxygen consumption rates have been measured in six species of intertidal chi tons with respect to zonation, size and oxygen concentration of the external medium. Those species occurring highest on the shore were found to have a lower rate of aquatic oxygen consumption than those ~i'eeies occurring lowest on the shore, with mid-shore species showing intermediate rates.

  10. Spermine metabolism and radiation-derived reactive oxygen species for future therapeutic implications in cancer: an additive or adaptive response.

    PubMed

    Amendola, Roberto; Cervelli, Manuela; Tempera, Giampiero; Fratini, Emiliano; Varesio, Luigi; Mariottini, Paolo; Agostinelli, Enzo

    2014-03-01

    Destruction of cells by irradiation-induced radical formation is one of the most frequent interventions in cancer therapy. An alternative to irradiation-induced radical formation is in principle drug-induced formation of radicals, and the formation of toxic metabolites by enzyme catalyzed reactions. Thus, combination therapy targeting polyamine metabolism could represent a promising strategy to fight hyper-proliferative disease. The aim of this work is to discuss and evaluate whether the presence of a DNA damage provoked by enzymatic ROS overproduction may act as an additive or adaptive response upon radiation and combination of hyperthermia with lysosomotropic compounds may improve the cytocidal effect of polyamines oxidation metabolites. Low level of X-irradiations delivers challenging dose of damage and an additive or adaptive response with the chronic damage induced by spermine oxidase overexpression depending on the deficiency of the DNA repair mechanisms. Since reactive oxygen species lead to membrane destabilization and cell death, we discuss the effects of BSAO and spermine association in multidrug resistant cells that resulted more sensitive to spermine metabolites than their wild-type counterparts, due to an increased mitochondrial activity. Since mammal spermine oxidase is differentially activated in a tissue specific manner, and cancer cells can differ in term of DNA repair capability, it could be of interest to open a scientific debate to use combinatory treatments to alter spermine metabolism and deliver differential response. PMID:23999645

  11. Azoxystrobin-induced excessive reactive oxygen species (ROS) production and inhibition of photosynthesis in the unicellular green algae Chlorella vulgaris.

    PubMed

    Liu, Lei; Zhu, Bin; Wang, Gao-Xue

    2015-05-01

    This study investigated the short-term toxicity of azoxystrobin (AZ), one of strobilurins used as an effective fungicidal agent to control the Asian soybean rust, on aquatic unicellular algae Chlorella vulgaris. The median percentile inhibition concentration (IC50) of AZ for C. vulgaris was found to be 510 ?g L(-1). We showed that the algal cells were obviously depressed or shrunk in 300 and 600 ?g L(-1) AZ treatments by using the electron microscopy. Furthermore, 19, 75, and 300 ?g L(-1) AZ treatments decreased the soluble protein content and chlorophyll concentrations in C. vulgaris and altered the energy-photosynthesis-related mRNA expression levels in 48- and 96-h exposure periods. Simultaneously, our results showed that AZ could increase the total antioxidant capacity (T-AOC) level and compromise superoxide dismutase (SOD), peroxidase (POD), glutathione S transferase (GST), glutathione peroxidase (GPx) activities, and glutathione (GSH) content. These situations might render C. vulgaris more vulnerable to oxidative damage. Overall, the present study indicated that AZ might be toxic to the growth of C. vulgaris, affect energy-photosynthesis-related mRNA expressions, and induce reactive oxygen species (ROS) overproduction in C. vulgaris. PMID:25672875

  12. Angiotensin II-Induced Production of Mitochondrial Reactive Oxygen Species: Potential Mechanisms and Relevance for Cardiovascular Disease

    PubMed Central

    Nazarewicz, Rafal R.

    2013-01-01

    Abstract Significance: The role of reactive oxygen species (ROS) in angiotensin II (AngII) induced endothelial dysfunction, cardiovascular and renal remodeling, inflammation, and fibrosis has been well documented. The molecular mechanisms of AngII pathophysiological activity involve the stimulation of NADPH oxidases, which produce superoxide and hydrogen peroxide. AngII also increases the production of mitochondrial ROS, while the inhibition of AngII improves mitochondrial function; however, the specific molecular mechanisms of the stimulation of mitochondrial ROS is not clear. Recent Advances: Interestingly, the overexpression of mitochondrial thioredoxin 2 or mitochondrial superoxide dismutase attenuates AngII-induced hypertension, which demonstrates the importance of mitochondrial ROS in AngII-mediated cardiovascular diseases. Critical Issues: Although mitochondrial ROS plays an important role in normal physiological cell signaling, AngII, high glucose, high fat, or hypoxia may cause the overproduction of mitochondrial ROS, leading to the feed-forward redox stimulation of NADPH oxidases. This vicious cycle may contribute to the development of pathological conditions and facilitate organ damage in hypertension, atherosclerosis, and diabetes. Future Directions: The development of antioxidant strategies specifically targeting mitochondria could be therapeutically beneficial in these disease conditions. Antioxid. Redox Signal. 19, 1085–1094. PMID:22443458

  13. Regulation of Reactive Oxygen Species Generation in Cell Signaling

    PubMed Central

    Bae, Yun Soo; Oh, Hyunjin; Rhee, Sue Goo; Yoo, Young Do

    2011-01-01

    Reactive oxygen species (ROS) including superoxide anion and hydrogen peroxide (H2O2) are thought to be byproducts of aerobic respiration with damaging effects on DNA, protein, and lipid. A growing body of evidence indicates, however, that ROS are involved in the maintenance of redox homeostasis and various cellular signaling pathways. ROS are generated from diverse sources including mitochondrial respiratory chain, enzymatic activation of cytochrome p450, and NADPH oxidases further suggesting involvement in a complex array of cellular processes. This review summarizes the production and function of ROS. In particular, how cytosolic and membrane proteins regulate ROS generation for intracellular redox signaling will be detailed. PMID:22207195

  14. Cellular Reactive Oxygen Species Inhibit MPYS Induction of IFN?

    PubMed Central

    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 IFN? expression during infection, is a ROS sensor. ROS induce intermolecular disulfide bonds formation in MPYS homodimer and inhibit MPYS IFN? stimulatory activity. Cys-64, -148, -292, -309 and the potential C88xxC91 redox motif in MPYS are indispensable for IFN? stimulation and IRF3 activation. Thus, our results identify a novel mechanism for ROS regulation of IFN? stimulation. PMID:21170271

  15. Myoglobin oxygenation and autoxidation in three reptilian species.

    PubMed

    Helbo, Signe; Bundgaard, Amanda G; Fago, Angela

    2015-09-01

    Differences between species in the oxygen (O2) affinity (P50) of myoglobin (Mb) may serve to fine tune O2 supply to cardiac and skeletal muscle in ectotherms. In support of this view, it has been shown that fish Mb O2 affinities differ between species when measured at the same temperature, but are in fact similar when adjusted for in vivo muscle temperatures, most likely to maintain intracellular O2 delivery in species adapted to different environments. It is unknown whether similar adaptations exist in the O2 affinity of Mb from reptiles, despite this group of ectothermic vertebrates displaying great variation in the tolerance to both temperature and hypoxia. In this study, we have purified Mb from muscle tissues of three reptilian species (turtle, tortoise and alligator) with different lifestyles. We have measured O2 binding characteristics and autoxidation rates of the three Mbs and measured the effects of temperature, lactate and blocking of reactive thiols on the O2 affinity of turtle Mb. Our data show that, at a constant temperature, reptilian Mbs have similar O2 affinities that are lower than those of mammalian Mbs, which may optimize intracellular O2 transport at lower body temperatures. Reptilian Mbs have lower autoxidation rates than both mammalian and fish Mbs, which may be beneficial during oxidative stress. Furthermore, the O2 affinity of turtle Mb is without allosteric control and independent of either lactate or thiol covalent modification. This study reveals some common adaptive patterns in the temperature-dependent regulation of Mb oxygenation in vertebrates. PMID:25899737

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

    PubMed Central

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

    2015-01-01

    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

  17. 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

  18. Reactive oxygen species: toxic molecules or spark of life?

    PubMed Central

    Magder, Sheldon

    2006-01-01

    Increases in reactive oxygen species (ROS) and tissue evidence of oxidative injury are common in patients with inflammatory processes or tissue injury. This has led to many clinical attempts to scavenge ROS and reduce oxidative injury. However, we live in an oxygen rich environment and ROS and their chemical reactions are part of the basic chemical processes of normal metabolism. Accordingly, organisms have evolved sophisticated mechanisms to control these reactive molecules. Recently, it has become increasingly evident that ROS also play a role in the regulation of many intracellular signaling pathways that are important for normal cell growth and inflammatory responses that are essential for host defense. Thus, simply trying to scavenge ROS is likely not possible and potentially harmful. The 'normal' level of ROS will also likely vary in different tissues and even in different parts of cells. In this paper, the terminology and basic chemistry of reactive species are reviewed. Examples and mechanisms of tissue injury by ROS as well as their positive role as signaling molecules are discussed. Hopefully, a better understanding of the nature of ROS will lead to better planned therapeutic attempts to manipulate the concentrations of these important molecules. We need to regulate ROS, not eradicate them. PMID:16469133

  19. Biochemical studies on hemoglobin modified with reactive oxygen species (ROS).

    PubMed

    Khaket, Tejinder Pal; Ahmad, Rizwan

    2011-08-01

    Hemoglobin is the iron-containing oxygen transporting metalloprotein in the red cells of blood in mammals and other animals. Hemoprotein-mediated oxidative stress is thought to play a major role in pathophysiology of cerebral hemorrhage, blast pressure injury, crush injury, myocardial ischemia reperfusion injury. Hemoglobin undergoes oxidation-reduction reactions that lead to both generation and consumption of highly reactive oxygen and nitrogen species. In the present study, hemoglobin molecule was treated with hydrogen peroxide and the modification so incurred was analyzed by UV spectra, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and detection of carbonyl content. Our observations suggest that carbonyl content increases with increase in concentration of hydrogen peroxide. Production of hydroxyl radical was assessed by using benzoate degradation analysis. Our results was in tandem with the fact that hemoglobin on treatment with hydrogen peroxide rapidly generates free-radical species that can degrade benzoate to thiobarbituric acid reactive material which on reacting with thiobarbituric acid gives color. The increase in absorbance of ROS-modified hemoglobin at 532 nm shows the increase in benzoate degradation, which is a parameter of hydroxyl radical formation with increase in concentration of hydrogen peroxide. Modified hemoglobin was treated with catalase, mannitol, thiourea, glutathion, sodium benzoate and their effect were detected by spectroscopy and SDS-PAGE (12%). Substantial scavenging effect of aforementioned antioxidants reiterates the formation of hydroxyl radical. Catalase shows the maximum scavenging effect followed by thiourea and mannitol. PMID:21416337

  20. Reactive oxygen species, ageing and the hormesis police

    PubMed Central

    Ludovico, Paula; Burhans, William C.

    2013-01-01

    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

  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 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

  3. Role of Reactive Oxygen Species in Antibiotic Action and Resistance

    PubMed Central

    Dwyer, Daniel J; Kohanski, Michael A; Collins, James J

    2009-01-01

    The alarming spread of bacterial strains exhibiting resistance to current antibiotic therapies necessitates that we elucidate the specific genetic and biochemical responses underlying drug-mediated cell killing, so as to increase the efficacy of available treatments and develop new antibacterials. Recent research aimed at identifying such cellular contributions has revealed that antibiotics induce changes in metabolism that promote the formation of reactive oxygen species, which play a role in cell death. Here we discuss the relationship between drug-induced oxidative stress, the SOS response and their potential combined contribution to resistance development. Additionally, we describe ways in which these responses are being taken advantage of to combat bacterial infections and arrest the rise of resistant strains. PMID:19647477

  4. Crosstalk of reactive oxygen species and NF-?B signaling

    PubMed Central

    Morgan, Michael J; Liu, Zheng-gang

    2011-01-01

    NF-?B proteins are a family of transcription factors that are of central importance in inflammation and immunity. NF-?B also plays important roles in other processes, including development, cell growth and survival, and proliferation, and is involved in many pathological conditions. Reactive Oxygen Species (ROS) are created by a variety of cellular processes as part of cellular signaling events. While certain NF-?B-regulated genes play a major role in regulating the amount of ROS in the cell, ROS have various inhibitory or stimulatory roles in NF-?B signaling. Here we review the regulation of ROS levels by NF-?B targets and various ways in which ROS have been proposed to impact NF-?B signaling pathways. PMID:21187859

  5. 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

  6. [Reactive oxygen species and stress signaling in plants].

    PubMed

    Kolupaev, Iu E; Karpets, Iu V

    2014-01-01

    Data on the basic processes and the compartments, involved in formation of reactive oxygen species (ROS) in plant cells, are generalised. The features of structure and regulation of NADPH-oxidase as the one of main enzymatic producers of ROS are characterized. The two-component histidine kinases, ROS-sensitive transcript-factors, ROS-sensitive protein kinase and redox-regulated ionic channels are discussed as the possible sensors of redox-signals in plant cells. The interaction between ROS and other signal mediators, in particular nitric oxide and calcium ions, is discussed. The ROS role as the signal mediators in the development of plant resistance to hyperthermia, osmotic shock and other abiotic stressors is analyzed. PMID:25509181

  7. Reactive oxygen species in endothelial function?- from disease to adaptation.

    PubMed

    Craige, Siobhan M; Kant, Shashi; Keaney, John F

    2015-05-25

    Endothelial function is largely dictated by its ability to rapidly sense environmental cues and adapt to these stimuli through changes in vascular tone, inflammation/immune recruitment, and angiogenesis. When any one of these abilities is compromised, the endothelium becomes dysfunctional, which ultimately leads to disease. Reactive oxygen species (ROS) have been established at the forefront of endothelial dysfunction; however, more careful examination has demonstrated that ROS are fundamental to each of the sensing/signaling roles of the endothelium. The purpose of this review is to document endothelial ROS production in both disease and physiological adaptation. Through understanding new endothelial signaling paradigms, we will gain insight into more targeted therapeutic strategies for vascular diseases. (Circ J 2015; 79: 1145-1155). PMID:25986771

  8. 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

  9. Diabetic peripheral neuropathy: role of reactive oxygen and nitrogen species.

    PubMed

    Premkumar, Louis S; Pabbidi, Reddy M

    2013-11-01

    The prevalence of diabetes has reached epidemic proportions. There are two forms of diabetes: type 1 diabetes mellitus is due to auto-immune-mediated destruction of pancreatic ?-cells resulting in absolute insulin deficiency and type 2 diabetes mellitus is due to reduced insulin secretion and or insulin resistance. Both forms of diabetes are characterized by chronic hyperglycemia, leading to the development of diabetic peripheral neuropathy (DPN) and microvascular pathology. DPN is characterized by enhanced or reduced thermal, chemical, and mechanical pain sensitivities. In the long-term, DPN results in peripheral nerve damage and accounts for a substantial number of non-traumatic lower-limb amputations. This review will address the mechanisms, especially the role of reactive oxygen and nitrogen species in the development and progression of DPN. PMID:23722999

  10. Focus Issue: Reactive Oxygen Species--Friend or Foe?

    NSDL National Science Digital Library

    Nancy R. Gough (DC; American Association for the Advancement of Science, Washington REV)

    2006-04-25

    Science’s STKE focuses on the signaling pathways activated in response to pathological accumulation of reactive oxygen species (ROS), as well as on mechanisms by which cells have harnessed these reactive molecules as active participants in signaling that leads to a desirable cellular response. ROS are chemically reactive because they contain unpaired electrons and, depending on the location of their production and the molecules with which they interact, they can cause cellular damage or trigger specific signaling events. Indeed, kinases and phosphatases are now recognized as key molecules that can be modified by interaction with ROS, and the Protocol by Wu and Terada describes a method for detecting oxidatively modified protein tyrosine phosphatases. In a Perspective, Michel et al. discuss how susceptibility to elevated ROS contributes to death of specific neurons and in a Review, Storz discusses the signaling pathways activated to detoxify ROS and how mitochondrial ROS may contribute to aging.

  11. 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

  12. The interaction of atmospheric pressure plasma jets with cancer and normal cells: generation of intracellular reactive oxygen species and changes of the cell proliferation and cell cycle

    NASA Astrophysics Data System (ADS)

    Chung, Tae Hun; Joh, Hea Min; Kim, Sun Ja; Leem, Sun Hee

    2013-09-01

    The possibility of atmospheric pressure plasmas is emerging as a candidate in cancer therapy. The primary role is played by reactive oxygen species (ROS), UV photons, charged particles and electric fields. Among them, intracellular ROS induced by plasma are considered to be the key constituents that induce cellular changes and apoptosis. In this study, the effects of atmospheric pressure plasma jet on cancer cells (human lung carcinoma cells) and normal cells (embryonic kidney cells and bronchial epithelial cells) were investigated. The plasma treatment was performed under different working gases, applied voltages, gas flow rates, and with and without additive oxygen flow. Using a detection dye, we observed that plasma exposure leads to the increase of the intracellular ROS and that the intracellular ROS production can be controlled by plasma parameters. A significant ROS generation was induced by plasma exposure on cancer cells and the overproduction of ROS contributes to the reduced cell proliferation. Normal cells were observed to be less affected by the plasma-mediated ROS and cell proliferation was less changed. The plasma treatment also resulted in the alteration of the cell cycle that contributes to the induction of apoptosis in cancer cells. The selective effect on cancer and normal cells provides a promising prospect of cold plasma as cancer therapy. The possibility of atmospheric pressure plasmas is emerging as a candidate in cancer therapy. The primary role is played by reactive oxygen species (ROS), UV photons, charged particles and electric fields. Among them, intracellular ROS induced by plasma are considered to be the key constituents that induce cellular changes and apoptosis. In this study, the effects of atmospheric pressure plasma jet on cancer cells (human lung carcinoma cells) and normal cells (embryonic kidney cells and bronchial epithelial cells) were investigated. The plasma treatment was performed under different working gases, applied voltages, gas flow rates, and with and without additive oxygen flow. Using a detection dye, we observed that plasma exposure leads to the increase of the intracellular ROS and that the intracellular ROS production can be controlled by plasma parameters. A significant ROS generation was induced by plasma exposure on cancer cells and the overproduction of ROS contributes to the reduced cell proliferation. Normal cells were observed to be less affected by the plasma-mediated ROS and cell proliferation was less changed. The plasma treatment also resulted in the alteration of the cell cycle that contributes to the induction of apoptosis in cancer cells. The selective effect on cancer and normal cells provides a promising prospect of cold plasma as cancer therapy. This work was supported by the National Research Foundation of Korea under Contract No. 2012R1A1A2002591 and 2012R1A1A3010213.

  13. Mitochondria: Much ado about nothing? How dangerous is reactive oxygen species production??

    PubMed Central

    Holzerová, Eliška; Prokisch, Holger

    2015-01-01

    For more than 50 years, reactive oxygen species have been considered as harmful agents, which can attack proteins, lipids or nucleic acids. In order to deal with reactive oxygen species, there is a sophisticated system developed in mitochondria to prevent possible damage. Indeed, increased reactive oxygen species levels contribute to pathomechanisms in several human diseases, either by its impaired defense system or increased production of reactive oxygen species. However, in the last two decades, the importance of reactive oxygen species in many cellular signaling pathways has been unraveled. Homeostatic levels were shown to be necessary for correct differentiation during embryonic expansion of stem cells. Although the mechanism is still not fully understood, we cannot only regard reactive oxygen species as a toxic by-product of mitochondrial respiration anymore. This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies. PMID:25666559

  14. Degradative action of reactive oxygen species on hyaluronan.

    PubMed

    Soltés, L; Mendichi, R; Kogan, G; Schiller, J; Stankovska, M; Arnhold, J

    2006-03-01

    Many human diseases are associated with harmful action of reactive oxygen species (ROS). These species are involved in the degradation of essential tissue or related components. One of such components is synovial fluid that contains a high-molecular-weight polymer--hyaluronan (HA). Uninhibited and/or inhibited hyaluronan degradation by the action of various ROS has been studied in many in vitro models. In these studies, the change of the molecular weight of HA or a related parameter, such as HA solution viscosity, has been used as a marker of inflicted damage. The aim of the presented review is to briefly summarize the available data. Their correct interpretation could contribute to the implementation of modern methods of evaluation of the antioxidative capacity of natural and synthetic substances and prospective drugs--potential inflammatory disease modifying agents. Another focus of this review is to evaluate briefly the impact of different available analytical techniques currently used to investigate the structure of native high-molecular-weight hyaluronan and/or of its fragments. PMID:16529395

  15. 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.

  16. 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 (? 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) ? 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 ? 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.

  17. 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

  18. Ethanol stimulates epithelial sodium channels by elevating reactive oxygen species.

    PubMed

    Bao, Hui-Fang; Song, John Z; Duke, Billie J; Ma, He-Ping; Denson, Donald D; Eaton, Douglas C

    2012-12-01

    Alcohol affects total body sodium balance, but the molecular mechanism of its effect remains unclear. We used single-channel methods to examine how ethanol affects epithelial sodium channels (ENaC) in A6 distal nephron cells. The data showed that ethanol significantly increased both ENaC open probability (P(o)) and the number of active ENaC in patches (N). 1-Propanol and 1-butanol also increased ENaC activity, but iso-alcohols did not. The effects of ethanol were mimicked by acetaldehyde, the first metabolic product of ethanol, but not by acetone, the metabolic product of 2-propanol. Besides increasing open probability and apparent density of active channels, confocal microscopy and surface biotinylation showed that ethanol significantly increased ?-ENaC protein in the apical membrane. The effects of ethanol on ENaC P(o) and N were abolished by a superoxide scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL) and blocked by the phosphatidylinositol 3-kinase inhibitor LY294002. Consistent with an effect of ethanol-induced reactive oxygen species (ROS) on ENaC, primary alcohols and acetaldehyde elevated intracellular ROS, but secondary alcohols did not. Taken together with our previous finding that ROS stimulate ENaC, the current results suggest that ethanol stimulates ENaC by elevating intracellular ROS probably via its metabolic product acetaldehyde. PMID:22895258

  19. Geochemical production of reactive oxygen species from biogeochemically reduced Fe.

    PubMed

    Murphy, Sarah A; Solomon, Benson M; Meng, Shengnan; Copeland, Justin M; Shaw, Timothy J; Ferry, John L

    2014-04-01

    The photochemical reduction of Fe(III) complexes to Fe(II) is a well-known initiation step for the production of reactive oxygen species (ROS) in sunlit waters. Here we show a geochemical mechanism for the same in dark environments based on the tidally driven, episodic movement of anoxic groundwaters through oxidized, Fe(III) rich sediments. Sediment samples were collected from the top 5 cm of sediment in a saline tidal creek in the estuary at Murrell's Inlet, South Carolina and characterized with respect to total Fe, acid volatile sulfides, and organic carbon content. These sediments were air-dried, resuspended in aerated solution, then exposed to aqueous sulfide at a range of concentrations chosen to replicate the conditions characteristic of a tidal cycle, beginning with low tide. No detectable ROS production occurred from this process in the dark until sulfide was added. Sulfide addition resulted in the rapid production of hydrogen peroxide, with maximum concentrations of 3.85 ?M. The mechanism of hydrogen peroxide production was tested using a simplified three factor representation of the system based on hydrogen sulfide, Fe(II) and Fe(III). The resulting predictive model for maximum hydrogen peroxide agreed with measured hydrogen peroxide in field-derived samples at the 95% level of confidence, although with a persistent negative bias suggesting a minor undiscovered peroxide source in sediments. PMID:24597860

  20. Cyclic Stretch, Reactive Oxygen Species, and Vascular Remodeling

    PubMed Central

    2009-01-01

    Abstract Blood vessels respond to changes in mechanical load from circulating blood in the form of shear stress and mechanical strain as the result of heart propulsions by changes in intracellular signaling leading to changes in vascular tone, production of vasoactive molecules, and changes in vascular permeability, gene regulation, and vascular remodeling. In addition to hemodynamic forces, microvasculature in the lung is also exposed to stretch resulting from respiratory cycles during autonomous breathing or mechanical ventilation. Among various cell signaling pathways induced by mechanical forces and reported to date, a role of reactive oxygen species (ROS) produced by vascular cells receives increasing attention. ROS play an essential role in signal transduction and physiologic regulation of vascular function. However, in the settings of chronic hypertension, inflammation, or acute injury, ROS may trigger signaling events that further exacerbate smooth muscle hypercontractility and vascular remodeling associated with hypertension and endothelial barrier dysfunction associated with acute lung injury and pulmonary edema. These conditions are also characterized by altered patterns of mechanical stimulation experienced by vasculature. This review will discuss signaling pathways regulated by ROS and mechanical stretch in the pulmonary and systemic vasculature and will summarize functional interactions between cyclic stretch- and ROS-induced signaling in mechanochemical regulation of vascular structure and function. Antioxid. Redox Signal. 11, 1651–1667. PMID:19186986

  1. Role of GLUT1 in regulation of reactive oxygen species

    PubMed Central

    Andrisse, Stanley; Koehler, Rikki M.; Chen, Joseph E.; Patel, Gaytri D.; Vallurupalli, Vivek R.; Ratliff, Benjamin A.; Warren, Daniel E.; Fisher, Jonathan S.

    2014-01-01

    In skeletal muscle cells, GLUT1 is responsible for a large portion of basal uptake of glucose and dehydroascorbic acid, both of which play roles in antioxidant defense. We hypothesized that conditions that would decrease GLUT1-mediated transport would cause increased reactive oxygen species (ROS) levels in L6 myoblasts, while conditions that would increase GLUT1-mediated transport would result in decreased ROS levels. We found that the GLUT1 inhibitors fasentin and phloretin increased the ROS levels induced by antimycin A and the superoxide generator pyrogallol. However, indinavir, which inhibits GLUT4 but not GLUT1, had no effect on ROS levels. Ataxia telangiectasia mutated (ATM) inhibitors and activators, previously shown to inhibit and augment GLUT1-mediated transport, increased and decreased ROS levels, respectively. Mutation of an ATM target site on GLUT1 (GLUT1-S490A) increased ROS levels and prevented the ROS-lowering effect of the ATM activator doxorubicin. In contrast, expression of GLUT1-S490D lowered ROS levels during challenge with pyrogallol, prevented an increase in ROS when ATM was inhibited, and prevented the pyrogallol-induced decrease in insulin signaling and insulin-stimulated glucose transport. Taken together, the data suggest that GLUT1 plays a role in regulation of ROS and could contribute to maintenance of insulin action in the presence of ROS. PMID:25101238

  2. Generator-specific targets of mitochondrial reactive oxygen species.

    PubMed

    Bleier, Lea; Wittig, Ilka; Heide, Heinrich; Steger, Mirco; Brandt, Ulrich; Dröse, Stefan

    2015-01-01

    To understand the role of reactive oxygen species (ROS) in oxidative stress and redox signaling it is necessary to link their site of generation to the oxidative modification of specific targets. Here we have studied the selective modification of protein thiols by mitochondrial ROS that have been implicated as deleterious agents in a number of degenerative diseases and in the process of biological aging, but also as important players in cellular signal transduction. We hypothesized that this bipartite role might be based on different generator sites for "signaling" and "damaging" ROS and a directed release into different mitochondrial compartments. Because two main mitochondrial ROS generators, complex I (NADH:ubiquinone oxidoreductase) and complex III (ubiquinol:cytochrome c oxidoreductase; cytochrome bc1 complex), are known to predominantly release superoxide and the derived hydrogen peroxide (H2O2) into the mitochondrial matrix and the intermembrane space, respectively, we investigated whether these ROS generators selectively oxidize specific protein thiols. We used redox fluorescence difference gel electrophoresis analysis to identify redox-sensitive targets in the mitochondrial proteome of intact rat heart mitochondria. We observed that the modified target proteins were distinctly different when complex I or complex III was employed as the source of ROS. These proteins are potential targets involved in mitochondrial redox signaling and may serve as biomarkers to study the generator-dependent dual role of mitochondrial ROS in redox signaling and oxidative stress. PMID:25451644

  3. 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

  4. A Mitochondrial Oscillator Dependent on Reactive Oxygen Species

    PubMed Central

    Cortassa, Sonia; Aon, Miguel A.; Winslow, Raimond L.; O'Rourke, Brian

    2004-01-01

    We describe a unique mitochondrial oscillator that depends on oxidative phosphorylation, reactive oxygen species (ROS), and mitochondrial inner membrane ion channels. Cell-wide synchronized oscillations in mitochondrial membrane potential (??m), NADH, and ROS production have been recently described in isolated cardiomyocytes, and we have hypothesized that the balance between superoxide anion efflux through inner membrane anion channels and the intracellular ROS scavenging capacity play a key role in the oscillatory mechanism. Here, we formally test the hypothesis using a computational model of mitochondrial energetics and Ca2+ handling including mitochondrial ROS production, cytoplasmic ROS scavenging, and ROS activation of inner membrane anion flux. The mathematical model reproduces the period and phase of the observed oscillations in ??m, NADH, and ROS. Moreover, we experimentally verify model predictions that the period of the oscillator can be modulated by altering the concentration of ROS scavengers or the rate of oxidative phosphorylation, and that the redox state of the glutathione pool oscillates. In addition to its role in cellular dysfunction during metabolic stress, the period of the oscillator can be shown to span a wide range, from milliseconds to hours, suggesting that it may also be a mechanism for physiological timekeeping and/or redox signaling. PMID:15345581

  5. Obesity Increases Cerebrocortical Reactive Oxygen Species And Impairs Brain Function

    PubMed Central

    Freeman, Linnea R.; Zhang, Le; Nair, Anand; Dasuri, Kalavathi; Francis, Joseph; Fernandez-Kim, Sun-Ok; Bruce-Keller, Annadora J.; Keller, Jeffrey N.

    2014-01-01

    Nearly two-thirds of the population in the United States is overweight or obese, and this unprecedented level of obesity will undoubtedly have a profound impact on overall health, although little is currently known about the effects of obesity on the brain. The objective of the current study was to investigate cerebral oxidative stress and cognitive decline in the context of diet-induced obesity (DIO). We demonstrate for the first time that DIO induces higher levels of reactive oxygen species (ROS) in the brain, and promotes cognitive impairment. Importantly, we also demonstrate for the first time in these studies that both body weight and adiposity are tightly correlated with the level of ROS. Interestingly, ROS were not correlated with cognitive decline in this model. Alterations in the antioxidant/detoxification Nrf2 pathway, superoxide dismutase, and catalase were not significantly altered in response to DIO. A significant impairment in glutathione peroxidase was observed in response to DIO. Taken together, these data demonstrate for the first time that DIO increases the level of total and individual ROS in the brain, and highlight a direct relationship between the amount of adiposity and the level of oxidative stress within the brain. These data have important implications for understanding the negative effects of obesity on the brain, and are vital to understanding the role of oxidative stress in mediating the effects of obesity on the brain. PMID:23116605

  6. 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

  7. How reactive oxygen species and proline face stress together.

    PubMed

    Ben Rejeb, Kilani; Abdelly, Chedly; Savouré, Arnould

    2014-07-01

    Reactive oxygen species (ROS) are continuously generated as a consequence of plant metabolic processes due to incomplete reduction of O2. Previously considered to be only toxic by-products of metabolism, ROS are now known to act as second messengers in intracellular signalling cascades to trigger tolerance of various abiotic and biotic stresses. The accumulation of proline is frequently observed during the exposure of plants to adverse environmental conditions. Interestingly proline metabolism may also contribute to ROS formation in mitochondria, which play notably a role in hypersensitive response in plants, life-span extension in worms and tumor suppression in animals. Here we review current knowledge about the regulation of proline metabolism in response to environmental constraints and highlight the key role of ROS in the regulation of this metabolism. The impact of proline on ROS generation is also investigated. Deciphering and integrating these relationships at the whole plant level will bring new perspectives on how plants adapt to environmental stresses. PMID:24813727

  8. 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-1? 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

  9. 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

  10. Reactive Oxygen Species Regulate Neutrophil Recruitment and Survival in Pneumococcal Pneumonia

    Microsoft Academic Search

    Helen M. Marriott; Laura E. Jackson; Thomas S. Wilkinson; A. John Simpson; Tim J. Mitchell; David J. Buttle; Simon S. Cross; Paul G. Ince; Paul G. Hellewell; Moira K. B. Whyte; David H. Dockrell

    2008-01-01

    Rationale: The role of NADPH oxidase activation in pneumonia is complex because reactive oxygen species contribute to both micro- bial killing and regulation of the acute pulmonary infiltrate. The rel- ative importance ofeachroleremainspoorlydefinedin community- acquired pneumonia. Objectives: We evaluated the contribution of NADPH oxidase- derived reactive oxygen species to the pathogenesis of pneumococ- calpneumonia,addressingboththecontributiontomicrobialkilling and regulation of the inflammatory response.

  11. Intracellular generation of reactive oxygen species by contracting skeletal muscle cells

    Microsoft Academic Search

    Francis McArdle; David M. Pattwell; Aphrodite Vasilaki; Anne McArdle; Malcolm J. Jackson

    2005-01-01

    The aim of this work was to examine the intracellular generation of reactive oxygen species in skeletal muscle cells at rest and during and following a period of contractile activity. Intracellular generation of reactive oxygen species was examined directly in skeletal muscle myotubes using 2?,7?-dichlorodihydrofluorescein (DCFH) as an intracellular probe. Preliminary experiments confirmed that DCFH located to the myotubes but

  12. Reactive oxygen species signaling in plants under abiotic stress.

    PubMed

    Choudhury, Shuvasish; Panda, Piyalee; Sahoo, Lingaraj; Panda, Sanjib Kumar

    2013-04-01

    Abiotic stresses like heavy metals, drought, salt, low temperature, etc. are the major factors that limit crop productivity and yield. These stresses are associated with production of certain deleterious chemical entities called reactive oxygen species (ROS), which include hydrogen peroxide (H?O?), superoxide radical (O?(-)), hydroxyl radical (OH(-)), etc. ROS are capable of inducing cellular damage by degradation of proteins, inactivation of enzymes, alterations in the gene and interfere in various pathways of metabolic importance. Our understanding on ROS in response to abiotic stress is revolutionized with the advancements in plant molecular biology, where the basic understanding on chemical behavior of ROS is better understood. Understanding the molecular mechanisms involved in ROS generation and its potential role during abiotic stress is important to identify means by which plant growth and metabolism can be regulated under acute stress conditions. ROS mediated oxidative stress, which is the key to understand stress related toxicity have been widely studied in many plants and the results in those studies clearly revealed that oxidative stress is the main symptom of toxicity. Plants have their own antioxidant defense mechanisms to encounter ROS that is of enzymic and non-enzymic nature . Coordinated activities of these antioxidants regulate ROS detoxification and reduces oxidative load in plants. Though ROS are always regarded to impart negative impact on plants, some reports consider them to be important in regulating key cellular functions; however, such reports in plant are limited. Molecular approaches to understand ROS metabolism and signaling have opened new avenues to comprehend its critical role in abiotic stress. ROS also acts as secondary messenger that signals key cellular functions like cell proliferation, apoptosis and necrosis. In higher eukaryotes, ROS signaling is not fully understood. In this review we summarize our understanding on ROS and its signaling behavior in plants under abiotic stress. PMID:23425848

  13. Are mitochondrial reactive oxygen species required for autophagy?

    SciTech Connect

    Jiang, Jianfei, E-mail: jjf73@pitt.edu [Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh (United States)] [Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh (United States); Maeda, Akihiro; Ji, Jing [Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh (United States)] [Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh (United States); Baty, Catherine J.; Watkins, Simon C. [Center for Biologic Imaging, Department of Cell Biology and Physiology, University of Pittsburgh (United States)] [Center for Biologic Imaging, Department of Cell Biology and Physiology, University of Pittsburgh (United States); Greenberger, Joel S. [Department of Radiation Oncology, University of Pittsburgh (United States)] [Department of Radiation Oncology, University of Pittsburgh (United States); Kagan, Valerian E., E-mail: kagan@pitt.edu [Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh (United States)

    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.

  14. 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.

  15. Mucin overproduction in chronic inflammatory lung disease

    PubMed Central

    Hauber, Hans-Peter; Foley, Susan C; Hamid, Qutayba

    2006-01-01

    Mucus overproduction and hypersecretion are commonly observed in chronic inflammatory lung disease. Mucins are gel-forming glycoproteins that can be stimulated by a variety of mediators. The present review addresses the mechanisms involved in the upregulation of secreted mucins. Mucin induction by neutrophil elastase, bacteria, cytokines, growth factors, smoke and cystic fibrosis transmembrane conductance regulator malfunction are also discussed. PMID:16983448

  16. The induction of reactive oxygen species and loss of mitochondrial Omi/HtrA2 is associated with S-nitrosoglutathione-induced apoptosis in human endothelial cells

    SciTech Connect

    Liu Qibing; Liu Lulu [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou, 310058 (China); Lu Yingmei [Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai (Japan); Tao Rongrong; Huang Jiyun [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou, 310058 (China); Shioda, Norifumi; Moriguchi, Shigeki; Fukunaga, Kohji [Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai (Japan); Han Feng, E-mail: changhuahan@zju.edu.c [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou, 310058 (China); Lou Yijia, E-mail: yijialou@zju.edu.c [Institute of Pharmacology, Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou, 310058 (China)

    2010-05-01

    The pathophysiological relevance of S-nitrosoglutathione (GSNO)-induced endothelial cell injury remains unclear. The main objective of this study was to elucidate the molecular mechanisms of GSNO-induced oxidative stress in endothelial cells. Morphological evaluation through DAPI staining and propidium iodide (PI) flow cytometry was used to detect apoptosis. In cultured EA.hy926 endothelial cells, exposure to GSNO led to a time- and dose-dependent apoptotic cascade. When intracellular reactive oxygen species (ROS) production was measured in GSNO-treated cells with the fluorescent probes 5-(and-6)-carboxy-2',7'-dichlorofluorescein diacetate, we observed elevated ROS levels and a concomitant loss in mitochondrial membrane potential, indicating that GSNO-induced death signaling is mediated through a ROS-mitochondrial pathway. Importantly, we found that peroxynitrite formation and Omi/HtrA2 release from mitochondria were involved in this phenomenon, whereas changes of death-receptor dependent signaling were not detected in the same context. The inhibition of NADPH oxidase activation and Omi/HtrA2 by a pharmacological approach provided significant protection against caspase-3 activation and GSNO-induced cell death, confirming that GSNO triggers the death cascade in endothelial cells in a mitochondria-dependent manner. Taken together, our results indicate that ROS overproduction and loss of mitochondrial Omi/HtrA2 play a pivotal role in reactive nitrogen species-induced cell death, and the modulation of these pathways can be of significant therapeutic benefit.

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

    SciTech Connect

    Zhang, Yuantao T.; He Jin [Shandong Provincial Key Lab of UHV Technology and Gas Discharge Physics, School of Electrical Engineering, Shandong University, Jinan, Shandong Province 250061 (China)

    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.

  18. Oxygen therapy does not increase production and damage induced by reactive oxygen species in focal cerebral ischemia.

    PubMed

    Sun, Li; Wolferts, Guido; Veltkamp, Roland

    2014-08-01

    Oxygen therapy with hyperbaric oxygen (HBO) or normobaric hyperoxia (NBO) improves outcome in experimental cerebral ischemia. However, an increased formation of reactive oxygen species (ROS) may be an undesirable side effect of oxygen therapy. We investigated the effect of both oxygen therapies on ROS production and adverse effects in murine focal ischemia. 25 min after 90 min filament-induced middle cerebral artery occlusion (MCAO), mice breathed either air, 100% O2 (NBO), or 100% O2 at 3 ata (HBO) for 60 min. ROS were depicted on tissue sections after preischemic injection of hydroethidine, a marker of in vivo superoxide production. Moreover, infarct sizes were quantified in experiments using peroxybutinitrite (PBN) in mice treated with HBO. Effects of oxygen therapy were also tested in superoxide 2 knock-out mice. Both NBO and HBO significantly reduced superoxide radicals compared to air. Application of PBN had no additional protective effect when combined with HBO. Infarct volumes did not differ among SOD2 knock-out mice receiving air (34.0 ± 19.6mm(3)), NBO (35.4 ± 14.3mm(3)) or HBO (33.4 ± 12.2mm(3)). In conclusion, brief episodes of oxygen therapy do not appear to promote damage inflicted by ROS in experimental stroke. PMID:24909618

  19. Rat colonic reactive oxygen species production and DNA damage are mediated by diet and age 

    E-print Network

    Henderson, Cara Aletha Everett

    2001-01-01

    Colon cancer is the second leading cause of death from cancer in the United States. Studies suggest that oxidative damage to DNA caused by reactive oxygen species (ROS) is a critical initiating event in carcinogenesis. Rates of colon cancer...

  20. Rat colonic reactive oxygen species production and DNA damage are mediated by diet and age

    E-print Network

    Henderson, Cara Aletha Everett

    2001-01-01

    with increased apoptosis but also elevated ROS levels and DNA fragmentation [7, 11, 30]. Various pro-apoptotic agents, including reactive oxygen species in the correct amounts, could serve as useful anticancer compounds by increasing apoptosis and thus...

  1. 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

  2. Overproduction timing errors in expert dancers.

    PubMed

    Minvielle-Moncla, Joëlle; Audiffren, Michel; Macar, Françoise; Vallet, Cécile

    2008-07-01

    The authors investigated how expert dancers achieve accurate timing under various conditions. They designed the conditions to interfere with the dancers' attention to time and to test the explanation of the interference effect provided in the attentional model of time processing. Participants were 17 expert contemporary dancers who performed a freely chosen duration while walking and executing a bilateral cyclic arm movement over a given distance. The dancers reproduced that duration in different situations of interference. The process yielded temporal overproductions, validating the attentional model and extending its application to expert populations engaged in complex motor situations. The finding that the greatest overproduction occurred in the transfer-with-improvisation condition suggests that improvisation within a time deadline requires specific training. PMID:18628106

  3. MEASUREMENT OF REACTIVE OXYGEN SPECIES AFTER PHOTODYNAMIC THERAPY IN VITRO

    Microsoft Academic Search

    A b s t r a c t Photodynamic therapy (PDT) is an emerging modality for the treatment of neoplastic and non- neoplastic diseases. It is based on the use of a sensitiser, which is localised in target tissue, light, and molecular oxygen. Sensitisers are activated with the appropriate wavelength of light and then are excited to the long-lived triplet

  4. Increases in reactive oxygen species enhance vascular endothelial cell migration through a mechanism dependent on the transient receptor potential melastatin 4 ion channel.

    PubMed

    Sarmiento, Daniela; Montorfano, Ignacio; Cerda, Oscar; Cáceres, Mónica; Becerra, Alvaro; Cabello-Verrugio, Claudio; Elorza, Alvaro A; Riedel, Claudia; Tapia, Pablo; Velásquez, Luis A; Varela, Diego; Simon, Felipe

    2015-03-01

    A hallmark of severe inflammation is reactive oxygen species (ROS) overproduction induced by increased inflammatory mediators secretion. During systemic inflammation, inflammation mediators circulating in the bloodstream interact with endothelial cells (ECs) raising intracellular oxidative stress at the endothelial monolayer. Oxidative stress mediates several pathological functions, including an exacerbated EC migration. Because cell migration critically depends on calcium channel-mediated Ca(2+) influx, the molecular identification of the calcium channel involved in oxidative stress-modulated EC migration has been the subject of intense investigation. The transient receptor potential melastatin 4 (TRPM4) protein is a ROS-modulated non-selective cationic channel that performs several cell functions, including regulating intracellular Ca(2+) overload and Ca(2+) oscillation. This channel is expressed in multiple tissues, including ECs, and contributes to the migration of certain immune cells. However, whether the TRPM4 ion channel participates in oxidative stress-mediated EC migration is not known. Herein, we investigate whether oxidative stress initiates or enhances EC migration and study the role played by the ROS-modulated TRPM4 ion channel in oxidative stress-mediated EC migration. We demonstrate that oxidative stress enhances, but does not initiate, EC migration in a dose-dependent manner. Notably, we demonstrate that the TRPM4 ion channel is critical in promoting H2O2-enhanced EC migration. These results show that TRPM4 is a novel pharmacological target for the possible treatment of severe inflammation and other oxidative stress-mediated inflammatory diseases. PMID:24518820

  5. Differential response of young and adult leaves to herbicide 2,4-dichlorophenoxyacetic acid in pea plants: role of reactive oxygen species.

    PubMed

    Pazmiño, Diana M; Rodríguez-Serrano, María; Romero-Puertas, María C; Archilla-Ruiz, Angustias; Del Río, Luis A; Sandalio, Luisa M

    2011-11-01

    In this work the differential response of adult and young leaves from pea (Pisum sativum L.) plants to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) (23 mm) applied by foliar spraying was investigated. The concentration of 2,4-D (23 mm) and the time of treatment (72 h) were previously optimized in order to visualize its toxic effects on pea plants. Under these conditions, the herbicide induced severe disturbances in mesophyll cells structure and proliferation of vascular tissue in young leaves and increased acyl-CoA oxidase (ACX), xanthine oxidase (XOD) and lipoxygenase (LOX) activities in young leaves, and only ACX and LOX in adult leaves. This situation produced reactive oxygen species (ROS) over-accumulation favoured by the absence of significant changes in the enzymatic antioxidants, giving rise to oxidative damages to proteins and membrane lipids. An increase of ethylene took place in both young and adult leaves and the induction of genes encoding the stress proteins, PRP4A and HSP 71,2, was observed mainly in young leaves. These results suggest that ROS overproduction is a key factor in the effect of high concentrations of 2,4-D, and ROS can trigger a differential response in young and adult leaves, either epinasty development in young leaves or senescence processes in adult tissues. PMID:21707656

  6. Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro

    SciTech Connect

    Park, Hae-Ryung, E-mail: heaven@umich.edu; Kamau, Patricia W.; Loch-Caruso, Rita

    2014-01-15

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds. Brominated diphenyl ether (BDE)-47 is one of the most prevalent PBDE congeners found in human breast milk, serum and placenta. Despite the presence of PBDEs in human placenta, effects of PBDEs on placental cell function are poorly understood. The present study investigated BDE-47-induced reactive oxygen species (ROS) formation and its role in BDE-47-stimulated proinflammatory cytokine release in a first trimester human extravillous trophoblast cell line, HTR-8/SVneo. Exposure of HTR-8/SVneo cells for 4 h to 20 ?M BDE-47 increased ROS generation 1.7 fold as measured by the dichlorofluorescein (DCF) assay. Likewise, superoxide anion production increased approximately 5 fold at 10 and 15 ?M and 9 fold at 20 ?M BDE-47 with a 1-h exposure, as measured by cytochrome c reduction. BDE-47 (10, 15 and 20 ?M) decreased the mitochondrial membrane potential by 47–64.5% at 4, 8 and 24 h as assessed with the fluorescent probe Rh123. Treatment with 15 and 20 ?M BDE-47 stimulated cellular release and mRNA expression of IL-6 and IL-8 after 12 and 24-h exposures: the greatest increases were a 35-fold increased mRNA expression at 12 h and a 12-fold increased protein concentration at 24 h for IL-6. Antioxidant treatments (deferoxamine mesylate, (±)?-tocopherol, or tempol) suppressed BDE-47-stimulated IL-6 release by 54.1%, 56.3% and 37.7%, respectively, implicating a role for ROS in the regulation of inflammatory pathways in HTR-8/SVneo cells. Solvent (DMSO) controls exhibited statistically significantly decreased responses compared with non-treated controls for IL-6 release and IL-8 mRNA expression, but these responses were not consistent across experiments and times. Nonetheless, it is possible that DMSO (used to dissolve BDE-47) may have attenuated the stimulatory actions of BDE-47 on cytokine responses. Because abnormal activation of proinflammatory responses can disrupt trophoblast functions necessary for placental development and successful pregnancy, further investigation is warranted of the impact of ROS and BDE-47 on trophoblast cytokine responses. - Highlights: • BDE-47 induced ROS overproduction and mitochondrial dysfunction. • BDE-47 stimulated production of proinflammatory cytokines. • Antioxidant treatment reduced BDE-47-stimulated ROS generation and cytokine release.

  7. 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.

  8. Metabolic regulation and overproduction of primary metabolites

    PubMed Central

    Sanchez, Sergio; Demain, Arnold L.

    2008-01-01

    Summary Overproduction of microbial metabolites is related to developmental phases of microorganisms. Inducers, effectors, inhibitors and various signal molecules play a role in different types of overproduction. Biosynthesis of enzymes catalysing metabolic reactions in microbial cells is controlled by well?known positive and negative mechanisms, e.g. induction, nutritional regulation (carbon or nitrogen source regulation), feedback regulation, etc. The microbial production of primary metabolites contributes significantly to the quality of life. Fermentative production of these compounds is still an important goal of modern biotechnology. Through fermentation, microorganisms growing on inexpensive carbon and nitrogen sources produce valuable products such as amino acids, nucleotides, organic acids and vitamins which can be added to food to enhance its flavour, or increase its nutritive values. The contribution of microorganisms goes well beyond the food and health industries with the renewed interest in solvent fermentations. Microorganisms have the potential to provide many petroleum?derived products as well as the ethanol necessary for liquid fuel. Additional applications of primary metabolites lie in their impact as precursors of many pharmaceutical compounds. The roles of primary metabolites and the microbes which produce them will certainly increase in importance as time goes on. In the early years of fermentation processes, development of producing strains initially depended on classical strain breeding involving repeated random mutations, each followed by screening or selection. More recently, methods of molecular genetics have been used for the overproduction of primary metabolic products. The development of modern tools of molecular biology enabled more rational approaches for strain improvement. Techniques of transcriptome, proteome and metabolome analysis, as well as metabolic flux analysis. have recently been introduced in order to identify new and important target genes and to quantify metabolic activities necessary for further strain improvement. PMID:21261849

  9. Direct detection of free radicals and reactive oxygen species in thylakoids.

    PubMed

    Hideg, Eva; Kálai, Tamás; Hideg, Kálmán

    2011-01-01

    In plants, reactive oxygen species (ROS), also known as active oxygen species (AOS), are associated with normal, physiologic processes as well as with responses to adverse conditions. ROS are connected to stress in many ways: as primary elicitors, as products and propagators of oxidative damage, or as signal molecules initiating defense or adaptation. The photosynthetic electron transport is a major site of oxidative stress by visible or ultraviolet light, high or low temperature, pollutants or herbicides. ROS production can be presumed from detecting oxidatively damaged lipids, proteins, or pigments as well as from the alleviating effects of added antioxidants. On the contrary, measuring ROS by special sensor molecules provides more direct information. This chapter focuses on the application of spin trapping electron paramagnetic resonance (EPR) spectroscopy for detecting ROS: singlet oxygen and oxygen free radicals in thylakoid membrane preparations. PMID:20960131

  10. Oxygen and Hydroxyl Species Induce Multiple Reaction Pathways for the Partial Oxidation of Allyl Alcohol on Gold

    E-print Network

    Henkelman, Graeme

    , acrolein, over oxygen-precovered gold surfaces occurs via multiple reaction pathways. Utilizing temperature -dehydrogenation via interaction with an oxygen adatom or surface hydroxyl species to generate acrolein. Mediation

  11. Generation of reactive oxygen species by a persulfide (BnSSH) Tonika Chatterji,

    E-print Network

    Gates, Kent. S.

    of molecular oxygen to reactive oxygen species (OÅÀ 2 , H2O2, and HOÅ ). Here, experiments with synthetic and varacin.4,8 RSSÀ þ O2 ! OÅÀ 2 ! H2O2 þ Mnþ ! HOÅ þ Mðnþ1Þþ ð1Þ To better understand the biological by Derbesy and Harpp for the synthesis of t-butyl hydrodisulfide (Scheme 1).9 Thus, acetyl sulfenyl chloride

  12. Bcl2 Inhibition of Neural Death: Decreased Generation of Reactive Oxygen Species

    Microsoft Academic Search

    Darci J. Kane; Theodore A. Sarafian; Rein Anton; Hejin Hahn; Edith Butler Gralla; Joan Selverstone Valentine; Tonis Ord; Dale E. Bredesen

    1993-01-01

    The proto-oncogene bcl-2 inhibits apoptotic and necrotic neural cell death. Expression of Bcl-2 in the GT1-7 neural cell line prevented death as a result of glutathione depletion. Intracellular reactive oxygen species and lipid peroxides rose rapidly in control cells depleted of glutathione, whereas cells expressing Bcl-2 displayed a blunted increase and complete survival. Modulation of the increase in reactive oxygen

  13. 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

  14. Influence of a broad temperature range on the oxygen consumption rates of three desert lizard species.

    PubMed

    Al-Sadoon, M K

    1986-01-01

    Oxygen consumption rates of three desert lizard species: (Acanthodactylus boskianus, Lacertidae; Scincus mitranus, Scincidae; Diplometopon zarudnyi, Amphisbaenidae) were determined in relation to ambient temperatures ranging from 10 to 35 degrees C using a double-chamber, volumetric closed system. The interspecific differences in the oxygen consumption rates were found to have a close relationship between the characteristics of the M-T curves, the thermoregulatory behaviour and the ecology of the respective species. The M-T curves of the studied lizards were specifically modified and adjusted to their climatic region. PMID:2873932

  15. 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.

  16. Reactive oxygen species in essential hypertension and non–insulin-dependent diabetes mellitus

    Microsoft Academic Search

    Nelson N. Orie; Walter Zidek; Martin Tepel

    1999-01-01

    To evaluate whether increased levels of reactive oxygen species (ROS) are involved in the pathogenesis of essential hypertension (EH) and non–insulin-dependent diabetes mellitus (NIDDM), both resting and stimulated levels of intracellular ROS were measured in lymphocytes from patients with EH (n = 10), NIDDM (n = 16) and age-matched healthy individuals (control subjects, n = 19). ROS was monitored with

  17. Chemiluminescent Detection and Imaging of Reactive Oxygen Species in Live Mouse Skin Exposed to UVA

    Microsoft Academic Search

    Hiroyuki Yasui; Hiromu Sakurai

    2000-01-01

    The recent increase of ultraviolet (UV) rays on Earth due to the increasing size of the ozone hole is suggested to be harmful to life and to accelerate premature photoaging of the skin. The detrimental effects of UV radiation on the skin are associated with the generation of reactive oxygen species (ROS) such as superoxide anion radical (•O?2), hydrogen peroxide

  18. Low levels of reactive oxygen species as modulators of cell function

    Microsoft Academic Search

    José Remacle; Martine Raes; Olivier Toussaint; Patricia Renard; Govind Rao

    1995-01-01

    In this paper, we present various arguments supporting the hypothesis that reactive oxygen species (ROS) could be responsible for the modulation of various cellular functions, besides their well known toxic effects.We first review the recent evidence indicating that ROS are able to modulate genome expression through specific and precise mechanisms during cell activation. The role of the nitrogen reactive radicals

  19. 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...

  20. Platelet activation through interaction with hemodialysis membranes induces neutrophils to produce reactive oxygen species

    Microsoft Academic Search

    Saotomo Itoh; Chie Susuki; Tsutomu Tsuji

    2006-01-01

    The intradialytic activation of leukocytes is one of the major causes of hemodialysis-associated complica- tions. During hemodialysis, the formation of microaggre- gates consisting of platelets and neutrophils has been ob- served to accompany the production of reactive oxygen species (ROS) by leukocytes. In this study, we investigated the interaction of platelets and neutrophils with hemodial- ysis membranes in vitro to

  1. Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain

    Microsoft Academic Search

    Hee Kee Kim; Soon Kwon Park; Jun-Li Zhou; Giulio Taglialatela; Kyungsoon Chung; Richard E. Coggeshall; Jin Mo Chung

    2004-01-01

    Reactive oxygen species (ROS) are free radicals produced in biological systems that are involved in various degenerative brain diseases. The present study tests the hypothesis that ROS also play an important role in neuropathic pain. In the rat spinal nerve ligation (SNL) model of neuropathic pain, mechanical allodynia develops fully 3 days after nerve ligation and persists for many weeks.

  2. 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...

  3. 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...

  4. Reactive Oxygen Species—Induced Apoptosis and Necrosis in Bovine Corneal Endothelial Cells

    Microsoft Academic Search

    Kyung-Sun Cho; Eunjoo H. Lee; Jun-Sub Choi; Choun-Ki Joo

    1999-01-01

    PURPOSE. The loss of corneal endothelial cells associated with aging and possibly other causes has been speculated to be related to exposure to reactive oxygen species (ROS). The current study was conducted to investigate, by use of photosensitizers, the underlying mechanisms involved in the death of bovine corneal endothelial cells (BCENs) caused by ROS. METHODS. BCEN cells in primary culture

  5. Role of redox potential and reactive oxygen species in stress signaling

    Microsoft Academic Search

    Victor Adler; Zhimin Yin; Kenneth D Tew; Ze'ev Ronai

    1999-01-01

    Stress-activated signaling cascades are affected by altered redox potential. Key contributors to altered redox potential are reactive oxygen species (ROS) which are formed, in most cases, by exogenous genotoxic agents including irradiation, inflammatory cytokines and chemical carcinogens. ROS and altered redox potential can be considered as the primary intracellular changes which regulate protein kinases, thereby serving as an important cellular

  6. Transient Influx of Nickel in Root Mitochondria Modulates Organic Acid and Reactive Oxygen Species Production in

    E-print Network

    Sparks, Donald L.

    Transient Influx of Nickel in Root Mitochondria Modulates Organic Acid and Reactive Oxygen Species Production in Nickel Hyperaccumulator Alyssum murale*S Received for publication,August 1, 2012 that nickel is localized in the mitochondria of Alyssum murale root epidermal cells. Conclusion

  7. Nox2-derived reactive oxygen species mediate neurovascular dysregulation in the aging mouse brain

    Microsoft Academic Search

    Josef Anrather; Helene Girouard; Ping Zhou; Costantino Iadecola

    2007-01-01

    Aging is associated with cerebrovascular dysregulation, which may underlie the increased susceptibility to ischemic stroke and vascular cognitive impairment occurring in the elder individuals. Although it has long been known that oxidative stress is responsible for the cerebrovascular dysfunction, the enzymatic system(s) generating the reactive oxygen species (ROS) have not been identified. In this study, we investigated whether the superoxide-producing

  8. Production of reactive oxygen species by hemocytes of Biomphalaria glabrata: carbohydrate-specific stimulation

    Microsoft Academic Search

    Ulrike K Hahn; Randall C Bender; Christopher J Bayne

    2000-01-01

    Recognition of specific carbohydrate structures, which occur commonly on the surfaces of invading pathogens, is thought to elicit internal defense mechanisms in invertebrates. To investigate the nature of carbohydrates that evoke a defensive response in hemocytes of the gastropod Biomphalaria glabrata, we tested eight different carbohydrates, conjugated to bovine serum albumin (BSA), for generation of reactive oxygen species (ROS). Six

  9. Release of reactive oxygen and nitrogen species from contracting skeletal muscle cells

    Microsoft Academic Search

    David M. Patwell; Anne McArdle; Jennifer E. Morgan; Terence A. Patridge; Malcolm J. Jackson

    2004-01-01

    A number of studies have indicated that exercise is associated with an increased oxidative stress in skeletal muscle tissue, but the nature of the increased oxidants and sites of their generation have not been clarified. The generation of extracellular reactive oxygen and nitrogen species has been studied in myotubes derived from an immortalized muscle cell line (H-2kb cells) that were

  10. Involvement of Angiotensin II and Reactive Oxygen Species in Pancreatic Fibrosis

    Microsoft Academic Search

    Toshiharu Sakurai; Masatoshi Kudo; Nobuhiro Fukuta; Tatsuya Nakatani; Masatomo Kimura; Ah-Mee Park; Hiroshi Munakata

    2011-01-01

    Background: Pancreatic cancers often develop in the context of pancreatic fibrosis caused by chronic pancreas inflammation, which also results in the accumulation of reactive oxygen species (ROS), pancreatic parenchymal cell death, and stellate cell activation. Angiotensin II, which is converted from angiotensin I by the angiotensin-converting enzyme (ACE), stimulates ROS production via NADPH oxidase. In stellate cells, angiotensin II activates

  11. Reactive Oxygen Species and Root Hairs in Arabidopsis Root Response to Nitrogen, Phosphorus and Potassium Deficiency

    Microsoft Academic Search

    Ryoung Shin; R. Howard Berg; Daniel P. Schachtman

    2005-01-01

    ; Plant root sensing and adaptation to changes in the nutrient status of soils is vital for long-term productivity and growth. Reactive oxygen species (ROS) have been shown to play a role in root response to potassium depriva- tion. To determine the role of ROS in plant response to nitrogen and phosphorus deficiency, studies were con- ducted using wild-type Arabidopsis

  12. Cytotoxic effect of formaldehyde with free radicals via increment of cellular reactive oxygen species

    Microsoft Academic Search

    Yoshiro Saito; Keiko Nishio; Yasukazu Yoshida; Etsuo Niki

    2005-01-01

    It is well known that formaldehyde (HCHO) and reactive oxygen species (ROS), such as free radicals, are cytotoxic as well as potentially carcinogenic. Although the individual effects of these reactants on cells have been investigated, the cytotoxicity exerted by the coexistence of HCHO and reactive radicals is poorly understood. The present study using Jurkat cells demonstrated that the coexistence of

  13. Quality Control of Reactive Oxygen Species Measurement by Luminol-Dependent Chemiluminescence Assay

    Microsoft Academic Search

    HIROSHI KOBAYASHI; ENRIQUE GIL-GUZMAN; AYMAN M. MAHRAN; RAKESH K. SHARMA; DAVID R. NELSON; ANTHONY J. THOMAS JR; ASHOK AGARWAL

    A total of 28 donor semen samples were used to eval- uate the characteristics of laboratory variability in measuring reactive oxygen species (ROS). The objectives of this study were to assess the interassay (same sample observed on different days by the same observers) variability; interdonor, intraobserver (replications of the same sample on the same day) variability; and interobserver (multiple observers

  14. Regulation of Apical Dominance in Aspergillus nidulans Hyphae by Reactive Oxygen Species

    Microsoft Academic Search

    Camile P. Semighini; Steven D. Harris

    2008-01-01

    In fungal hyphae, apical dominance refers to the suppression of secondary polarity axes in the general vicinity of a growing hyphal tip. The mechanisms underlying apical dominance remain largely undefined, although calcium signaling may play a role. Here, we describe the localized accumulation of reactive oxygen species (ROS) in the apical region of Aspergillus nidulans hyphae. Our analysis of atmA

  15. Oxidases and peroxidases in cardiovascular and lung disease: New concepts in reactive oxygen species signaling

    Microsoft Academic Search

    Imad Al Ghouleh; Nicholas K. H. Khoo; Ulla G. Knaus; Kathy K. Griendling; Rhian M. Touyz; Victor J. Thannickal; Aaron Barchowsky; William M. Nauseef; Eric E. Kelley; Phillip M. Bauer; Victor Darley-Usmar; Sruti Shiva; Eugenia Cifuentes-Pagano; Bruce A. Freeman; Mark T. Gladwin; Patrick J. Pagano

    2011-01-01

    Reactive oxygen species (ROS) are involved in numerous physiological and pathophysiological responses. Increasing evidence implicates ROS as signaling molecules involved in the propagation of cellular pathways. The NADPH oxidase (Nox) family of enzymes is a major source of ROS in the cell and has been related to the progression of many diseases and even environmental toxicity. The complexity of this

  16. 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...

  17. 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...

  18. Reactive Oxygen Species and Acute Modulation of Albumin Microvascular Leakage in the Microcirculation of Diabetic Rats in vivo

    Microsoft Academic Search

    E. Bonnardel-Phu; E. Vicaut

    2000-01-01

    Endothelial cells have been reported to generate reactive oxygen species such as the superoxide anion, hydrogen peroxide, and the hydroxyl radical. The aim of this work was to evaluate the role of reactive oxygen species in diabetes-induced changes in vascular permeability. Intravital videomicroscopy was used to study albumin microvascular leakage in the cremaster muscle. The extravasation of a fluorescent macromolecular

  19. Secretion of MCP-1 and IL6 by cytokine stimulated production of reactive oxygen species in endothelial cells

    Microsoft Academic Search

    Thomas Volk; Mario Hensel; Horst Schuster; Wolfgang J. Kox

    2000-01-01

    Endothelial cells are known to produce reactive oxygen species by several mechanisms. Functional consequences of increased production of reactive oxygen species were investigated in vitro after stimulation with several proinflammatory cytokines. Time dependent increases in DCF-fluorescence as a measure of reactive oxygen load were quantified in single cells after incubation with TNF-a, IL-1 and IFN-?. The increased DCF-fluorescence was inhibited

  20. Prostaglandins and radical oxygen species are involved in microvascular effects of hyperoxia.

    PubMed

    Rousseau, A; Tesselaar, E; Henricson, J; Sjöberg, F

    2010-01-01

    Hyperoxia causes vasoconstriction in most tissues, by mechanisms that are not fully understood. We investigated microvascular effects of breathing 100% oxygen in healthy volunteers, using iontophoresis to deliver acetylcholine (ACh) and sodium nitroprusside (SNP). Aspirin and vitamin C were used to test for involvement of prostaglandins and radical oxygen species. Forearm skin perfusion was measured using laser Doppler perfusion imaging. Results were analysed using dose-response modelling. The response to ACh was reduced by 30% during oxygen breathing compared to air breathing [0.98 (0.81-1.15) PU vs. 1.45 (1.30-1.60) PU, p < 0.001]. ED(50) values were unchanged [2.25 (1.84-2.75) vs. 2.21 (1.79-2.74), not significant]. Aspirin pre-treatment abolished the difference in response between oxygen breathing and air breathing [maximum: 1.03 (0.90-1.16) vs. 0.89 (0.77-1.01), not significant; ED(50): 1.83 (1.46-2.30) vs. 1.95 (1.65-2.30), not significant]. ACh-mediated vasodilatation during 100% oxygen breathing was partially restored after pre-treatment with vitamin C. Breathing 100% oxygen did not change the microvascular response to SNP [1.45 (1.28-1.62) vs. 1.40 (1.26-1.53), not significant]. These results favour the hypothesis that hyperoxic vasoconstriction is mediated by inhibition of prostaglandin synthesis. Radical oxygen species may be involved as vitamin C, independently of aspirin, partially restored ACh-mediated vasodilatation during hyperoxia. PMID:20145417

  1. 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.

  2. The contribution of reactive oxygen species to the photobleaching of organic fluorophores.

    PubMed

    Zheng, Qinsi; Jockusch, Steffen; Zhou, Zhou; Blanchard, Scott C

    2014-01-01

    Photoexcitation of fluorophores commonly used for biological imaging applications generates reactive oxygen species (ROS) which can cause bleaching of the fluorophore and damage to the biological system under investigation. In this study, we show that singlet oxygen contributes relatively little to Cy5 and ATTO 647N photobleaching at low concentrations in aqueous solution. We also show that Cy5 generates significantly less ROS when covalently linked to the protective agents, cyclooctatetraene (COT), nitrobenzyl alcohol (NBA) or Trolox. Such fluorophores exhibit enhanced photostability both in bulk solutions and in single-molecule fluorescence measurements. While the fluorophores ATTO 647N and ATTO 655 showed greater photostability than Cy5 and the protective-agent-linked Cy5 derivatives investigated here, both of ATTO 647N and ATTO 655 generated singlet oxygen and hydroxyl radicals at relatively rapid rates, suggesting that they may be substantially more phototoxic than Cy5 and its derivatives. PMID:24188468

  3. Comparison of sensitizers by detecting reactive oxygen species after photodynamic reaction in vitro.

    PubMed

    Kolarova, H; Bajgar, R; Tomankova, K; Nevrelova, P; Mosinger, J

    2007-10-01

    The production of reactive oxygen species (ROS) has a crucial effect on the result of photodynamic therapy (PDT). Because of this fact, we examined the ROS formation by means of three porphyrin sensitizers (TPPS(4), ZnTPPS(4) and PdTPPS(4)) and compared their effectivity for induction of cell death in the G361 (human melanoma) cell line. The porphyrins used are very efficient water-soluble aromatic dyes with a potential application in photomedicine and have a high tendency to accumulate in the membranes of intracellular organelles such as lysosomes and mitochondria. Interaction between the triplet excited state of the sensitizer and molecular oxygen leads to the production singlet oxygen and other reactive oxygen species to induce cell death. Production of ROS was investigated by molecular probe CM-H(2)DCFDA. Our results demonstrated that ZnTPPS(4) induces the highest ROS production in the cell line compared to TPPS(4) and PdTPPS(4) at concentrations of 1, 10, and 100 microM and light dose of 1 J cm(-2). We also observed a consequence between ROS production and cell survival. In conclusion, these results demonstrate that photodynamic effect depends on sensitizer type, its concentration and light dose. PMID:17561369

  4. Annato extract and ?-carotene modulate the production of reactive oxygen species/nitric oxide in neutrophils from diabetic rats

    PubMed Central

    Rossoni-Júnior, Joamyr Victor; Araújo, Glaucy Rodrigues; Pádua, Bruno da Cruz; Chaves, Míriam Martins; Pedrosa, Maria Lúcia; Silva, Marcelo Eustáquio; Costa, Daniela Caldeira

    2012-01-01

    Annatto has been identified as carotenoids that have antioxidative effects. It is well known that one of the key elements in the development of diabetic complications is oxidative stress. The immune system is especially vulnerable to oxidative damage because many immune cells, such as neutrophils, produce reactive oxygen species and reactive nitrogen species as part of the body’s defense mechanisms to destroy invading pathogens. Reactive oxygen species/reactive nitrogen species are excessively produced by active peripheral neutrophils, and may damage essential cellular components, which in turn can cause vascular complications in diabetes. The present study was undertaken to evaluate the possible protective effects of annatto on the reactive oxygen species and nitric oxide (NO) inhibition in neutrophils from alloxan-induced diabetic rats. Adult female rats were divided into six groups based on receiving either a standard diet with or without supplementation of annatto extract or beta carotene. All animals were sacrificed 30 days after treatment and the neutrophils were isolated using two gradients of different densities. The reactive oxygen species and NO were quantified by a chemiluminescence and spectrophotometric assays, respectively. Our results show that neutrophils from diabetic animals produce significantly more reactive oxygen species and NO than their respective controls and that supplementation with beta carotene and annatto is able to modulate the production of these species. Annatto extract may have therapeutic potential for modulation of the balance reactive oxygen species/NO induced by diabetes. PMID:22573917

  5. Zinc protects Ceratophyllum demersum L. (free-floating hydrophyte) against reactive oxygen species induced by cadmium

    Microsoft Academic Search

    P. Aravind; M. N. V. Prasad; P. Malec; A. Waloszek; K. Strza?ka

    2009-01-01

    Evidence for Zn protection against Cd-induced reactive oxygen species in the free-floating hydrophyte Ceratophyllum demersum L. is presented in this paper. Metal treatments of 10?mol\\/L Cd, 10 Cd?mol\\/L supplemented with Zn (10, 50, 100 and 200?mol\\/L) and Zn-alone treatments of the same concentrations were used. Using 5,5 dimethyl pyrroline-N-oxide as the spin-probe, electron spin resonance spectra indicated a drastic increase

  6. Reactive oxygen species, cell growth, and taxol production of Taxus cuspidata cells immobilized on polyurethane foam

    Microsoft Academic Search

    De-Ming Yin; Jin-Chuan Wu; Ying-Jin Yuan

    2005-01-01

    Dynamic changes in reactive oxygen species (ROS) of Taxus cuspidata cells immobilized on polyurethane foam were investigated and the relation between ROS content and taxol production was discussed.\\u000a Immobilization shortened the lag period of cell growth and moderately increased H2O2 and O2\\u000a ?• contents inside the microenvironment within the first 15 d. After 20 d, excessive production of H2O2 and

  7. Nadolol inhibits reactive oxygen species generation by leukocytes and linoleic acid oxidation

    Microsoft Academic Search

    Cesar H Magsino; Wael Hamouda; Vini Bapna; Husam Ghanim; Ihab A Abu-Reish; Ahmad Aljada; Paresh Dandona

    2000-01-01

    We studied the effect of short-term nadolol administration on the reactive oxygen species (ROS) generation by polymorphonuclear leukocytes and mononuclear cells in 8 normal subjects. At a oral dose of 40 mg\\/day for 5 days, nadolol produced a decrease in the ROS generation by leukocytes. ROS generation by polymorphonuclear leukocytes decreased by 38% from 134 ± 44 mV at baseline

  8. Reactive oxygen species downregulate the expression of pro-inflammatory genes by human chondrocytes

    Microsoft Academic Search

    M. Mathy-Hartert; G. Martin; P. Devel; G. Deby-Dupont; J.-P. Pujol; J.-Y. Reginster; Y. Henrotin

    2003-01-01

    Objectives: To determine the regulatory effects of reactive oxygen species (ROS) on the expression by human osteoarthritic chondrocytes of interleukin (IL)-1#, -6 and -8, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene in response to interleukin (IL)-1# or lipopolysaccharide (LPS).¶ Methods: Human chondrocytes in monolayer culture were incubated for 3 h with ROS generating molecules such as S-nitroso-N-acetyl-D,L-penicillamine (SNAP,

  9. Diastereoselective protein methionine oxidation by reactive oxygen species and diastereoselective repair by methionine sulfoxide reductase

    Microsoft Academic Search

    Victor S. Sharov; Christian Schöneich

    2000-01-01

    Recent studies have shown that the “calcium-sensor” protein calmodulin (CaM) suffers an age-dependent oxidation of methionine (Met) to methionine sulfoxide (MetSO) in vivo. However, MetSO did not accumulate on the Met residues that show the highest solvent-exposure. Hence, the pattern of Met oxidation in vivo may give hints as to which reactive oxygen species and oxidation mechanisms participate in the

  10. UV induces reactive oxygen species, damages sperm, and impairs fertilisation in the sea urchin Anthocidaris crassispina

    Microsoft Academic Search

    X. Y. Lu; R. S. S. Wu

    2005-01-01

    We demonstrated that environmentally relevant levels of UVA and UVB can reduce sperm motility (UVA: by 38–58%; UVB: by 42–85%; P P Anthocidaris crassispina) in a dose-dependent manner, implicating that recruitment of urchin populations might be reduced by UVR (ultraviolet radiation) prevailing in their natural habitats. Concomitantly, reactive oxygen species (ROS) production was enhanced by UVA and UVB in a

  11. Two phases of intracellular reactive oxygen species production during victorin-induced cell death in oats

    Microsoft Academic Search

    Masaru Sakamoto; Yasuomi Tada; Hitoshi Nakayashiki; Yukio Tosa; Shigeyuki Mayama

    2005-01-01

    Reactive oxygen species (ROS) are thought to be involved in various forms of programmed cell death (PCD) in animal and plant\\u000a cells. PCD, along with the production of ROS, occurs during plant–pathogen interactions. Here we show that victorin, a host-specific\\u000a toxin produced by Cochliobolus victoriae, which causes victoria blight of oats, induces two phases of intracellular ROS production in victorin-sensitive

  12. Nitric oxide counteracts cytotoxic processes mediated by reactive oxygen species in plant tissues

    Microsoft Academic Search

    María Verónica Beligni; Lorenzo Lamattina

    1999-01-01

    .   Many environmental conditions subject plants to oxidative stress, in which reactive oxygen species (ROS) are overproduced.\\u000a These ROS act as transduction signals in plant defense responses, but also cause effects that result in cellular damage. Since\\u000a nitric oxide (NO) is a bioactive molecule able to scavenge ROS, we analyzed its effect on some cytotoxic processes produced\\u000a by ROS in

  13. p38? MAP Kinase as a Sensor of Reactive Oxygen Species in Tumorigenesis

    Microsoft Academic Search

    Ignacio Dolado; Aneta Swat; Nuria Ajenjo; Gabriella De Vita; Ana Cuadrado; Angel R. Nebreda

    2007-01-01

    SUMMARY p38a is a stress-activated protein kinase that negatively regulates malignant transformation induced by oncogenic H-Ras, although the mechanisms involved are not fully understood. Here, we show that p38a is not a general inhibitor of oncogenic signaling, but that it specifically modulates transfor- mation induced by oncogenes that produce reactive oxygen species (ROS). This inhibitory effect is due to the

  14. Modification of reactive oxygen species scavenging capacity of chloroplasts through plastid transformation

    Microsoft Academic Search

    Miranda Poage; Bénédicte Le Martret; Marcel A. K. Jansen; Gregory D. Nugent; Philip J. Dix

    2011-01-01

    Reactive oxygen species (ROS), including superoxide anions, hydrogen peroxide and hydroxyl radicals are generated through\\u000a normal biochemical processes, but their production is increased by abiotic stresses. The prospects for enhancing ROS scavenging,\\u000a and hence stress tolerance, by direct gene expression in a vulnerable cell compartment, the chloroplast, have been explored\\u000a in tobacco. Several plastid transformants were generated which contained either

  15. Non-thermal dielectric barrier discharge plasma induces angiogenesis through reactive oxygen species

    Microsoft Academic Search

    Krishna P. Arjunan; Alisa Morss Clyne

    2011-01-01

    Vascularization plays a key role in processes such as wound healing and tissue engineering. Non-thermal plasma, which primarily produces reactive oxygen species (ROS), recently emerged as an efficient tool in medical applications. Liquids and endothelial cells were treated with a non-thermal dielectric barrier discharge plasma. Plasma treatment of phosphate buffered saline (PBS) and serum-free medium increased ROS concentration in a

  16. Bufalin Induces Reactive Oxygen Species Dependent Bax Translocation and Apoptosis in ASTC-a-1 Cells

    Microsoft Academic Search

    Lei Sun; Tongsheng Chen; Xiaoping Wang; Yun Chen; Xunbin Wei

    2009-01-01

    Bufalin has been shown to induce cancer cell death through apoptotic pathways. However, the molecular mechanisms are not well understood. In this study, we used the confocal fluorescence microscopy (CFM) to monitor the spatio-temporal dynamics of reactive oxygen species (ROS) production, Bax translocation and caspase-3 activation during bufalin-induced apoptosis in living human lung adenocarcinoma (ASTC-a-1) cells. Bufalin induced ROS production

  17. NADPH oxidase 4 mediates reactive oxygen species induction of CD146 dimerization in VEGF signal transduction

    Microsoft Academic Search

    Jie Zhuang; Tianxia Jiang; Di Lu; Yongting Luo; Chaogu Zheng; Jing Feng; Dongling Yang; Chang Chen; Xiyun Yan

    2010-01-01

    CD146 dimerization plays an important role in tumor-induced angiogenesis. Stimulation of target cells with vascular endothelial growth factor (VEGF), a major angiogenic factor produced by tumor cells, elicits a burst of reactive oxygen species (ROS) that enhances angiogenesis. However, the molecular mechanism coupling CD146 dimerization with the VEGF-related oxidant-generating apparatus has not been elucidated. Here, we show that CD146 dimerization

  18. NADPH oxidases in fungi: Diverse roles of reactive oxygen species in fungal cellular differentiation

    Microsoft Academic Search

    Daigo Takemoto; Aiko Tanaka; Barry Scott

    2007-01-01

    Synthesis of reactive oxygen species (ROS) by specific NADPH oxidases (Nox) can serve both defense and differentiation signaling roles in animals and plants. Fungi have three subfamilies of NADPH oxidase. NoxA and NoxB have a structure very similar to the human gp91phox. NoxC has in addition a Ca2+ binding motif as found in the human Nox5 and plant Rboh families

  19. Comparison of sensitizers by detecting reactive oxygen species after photodynamic reaction in vitro

    Microsoft Academic Search

    H. Kolarova; R. Bajgar; K. Tomankova; P. Nevrelova; J. Mosinger

    2007-01-01

    The production of reactive oxygen species (ROS) has a crucial effect on the result of photodynamic therapy (PDT). Because of this fact, we examined the ROS formation by means of three porphyrin sensitizers (TPPS4, ZnTPPS4 and PdTPPS4) and compared their effectivity for induction of cell death in the G361 (human melanoma) cell line. The porphyrins used are very efficient water-soluble

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

    SciTech Connect

    Cassir, M.; Moutiers, G.; Devynck, J. (Ecole Nationale Superieure de Chimie, Paris (France). 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.

  1. Involvement of reactive oxygen species in capsaicinoid-induced apoptosis in transformed cells.

    PubMed

    Macho, Antonio; Sancho, Rocío; Minassi, Alberto; Appendino, Giovanni; Lawen, Alfons; Muñoz, Eduardo

    2003-06-01

    Some varieties of sweet pepper accumulate non-pungent isosters of capsaicin, a type of compounds exemplified by capsiate. The only structural difference between capsaicin and capsiate is the link between the vanillyl and the acyl moieties, via an amide bond in the former and via an ester bond in the latter. By flow cytometry analyses we have determined that nor-dihydrocapsiate, a simplified analogue of capsiate, is a pro-oxidant compound that induces apoptosis in the Jurkat tumor cell line. The nuclear DNA fragmentation induced by nor-dihydrocapsiate is preceded by an increase in the production of reactive oxygen species and by a subsequent disruption of mitochondria transmembrane potential. Capsiate-induced apoptosis is initiated at the S phase of the cell cycle and is mediated by a caspase-3-dependent pathway. The accumulation of intracellular reactive oxygen species in capsiate-treated cells is greatly prevented by the presence of ferricyanide, suggesting that capsiates target a cellular redox system distinct from the one involved in the mitochondrial electron-chain transport. Methylation of the phenolic hydroxyl of nor-dihydrocapsiate completely abrogated the ability to induce reactive oxygen species and apoptosis, highlighting the relevance of the presence of a free phenolic hydroxyl for the pro-oxidant properties of capsaicinoids. PMID:12868488

  2. [Effects of allelochemical dibutyl phthalate on Gymnodinium breve reactive oxygen species].

    PubMed

    Bie, Cong-Cong; Li, Feng-Min; Li, Yuan-Yuan; Wang, Zhen-Yu

    2012-02-01

    The purpose of this study was to investigate the mechanism of inhibitory action of dibutyl phthalate (DBP) on red tide algae Gymnodinium breve. Reactive oxygen species (ROS) level, contents of *OH and H2O2, and O2*(-) production rate were investigated, and also for the effects of electron transfer inhibitors on the ROS induction of DBP. The results showed that DBP triggered the synthesis of reactive oxygen species ROS, and with the increase of concentration of DBP, *OH and H2O2 contents in cells accumulated, as for the 3 mg x L(-1) DBP treated algae cultures, OH showed a peak of 33 U x mL(-1) at 48 h, which was about 2. 4 times higher than that in the controlled, and H2O2 contents was about 250 nmol x (10(7) cells)(-1) at 72 h, which was about 5 times higher and also was the highest during the whole culture. Rotenone (an inhibitor of complex I in the mitochondria electron transport chain) decreased the DBP induced ROS production, and dicumarol (an inhibitor of the redox enzyme system in the plasma membrane) stimulated the DBP induced ROS production. Taken all together, the results demonstrated DBP induced over production of reactive oxygen species in G. breve, which is the main inhibitory mechanism, and mitochondria and plasma membrane seem to be the main target site of DBP. These conclusions were of scientific meaning on uncovering the inhibitory mechanism of allelochemical on algae. PMID:22509579

  3. 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. (Center for Nanoscale Materials); ( CSE); (McGill Univ.)

    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.

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

    PubMed

    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

    2013-11-01

    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 in molecular oxygen. Four major ROS are recognized comprising superoxide (O2•-), hydrogen peroxide (H2O2), hydroxyl radical (•OH), and singlet oxygen ((1)O2), but they display very different kinetics and levels of activity. The effects of O2•- and H2O2 are less acute than those of •OH and (1)O2, because the former are much less reactive and can be detoxified by endogenous antioxidants (both enzymatic and nonenzymatic) that are induced by oxidative stress. In contrast, no enzyme can detoxify •OH or (1)O2, 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 nonpharmacological 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

  5. Asbestos induces apoptosis of human and rabbit pleural mesothelial cells via reactive oxygen species.

    PubMed Central

    Broaddus, V C; Yang, L; Scavo, L M; Ernst, J D; Boylan, A M

    1996-01-01

    Mesothelial cells, the progenitor cell of the asbestos-induced tumor mesothelioma, are particularly sensitive to the toxic effects of asbestos, although the molecular mechanisms by which asbestos induces injury in mesothelial cells are not known. We asked whether asbestos induced apoptosis in mesothelial cells and whether reactive oxygen species were important. Pleural mesothelial cells (rabbit or human) were exposed to asbestos (crocidolite, amosite, or chrysotile) or control particles at moderate doses (1-10 microg/cm2) over 24 h and evaluated for oligonucleosomal DNA fragmentation, loss of membrane phospholipid asymmetry, and nuclear condensation. Asbestos fibers, not control particles, induced apoptosis in mesothelial cells by all assays and induction of apoptosis was dose dependent for all types of asbestos, with crocidolite (5 microg/cm2) inducing 15.0+/-1.1% (mean+/-SE; n = 12) apoptosis versus control particles < 4%. Apoptosis induced by asbestos, but not by actinomycin D, was inhibited by extracellular catalase, superoxide dismutase in the presence of catalase, hypoxia (8% oxygen), deferoxamine, 3-aminobenzamide [an inhibitor of poly(ADP-ribosyl) polymerase], and cytochalasin B. Only catalase and cytochalasin B decreased fiber uptake. We conclude that asbestos induces apoptosis in mesothelial cells via reactive oxygen species. Escape from this pathway could allow the abnormal survival of mesothelial cells with asbestos-induced mutations. PMID:8903324

  6. Preliminary Crystallographic Study of Hemoglobin from Buffalo (Bubalus bubalis): A Low Oxygen Affinity Species.

    PubMed

    Balasubramanian, Moovarkumudalvan; Moorthy, Ponnuraj Sathya; Neelagandan, Kamariah; Ponnuswamy, Mondikalipudur Nanjappa Gounder

    2009-01-01

    Hemoglobin is a tetrameric, iron-containing metalloprotein, which plays a vital role in the transportation of oxygen from lungs to tissues and carbon dioxide back to lungs. Though good amount of work has already been done on hemoglobins, the scarcity of data on three dimensional structures pertaining to low oxygen affinity hemoglobins from mammalian species, motivated our group to work on this problem specifically. Herein, we report the preliminary crystallographic analysis of buffalo hemoglobin, which belongs to low oxygen affinity species. The buffalo blood was collected, purified by anion exchange chromatography and crystallized with PEG 3350 using 50mM phosphate buffer at pH 6.7 as a precipitant by hanging drop vapor diffusion method. Data collection was carried out using mar345dtb image plate detector system. Buffalo hemoglobin crystallizes in orthorhombic space group P2(1)2(1)2(1) with one whole biological molecule (alpha2beta2) in the asymmetric unit with cell dimensions a=63.064A, b=74.677A, c=110.224A. PMID:19200047

  7. MINIMAL ROLE FOR REACTIVE OXYGEN SPECIES IN DICHLOROACETIC ACID-INDUCED DYSMORPHOLOGY IN MOUSE WHOLE EMBRYO CULTURE.

    EPA Science Inventory

    Administration of dichloroacetate (DCA) to pregnant rats produces craniofacial, heart and other defects in their offspring. Exposure of zebrafish to DCA induces malformations and increases superoxide and nitric oxide production suggesting that reactive oxygen species (ROS) are as...

  8. Reactive oxygen species and Udx1 during early sea urchin development Julian L. Wong, Gary M. Wessel*

    E-print Network

    Wessel, Gary M.

    Reactive oxygen species and Udx1 during early sea urchin development Julian L. Wong, Gary M. Wessel Abstract Sea urchin fertilization is marked by a massive conversion of molecular oxygen to hydrogen peroxide by a sea urchin dual oxidase, Udx1. This enzyme is essential for completing the physical block

  9. The association of elevated reactive oxygen species levels from neutrophils with low-grade inflammation in the elderly

    Microsoft Academic Search

    Kishiko Ogawa; Katsuhiko Suzuki; Mitsuharu Okutsu; Kyoko Yamazaki; Shoji Shinkai

    2008-01-01

    BACKGROUND: Reactive oxygen species (ROS), including free radicals, oxygen ions, and peroxides, are implicated in cell damage. The objective of this study was to investigate whether the spontaneous production of ROS from neutrophils changes with age and is associated with the conventional inflammatory markers. RESULTS: Thirty-seven elderly subjects (median age, 87, range 70–95 years) and 22 young subjects (median age,

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

    SciTech Connect

    Popolan, Denisia M.; Bernhardt, Thorsten M. [Institute of Surface Chemistry and Catalysis, University of Ulm, Albert-Einstein-Allee 47, 89069 Ulm (Germany)

    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.

  11. Reaction mechanism of melatonin oxidation by reactive oxygen species in vitro.

    PubMed

    Bonnefont-Rousselot, Dominique; Collin, Fabrice; Jore, Daniel; Gardès-Albert, Monique

    2011-04-01

    Melatonin (N-acetyl-5-hydroxytryptamine) is a pineal hormone widely known for its antioxidant properties, both in vivo and by direct capture of free radicals in vitro. Although some metabolites and oxidation products of melatonin have been identified, the molecular mechanism by which melatonin exerts its antioxidant properties has not been totally unravelled. This study investigated the reaction mechanism of oxidation of melatonin by radio-induced reactive oxygen species, generated by gamma radiolysis of water for aqueous solutions of melatonin (from 20 to 200 ?m), in the presence or absence of molecular oxygen. The hydroxyl radical was found to be the unique species able to initiate the oxidation process, leading to three main products, e.g. N(1)-acetyl-N(2)-formyl-5-methoxykynurenin (AFMK), N(1)-acetyl-5-methoxykynurenin (AMK) and hydroxymelatonin (HO-MLT). The generation of AFMK and HO-MLT strongly depended on the presence of molecular oxygen in solution: AFMK was the major product in aerated solutions (84%), whereas HO-MLT was favoured in the absence of oxygen (86%). Concentrations of AMK remained quite low, and AMK was proposed to result from a chemical hydrolysis of AFMK in solution. A K-value of 1.1 × 10(-4) was calculated for this equilibrium. Both hydrogen peroxide and superoxide dismutase had no effect on the radio-induced oxidation of melatonin, in good accordance for the second case with the poor reactivity of the superoxide anion towards melatonin. Finally, a reaction mechanism was proposed for the oxidation of melatonin in vitro. PMID:21244479

  12. Peroxisome Proliferation in Foraminifera Inhabiting the Chemocline: An Adaptation to Reactive Oxygen Species Exposure?1

    PubMed Central

    BERNHARD, JOAN M.; BOWSER, SAMUEL S.

    2009-01-01

    Certain foraminiferal species are abundant within the chemocline of marine sediments. Ultrastructurally, most of these species possess numerous peroxisomes complexed with the endoplasmic reticulum; mitochondria are often interspersed among these complexes. In the Santa Barbara Basin, pore-water bathing Foraminifera and co-occurring sulfur-oxidizing microbial mats had micromolar levels of hydrogen peroxide, a reactive oxygen species that can be detrimental to biological membranes. Experimental results indicate that adenosine triphosphate concentrations are significantly higher in Foraminifera incubated in 16 ?M H2O2 than in specimens incubated in the absence of H2O2. New ultrastructural and experimental observations, together with published results, lead us to propose that foraminiferans can utilize oxygen derived from the breakdown of environmentally and metabolically produced H2O2. Such a capability could explain foraminiferal adaptation to certain chemically inhospitable environments; it would also force us to reassess the role of protists in biogeochemistry, especially with respect to hydrogen and iron. The ecology of these protists also appears to be tightly linked to the sulfur cycle. Finally, given that some Foraminifera bearing peroxisome-endoplasmic reticulum complexes belong to evolutionarily basal groups, an early acquisition of the capability to use environmental H2O2 could have facilitated diversification of foraminiferans during the Neoproterozoic. PMID:18460150

  13. Oleic acid increases mitochondrial reactive oxygen species production and decreases endothelial nitric oxide synthase activity in cultured endothelial cells.

    PubMed

    Gremmels, Hendrik; Bevers, Lonneke M; Fledderus, Joost O; Braam, Branko; van Zonneveld, Anton Jan; Verhaar, Marianne C; Joles, Jaap A

    2015-03-15

    Elevated plasma levels of free fatty acids (FFA) are associated with increased cardiovascular risk. This may be related to FFA-induced elevation of oxidative stress in endothelial cells. We hypothesized that, in addition to mitochondrial production of reactive oxygen species, endothelial nitric oxide synthase (eNOS)-mediated reactive oxygen species production contributes to oleic acid (OA)-induced oxidative stress in endothelial cells, due to eNOS uncoupling. We measured reactive oxygen species production and eNOS activity in cultured endothelial cells (bEnd.3) in the presence of OA bound to bovine serum albumin, using the CM-H2DCFDA assay and the L-arginine/citrulline conversion assay, respectively. OA induced a concentration-dependent increase in reactive oxygen species production, which was inhibited by the mitochondrial complex II inhibitor thenoyltrifluoroacetone (TTFA). OA had little effect on eNOS activity when stimulated by a calcium-ionophore, but decreased both basal and insulin-induced eNOS activity, which was restored by TTFA. Pretreatment of bEnd.3 cells with tetrahydrobiopterin (BH4) prevented OA-induced reactive oxygen species production and restored inhibition of eNOS activity by OA. Elevation of OA levels leads to both impairment in receptor-mediated stimulation of eNOS and to production of mitochondrial-derived reactive oxygen species and hence endothelial dysfunction. PMID:25595727

  14. Antagonistic effect of flavonoids on NSC-741909-mediated antitumor activity via scavenging of reactive oxygen species

    PubMed Central

    Guo, Wei; Wei, Xiaoli; Wu, Shuhong; Wang, Li; Peng, Henry; Wang, Ji; Fang, Bingliang

    2010-01-01

    NSC-741909 (1-[(4-chlorophenyl)methyl]-1H-Indole-3-methanol) is a novel anticancer agent that is highly active against several NCI-60 cancer cell lines. This agent induces sustained activation of mitogen-activated protein kinases (MAPK), including JNK and p38 MAP kinases. However, the mechanisms of its selective anti-tumor activity in some cancer cell lines remain unknown. We tested the combined effects of NSC-741909 and several kinase inhibitors that target the Raf/MEK/ERK1/2 or PI3K/AKT pathways in two sensitive lung cancer cells. We found that PD98059 (2'-amino-3'-methoxyflavone), a flavone derivative and a selective MEK inhibitor, can dramatically block the cell killing effect of NSC-741909. To determine whether this inhibitory effect is associated with MEK inhibition or other mechanisms, we evaluated the effects of other MEK inhibitors with different chemical structures and flavone derivatives that do not have an effect on MEK. We found that several flavonoids can markedly block NSC-741909-induced apoptosis and JNK activation in a time-dependent manner, regardless of whether they inhibit MEK or not. In contrast, NSC-741909-induced JNK activation and apoptosis were not blocked by other MEK-specific inhibitors U0126 and CI-1040. Our results also showed that NSC-741909 induced a dramatic increase of reactive oxygen species in sensitive cells and that flavonoids effectively blocked the NSC-741909-induced reactive oxygen species production which are associated with flavonoids’ antagonistic effects on NSC-741909-induced JNK activation and apoptosis. Those results demonstrated that flavonoids mediated antagonist effect is through scavenging of reactive oxygen species. Our results may have implication on the design of clinical evaluation of antitumor activity of NSC-741909 or its analogues. PMID:20854805

  15. Characterizing semen parameters and their association with reactive oxygen species in infertile men

    PubMed Central

    2014-01-01

    Background A routine semen analysis is a first step in the laboratory evaluation of the infertile male. In addition, other tests such as measurement of reactive oxygen species can provide additional information regarding the etiology of male infertility. The objective of this study was to investigate the association of semen parameters with reactive oxygen species (ROS) in two groups: healthy donors of unproven and proven fertility and infertile men. In addition, we sought to establish an ROS cutoff value in seminal plasma at which a patient may be predicted to be infertile. Methods Seminal ejaculates from 318 infertile patients and 56 donors, including those with proven fertility were examined for semen parameters and ROS levels. Correlations were determined between traditional semen parameters and levels of ROS among the study participants. ROS levels were measured using chemiluminescence assay. Receiver operating characteristic curves were obtained to calculate a cutoff value for these tests. Results Proven Donors (n?=?28) and Proven Donors within the past 2 years (n?=?16) showed significantly better semen parameters than All Patients group (n?=?318). Significantly lower ROS levels were seen in the two Proven Donor groups compared with All Patients. The cutoff value of ROS in Proven Donors was determined to be 91.9 RLU/s with a specificity of 68.8% and a sensitivity of 93.8%. Conclusions Infertile men, irrespective of their clinical diagnoses, have reduced semen parameters and elevated ROS levels compared to proven fertile men who have established a pregnancy recently or in the past. Reactive oxygen species are negatively correlated with traditional semen parameters such as concentration, motility and morphology. Measuring ROS levels in the seminal ejaculates provides clinically-relevant information to clinicians. PMID:24885775

  16. Reactive oxygen species and antioxidant enzymes activity of Anabaena sp. PCC 7120 (Cyanobacterium) under simulated microgravity

    NASA Astrophysics Data System (ADS)

    Li, Gen-bao; Liu, Yong-ding; Wang, Gao-hong; Song, Li-rong

    2004-12-01

    It was found that reactive oxygen species in Anabaena cells increased under simulated microgravity provided by clinostat. Activities of intracellular antioxidant enzymes, such as superoxide dismutase, catalase were higher than those in the controlled samples during the 7 days' experiment. However, the contents of gluathione, an intracellular antioxidant, decreased in comparison with the controlled samples. The results suggested that microgravity provided by clinostat might break the oxidative/antioxidative balance. It indicated a protective mechanism in algal cells, that the total antioxidant system activity increased, which might play an important role for algal cells to adapt the environmental stress of microgravity.

  17. NQO2 Is a Reactive Oxygen Species Generating Off-Target for Acetaminophen

    PubMed Central

    2014-01-01

    The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity. We suggest that NQO2 mediated superoxide production may function as a novel mechanism augmenting acetaminophen toxicity. PMID:25313982

  18. Molecular Crosstalk between Integrins and Cadherins: Do Reactive Oxygen Species Set the Talk?

    PubMed Central

    Goitre, Luca; Pergolizzi, Barbara; Ferro, Elisa; Trabalzini, Lorenza; Retta, Saverio Francesco

    2012-01-01

    The coordinate modulation of the cellular functions of cadherins and integrins plays an essential role in fundamental physiological and pathological processes, including morphogenesis, tissue differentiation and renewal, wound healing, immune surveillance, inflammatory response, tumor progression, and metastasis. However, the molecular mechanisms underlying the fine-tuned functional communication between cadherins and integrins are still elusive. This paper focuses on recent findings towards the involvement of reactive oxygen species (ROS) in the regulation of cell adhesion and signal transduction functions of integrins and cadherins, pointing to ROS as emerging strong candidates for modulating the molecular crosstalk between cell-matrix and cell-cell adhesion receptors. PMID:22203898

  19. Generation of reactive oxygen species from Hinokitiol under near-UV irradiation.

    PubMed

    Shibata, Hitoshi; Nagamine, Takayuki; Wang, Yong; Ishikawa, Takahiro; Sawa, Yoshihiro

    2003-09-01

    Near-UV irradiation caused the decomposition of hinokitiol in an aqueous solution. During the photochemical reaction, the distinct electron spin resonance signal characteristic of the adduct of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) with the hydroxyl radical was accompanied by small signals corresponding to the adduct of DMPO with the superoxide anion radical. More than 95% of Escherichia coli cells were killed by the incubation with hinokitiol under near-UV irradiation by BLB fluorescent lamps. These results indicated the generation of reactive oxygen species during photochemical reaction of hinokitiol under near-UV irradiation. PMID:14519989

  20. 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

  1. Alternative Oxidase Expression in the Mouse Enables Bypassing Cytochrome c Oxidase Blockade and Limits Mitochondrial ROS Overproduction

    PubMed Central

    El-Khoury, Riyad; Dufour, Eric; Rak, Malgorzata; Ramanantsoa, Nelina; Grandchamp, Nicolas; Csaba, Zsolt; Duvillié, Bertrand; Bénit, Paule; Gallego, Jorge; Gressens, Pierre; Sarkis, Chamsy; Jacobs, Howard T.; Rustin, Pierre

    2013-01-01

    Cyanide-resistant non-phosphorylating respiration is known in mitochondria from plants, fungi, and microorganisms but is absent in mammals. It results from the activity of an alternative oxidase (AOX) that conveys electrons directly from the respiratory chain (RC) ubiquinol pool to oxygen. AOX thus provides a bypath that releases constraints on the cytochrome pathway and prevents the over-reduction of the ubiquinone pool, a major source of superoxide. RC dysfunctions and deleterious superoxide overproduction are recurrent themes in human pathologies, ranging from neurodegenerative diseases to cancer, and may be instrumental in ageing. Thus, preventing RC blockade and excess superoxide production by means of AOX should be of considerable interest. However, because of its energy-dissipating properties, AOX might produce deleterious effects of its own in mammals. Here we show that AOX can be safely expressed in the mouse (MitAOX), with major physiological parameters being unaffected. It neither disrupted the activity of other RC components nor decreased oxidative phosphorylation in isolated mitochondria. It conferred cyanide-resistance to mitochondrial substrate oxidation and decreased reactive oxygen species (ROS) production upon RC blockade. Accordingly, AOX expression was able to support cyanide-resistant respiration by intact organs and to afford prolonged protection against a lethal concentration of gaseous cyanide in whole animals. Taken together, these results indicate that AOX expression in the mouse is innocuous and permits to overcome a RC blockade, while reducing associated oxidative insult. Therefore, the MitAOX mice represent a valuable tool in order to investigate the ability of AOX to counteract the panoply of mitochondrial-inherited diseases originating from oxidative phosphorylation defects. PMID:23300486

  2. 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 (? 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

  3. Mitochondrial free radical overproduction due to respiratory chain impairment in the brain of a mouse model of Rett syndrome: protective effect of CNF1.

    PubMed

    De Filippis, Bianca; Valenti, Daniela; de Bari, Lidia; De Rasmo, Domenico; Musto, Mattia; Fabbri, Alessia; Ricceri, Laura; Fiorentini, Carla; Laviola, Giovanni; Vacca, Rosa Anna

    2015-06-01

    Rett syndrome (RTT) is a pervasive neurodevelopmental disorder mainly caused by mutations in the X-linked MECP2 gene associated with severe intellectual disability, movement disorders, and autistic-like behaviors. Its pathogenesis remains mostly not understood and no effective therapy is available. High circulating levels of oxidative stress markers in patients and the occurrence of oxidative brain damage in MeCP2-deficient mouse models suggest the involvement of oxidative stress in RTT pathogenesis. However, the molecular mechanism and the origin of the oxidative stress have not been elucidated. Here we demonstrate that a redox imbalance arises from aberrant mitochondrial functionality in the brain of MeCP2-308 heterozygous female mice, a condition that more closely recapitulates that of RTT patients. The marked increase in the rate of hydrogen peroxide generation in the brain of RTT mice seems mainly produced by the dysfunctional complex II of the mitochondrial respiratory chain. In addition, both membrane potential generation and mitochondrial ATP synthesis are decreased in RTT mouse brains when succinate, the complex II respiratory substrate, is used as an energy source. Respiratory chain impairment is brain area specific, owing to a decrease in either cAMP-dependent phosphorylation or protein levels of specific complex subunits. Further, we investigated whether the treatment of RTT mice with the bacterial protein CNF1, previously reported to ameliorate the neurobehavioral phenotype and brain bioenergetic markers in an RTT mouse model, exerts specific effects on brain mitochondrial function and consequently on hydrogen peroxide production. In RTT brains treated with CNF1, we observed the reactivation of respiratory chain complexes, the rescue of mitochondrial functionality, and the prevention of brain hydrogen peroxide overproduction. These results provide definitive evidence of mitochondrial reactive oxygen species overproduction in RTT mouse brain and highlight CNF1 efficacy in counteracting RTT-related mitochondrial defects. PMID:25708779

  4. Hypoxia-inducible Factor ? Subunit Stabilization by NEDD8 Conjugation Is Reactive Oxygen Species-dependent*

    PubMed Central

    Ryu, Ji-Hye; Li, Shan-Hua; Park, Hyoung-Sook; Park, Jong-Wan; Lee, ByungLan; Chun, Yang-Sook

    2011-01-01

    Hypoxia-inducible factor ? proteins (HIF-?s) are regulated oxygen dependently and transactivate numerous genes essential for cellular adaptation to hypoxia. NEDD8, a member of the ubiquitin-like family, covalently binds to its substrate proteins, and thus, regulates their stabilities and functions. In the present study, we examined the possibility that the HIF signaling is regulated by the neddylation. HIF-1? expression and activity were inhibited by knocking down APPBP1 E1 enzyme for NEDD8 conjugation but enhanced by ectopically expressing NEDD8. HIF-1? and HIF-2? were identified to be covalently modified by NEDD8. NEDD8 stabilized HIF-1? even in normoxia and further increased its level in hypoxia, which also occurred in von Hippel-Lindau (VHL) protein- or p53-null cell lines. The HIF-1?-stabilizing effect of NEDD8 was diminished by antioxidants and mitochondrial respiratory chain blockers. This suggests that the NEDD8 effect is concerned with reactive oxygen species driven from mitochondria rather than with the prolyl hydroxylase (PHD)/VHL-dependent oxygen-sensing system. Based on these findings, we propose that NEDD8 is an ancillary player to regulate the stability of HIF-1?. Furthermore, given the positive role played by HIF-?s in cancer promotion, the NEDD8 conjugation process could be a potential target for cancer therapy. PMID:21193393

  5. 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

  6. Production of reactive oxygen species after photodynamic therapy by porphyrin sensitizers.

    PubMed

    Kolarova, H; Nevrelova, P; Tomankova, K; Kolar, P; Bajgar, R; Mosinger, J

    2008-06-01

    The objectives of this study was to investigate the production of reactive oxygen species (ROS) after photodynamic therapy (PDT) in vitro. We examined second generation sensitizers, porphyrines (TPPS4, ZnTPPS4 and PdTPPS4) and compared their effectivity on ROS generation in G361 cell line. Used porphyrines are very efficient water-soluble aromatic dyes with potential to use in photomedicine and have a high propensity to accumulate in the membranes of intracellular organelles like lysosomes and mitochondria. Interaction between the triplet excited state of the sensitizer and molecular oxygen leads to produce singlet oxygen and other ROS to induce cell death. Production of ROS was verificated by molecular probe CM-H2DCFDA and viability of cells was determined by MTT assay. Our results demonstrated that ZnTPPS4 induces the highest ROS production in cell line compared to TPPS4 and PdTPPS4 at each used concentration and light dose. These results consist with a fact that photodynamic effect depends on sensitizer type, its concentration and light dose. PMID:18645224

  7. Response of Bacillus sp. F26 to Different Reactive Oxygen Species Stress Characterized by Antioxidative Enzymes Synthesis

    Microsoft Academic Search

    Guoliang Yan; Zhaozhe Hua; Guocheng Du; Jian Chen

    2008-01-01

    The oxidative response of Bacillus sp F26 to different forms of reactive oxygen species (ROS) stress including H2O2, O2? ? ? ? ? ?and OH· was investigated using diverse generating source of ROS, which was characterized by the synthesis of antioxidative enzymes. It was seen that the responses of cells to oxidative stress are largely dependent on species, mode (shock

  8. Cytoplasmic localization and ubiquitination of p21{sup Cip1} by reactive oxygen species

    SciTech Connect

    Hwang, Chae Young [Laboratory of Cell Signaling, Proteome Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333 (Korea, Republic of); Kim, Ick Young [Laboratory of Cellular and Molecular Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Kwon, Ki-Sun [Laboratory of Cell Signaling, Proteome Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333 (Korea, Republic of)]. E-mail: kwonks@kribb.re.kr

    2007-06-22

    Reactive oxygen species were previously shown to trigger p21{sup Cip1} protein degradation through a proteasome-dependent pathway, however the detailed mechanism of degradation remains to be elucidated. In this report, we showed that p21{sup Cip1} was degraded at an early phase after low dose H{sub 2}O{sub 2} treatment of a variety of cell types and that preincubation of cells with the antioxidant, N-acetylcysteine, prolonged p21{sup Cip1} half-life. A mutant p21{sup Cip1} in which all six lysines were changed to arginines was protected against H{sub 2}O{sub 2} treatment. Direct interaction between p21{sup Cip1} and Skp2 was elevated in the H{sub 2}O{sub 2}-treated cells. Disruption of the two nuclear export signal (NES) sequences in p21{sup Cip1}, or treatment with leptomycin B blocked H{sub 2}O{sub 2}-induced p21{sup Cip1} degradation. Altogether, these results demonstrate that reactive oxygen species induce p21{sup Cip1} degradation through an NES-, Skp2-, and ubiquitin-dependent pathway.

  9. Covariance of oxygen and hydrogen isotopic composition in plant water: Species effects

    SciTech Connect

    Cooper, L.W.; DeNiro, M.J. (Univ. of California, Los Angeles (United States))

    1989-12-01

    Leaf water becomes enriched in the heavy isotopes of oxygen and hydrogen during evapotranspiration. The magnitude of the enrichment has been shown to be influenced by temperature and humidity, but the effects of species-specific factors on leaf water enrichment of D and {sup 18}O have not been studied for different plants growing together. To learn whether leaf water enrichment patterns and processes for D and {sup 18}O are different for individual species growing under the same environmental conditions the authors tested the proposal that leaf waters in plants with crassulacean acid metabolism (CAM) show high sloped (m in the leaf water equation {delta}D = m {delta}{sup 18}O + b) than in C{sub 3} plants. They determined the relationships between the stable hydrogen ({delta}D) and oxygen ({delta}{sup 18}O) isotope ratios of leaf waters collected during the diurnal cycle of evapotranspiration for Yucca schidigera, Ephedra aspera, Agave deserti, Prunus ilicifolia, Yucca whipplei, Heteromeles arbutifolia, Dyckia fosteriana, Simmondsia chinensis, and Encelia farinosa growing at two sites in southern California. The findings indicate that m in the aforementioned equation is related to the overall residence time for water in the leaf and proportions of water subjected to repeated evapotranspiration enrichments of heavy isotopes.

  10. Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation

    SciTech Connect

    Meeran, Syed M.; Katiyar, Suchitra [Department of Dermatology, University of Alabama at Birmingham (United States); Katiyar, Santosh K. [Department of Dermatology, University of Alabama at Birmingham (United States); Department of Environmental Health Sciences, University of Alabama at Birmingham (United States); Clinical Nutrition Research Center, University of Alabama at Birmingham (United States); Comprehensive Cancer Center, University of Alabama at Birmingham (United States); Birmingham VA Medical Center, Birmingham, AL, 35294 (United States)], E-mail: skatiyar@uab.edu

    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.

  11. ?-Glutamylcysteine detoxifies reactive oxygen species by acting as glutathione peroxidase-1 cofactor

    PubMed Central

    Quintana-Cabrera, Ruben; Fernandez-Fernandez, Seila; Bobo-Jimenez, Veronica; Escobar, Javier; Sastre, Juan; Almeida, Angeles; Bolaños, Juan P.

    2012-01-01

    Reactive oxygen species regulate redox-signaling processes, but in excess they can cause cell damage, hence underlying the aetiology of several neurological diseases. Through its ability to down modulate reactive oxygen species, glutathione is considered an essential thiol-antioxidant derivative, yet under certain circumstances it is dispensable for cell growth and redox control. Here we show, by directing the biosynthesis of ?-glutamylcysteine—the immediate glutathione precursor—to mitochondria, that it efficiently detoxifies hydrogen peroxide and superoxide anion, regardless of cellular glutathione concentrations. Knocking down glutathione peroxidase-1 drastically increases superoxide anion in cells synthesizing mitochondrial ?-glutamylcysteine. In vitro, ?-glutamylcysteine is as efficient as glutathione in disposing of hydrogen peroxide by glutathione peroxidase-1. In primary neurons, endogenously synthesized ?-glutamylcysteine fully prevents apoptotic death in several neurotoxic paradigms and, in an in vivo mouse model of neurodegeneration, ?-glutamylcysteine protects against neuronal loss and motor impairment. Thus, ?-glutamylcysteine takes over the antioxidant and neuroprotective functions of glutathione by acting as glutathione peroxidase-1 cofactor. PMID:22395609

  12. 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

  13. Pyrene-stimulated reactive oxygen species generation and oxidative damage in Carassius auratus.

    PubMed

    Yin, Ying; Jia, Jun; Guo, Hong Y; Yang, Liu Y; Wang, Xiao R; Sun, Yuan Y

    2014-01-01

    Laboratory experiments were carried out to understand the toxicology of pyrene in the goldfish Carassius auratus and investigate the potential oxidative stress induced by reactive oxygen species (ROS) in vivo in a time-dependent manner. Pyrene bioaccumulation, induction of reactive oxygen species and the consequent biochemical responses in the liver of the fish were examined. Fish were exposed to 0.05 mg/L pyrene for different periods. The pyrene concentration in fish liver was analyzed by high performance liquid chromatography (HPLC). Free radicals were detected by electron paramagnetic resonance (EPR). The activities of antioxidant enzymes, contents of nonenzymatic antioxidants and malondialdehyde (MDA) in fish liver were also determined. Results indicated that the pyrene concentrations in fish liver reached a maximum level on day 1, and then declined to a low steady state level over 7 days. The free radical significantly increased at 6 h and reached a maximum on day 2, while the superoxide dismutase (SOD) activity and MDA content were induced, and the reduced glutathione (GSH) content was inhibited by day 2. The catalase (CAT) and glutathione-S-transferase (GST) activities were significantly induced at 12 h. These results indicated that pyrene was rapidly bioaccumulated in fish resulting in redox cycling, and the production of free radical is an important mechanism of pyrene toxicity in C. auratus. The indicators of antioxidant system are sensitive and useful for the study of early biomarkers of pyrene exposure in fish. PMID:24171415

  14. 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

  15. Network Rigidity and Metabolic Engineering in Metabolite Overproduction

    Microsoft Academic Search

    Gregory Stephanopoulos; Joseph J. Vallino

    1991-01-01

    In order to enhance the yield and productivity of metabolite production, researchers have focused almost exclusively on enzyme amplification or other modifications of the product pathway. However, overproduction of many metabolites requires significant redirection of flux distributions in the primary metabolism, which may not readily occur following product deregulation because metabolic pathways have evolved to exhibit control architectures that resist

  16. Alginate Overproduction Affects Pseudomonas aeruginosa Biofilm Structure and Function

    Microsoft Academic Search

    M. Hentzer; GAIL M. TEITZEL; GRANT J. BALZER; A. Heydorn; S. Molin; M. Givskov; MATTHEW R. PARSEK

    2001-01-01

    During the course of chronic cystic fibrosis (CF) infections, Pseudomonas aeruginosa undergoes a conversion to a mucoid phenotype, which is characterized by overproduction of the exopolysaccharide alginate. Chronic P. aeruginosa infections involve surface-attached, highly antibiotic-resistant communities of microorganisms organized in biofilms. Although biofilm formation and the conversion to mucoidy are both important aspects of CF pathogenesis, the relationship between them

  17. Exceptional overproduction of a functional human membrane protein

    Microsoft Academic Search

    Maria Nyblom; Fredrik Öberg; Karin Lindkvist-Petersson; Karin Hallgren; Heather Findlay; Jennie Wikström; Anders Karlsson; Örjan Hansson; Paula J. Booth; Roslyn M. Bill; Richard Neutze; Kristina Hedfalk

    2007-01-01

    Eukaryotic—especially human—membrane protein overproduction remains a major challenge in biochemistry. Heterologously overproduced and purified proteins provide a starting point for further biochemical, biophysical and structural studies, and the lack of sufficient quantities of functional membrane proteins is frequently a bottleneck hindering this. Here, we report exceptionally high production levels of a correctly folded and crystallisable recombinant human integral membrane protein

  18. Protective effect of flavonoids against reactive oxygen species production in sickle cell anemia patients treated with hydroxyurea

    PubMed Central

    Henneberg, Railson; Otuki, Michel Fleith; Furman, Aline Emmer Ferreira; Hermann, Priscila; do Nascimento, Aguinaldo José; Leonart, Maria Suely Soares

    2013-01-01

    Objective The aim of this study was to evaluate the protective effects of quercetin, rutin, hesperidin and myricetin against reactive oxygen species production with the oxidizing action of tert-butylhydroperoxide in erythrocytes from normal subjects and sickle cell anemia carriers treated with hydroxyurea. Methods Detection of intracellular reactive oxygen species was carried out using a liposoluble probe, 2',7'-dichlorfluorescein-diacetate (DCFH-DA). A 10% erythrocyte suspension was incubated with flavonoids (quercetin, rutin, hesperidin or myricetin; 30, 50, and 100 µmol/L), and then incubated with tert-butylhydroperoxide (75 µmol/L). Untreated samples were used as controls. Results Red blood cell exposure to tert-butylhydroperoxide resulted in significant increases in the generation of intracellular reactive oxygen species compared to basal levels. Reactive oxygen species production was significantly inhibited when red blood cells were pre-incubated with flavonoids, both in normal individuals and in patients with sickle cell anemia. Quercetin and rutin had the highest antioxidant activity, followed by myricetin and hesperidin. CONCLUSION: Flavonoids, in particular quercetin and rutin, showed better antioxidant effects against damage caused by excess reactive oxygen species characteristic of sickle cell anemia. Results obtained with patients under treatment with hydroxyurea suggest an additional protective effect when associated with the use of flavonoids. PMID:23580885

  19. 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

  20. Reactive oxygen species and glutathione dual redox-responsive micelles for selective cytotoxicity of cancer.

    PubMed

    Chiang, Yi-Ting; Yen, Yu-Wei; Lo, Chun-Liang

    2015-08-01

    This study developed reactive oxygen species (ROS) and glutathione (GSH) dual redox-responsive micelles, which encapsulate anticancer drug camptothecin (CPT), protect CPT activity, and trigger CPT release in cancer cell H2O2- or GSH-rich surroundings. Experimental results show that CPT-loaded dual redox-responsive micelles remain stable at low levels of ROS and GSH in blood circulation, have high redox sensitivities needed to CPT release in cancer cells with high ROS or GSH (e.g., lung, gastric, and colon cancer cells), and prevent undersigned CPT toxicity in ROS/GSH balanced normal cells (e.g., fibroblast cells, etc.) or normal organs (e.g., liver, kidney, etc.). The CPT-loaded dual redox-responsive micelles also had high in vivo antitumor efficacy. This study demonstrates that ROS and GSH dual redox-responsive micelles have potential use as anticancer therapeutic nanomedicine in various cancer therapies. PMID:26002788

  1. Using Consensus Bayesian Network to Model the Reactive Oxygen Species Regulatory Pathway

    PubMed Central

    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 's ROS pathway. PMID:23457624

  2. Temperature controls oxidative phosphorylation and reactive oxygen species production through uncoupling in rat skeletal muscle mitochondria.

    PubMed

    Jarmuszkiewicz, Wieslawa; Woyda-Ploszczyca, Andrzej; Koziel, Agnieszka; Majerczak, Joanna; Zoladz, Jerzy A

    2015-06-01

    Mitochondrial respiratory and phosphorylation activities, mitochondrial uncoupling, and hydrogen peroxide formation were studied in isolated rat skeletal muscle mitochondria during experimentally induced hypothermia (25°C) and hyperthermia (42°C) compared to the physiological temperature of resting muscle (35°C). For nonphosphorylating mitochondria, increasing the temperature from 25 to 42°C led to a decrease in membrane potential, hydrogen peroxide production, and quinone reduction levels. For phosphorylating mitochondria, no temperature-dependent changes in these mitochondrial functions were observed. However, the efficiency of oxidative phosphorylation decreased, whereas the oxidation and phosphorylation rates and oxidative capacities of the mitochondria increased, with increasing assay temperature. An increase in proton leak, including uncoupling protein-mediated proton leak, was observed with increasing assay temperature, which could explain the reduced oxidative phosphorylation efficiency and reactive oxygen species production. PMID:25701433

  3. Effects of Hepatitis C core protein on mitochondrial electron transport and production of reactive oxygen species

    PubMed Central

    Campbell, Roosevelt V.; Yang, Yuanzheng; Wang, Ting; Rachamallu, Aparna; Li, Yanchun; Watowich, Stanley J.; Weinman, Steven A.

    2014-01-01

    Viral infections frequently alter mitochondrial function with suppression or induction of apoptosis and enhanced generation of reactive oxygen species. The mechanisms of these effects are varied and mitochondria are affected by both direct interactions with viral proteins as well as by secondary effects of viral activated signaling cascades. This chapter describes methods used in our laboratory to assess the effects of the Hepatitis C virus core protein on mitochondrial ROS production, electron transport and Ca2+ uptake. These include measurements of the effects of in vitro incubation of liver mitochondria with purified core protein as well as assessment of the function of mitochondria in cells and tissues expressing core and other viral proteins. These methods are generally applicable to the study of viral-mitochondrial interactions. PMID:19348899

  4. 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

  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. Research on killing Escherichia Coli by reactive oxygen species based on strong ionization discharging plasma

    NASA Astrophysics Data System (ADS)

    Li, Y. J.; Tian, Y. P.; Li, R. H.; Gao, J. Y.; Cai, L. J.; Zhang, Z. T.

    2013-03-01

    Reactive oxygen species solution produced by strong ionization discharging plasma was used to kill Escherichia coli by spraying. Several effect factors such as pH value, solution temperature, spraying time and exposure time were observed in this study, and their effects on killing rate of Escherichia coli were discussed and analysed. Results show that the treating efficiency of ROS solution for Escherichia coli is higher in alkaline solution than that in acid solution. The killing rate of Escherichia coli increases while the spraying time and exposure time are longer and the temperature is lower. The effects of different factors on killing rate of Escherichia coli are as follows: spraying time > pH value > exposure time > solution temperature.

  7. CNS SIRT3 Expression Is Altered by Reactive Oxygen Species and in Alzheimer’s Disease

    PubMed Central

    Weir, Heather J. M.; Murray, Tracey K.; Kehoe, Patrick G.; Love, Seth; Verdin, Eric M.; O’Neill, Michael J.; Lane, Jon D.; Balthasar, Nina

    2012-01-01

    Progressive mitochondrial dysfunction contributes to neuronal degeneration in age-mediated disease. An essential regulator of mitochondrial function is the deacetylase, sirtuin 3 (SIRT3). Here we investigate a role for CNS Sirt3 in mitochondrial responses to reactive oxygen species (ROS)- and Alzheimer’s disease (AD)-mediated stress. Pharmacological augmentation of mitochondrial ROS increases Sirt3 expression in primary hippocampal culture with SIRT3 over-expression being neuroprotective. Furthermore, Sirt3 expression mirrors spatiotemporal deposition of ?-amyloid in an AD mouse model and is also upregulated in AD patient temporal neocortex. Thus, our data suggest a role for SIRT3 in mechanisms sensing and tackling ROS- and AD-mediated mitochondrial stress. PMID:23139766

  8. 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

  9. 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.

  10. Salicylic acid and reactive oxygen species interplay in the transcriptional control of defense genes expression

    PubMed Central

    Herrera-Vásquez, Ariel; Salinas, Paula; Holuigue, Loreto

    2015-01-01

    It is well established that salicylic acid (SA) plays a critical role in the transcriptional reprograming that occurs during the plant defense response against biotic and abiotic stress. In the course of the defense response, the transcription of different sets of defense genes is controlled in a spatio-temporal manner via SA-mediated mechanisms. Interestingly, different lines of evidence indicate that SA interplays with reactive oxygen species (ROS) and glutathione (GSH) in stressed plants. In this review we focus on the evidence that links SA, ROS, and GSH signals to the transcriptional control of defense genes. We discuss how redox modifications of regulators and co-regulators involved in SA-mediated transcriptional responses control the temporal patterns of gene expression in response to stress. Finally, we examine how these redox sensors are coordinated with the dynamics of cellular redox changes occurring in the defense response to biotic and abiotic stress. PMID:25852720

  11. Biological and physiological role of reactive oxygen species - the good, the bad and the ugly.

    PubMed

    Zuo, L; Zhou, T; Pannell, B K; Ziegler, A C; Best, T M

    2015-07-01

    Reactive oxygen species (ROS) are chemically reactive molecules that are naturally produced within biological systems. Research has focused extensively on revealing the multi-faceted and complex roles that ROS play in living tissues. In regard to the good side of ROS, this article explores the effects of ROS on signalling, immune response and other physiological responses. To review the potentially bad side of ROS, we explain the consequences of high concentrations of molecules that lead to the disruption of redox homeostasis, which induces oxidative stress damaging intracellular components. The ugly effects of ROS can be observed in devastating cardiac, pulmonary, neurodegenerative and other disorders. Furthermore, this article covers the regulatory enzymes that mitigate the effects of ROS. Glutathione peroxidase, superoxide dismutase and catalase are discussed in particular detail. The current understanding of ROS is incomplete, and it is imperative that future research be performed to understand the implications of ROS in various therapeutic interventions. PMID:25912260

  12. Nafamostat Mesilate Inhibits TNF-?-Induced Vascular Endothelial Cell Dysfunction by Inhibiting Reactive Oxygen Species Production

    PubMed Central

    Kang, Min-Woong; Song, Hee-Jung; Kang, Shin Kwang; Kim, Yonghwan; Jung, Saet-byel; Jee, Sungju; Moon, Jae Young; Suh, Kwang-sun; Lee, Sang Do; Jeon, Byeong Hwa

    2015-01-01

    Nafamostat mesilate (NM) is a serine protease inhibitor with anticoagulant and anti-inflammatory effects. NM has been used in Asia for anticoagulation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation. Oxidative stress is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial function. We investigated whether NM could inhibit endothelial dysfunction induced by tumor necrosis factor-? (TNF-?). Human umbilical vein endothelial cells (HUVECs) were treated with TNF-? for 24 h. The effects of NM on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) protein expression, p38 mitogen-activated protein kinase (MAPK) activation, and intracellular superoxide production were then examined. NM (0.01~100 µg/mL) did not affect HUVEC viability; however, it inhibited the increases in reactive oxygen species (ROS) production and p66shc expression elicited by TNF-? (3 ng/mL), and it dose dependently prevented the TNF-?-induced upregulation of endothelial VCAM-1 and ICAM-1. In addition, it mitigated TNF-?-induced p38 MAPK phosphorylation and the adhesion of U937 monocytes. These data suggest that NM mitigates TNF-?-induced monocyte adhesion and the expression of endothelial cell adhesion molecules, and that the anti-adhesive effect of NM is mediated through the inhibition of p66shc, ROS production, and p38 MAPK activation. PMID:25954127

  13. Enterovirus 71 Induces Mitochondrial Reactive Oxygen Species Generation That is Required for Efficient Replication

    PubMed Central

    Cheng, Mei-Ling; Weng, Shiue-Fen; Kuo, Chih-Hao; Ho, Hung-Yao

    2014-01-01

    Redox homeostasis is an important host factor determining the outcome of infectious disease. Enterovirus 71 (EV71) infection has become an important endemic disease in Southeast Asia and China. We have previously shown that oxidative stress promotes viral replication, and progeny virus induces oxidative stress in host cells. The detailed mechanism for reactive oxygen species (ROS) generation in infected cells remains elusive. In the current study, we demonstrate that mitochondria were a major ROS source in EV71-infected cells. Mitochondria in productively infected cells underwent morphologic changes and exhibited functional anomalies, such as a decrease in mitochondrial electrochemical potential ??m and an increase in oligomycin-insensitive oxygen consumption. Respiratory control ratio of mitochondria from infected cells was significantly lower than that of normal cells. The total adenine nucleotide pool and ATP content of EV71-infected cells significantly diminished. However, there appeared to be a compensatory increase in mitochondrial mass. Treatment with mito-TEMPO reduced eIF2? phosphorylation and viral replication, suggesting that mitochondrial ROS act to promote viral replication. It is plausible that EV71 infection induces mitochondrial ROS generation, which is essential to viral replication, at the sacrifice of efficient energy production, and that infected cells up-regulate biogenesis of mitochondria to compensate for their functional defect. PMID:25401329

  14. 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

  15. 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

  16. Reactive oxygen species as universal constraints in life-history evolution

    PubMed Central

    Dowling, Damian K.; Simmons, Leigh W.

    2009-01-01

    Evolutionary theory is firmly grounded on the existence of trade-offs between life-history traits, and recent interest has centred on the physiological mechanisms underlying such trade-offs. Several branches of evolutionary biology, particularly those focusing on ageing, immunological and sexual selection theory, have implicated reactive oxygen species (ROS) as profound evolutionary players. ROS are a highly reactive group of oxygen-containing molecules, generated as common by-products of vital oxidative enzyme complexes. Both animals and plants appear to intentionally harness ROS for use as molecular messengers to fulfil a wide range of essential biological processes. However, at high levels, ROS are known to exert very damaging effects through oxidative stress. For these reasons, ROS have been suggested to be important mediators of the cost of reproduction, and of trade-offs between metabolic rate and lifespan, and between immunity, sexual ornamentation and sperm quality. In this review, we integrate the above suggestions into one life-history framework, and review the evidence in support of the contention that ROS production will constitute a primary and universal constraint in life-history evolution. PMID:19324792

  17. 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

  18. Reactive oxygen species initiate a metabolic collapse in hippocampal slices: potential trigger of cortical spreading depression.

    PubMed

    Malkov, Anton; Ivanov, Anton I; Popova, Irina; Mukhtarov, Marat; Gubkina, Olena; Waseem, Tatsiana; Bregestovski, Piotr; Zilberter, Yuri

    2014-09-01

    Excessive accumulation of reactive oxygen species (ROS) underlies oxidative damage. We find that in hippocampal slices, decreased activity of glucose-based antioxidant system induces a massive, abrupt, and detrimental change in cellular functions. We call this phenomenon metabolic collapse (MC). This collapse manifested in long-lasting silencing of synaptic transmission, abnormal oxidation of NAD(P)H and FADH2 associated with immense oxygen consumption, and massive neuronal depolarization. MC occurred without any preceding deficiency in neuronal energy supply or disturbances of ionic homeostasis and spread throughout the hippocampus. It was associated with a preceding accumulation of ROS and was largely prevented by application of an efficient antioxidant Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl). The consequences of MC resemble cortical spreading depression (CSD), a wave of neuronal depolarization that occurs in migraine, brain trauma, and stroke, the cellular initiation mechanisms of which are poorly understood. We suggest that ROS accumulation might also be the primary trigger of CSD. Indeed, we found that Tempol strongly reduced occurrence of CSD in vivo, suggesting that ROS accumulation may be a key mechanism of CSD initiation. PMID:25027308

  19. Ultraviolet Irradiation-Dependent Fluorescence Enhancement of Hemoglobin Catalyzed by Reactive Oxygen Species

    PubMed Central

    Pan, Leiting; Wang, Xiaoxu; Yang, Shuying; Wu, Xian; Lee, Imshik; Zhang, Xinzheng; Rupp, Romano A.; Xu, Jingjun

    2012-01-01

    Ultraviolet (UV) light has a potent effect on biological organisms. Hemoglobin, an oxygen-transport protein, plays an irreplaceable role in sustaining life of all vertebrates. In this study we scrutinize the effects of ultraviolet irradiation (UVI) as well as visible irradiation on the fluorescence characteristics of bovine hemoglobin (BHb) in vitro. Data show that UVI results in fluorescence enhancement of BHb in a dose-dependant manner. Furthermore, UVI-induced fluorescence enhancement is significantly increased when BHb is pretreated with hydrogen peroxide (H2O2), a type of reactive oxygen species (ROS). Meanwhile, The water-soluble antioxidant vitamin C suppresses this UVI-induced fluorescence enhancement. In contrast, green light irradiation does not lead to fluorescence enhancement of BHb no matter whether H2O2 is acting on the BHb solution or not. Taken together, these results indicate that catalysis of ROS and UVI-dependent irradiation play two key roles in the process of UVI-induced fluorescence enhancement of BHb. PMID:22952902

  20. 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 the environment, but they can also originate endogenously, initiated by electron reduction of molecular oxygen. These molecules have important biological signaling activities, but they cause oxidative stress when dysfunction within the antioxidant system occurs. Excess ROS in living organisms can lead to problems, such as protein oxidation-through either cleavage of the polypeptide chain or modification of amino acid side chains-and lipid oxidation. PMID:25688469

  1. Involvement of Reactive Oxygen Species in Sonodynamically Induced Apoptosis Using a Novel Porphyrin Derivative

    PubMed Central

    Yumita, Nagahiko; Iwase, Yumiko; Nishi, Koji; Komatsu, Hajime; Takeda, Kazuyoshi; Onodera, Kenji; Fukai, Toshio; Ikeda, Toshihiko; Umemura, Shin-ichiro; Okudaira, Kazuho; Momose, Yasunori

    2012-01-01

    In this study, we investigated the induction of apoptosis by ultrasound in the presence of the novel porphyrin derivative DCPH-P-Na(I). HL-60 cells were exposed to ultrasound for up to 3 min in the presence and absence of DCPH-P-Na(I), and the induction of apoptosis was examined by analyzing cell morphology, DNA fragmentation, and caspase-3 activity. Reactive oxygen species were measured by means of ESR and spin trapping technique. Cells treated with 8 ?M DCPH-P-Na(I) and ultrasound clearly showed membrane blebbing and cell shrinkage, whereas significant morphologic changes were not observed in cells exposed to either ultrasound or DCPH-P-Na(I) alone. Also, DNA ladder formation and caspase-3 activation were observed in cells treated with both ultrasound and DCPH-P-Na(I) but not in cells treated with ultrasound or DCPH-P-Na(I) alone. In addition, the combination of DCPH-P-Na(I) and the same acoustical arrangement of ultrasound substantially enhanced nitroxide generation by the cells. Sonodynamically induced apoptosis, caspase-3 activation, and nitroxide generation were significantly suppressed by histidine. These results indicate that the combination of ultrasound and DCPH-P-Na(I) induced apoptosis in HL-60 cells. The significant reduction in sonodynamically induced apoptosis, nitroxide generation, and caspase-3 activation by histidine suggests active species such as singlet oxygen are important in the sonodynamic induction of apoptosis. These experimental results support the possibility of sonodynamic treatment for cancer using the induction of apoptosis. PMID:23082100

  2. Synergistic effect of active oxygen species and alginate on chitinase production by Wasabia japonica cells and its application.

    PubMed

    Akimoto, C; Aoyagi, H; Dicosmo, F; Tanaka, H

    2000-01-01

    The specific chitinase productivity of a Wasabia japonica cell suspension culture under pure oxygen aeration was 3.8 times higher than that of a suspension culture aerated with ordinary air. During aeration with pure oxygen, both oxygen consumption by the cells and the H2O2 concentration in the medium increased. Addition of H2O2 to the cultivation medium also promoted the specific chitinase productivity. H2O2 could pass freely through the cell membrane. It was assumed that the excess oxygen was converted into active oxygen species such as H2O2, and that the promotion of chitinase production was probably due to the generated active oxygen species. Addition of alginate oligomer (AO, an endogenous elicitor-like substance) to cultures aerated with pure oxygen or supplemented with H2O2 resulted in synergistic increases in chitinase production. Based on these results, the development of a simple and efficient chitinase production system was investigated. Cells were immobilized in alginate gel (instead of adding AO to the medium) and cultivated in a medium containing H2O2. The specific chitinase productivity increased to the levels observed in the suspension culture system. During repeated batch cultivation of immobilized cells, the chitinase production remained stable for three repeated batches. When immobilized protoplasts were cultivated in a medium containing H2O2, there was 7-fold increase in chitinase production compared with that of immobilized cells. PMID:16232715

  3. Cobalt Protoporphyrin Induces HO-1 Expression Mediated Partially by FOXO1 and Reduces Mitochondria-Derived Reactive Oxygen Species Production

    PubMed Central

    Li, Meixia; Xu, Haifeng; Zuo, Jin; Fang, Fude; Chang, Yongsheng

    2013-01-01

    Background Reactive oxygen species arise in the mitochondria as byproducts of respiration and oxidase activity and have important roles in many physiological and pathophysiological conditions. The level of reactive oxygen species is regulated by a number of enzymes and physiological antioxidants, including HO-1, Sod2, catalase and COX-2, etc. And HO-1 against oxidative stress requires an increase in stress-responsive genes, such as Sod2 and catalase. Especially for the activity of HO-1, cobalt protoporphyrin is known to be a potent and effective inducer in many tissues. The transcription factor, FOXO1 is resistant to oxidative stress through downregulating reactive oxygen species production. Previous study showed that FOXO1 induces HO-1 expression by binding to HO-1 promoter. The question whether cobalt protoporphyrin induces HO-1 expression mediated by FOXO1 and subsequently lessens reactive oxygen species production remains to be elucidated. Results Cobalt protoporphyrin enhances the expression of FOXO1 and facilitates FOXO1 binding to HO-1 promoter and increasing its transcriptional activity without influencing the FOXO1 protein stability. CoPP induces HO-1 and other oxidative stress-responsive genes expression, such as catalase, cytochrome c, Sod2, and COX-2, and decreases mitochondria-derived reactive oxygen species production, which are mediated partially by FOXO1. Conclusions Cobalt protoporphyrin induces HO-1 and other oxidative stress-responsive genes expression mediated partially by FOXO1, and has an important role in reducing cellular reactive oxygen species level. Cobalt protoporphyrin may be a more promising therapeutic agent to upregulate some antioxidantive genes. PMID:24255720

  4. Detection of reactive oxygen species in isolated, perfused lungs by electron spin resonance spectroscopy

    PubMed Central

    Weissmann, Norbert; Kuzkaya, Nermin; Fuchs, Beate; Tiyerili, Vedat; Schäfer, Rolf U; Schütte, Hartwig; Ghofrani, Hossein A; Schermuly, Ralph T; Schudt, Christian; Sydykov, Akylbek; Egemnazarow, Bakytbek; Seeger, Werner; Grimminger, Friedrich

    2005-01-01

    Background The sources and measurement of reactive oxygen species (ROS) in intact organs are largely unresolved. This may be related to methodological problems associated with the techniques currently employed for ROS detection. Electron spin resonance (ESR) with spin trapping is a specific method for ROS detection, and may address some these technical problems. Methods We have established a protocol for the measurement of intravascular ROS release from isolated buffer-perfused and ventilated rabbit and mouse lungs, combining lung perfusion with the spin probe l-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine (CPH) and ESR spectroscopy. We then employed this technique to characterize hypoxia-dependent ROS release, with specific attention paid to NADPH oxidase-dependent superoxide formation as a possible vasoconstrictor pathway. Results While perfusing lungs with CPH over a range of inspired oxygen concentrations (1–21 %), the rate of CP• formation exhibited an oxygen-dependence, with a minimum at 2.5 % O2. Addition of superoxide dismutase (SOD) to the buffer fluid illustrated that a minor proportion of this intravascular ROS leak was attributable to superoxide. Stimulation of the lungs by injection of phorbol-12-myristate-13-acetate (PMA) into the pulmonary artery caused a rapid increase in CP• formation, concomitant with pulmonary vasoconstriction. Both the PMA-induced CPH oxidation and the vasoconstrictor response were largely suppressed by SOD. When the PMA challenge was performed at different oxygen concentrations, maximum superoxide liberation and pulmonary vasoconstriction occurred at 5 % O2. Using a NADPH oxidase inhibitor and NADPH-oxidase deficient mice, we illustrated that the PMA-induced superoxide release was attributable to the stimulation of NADPH oxidases. Conclusion The perfusion of isolated lungs with CPH is suitable for detection of intravascular ROS release by ESR spectroscopy. We employed this technique to demonstrate that 1) PMA-induced vasoconstriction is caused "directly" by superoxide generated from NADPH oxidases and 2) this pathway is pronounced in hypoxia. NADPH oxidases thus may contribute to the hypoxia-dependent regulation of pulmonary vascular tone. PMID:16053530

  5. Enhancement of photosynthetic CO2 assimilation in the absence of oxygen, as dependent upon species and temperature.

    PubMed

    Hesketh, J

    1967-12-01

    The assimilation of CO2 was enhanced in seven plant species by 44% at 30° in the absence of oxygen, and in three of the species by 85% at 40°. Net assimilation of CO2 was not significantly greater in the absence of O2 than it was in air with leaves of three tropical grasses and of one dicotyledonous species, Amaranthus palmeri. For two species in 30°, the enhanced CO2 assimilation values were similar to those of the tropical grasses and of A. palmeri. The absence of O2 did not enhance net CO2 assimilation in maize even in light of low intensity. PMID:24549501

  6. Determination of reactive oxygen species from ZnO micro-nano structures with shape-dependent photocatalytic activity

    SciTech Connect

    He, Weiwei; Zhao, Hongxiao; Jia, Huimin [Key Laboratory of Micro-Nano Materials for Energy Storage and Conversion of Henan Province, Institute of Surface Micro and Nano Materials, Xuchang University, Henan 461000 (China); Yin, Jun-Jie [Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, College Park, MD 20740 (United States); Zheng, Zhi, E-mail: zhengzhi99999@gmail.com [Key Laboratory of Micro-Nano Materials for Energy Storage and Conversion of Henan Province, Institute of Surface Micro and Nano Materials, Xuchang University, Henan 461000 (China)

    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.

  7. Contrasting reactive oxygen species and transition metal concentrations in combustion aerosols.

    PubMed

    See, S W; Wang, Y H; Balasubramanian, R

    2007-03-01

    The presence of reactive oxygen species (ROS) and 10 transition metals (Ag, Cd, Co, Cu, Fe, Mn, Ni, Ti, V and Zn) in both the acid-soluble and water-soluble fractions of fine particles of combustion origin were determined. ROS was analyzed using the dichlorofluorescin fluorescence technique. Particles emitted from on-road vehicles, gas cooking, incense burning, and cigarette smoke were characterized along with those in the background air of outdoor and indoor environments. In addition, this study evaluated the possible relationships between ROS and individual transition metals. It is found that cigarette smoke which had the highest concentration of metals also contained the highest concentration of ROS. Regression analysis performed showed that water-soluble metals including Cd, Co, Cu, Fe, Mn, and Ni showed better correlation with ROS concentration as compared to acid-soluble (total) metals. The findings demonstrated that water-soluble metals could be one of the species influencing ROS formation in ambient air. PMID:17011545

  8. Reactive Oxygen and Nitrogen Species in Pathogenesis of Vascular Complications of Diabetes

    PubMed Central

    2012-01-01

    Macrovascular and microvascular diseases are currently the principal causes of morbidity and mortality in subjects with diabetes. Disorders of the physiological signaling functions of reactive oxygen species (superoxide and hydrogen peroxide) and reactive nitrogen species (nitric oxide and peroxynitrite) are important features of diabetes. In the absence of an appropriate compensation by the endogenous antioxidant defense network, increased oxidative stress leads to the activation of stress-sensitive intracellular signaling pathways and the formation of gene products that cause cellular damage and contribute to the vascular complications of diabetes. It has recently been suggested that diabetic subjects with vascular complications may have a defective cellular antioxidant response against the oxidative stress generated by hyperglycemia. This raises the concept that antioxidant therapy may be of great benefit to these subjects. Although our understanding of how hyperglycemia-induced oxidative stress ultimately leads to tissue damage has advanced considerably in recent years, effective therapeutic strategies to prevent or delay the development of this damage remain limited. Thus, further investigation of therapeutic interventions to prevent or delay the progression of diabetic vascular complications is needed. PMID:22737658

  9. Measurement of DCF fluorescence as a measure of reactive oxygen species in murine islets of Langerhans

    PubMed Central

    Wang, Xue; Roper, Michael G.

    2014-01-01

    In islets of Langerhans, oxidative stress induced by reactive oxygen species (ROS) is thought to be critically involved in ?-cell dysfunction during the development of diabetes. However, ROS have also been hypothesized to play a role in cellular signalling. To aid in delineating the effects of ROS in living islets of Langerhans, the endocrine portion of the pancreas that contain ?-cells, we sought to develop a robust and reproducible protocol to measure these species using the fluorescent dye, 2’,7’-dichlorodihydrofluorescein diacetate (H2DCF-DA). The protocol that was developed minimized photobleaching and leakage of H2DCF from murineislets and utilized a normalization procedure to further reduce experimental variability. The method allowed for ~25 min of DCF measurement in living islets. We used the developed protocol to compare DCF fluorescence from batches of islets incubated in varying glucose concentrations and observed ~1.5-fold higher fluorescence signals in 3 vs. 20 mM glucose. The effects of diazoxide, which clamps open K+ATP channels reducing intracellular [Ca2+] ([Ca2+]i) without affecting glucose metabolism, were also investigated. The presence of diazoxide increased DCF fluorescence at all glucose concentrations tested while addition of 30 mM K+ to increase [Ca2+]i reduced the fluorescence by ~15%. With the developed protocol, all experimental methods tested to increase [Ca2+]i resulted in a decrease in DCF fluorescence, potentially indicating involvement of ROS in intracellular signalling cascades. PMID:24955137

  10. Cell signalling following plant\\/pathogen interactions involves the generation of reactive oxygen and reactive nitrogen species

    Microsoft Academic Search

    John T. Hancock; Radhika Desikan; Andrew Clarke; Roger D. Hurst; Steven J. Neill

    2002-01-01

    It is now clear that reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), and reactive nitrogen species, such as nitric oxide (NO), are produced by plant cells in response to a variety of stresses, including pathogen challenge. Such molecules may be involved in direct defence mechanisms, such as cross-linking of plant cell walls, or as antimicrobial agents. However, it

  11. Oxygen Metabolic Responses of Three Species of Large Benthic Foraminifers with Algal Symbionts to Temperature Stress

    PubMed Central

    Fujita, Kazuhiko; Okai, Takaaki; Hosono, Takashi

    2014-01-01

    Water temperature affects the physiology of large benthic foraminifers (LBFs) with algal symbionts dwelling in coral reef environments. However, the detailed physiological responses of LBF holobionts to temperature ranges occurring in their habitats are not known. We report net oxygen (O2) production and respiration rates of three LBF holobionts (Baculogypsina sphaerulata and Calcarina gaudichaudii hosting diatom symbionts, and Amphisorus kudakajimensis hosting dinoflagellate symbionts) measured in the laboratory at water temperatures ranging from 5°C to 45°C in 2.5°C or 5°C intervals and with light saturation levels of ?500 µmol m?2 s?1. In addition, the recovery of net O2 production and respiration rates after exposure to temperature stress was assessed. The net O2 production and respiration rates of the three LBF holobionts peaked at ?30°C, indicating their optimal temperature for a short exposure period. At extreme high temperatures (?40°C), the net O2 production rates of all three LBF holobionts declined to less than zero and the respiration rates slightly decreased, indicating that photosynthesis of algal symbionts was inactivated. At extreme low temperatures (?10°C for two calcarinid species and ?5°C for A. kudakajimensis), the net O2 production and respiration rates were near zero, indicating a weakening of holobiont activity. After exposure to extreme high or low temperature, the net O2 production rates did not recover until the following day, whereas the respiration rates recovered rapidly, suggesting that a longer time (days) is required for recovery from damage to the photosystem by temperature stress compared to the respiration system. These results indicate that the oxygen metabolism of LBF holobionts can generally cope well with conditions that fluctuate diurnally and seasonally in their habitats. However, temporal heat and cold stresses with high light levels may induce severe damage to algal symbionts and also damage to host foraminifers. PMID:24594773

  12. Release of Proteins from Intact Chloroplasts Induced by Reactive Oxygen Species during Biotic and Abiotic Stress

    PubMed Central

    Singh, Nameirakpam D.; Daniell, Henry

    2013-01-01

    Plastids sustain life on this planet by providing food, feed, essential biomolecules and oxygen. Such diverse metabolic and biosynthetic functions require efficient communication between plastids and the nucleus. However, specific factors, especially large molecules, released from plastids that regulate nuclear genes have not yet been fully elucidated. When tobacco and lettuce transplastomic plants expressing GFP within chloroplasts, were challenged with Erwinia carotovora (biotic stress) or paraquat (abiotic stress), GFP was released into the cytoplasm. During this process GFP moves gradually towards the envelope, creating a central red zone of chlorophyll fluorescence. GFP was then gradually released from intact chloroplasts into the cytoplasm with an intact vacuole and no other visible cellular damage. Different stages of GFP release were observed inside the same cell with a few chloroplasts completely releasing GFP with detection of only red chlorophyll fluorescence or with no reduction in GFP fluorescence or transitional steps between these two phases. Time lapse imaging by confocal microscopy clearly identified sequence of these events. Intactness of chloroplasts during this process was evident from chlorophyll fluorescence emanated from thylakoid membranes and in vivo Chla fluorescence measurements (maximum quantum yield of photosystem II) made before or after infection with pathogens to evaluate their photosynthetic competence. Hydrogen peroxide and superoxide anion serve as signal molecules for generation of reactive oxygen species and Tiron, scavenger of superoxide anion, blocked release of GFP from chloroplasts. Significant increase in ion leakage in the presence of paraquat and light suggests changes in the chloroplast envelope to facilitate protein release. Release of GFP-RC101 (an antimicrobial peptide), which was triggered by Erwinia infection, ceased after conferring protection, further confirming this export phenomenon. These results suggest a novel signaling mechanism, especially for participation of chloroplast proteins (e.g. transcription factors) in retrograde signaling, thereby offering new opportunities to regulate pathways outside chloroplasts. PMID:23799142

  13. 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

  14. Oxygen metabolic responses of three species of large benthic foraminifers with algal symbionts to temperature stress.

    PubMed

    Fujita, Kazuhiko; Okai, Takaaki; Hosono, Takashi

    2014-01-01

    Water temperature affects the physiology of large benthic foraminifers (LBFs) with algal symbionts dwelling in coral reef environments. However, the detailed physiological responses of LBF holobionts to temperature ranges occurring in their habitats are not known. We report net oxygen (O2) production and respiration rates of three LBF holobionts (Baculogypsina sphaerulata and Calcarina gaudichaudii hosting diatom symbionts, and Amphisorus kudakajimensis hosting dinoflagellate symbionts) measured in the laboratory at water temperatures ranging from 5°C to 45°C in 2.5°C or 5°C intervals and with light saturation levels of ?500 µmol m(-2) s(-1). In addition, the recovery of net O2 production and respiration rates after exposure to temperature stress was assessed. The net O2 production and respiration rates of the three LBF holobionts peaked at ?30°C, indicating their optimal temperature for a short exposure period. At extreme high temperatures (?40°C), the net O2 production rates of all three LBF holobionts declined to less than zero and the respiration rates slightly decreased, indicating that photosynthesis of algal symbionts was inactivated. At extreme low temperatures (?10°C for two calcarinid species and ?5°C for A. kudakajimensis), the net O2 production and respiration rates were near zero, indicating a weakening of holobiont activity. After exposure to extreme high or low temperature, the net O2 production rates did not recover until the following day, whereas the respiration rates recovered rapidly, suggesting that a longer time (days) is required for recovery from damage to the photosystem by temperature stress compared to the respiration system. These results indicate that the oxygen metabolism of LBF holobionts can generally cope well with conditions that fluctuate diurnally and seasonally in their habitats. However, temporal heat and cold stresses with high light levels may induce severe damage to algal symbionts and also damage to host foraminifers. PMID:24594773

  15. Functional inactivation of the oestrogen receptor by the antioestrogen, ZM 182780, sensitises tumour cells to reactive oxygen species

    Microsoft Academic Search

    C J Newton; N Drummond; C H Burgoyne; V Speirs; G K Stalla; S L Atkin

    1999-01-01

    Reactive oxygen species (ROS) play a fundamental role in both apoptotic and necrotic cell death. Their importance is highlighted by studies showing that they mediate cell death in response to radiotherapy and to some forms of chemotherapy. Here we provide the first evidence for a role of ROS in response to an antiendocrine agent currently undergoing clinical trials. Using the

  16. Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain.

    PubMed

    Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-Il

    2011-11-01

    Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

  17. Mitochondrial Dysfunction and Reactive Oxygen Species in Excitotoxicity and Apoptosis: Implications for the Pathogenesis of Neurodegenerative Diseases

    Microsoft Academic Search

    A. Cristina Rego; Catarina R. Oliveira

    2003-01-01

    In recent years we have witnessed a major interest in the study of the role of mitochondria, not only as ATP producers through oxidative phosphorylation but also as regulators of intracellular Ca2+ homeostasis and endogenous producers of reactive oxygen species (ROS). Interestingly, the mitochondria have been also implicated as central executioners of cell death. Increased mitochondrial Ca2+ overload as a

  18. Activation of APE\\/Ref1 redox activity is mediated by reactive oxygen species and PKC phosphorylation

    Microsoft Academic Search

    Marlene M. Hsieh; Vijay Hegde; Mark R. Kelley; Walter A. Deutsch

    2001-01-01

    Reactive oxygen species (ROS) arise through normal cellular aerobic respiration, and, in combination with external sources such as ionizing radiation, cigarette tar and smoke, and particulate matter generated by combustion, can have a profound negative effect on cellular macromolecules such as DNA that may lead to a number of human pathological disorders including accelerated aging and cancer. A major end

  19. Leaching of bisphenol A (BPA) from polycarbonate plastic to water containing amino acids and its degradation by radical oxygen species

    Microsoft Academic Search

    Junko Sajiki; Jun Yonekubo

    2004-01-01

    In this study, (1) the change in the concentration of bisphenol A (BPA) leached from polycarbonate plastic (PCP) tube to water samples containing phosphate, sodium barbital, glycine, methionine or albumin at 37 °C as a function of time, and (2) the degradation rate of BPA leached from PCP tube to amino acid solutions in the presence of radical oxygen species

  20. Using fluorescence-activated flow cytometry to determine reactive oxygen species formation and membrane lipid peroxidation in viable boar spermatozoa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fluorescence-activated flow cytometry analyses were developed for determination of reactive oxygen species (ROS) formation and membrane lipid peroxidation in live spermatozoa loaded with, respectively, hydroethidine (HE) or the lipophilic probe 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-d...

  1. Generation of Reactive Oxygen and Anti-Oxidant Species by Hydrodynamically-Stressed Suspensions of Morinda citrofolia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The generation of reactive oxygen species (ROS) by plant cell suspension cultures, in response to the imposition of both biotic and abiotic stress, is well-documented. This study investigated the generation of hydrogen peroxide by hydrodynamically-stressed cultures of Morinda citrifolia, over a 5-ho...

  2. Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain

    PubMed Central

    Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-il

    2011-01-01

    Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

  3. Serotonin 5-HT2B Receptor Blockade Prevents Reactive Oxygen SpeciesInduced Cardiac Hypertrophy in Mice

    E-print Network

    Boyer, Edmond

    hypertrophy through the regulation of hypertrophic cytokines in cardiac fibroblasts. Moreover, the generation investigated whether 5-HT2B receptors could be involved in the development of cardiac hypertrophy associatedSerotonin 5-HT2B Receptor Blockade Prevents Reactive Oxygen Species­Induced Cardiac Hypertrophy

  4. Oxidative Injury and Inflammatory Periodontal Diseases : the Challenge of AntiOxidants to Free Radicals and Reactive Oxygen Species

    Microsoft Academic Search

    M. Battino; P. Bullon; M. Wilson; H. Newman

    1999-01-01

    In recent years, there has been a tremendous expansion in medical and dental research concerned with free radicals, reactive oxygen species, and anti-oxidant defense mechanisms. This review is intended to provide a critical, up-to-date summary of the field, with particular emphasis on its implications for the application of \\

  5. Production of reactive oxygen species by peritoneal macrophages and hepatic mitochondria and microsomes from endrin-treated rats.

    PubMed

    Bagchi, M; Hassoun, E A; Bagchi, D; Stohs, S J

    1993-02-01

    Recent studies have shown that the administration of endrin to rodents induces lipid peroxidation in various tissues and decreases glutathione content. These results suggest that endrin produces reactive oxygen species and/or free radicals. We have therefore examined the effect of endrin (4.5 mg/kg) on the production of reactive oxygen species by peritoneal macrophages and hepatic mitochondria and microsomes in rats. The effects of endrin on hepatic mitochondrial and microsomal lipid peroxidation and membrane fluidity as well as the incidence of hepatic nuclear DNA damage were also examined. Twenty-four hours after endrin administration, significant increases in the production of chemiluminescence by the three tissue fractions were observed. Furthermore, peritoneal macrophages from endrin-treated animals resulted in 3.0- and 2.8-fold increases in cytochrome c and iodonitrotetrazolium (INT) reduction, indicating enhanced production of superoxide anion. Endrin administration also resulted in significant increases in lipid peroxidation of mitochondrial and microsomal membranes as well as decreases in the fluidity of these two membranous fractions. A significant increase in hepatic nuclear DNA single-strand breaks also occurred in response to endrin administration. The results indicate that macrophage, mitochondria, and microsomes produce reactive oxygen species following endrin administration, and these reactive oxygen species may contribute to the toxic manifestations of endrin. PMID:8381102

  6. Reactive oxygen species (ROS) mediates the mitochondrial-dependent apoptosis induced by transforming growth factor b in fetal hepatocytes

    Microsoft Academic Search

    BLANCA HERRERA; M. ALVAREZ; ARANZAZU SANCHEZ; MARGARITA FERNANDEZ; CESAR RONCERO; MANUEL BENITO; ISABEL FABREGAT

    Treatment of fetal rat hepatocytes with transforming growth factor beta (TGF-b) is followed by apoptotic cell death. Analysis of radical oxygen species (ROS) content and mitochondrial transmembrane po- tential (Dcm), using specific fluorescent probes in FACScan and confocal microscopy, showed that TGF-b mediates ROS production that precedes the loss of Dcm, the release of cytochrome c, and the activation of

  7. Propolis protects human spermatozoa from DNA damage caused by benzo[ a]pyrene and exogenous reactive oxygen species

    Microsoft Academic Search

    A. Russo; N. Troncoso; F. Sanchez; J. A. Garbarino; A. Vanella

    2006-01-01

    Many environmental, physiological and genetic factors have been implicated in defective sperm function, the most common cause of infertility. In addition, sperm preparation techniques such as centrifugation, used prior to in vitro fertilization, are associated with the generation of reactive oxygen species (ROS) and an increase in the level of DNA damage. Factors that can offer spermatozoa protection are, therefore,

  8. Aclarubicin-induced differentiation and invasiveness Involvement of reactive oxygen species in aclarubicin-induced diferentiation and

    E-print Network

    Paris-Sud XI, Université de

    Aclarubicin-induced differentiation and invasiveness 1 Involvement of reactive oxygen species in aclarubicin-induced diferentiation and invasiveness of HL-60 leukemia cells Doriane Richard, Patrick Hollender-induced differentiation and invasiveness. hal-00422906,version1-8Oct2009 Author manuscript, published in "International

  9. Mitochondrial reactive oxygen species accelerate the expression of heme carrier protein 1 and enhance photodynamic cancer therapy effect

    PubMed Central

    Ito, Hiromu; Matsui, Hirofumi; Tamura, Masato; Majima, Hideyuki J.; Indo, Hiroko P.; Hyodo, Ichinosuke

    2014-01-01

    Photodynamic therapy using hematoporphyrin and its derivatives is clinically useful for cancer treatments. It has been reported that cancer cells incorporate hematoporphyrin and its derivatives via heme carrier protein 1, which is a proton-coupled folate transporter. However, the mechanism of this protein expression has not been elucidated. In general, the concentration of reactive oxygen species in cancer cells is higher than that in normal cells. We previously reported that reactive oxygen species from mitochondria involved in the expression of peptide transporter 1 and accelerate the uptake of 5-aminolevulinic acid, which is a precursor of protoporphyrin IX. We suggested mitochondrial reactive oxygen species also regulated the expression of heme carrier protein 1. In this study, we used a rat gastric mucosal cell line RGM1 and its cancer-like mutated cell line RGK1. We clarified the expression of heme carrier protein 1 increased in cancer cells and it decreased in manganese superoxide dismutase expressed cancer cells. In addition, the uptake level of hematoporphyrin and photodynamic therapeutic effect were also decreased in manganese superoxide dismutase expressed cancer cells in comparison with cancer cells. Thus, we concluded that mitochondrial reactive oxygen species regulated heme carrier protein 1 expression and photodynamic therapeutic effect. PMID:25120282

  10. Inhibition of human neutrophil reactive oxygen species production and p67 phox translocation by cigarette smoke extract

    Microsoft Academic Search

    John S. Dunn; Brian M. Freed; Daniel L. Gustafson; Kathleen A. Stringer

    2005-01-01

    The association between cigarette smoking and atherogenesis is well established. Inflammatory cells may participate in atherogenesis via activation of the NADPH oxidase and the subsequent production of reactive oxygen species (ROS), which exacerbates endothelial injury. However, little is known about the ability of cigarette smoke (CS) to modulate NADPH oxidase protein function. In this study, we investigated the ability of

  11. Study of the photochemically generated of oxygen species by fullerene photosensitized CoS{sub 2} nanocompounds

    SciTech Connect

    Meng, Ze-Da; Zhu, Lei; Ullah, Kefayat; Ye, Shu; Sun, Qian [Department of Advanced Materials Science and Engineering, Hanseo University, Seosan-si, Chungnam-do 356-706 (Korea, Republic of); Jang, Won Kweon [Division of Electronic, Computer and Communication Engineering, Hanseo University, Seosan-si, Chungcheongnam-do 356-706 (Korea, Republic of); Oh, Won-Chun, E-mail: wc_oh@hanseo.ac.kr [Department of Advanced Materials Science and Engineering, Hanseo University, Seosan-si, Chungnam-do 356-706 (Korea, Republic of)

    2014-01-01

    Graphical abstract: - Highlights: • Reactive oxygen species was detected through oxidation reaction from DPCI to DPCO. • Generated reactive oxygen species and hydroxyl radicals can be analysis by DPCI degradation. • C{sub 60} has good effect during the photo-degradation processes. • Photocatalytic activity attributed to photo-absorption effect by C{sub 60} and cooperative effect of CoS{sub 2}. - Abstract: Reactive oxygen species (ROS) can be produced by interactions between sunlight and light-absorbing substance in natural water environment and can completely destroy various organic pollutants in wastewaters. In this study, CoS{sub 2} and CoS{sub 2}–fullerene were irradiated by visible light respectively. The generation of reactive oxygen species were detected through the oxidation reaction from 1,5-diphenyl carbazide (DPCI) to 1,5-diphenyl carbazone (DPCO). In comparison with the separate effects of CoS{sub 2} and fullerene nanoparticles, the photochemically effect of the fullerene photosensitized CoS{sub 2} composites is increased significantly due to the synergetic effect between the fullerene and the CoS{sub 2} nanoparticles.

  12. The extracellular A-loop of dual oxidases affects the specificity of reactive oxygen species release.

    PubMed

    Ueyama, Takehiko; Sakuma, Megumi; Ninoyu, Yuzuru; Hamada, Takeshi; Dupuy, Corinne; Geiszt, Miklós; Leto, Thomas L; Saito, Naoaki

    2015-03-01

    NADPH oxidase (Nox) family proteins produce superoxide (O2 (?)) directly by transferring an electron to molecular oxygen. Dual oxidases (Duoxes) also produce an O2 (?) intermediate, although the final species secreted by mature Duoxes is H2O2, suggesting that intramolecular O2 (?) dismutation or other mechanisms contribute to H2O2 release. We explored the structural determinants affecting reactive oxygen species formation by Duox enzymes. Duox2 showed O2 (?) leakage when mismatched with Duox activator 1 (DuoxA1). Duox2 released O2 (?) even in correctly matched combinations, including Duox2 + DuoxA2 and Duox2 + N-terminally tagged DuoxA2 regardless of the type or number of tags. Conversely, Duox1 did not release O2 (?) in any combination. Chimeric Duox2 possessing the A-loop of Duox1 showed no O2 (?) leakage; chimeric Duox1 possessing the A-loop of Duox2 released O2 (?). Moreover, Duox2 proteins possessing the A-loops of Nox1 or Nox5 co-expressed with DuoxA2 showed enhanced O2 (?) release, and Duox1 proteins possessing the A-loops of Nox1 or Nox5 co-expressed with DuoxA1 acquired O2 (?) leakage. Although we identified Duox1 A-loop residues (His(1071), His(1072), and Gly(1074)) important for reducing O2 (?) release, mutations of these residues to those of Duox2 failed to convert Duox1 to an O2 (?)-releasing enzyme. Using immunoprecipitation and endoglycosidase H sensitivity assays, we found that the A-loop of Duoxes binds to DuoxA N termini, creating more stable, mature Duox-DuoxA complexes. In conclusion, the A-loops of both Duoxes support H2O2 production through interaction with corresponding activators, but complex formation between the Duox1 A-loop and DuoxA1 results in tighter control of H2O2 release by the enzyme complex. PMID:25586178

  13. Mobile Phone Radiation Induces Reactive Oxygen Species Production and DNA Damage in Human Spermatozoa In Vitro

    PubMed Central

    De Iuliis, Geoffry N.; Newey, Rhiannon J.; King, Bruce V.; Aitken, R. John

    2009-01-01

    Background In recent times there has been some controversy over the impact of electromagnetic radiation on human health. The significance of mobile phone radiation on male reproduction is a key element of this debate since several studies have suggested a relationship between mobile phone use and semen quality. The potential mechanisms involved have not been established, however, human spermatozoa are known to be particularly vulnerable to oxidative stress by virtue of the abundant availability of substrates for free radical attack and the lack of cytoplasmic space to accommodate antioxidant enzymes. Moreover, the induction of oxidative stress in these cells not only perturbs their capacity for fertilization but also contributes to sperm DNA damage. The latter has, in turn, been linked with poor fertility, an increased incidence of miscarriage and morbidity in the offspring, including childhood cancer. In light of these associations, we have analyzed the influence of RF-EMR on the cell biology of human spermatozoa in vitro. Principal Findings Purified human spermatozoa were exposed to radio-frequency electromagnetic radiation (RF-EMR) tuned to 1.8 GHz and covering a range of specific absorption rates (SAR) from 0.4 W/kg to 27.5 W/kg. In step with increasing SAR, motility and vitality were significantly reduced after RF-EMR exposure, while the mitochondrial generation of reactive oxygen species and DNA fragmentation were significantly elevated (P<0.001). Furthermore, we also observed highly significant relationships between SAR, the oxidative DNA damage bio-marker, 8-OH-dG, and DNA fragmentation after RF-EMR exposure. Conclusions RF-EMR in both the power density and frequency range of mobile phones enhances mitochondrial reactive oxygen species generation by human spermatozoa, decreasing the motility and vitality of these cells while stimulating DNA base adduct formation and, ultimately DNA fragmentation. These findings have clear implications for the safety of extensive mobile phone use by males of reproductive age, potentially affecting both their fertility and the health and wellbeing of their offspring. PMID:19649291

  14. Identification of the reactive oxygen species responsible for carbon tetrachloride degradation in modified Fenton's systems.

    PubMed

    Smith, Brant A; Teel, Amy L; Watts, Richard J

    2004-10-15

    The reactive oxygen species responsible for the transformation of carbon tetrachloride (tetrachloromethane, CT) by modified Fenton's reagent using hydrogen peroxide (H2O2) concentrations >0.1 M was investigated. Addition of the hydroxyl radical scavenger 2-propanol to modified Fenton's reactions did not significantly lower CT transformation rates. Scavenging by 2-propanol not only confirmed that hydroxyl radicals are not responsible for CT destruction, but also suggested that a major product of an iron (III)-driven initiation reaction, superoxide radical anion (O2-), is the species responsible for CT transformation. To investigate this hypothesis, CT degradation was studied in aqueous KO2 reactions. Minimal CT degradation was found in CT-KO2 reactions; however, when H2O2 was added to the KO2 reactions at concentrations similar to those in the modified Fenton's reactions (0.1, 0.5, and 1 M), CT degradation increased significantly. Similar results were obtained when 1 M concentrations of other solvents were added to aqueous KO2 reactions, and the observed first-order rate constant for CT degradation correlated strongly (R2 = 0.986) with the empirical solvent polarity (E(T)N) of the added solvents. The results indicate that even dilute concentrations of solvents, including H202, can increase the reactivity of O2- in water, probably by changing its solvation sphere. The higher reactivity of O2- generated in modified Fenton's reagent, which has a less polar nature due to the presence of H2O2, may result in a wider range of contaminant degradation than previously thought possible. PMID:15543752

  15. Non-thermal dielectric barrier discharge plasma induces angiogenesis through reactive oxygen species

    PubMed Central

    Arjunan, Krishna Priya; Friedman, Gary; Fridman, Alexander; Clyne, Alisa Morss

    2012-01-01

    Vascularization plays a key role in processes such as wound healing and tissue engineering. Non-thermal plasma, which primarily produces reactive oxygen species (ROS), has recently emerged as an efficient tool in medical applications including blood coagulation, sterilization and malignant cell apoptosis. Liquids and porcine aortic endothelial cells were treated with a non-thermal dielectric barrier discharge plasma in vitro. Plasma treatment of phosphate-buffered saline (PBS) and serum-free medium increased ROS concentration in a dose-dependent manner, with a higher concentration observed in serum-free medium compared with PBS. Species concentration inside cells peaked 1 h after treatment, followed by a decrease 3 h post treatment. Endothelial cells treated with a plasma dose of 4.2 J cm–2 had 1.7 times more cells than untreated samples 5 days after plasma treatment. The 4.2 J cm–2 plasma dose increased two-dimensional migration distance by 40 per cent compared with untreated control, while the number of cells that migrated through a three-dimensional collagen gel increased by 15 per cent. Tube formation was also enhanced by plasma treatment, with tube lengths in plasma-treated samples measuring 2.6 times longer than control samples. A fibroblast growth factor-2 (FGF-2) neutralizing antibody and ROS scavengers abrogated these angiogenic effects. These data indicate that plasma enhanced proliferation, migration and tube formation is due to FGF-2 release induced by plasma-produced ROS. Non-thermal plasma may be used as a potential tool for applying ROS in precise doses to enhance vascularization. PMID:21653568

  16. Mitochondrial Reactive Oxygen Species Promote Epidermal Differentiation and Hair Follicle Development

    PubMed Central

    Hamanaka, Robert B.; Glasauer, Andrea; Hoover, Paul; Yang, Shuangni; Blatt, Hanz; Mullen, Andrew R.; Getsios, Spiro; Gottardi, Cara J.; DeBerardinis, Ralph J.; Lavker, Robert M.; Chandel, Navdeep S.

    2014-01-01

    Proper regulation of keratinocyte differentiation within the epidermis and follicular epithelium is essential for maintenance of epidermal barrier function and hair growth. The signaling intermediates that regulate the morphological and genetic changes associated with epidermal and follicular differentiation remain poorly understood. We tested the hypothesis that reactive oxygen species (ROS) generated by mitochondria are an important regulator of epidermal differentiation by generating mice with a keratinocyte-specific deficiency in mitochondrial transcription factor A (TFAM), which is required for the transcription of mitochondrial genes encoding electron transport chain subunits. Ablation of TFAM in keratinocytes impaired epidermal differentiation and hair follicle growth and resulted in death 2 weeks after birth. TFAM-deficient keratinocytes failed to generate mitochondria-derived ROS, a deficiency that prevented the transmission of Notch and ?-catenin signals essential for epidermal differentiation and hair follicle development, respectively. In vitro keratinocyte differentiation was inhibited in the presence of antioxidants, and the decreased differentiation marker abundance in TFAM-deficient keratinocytes was partly rescued by application of exogenous hydrogen peroxide. These findings indicate that mitochondria-generated ROS are critical mediators of cellular differentiation and tissue morphogenesis. PMID:23386745

  17. Use of Potentiometric Fluorophores in the Measurement of Mitochondrial Reactive Oxygen Species

    PubMed Central

    Polster, Brian M.; Nicholls, David G.; Ge, Shealinna X.; Roelofs, Brian A.

    2015-01-01

    Mitochondrial reactive oxygen species (ROS) are implicated in signal transduction, inflammation, neurodegenerative disorders, and normal aging. Net ROS release by isolated brain mitochondria derived from a mixture of neurons and glia is readily quantified using fluorescent dyes. Measuring intracellular ROS in intact neurons or glia and assigning the origin to mitochondria are far more difficult. In recent years, the protonmotive force crucial to mitochondrial function has been exploited to target a variety of compounds to the highly negative mitochondrial matrix using the lipophilic triphenylphosphonium cation (TPP+) as a “delivery” conjugate. Among these, MitoSOX Red, also called mito-hydroethidine or mitodihydroethidium, is prevalently used for mitochondrial ROS estimation. Although the TPP+ moiety of MitoSOX enables the many-fold accumulation of ROS-sensitive hydroethidine in the mitochondrial matrix, the membrane potential sensitivity conferred by TPP+ creates a daunting set of challenges not often considered in the application of this dye. This chapter provides recommendations and cautionary notes on the use of potentiometric fluorescent indicators for the approximation of mitochondrial ROS in live neurons, with principles that can be extrapolated to non-neuronal cell types. It is concluded that mitochondrial membrane potential changes render accurate estimation of mitochondrial ROS using MitoSOX difficult to impossible. Consequently, knowledge of mitochondrial membrane potential is essential to the application of potentiometric fluorophores for the measurement of intramitochondrial ROS. PMID:25416361

  18. Reactive Oxygen Species Originating from Mitochondria Regulate the Cardiac Sodium Channel

    PubMed Central

    Liu, Man; Liu, Hong; Dudley, Samuel C.

    2010-01-01

    Rationale Pyridine nucleotides regulate the cardiac Na+ current (INa) through generation of reactive oxygen species (ROS). Objective We investigated the source of ROS induced by elevated NADH. Methods and Results In HEK cells stably expressing the cardiac Na+ channel, the decrease of INa (52±9%; P<0.01) induced by cytosolic NADH application (100 ?mol/L) was reversed by mitoTEMPO, rotenone, malonate, DIDS, PK11195 and 4?-chlorodiazepam, a specific scavenger of mitochondrial superoxide and inhibitors of the mitochondrial complex I, complex II, voltage-dependent anion channels, and benzodiazepine receptor, respectively. Antimycin A (20 ?mol/L), a complex III inhibitor known to generate ROS, decreased INa (51±4%, P<0.01). This effect was blocked by NAD+, forskolin, or rotenone. Inhibitors of complex IV, nitric oxide synthase, the NADPH oxidases, xanthine oxidases, the mitochondrial permeability transition pore, and the mitochondrial ATP-sensitive K+ channel did not change the NADH effect on INa. Analogous results were observed in cardiomyocytes. Rotenone, mitoTEMPO, and 4?-chlorodiazepam also blocked the mutant A280V glycerol-3-phosphate dehydrogenase 1-like effect on reducing INa, indicating a role for mitochondria in the Brugada Syndrome caused by this mutation. Fluorescent microscopy confirmed mitochondrial ROS generation with elevated NADH and ROS inhibition by NAD+. Conclusions Altering the oxidized to reduced NAD(H) balance can activate mitochondrial ROS production, leading to reduced INa. This signaling cascade may help explain the link between altered metabolism, conduction block, and arrhythmic risk. PMID:20724705

  19. Conundrum of pathogenesis of diabetic cardiomyopathy: role of vascular endothelial dysfunction, reactive oxygen species, and mitochondria.

    PubMed

    Joshi, Mandip; Kotha, Sainath R; Malireddy, Smitha; Selvaraju, Vaithinathan; Satoskar, Abhay R; Palesty, Alexender; McFadden, David W; Parinandi, Narasimham L; Maulik, Nilanjana

    2014-01-01

    Diabetic cardiomyopathy and heart failure have been recognized as the leading causes of mortality among diabetics. Diabetic cardiomyopathy has been characterized primarily by the manifestation of left ventricular dysfunction that is independent of coronary artery disease and hypertension among the patients affected by diabetes mellitus. A complex array of contributing factors including the hypertrophy of left ventricle, alterations of metabolism, microvascular pathology, insulin resistance, fibrosis, apoptotic cell death, and oxidative stress have been implicated in the pathogenesis of diabetic cardiomyopathy. Nevertheless, the exact mechanisms underlying the pathogenesis of diabetic cardiomyopathy are yet to be established. The critical involvement of multifarious factors including the vascular endothelial dysfunction, microangiopathy, reactive oxygen species (ROS), oxidative stress, mitochondrial dysfunction has been identified in the mechanism of pathogenesis of diabetic cardiomyopathy. Although it is difficult to establish how each factor contributes to disease, the involvement of ROS and mitochondrial dysfunction are emerging as front-runners in the mechanism of pathogenesis of diabetic cardiomyopathy. This review highlights the role of vascular endothelial dysfunction, ROS, oxidative stress, and mitochondriopathy in the pathogenesis of diabetic cardiomyopathy. Furthermore, the review emphasizes that the puzzle has to be solved to firmly establish the mitochondrial and/or ROS mechanism(s) by identifying their most critical molecular players involved at both spatial and temporal levels in diabetic cardiomyopathy as targets for specific and effective pharmacological/therapeutic interventions. PMID:24307101

  20. Iron- and ferritin-dependent reactive oxygen species distribution: impact on Arabidopsis root system architecture.

    PubMed

    Reyt, Guilhem; Boudouf, Soukaina; Boucherez, Jossia; Gaymard, Frédéric; Briat, Jean-Francois

    2015-03-01

    Iron (Fe) homeostasis is integrated with the production of reactive oxygen species (ROS), and distribution at the root tip participates in the control of root growth. Excess Fe increases ferritin abundance, enabling the storage of Fe, which contributes to protection of plants against Fe-induced oxidative stress. AtFer1 and AtFer3 are the two ferritin genes expressed in the meristematic zone, pericycle and endodermis of the Arabidopsis thaliana root, and it is in these regions that we observe Fe stained dots. This staining disappears in the triple fer1-3-4 ferritin mutant. Fe excess decreases primary root length in the same way in wild-type and in fer1-3-4 mutant. In contrast, the Fe-mediated decrease of lateral root (LR) length and density is enhanced in fer1-3-4 plants due to a defect in LR emergence. We observe that this interaction between excess Fe, ferritin, and root system architecture (RSA) is in part mediated by the H2O2/O2·- balance between the root cell proliferation and differentiation zones regulated by the UPB1 transcription factor. Meristem size is also decreased in response to Fe excess in ferritin mutant plants, implicating cell cycle arrest mediated by the ROS-activated SMR5/SMR7 cyclin-dependent kinase inhibitors pathway in the interaction between Fe and RSA. PMID:25624148

  1. Reactive oxygen species, abscisic acid and ethylene interact to regulate sunflower seed germination.

    PubMed

    El-Maarouf-Bouteau, Hayat; Sajjad, Yasar; Bazin, Jérémie; Langlade, Nicolas; Cristescu, Simona M; Balzergue, Sandrine; Baudouin, Emmanuel; Bailly, Christophe

    2015-02-01

    Sunflower (Helianthus annuus L.) seed dormancy is regulated by reactive oxygen species (ROS) and can be alleviated by incubating dormant embryos in the presence of methylviologen (MV), a ROS-generating compound. Ethylene alleviates sunflower seed dormancy whereas abscisic acid (ABA) represses germination. The purposes of this study were to identify the molecular basis of ROS effect on seed germination and to investigate their possible relationship with hormone signalling pathways. Ethylene treatment provoked ROS generation in embryonic axis whereas ABA had no effect on their production. The beneficial effect of ethylene on germination was lowered in the presence of antioxidant compounds, and MV suppressed the inhibitory effect of ABA. MV treatment did not alter significantly ethylene nor ABA production during seed imbibition. Microarray analysis showed that MV treatment triggered differential expression of 120 probe sets (59 more abundant and 61 less abundant genes), and most of the identified transcripts were related to cell signalling components. Many transcripts less represented in MV-treated seeds were involved in ABA signalling, thus suggesting an interaction between ROS and ABA signalling pathways at the transcriptional level. Altogether, these results shed new light on the crosstalk between ROS and plant hormones in seed germination. PMID:24811898

  2. Reactive oxygen species as a signal in glucose-stimulated insulin secretion.

    PubMed

    Pi, Jingbo; Bai, Yushi; Zhang, Qiang; Wong, Victoria; Floering, Lisa M; Daniel, Kiefer; Reece, Jeffrey M; Deeney, Jude T; Andersen, Melvin E; Corkey, Barbara E; Collins, Sheila

    2007-07-01

    One of the unique features of beta-cells is their relatively low expression of many antioxidant enzymes. This could render beta-cells susceptible to oxidative damage but may also provide a system that is sensitive to reactive oxygen species as signals. In isolated mouse islets and INS-1(832/13) cells, glucose increases intracellular accumulation of H2O2. In both models, insulin secretion could be stimulated by provision of either exogenous H2O2 or diethyl maleate, which raises intracellular H2O2 levels. Provision of exogenous H2O2 scavengers, including cell permeable catalase and N-acetyl-L-cysteine, inhibited glucose-stimulated H2O2 accumulation and insulin secretion (GSIS). In contrast, cell permeable superoxide dismutase, which metabolizes superoxide into H2O2, had no effect on GSIS. Because oxidative stress is an important risk factor for beta-cell dysfunction in diabetes, the relationship between glucose-induced H2O2 generation and GSIS was investigated under various oxidative stress conditions. Acute exposure of isolated mouse islets or INS-1(832/13) cells to oxidative stressors, including arsenite, 4-hydroxynonenal, and methylglyoxal, led to decreased GSIS. This impaired GSIS was associated with increases in a battery of endogenous antioxidant enzymes. Taken together, these findings suggest that H2O2 derived from glucose metabolism is one of the metabolic signals for insulin secretion, whereas oxidative stress may disturb its signaling function. PMID:17400930

  3. Reactive oxygen species and uncoupling protein 2 in pancreatic ?-cell function.

    PubMed

    Pi, J; Collins, S

    2010-10-01

    Growing evidence indicates that reactive oxygen species (ROS) are not just deleterious by-products of respiratory metabolism in mitochondria, but can be essential elements for many biological responses, including in pancreatic ?-cells. ROS can be a 'second-messenger signal' in response to hormone/receptor activation that serves as part of the 'code' to trigger the ultimate biological response, or it can be a 'protective signal' to increase the levels of antioxidant enzymes and small molecules to scavenge ROS, thus restoring cellular redox homeostasis. In pancreatic ?-cells evidence is emerging that acute and transient glucose-dependent ROS contributes to normal glucose-stimulated insulin secretion (GSIS). However, chronic and persistent elevation of ROS, resulting from inflammation or excessive metabolic fuels such as glucose and fatty acids, may elevate antioxidant enzymes such that they blunt ROS and redox signalling, thus impairing ?-cell function. An interesting mitochondrial protein whose main function appears to be the control of ROS is uncoupling protein 2 (UCP2). Despite continuing investigation of the exact mechanism by which UCP2 is 'activated', it is clear that UCP2 levels and/or activity impact the efficacy of GSIS in pancreatic islets. This review will focus on the paradoxical roles of ROS in pancreatic ?-cell function and the regulatory role of UCP2 in ROS signalling and GSIS. PMID:21029311

  4. Deficient plastidic fatty acid synthesis triggers cell death by modulating mitochondrial reactive oxygen species

    PubMed Central

    Wu, Jian; Sun, Yuefeng; Zhao, Yannan; Zhang, Jian; Luo, Lilan; Li, Meng; Wang, Jinlong; Yu, Hong; Liu, Guifu; Yang, Liusha; Xiong, Guosheng; Zhou, Jian-Min; Zuo, Jianru; Wang, Yonghong; Li, Jiayang

    2015-01-01

    Programmed cell death (PCD) is of fundamental importance to development and defense in animals and plants. In plants, a well-recognized form of PCD is hypersensitive response (HR) triggered by pathogens, which involves the generation of reactive oxygen species (ROS) and other signaling molecules. While the mitochondrion is a master regulator of PCD in animals, the chloroplast is known to regulate PCD in plants. Arabidopsis Mosaic Death 1 (MOD1), an enoyl-acyl carrier protein (ACP) reductase essential for fatty acid biosynthesis in chloroplasts, negatively regulates PCD in Arabidopsis. Here we report that PCD in mod1 results from accumulated ROS and can be suppressed by mutations in mitochondrial complex I components, and that the suppression is confirmed by pharmaceutical inhibition of the complex I-generated ROS. We further show that intact mitochondria are required for full HR and optimum disease resistance to the Pseudomonas syringae bacteria. These findings strongly indicate that the ROS generated in the electron transport chain in mitochondria plays a key role in triggering plant PCD and highlight an important role of the communication between chloroplast and mitochondrion in the control of PCD in plants. PMID:25906995

  5. Diminished Macrophage Apoptosis and Reactive Oxygen Species Generation after Phorbol Ester Stimulation in Crohn's Disease

    PubMed Central

    Palmer, Christine D.; Rahman, Farooq Z.; Sewell, Gavin W.; Ahmed, Afshan; Ashcroft, Margaret; Bloom, Stuart L.; Segal, Anthony W.; Smith, Andrew M.

    2009-01-01

    Background Crohn's Disease (CD) is a chronic relapsing disorder characterized by granulomatous inflammation of the gastrointestinal tract. Although its pathogenesis is complex, we have recently shown that CD patients have a systemic defect in macrophage function, which results in the defective clearance of bacteria from inflammatory sites. Methodology/Principal Findings Here we have identified a number of additional macrophage defects in CD following diacylglycerol (DAG) homolog phorbol-12-myristate-13-acetate (PMA) activation. We provide evidence for decreased DNA fragmentation, reduced mitochondrial membrane depolarization, impaired reactive oxygen species production, diminished cytochrome c release and increased IL-6 production compared to healthy subjects after PMA exposure. The observed macrophage defects in CD were stimulus-specific, as normal responses were observed following p53 activation and endoplasmic reticulum stress. Conclusion These findings add to a growing body of evidence highlighting disordered macrophage function in CD and, given their pivotal role in orchestrating inflammatory responses, defective apoptosis could potentially contribute to the pathogenesis of CD. PMID:19907654

  6. Mitochondrial phospholipase A2 activated by reactive oxygen species in heart mitochondria induces mild uncoupling.

    PubMed

    Ježek, J; Jab?rek, M; Zelenka, J; Ježek, P

    2010-01-01

    Homeostasis of reactive oxygen species (ROS) in cardiomyocytes is critical for elucidation of normal heart physiology and pathology. Mitochondrial phospholipases A2 (mt-PLA2) have been previously suggested to be activated by ROS. Therefore, we have attempted to elucidate physiological role of such activation. We have found that function of a specific i-isoform of mitochondrial phospholipase A2 (mt-iPLA2) is activated by tert-butylhydroperoxide in isolated rat heart mitochondria. Isoform specificity was judged from the inhibition by bromoenol lactone (BEL), a specific iPLA2 inhibitor. Concomitant uncoupling has been caused by free fatty acids, since it was inhibited by bovine serum albumin. The uncoupling was manifested as a respiration burst accompanied by a slight decrease in mitochondrial inner membrane potential. Since this uncoupling was sensitive to carboxyatractyloside and purine nucleotide di- and tri-phosphates, we conclude that it originated from the onset of fatty acid cycling mediated by the adenine nucleotide translocase (major contribution) and mitochondrial uncoupling protein(s) (minor contribution), respectively. Such a mild uncoupling may provide a feedback downregulation of oxidative stress, since it can further attenuate mitochondrial production of ROS. In conclusion, ROS-induced function of cardiac mt-iPLA2 may stand on a pro-survival side of ischemia-reperfusion injury. PMID:20406040

  7. Isoalantolactone Induces Reactive Oxygen Species Mediated Apoptosis in Pancreatic Carcinoma PANC-1 Cells

    PubMed Central

    Khan, Muhammad; Ding, Chuan; Rasul, Azhar; Yi, Fei; Li, Ting; Gao, Hongwen; Gao, Rong; Zhong, Lili; Zhang, Kun; Fang, Xuedong; Ma, Tonghui

    2012-01-01

    Isoalantolactone, a sesquiterpene lactone compound possesses antifungal, antibacteria, antihelminthic and antiproliferative activities. In the present study, we found that isoalantolactone inhibits growth and induces apoptosis in pancreatic cancer cells. Further mechanistic studies revealed that induction of apoptosis is associated with increased generation of reactive oxygen species, cardiolipin oxidation, reduced mitochondrial membrane potential, release of cytochrome c and cell cycle arrest at S phase. N-Acetyl Cysteine (NAC), a specific ROS inhibitor restored cell viability and completely blocked isoalantolactone-mediated apoptosis in PANC-1 cells indicating that ROS are involved in isoalantolactone-mediated apoptosis. Western blot study showed that isoalantolactone increased the expression of phosphorylated p38 MAPK, Bax, and cleaved caspase-3 and decreased the expression of Bcl-2 in a dose-dependent manner. No change in expression of phosphorylated p38 MAPK and Bax was found when cells were treated with isoalantolactone in the presence of NAC, indicating that activation of these proteins is directly dependent on ROS generation. The present study provides evidence for the first time that isoalantolactone induces ROS-dependent apoptosis through intrinsic pathway. Furthermore, our in vivo toxicity study demonstrated that isoalantolactone did not induce any acute or chronic toxicity in liver and kidneys of CD1 mice at dose of 100 mg/kg body weight. Therefore, isoalantolactone may be a safe chemotherapeutic candidate for the treatment of human pancreatic carcinoma. PMID:22532787

  8. Zinc protects Ceratophyllum demersum L. (free-floating hydrophyte) against reactive oxygen species induced by cadmium.

    PubMed

    Aravind, P; Prasad, M N V; Malec, P; Waloszek, A; Strza?ka, K

    2009-01-01

    Evidence for Zn protection against Cd-induced reactive oxygen species in the free-floating hydrophyte Ceratophyllum demersum L. is presented in this paper. Metal treatments of 10 micromol/L Cd, 10 Cd micromol/L supplemented with Zn (10, 50, 100 and 200 micromol/L) and Zn-alone treatments of the same concentrations were used. Using 5,5 dimethyl pyrroline-N-oxide as the spin-probe, electron spin resonance spectra indicated a drastic increase in hydroxyl radicals (OH()) in Cd-10 micromol/L treatments, which was closely correlating with the enhanced formation of hydrogen peroxide (H(2)O(2)) and generation of superoxide radical (O(2)(-)) triggered by the oxidation of NADPH. The supplementation of adding Zn (10-200 micromol/L) to the Cd-10 micromol/L treatments significantly decreased the production of free radicals especially by eliminating the precursors of OH() through inhibition of NADPH oxidation. Cd-enhanced ROS production which substantially increased the oxidative products of proteins measured as carbonyls was effectively inhibited by Zn supplementation. PMID:19203717

  9. Mitochondrial reactive oxygen species modulate innate immune response to influenza A virus in human nasal epithelium.

    PubMed

    Kim, Sujin; Kim, Min-Ji; Park, Do Yang; Chung, Hyo Jin; Kim, Chang-Hoon; Yoon, Joo-Heon; Kim, Hyun Jik

    2015-07-01

    The innate immune system of the nasal epithelium serves as a first line of defense against invading respiratory viruses including influenza A virus (IAV). Recently, it was verified that interferon (IFN)-related immune responses play a critical role in local antiviral innate immunity. Reactive oxygen species (ROS) generation by exogenous pathogens has also been demonstrated in respiratory epithelial cells and modulation of ROS has been reported to be important for respiratory virus-induced innate immune mechanisms. Passage-2 normal human nasal epithelial (NHNE) cells were inoculated with IAV (WS/33, H1N1) to assess the sources of IAV-induced ROS and the relationship between ROS and IFN-related innate immune responses. Both STAT1 and STAT2 phosphorylation and the mRNA levels of IFN-stimulated genes, including Mx1, 2,5-OAS1, IFIT1, and CXCL10, were induced after IAV infection up to three days post infection. Similarly, we observed that mitochondrial ROS generation increased maximally at 2days after IAV infection. After suppression of mitochondrial ROS generation, IAV-induced phosphorylation of STAT and mRNA levels of IFN-stimulated genes were attenuated and actually, viral titers of IAV were significantly higher in cases with scavenging ROS. Our findings suggest that mitochondrial ROS might be responsible for controlling IAV infection and may be potential sources of ROS generation, which is required to initiate an innate immune response in NHNE cells. PMID:25930096

  10. Phenolic extract of Dialium guineense pulp enhances reactive oxygen species detoxification in aflatoxin B? hepatocarcinogenesis.

    PubMed

    Adeleye, Abdulwasiu O; Ajiboye, Taofeek O; Iliasu, Ganiyat A; Abdussalam, Folakemi A; Balogun, Abdulazeez; Ojewuyi, Oluwayemisi B; Yakubu, Musa T

    2014-08-01

    This study investigated the effect of Dialium guineense pulp phenolic extract on aflatoxin B1 (AFB1)-induced oxidative imbalance in rat liver. Reactive oxygen species (ROS) scavenging potentials of free and bound phenolic extract of D. guineense (0.2-1.0?mg/mL) were investigated in vitro using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide ion (O2(-)), hydrogen peroxide (H2O2), hydroxyl radical, and ferric ion reducing system. In the in vivo study, 35 animals were randomized into seven groups of five rats each. Free and bound phenolic extract (1?mg/mL) produced 66.42% and 93.08%, 57.1% and 86.0%, 62.0% and 90.05%, and 60.11% and 72.37% scavenging effect on DPPH radical, O2(-) radical, H2O2, and hydroxyl radical, while ferric ion was significantly reduced. An AFB1-mediated decrease in the activities of ROS detoxifying enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose 6 phosphate dehydrogenase) was significantly attenuated (P<.05). AFB1-mediated elevation in the concentrations of oxidative stress biomarkers; malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl, and percentage DNA fragmentation were significantly lowered by D. guineense phenolic extract (P<.05). Overall, the in vitro and in vivo effects suggest that D. guineense phenolic extract elicited ROS scavenging and detoxification potentials, as well as the capability of preventing lipid peroxidation, protein oxidation, and DNA fragmentation. PMID:24892362

  11. Mitochondrial reactive oxygen species: A double edged sword in ischemia/reperfusion vs preconditioning

    PubMed Central

    Kalogeris, Theodore; Bao, Yimin; Korthuis, Ronald J.

    2014-01-01

    Reductions in the blood supply produce considerable injury if the duration of ischemia is prolonged. Paradoxically, restoration of perfusion to ischemic organs can exacerbate tissue damage and extend the size of an evolving infarct. Being highly metabolic organs, the heart and brain are particularly vulnerable to the deleterious effects of ischemia/reperfusion (I/R). While the pathogenetic mechanisms contributing to I/R-induced tissue injury and infarction are multifactorial, the relative importance of each contributing factor remains unclear. However, an emerging body of evidence indicates that the generation of reactive oxygen species (ROS) by mitochondria plays a critical role in damaging cellular components and initiating cell death. In this review, we summarize our current understanding of the mechanisms whereby mitochondrial ROS generation occurs in I/R and contributes to myocardial infarction and stroke. In addition, mitochondrial ROS have been shown to participate in preconditioning by several pharmacologic agents that target potassium channels (e.g., ATP-sensitive potassium (mKATP) channels or large conductance, calcium-activated potassium (mBKCa) channels) to activate cell survival programs that render tissues and organs more resistant to the deleterious effects of I/R. Finally, we review novel therapeutic approaches that selectively target mROS production to reduce postischemic tissue injury, which may prove efficacious in limiting myocardial dysfunction and infarction and abrogating neurocognitive deficits and neuronal cell death in stroke. PMID:24944913

  12. Antiallodynic effect of intrathecal epigallocatechin-3-gallate due to suppression of reactive oxygen species

    PubMed Central

    An, Sang Soon; Kim, Yeo Ok; Park, Cheon Hee; Lin, Hai

    2014-01-01

    Background Green tea modulates neuropathic pain. Reactive oxygen species (ROS) are suggested as a key molecule in the underlying mechanism of neuropathic pain in the spinal cord. We examined the effect of epigallocatechin-3-gallate (EGCG), the major catechin in green tea, in neuropathic pain and clarified the involvement of ROS on the activity of EGCG. Methods Neuropathic pain was induced in male Sprague-Dawley rats by spinal nerve ligation (SNL). A polyethylene tube was intrathecally located. Nociceptive degree was estimated by a von Frey filament and expressed as a paw withdrawal threshold (PWT). To determine the role of ROS on the effect of EGCG, a free radical donor (tert-BuOOH) was pretreated before administration of EGCG. ROS activity was assayed by xanthine oxidase (XO) and malondialdehyde (MDA). Results SNL decreased the PWT compared to sham rats. The decrease remained during the entire observation period. Intrathecal EGCG increased the PWT at the SNL site. Intrathecal tert-BuOOH significantly decreased the effect of EGCG. The levels of both XO and MDA in the spinal cord were increased in SNL rats compared to sham. Intrathecal EGCG decreased the level of XO and MDA. Conclusions EGCG may reduce neuropathic pain by SNL due to the suppression of ROS in the spinal cord. PMID:25237449

  13. The impact of reactive oxygen species and genetic mitochondrial mutations in Parkinson's disease.

    PubMed

    Zuo, Li; Motherwell, Michael S

    2013-12-10

    The exact pathogenesis of Parkinson's disease (PD) is still unknown and proper mechanisms that correspond to the disease remain unidentified. It is understood that PD is age-related; as age increases, the chance of onset responds accordingly. Although there are no current means of curing PD, the understanding of reactive oxygen species (ROS) provides significant insight to possible treatments. Complex I deficiencies of the respiratory chain account for the majority of unfavorable neural apoptosis generation in PD. Dopaminergic neurons are severely damaged as a result of the deficiency. Symptoms such as inhibited cognitive ability and loss of smooth motor function are the results of such impairment. The genetic mutations of Parkinson's related proteins such as PINK1 and LRRK2 contribute to mitochondrial dysfunction which precedes ROS formation. Various pathways are inhibited by these mutations, and inevitably causing neural cell damage. Antioxidants are known to negate the damaging effects of free radical overexpression. This paper expands on the specific impact of mitochondrial genetic change and production of free radicals as well as its correlation to the neurodegeneration in Parkinson's disease. PMID:23954870

  14. Identification and biological activities of a new antiangiogenic small molecule that suppresses mitochondrial reactive oxygen species

    SciTech Connect

    Kim, Ki Hyun; Park, Ju Yeol; Jung, Hye Jin [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)] [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kwon, Ho Jeong, E-mail: kwonhj@yonsei.ac.kr [Chemical Genomics National Research Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2011-01-07

    Research highlights: {yields} YCG063 was screened as a new angiogenesis inhibitor which suppresses mitochondrial ROS generation in a phenotypic cell-based screening of a small molecule-focused library. {yields} The compound inhibited in vitro and in vivo angiogenesis in a dose-dependent manner. {yields} This new small molecule tool will provide a basis for a better understanding of angiogenesis driven under hypoxic conditions. -- Abstract: Mitochondrial reactive oxygen species (ROS) are associated with multiple cellular functions such as cell proliferation, differentiation, and apoptosis. In particular, high levels of mitochondrial ROS in hypoxic cells regulate many angiogenesis-related diseases, including cancer and ischemic disorders. Here we report a new angiogenesis inhibitor, YCG063, which suppressed mitochondrial ROS generation in a phenotypic cell-based screening of a small molecule-focused library with an ArrayScan HCS reader. YCG063 suppressed mitochondrial ROS generation under a hypoxic condition in a dose-dependent manner, leading to the inhibition of in vitro angiogenic tube formation and chemoinvasion as well as in vivo angiogenesis of the chorioallantoic membrane (CAM) at non-toxic doses. In addition, YCG063 decreased the expression levels of HIF-1{alpha} and its target gene, VEGF. Collectively, a new antiangiogenic small molecule that suppresses mitochondrial ROS was identified. This new small molecule tool will provide a basis for a better understanding of angiogenesis driven under hypoxic conditions.

  15. Reactive oxygen species-scavenging nanomedicines for the treatment of oxidative stress injuries.

    PubMed

    Yoshitomi, Toru; Nagasaki, Yukio

    2014-08-01

    This Progress Report describes a development of two types of reactive oxygen species (ROS)-scavenging nanomedicines for the treatment of oxidative stress injuries, referred to as pH-sensitive redox nanoparticle (RNP(N) ) and pH-insensitive redox nanoparticle (RNP(O) ), which are prepared by self-assembling amphiphilic block copolymers possessing nitroxide radicals as a side chain of hydrophobic segment via amine and ether linkages, respectively. Due to a protonation of amino groups in hydrophobic core, RNP(N) disintegrates in low pH environments such as ischemic, inflamed, and tumor tissues, resulting in increased ROS-scavenging activity because of the exposed nitroxide radicals from the core. Utilizing pH-responsiveness of RNP(N) , it shows remarkable therapeutic effects on oxidative stress injuries such as renal and cerebral ischemia-reperfusion injuries after intravenous administration. Moreover, RNP(N) shows an enhancement of the activity of anticancer drugs by suppression of activation of transcription factors in tumor due to the ROS scavenging. On the other hand, orally administered RNP(O) has notable characteristics such as preferential accumulation in mucosa and inflamed area of gastrointestinal tract and no uptake into blood stream. Based on these characters, RNP(O) shows a remarkable therapeutic effect for the gastrointestinal inflammation without any adverse effects. Thus, ROS-scavenging nanomedicines have therapeutic efficacy in numerous oxidative stress diseases. PMID:24482427

  16. KETONES INHIBIT MITOCHONDRIAL PRODUCTION OF REACTIVE OXYGEN SPECIES PRODUCTION FOLLOWING GLUTAMATE EXCITOTOXICITY BY INCREASING NADH OXIDATION

    PubMed Central

    Maalouf, Marwan; Sullivan, Patrick G.; Davis, Laurie; Kim, Do Young; Rho, Jong M.

    2007-01-01

    Dietary protocols that increase serum levels of ketones, such as calorie restriction and the ketogenic diet, offer robust protection against a multitude of acute and chronic neurological diseases. The underlying mechanisms, however, remain unclear. Previous studies have suggested that the ketogenic diet may reduce free radical levels in the brain. Thus, one possibility is that ketones may mediate neuroprotection through antioxidant activity. In the present study, we examined the effects of the ketones ?-hydroxybutyrate and acetoacetate on acutely dissociated rat neocortical neurons subjected to glutamate excitotoxicity using cellular electrophysiological and single-cell fluorescence imaging techniques. Further, we explored the effects of ketones on acutely isolated mitochondria exposed to high levels of calcium. A combination of ?-hydroxybutyrate and acetoacetate (1 mM each) decreased neuronal death and prevented changes in neuronal membrane properties induced by 10 ?M glutamate. Ketones also significantly decreased mitochondrial production of reactive oxygen species and the associated excitotoxic changes by increasing NADH oxidation in the mitochondrial respiratory chain, but did not affect levels of the endogenous antioxidant glutathione. In conclusion, we demonstrate that ketones reduce glutamate-induced free radical formation by increasing the NAD+/NADH ratio and enhancing mitochondrial respiration in neocortical neurons. This mechanism may, in part, contribute to the neuroprotective activity of ketones by restoring normal bioenergetic function in the face of oxidative stress. PMID:17240074

  17. MSP Hormonal Control of the Oocyte MAP Kinase Cascade and Reactive Oxygen Species Signaling

    PubMed Central

    Yang, Youfeng; Han, Sung Min; Miller, Michael A.

    2014-01-01

    The MSP domain is a conserved immunoglobulin-like structure that is important for C. elegans reproduction and human motor neuron survival. C. elegans MSPs are the most abundant proteins in sperm, where they function as intracellular cytoskeletal proteins and secreted hormones. Secreted MSPs bind to multiple receptors on oocyte and ovarian sheath cell surfaces to induce oocyte maturation and sheath contraction. MSP binding stimulates oocyte MPK-1 ERK MAP Kinase (MAPK) phosphorylation, but the function and mechanism are not well understood. Here we show that the Shp class protein-tyrosine phosphatase PTP-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote MSP-induced MPK-1 phosphorylation. PTP-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. We also provide evidence that MSP promotes production of reactive oxygen species (ROS), which act as second messengers to augment MPK-1 phosphorylation. The Cu/Zn superoxide dismutase SOD-1, an enzyme that catalyzes ROS breakdown in the cytoplasm, inhibits MPK-1 phosphorylation downstream of or in parallel to ptp-2. Our results support the model that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation. We propose that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling. PMID:20380830

  18. Induction of apoptosis by cordycepin via reactive oxygen species generation in human leukemia cells.

    PubMed

    Jeong, Jin-Woo; Jin, Cheng-Yun; Park, Cheol; Hong, Su Hyun; Kim, Gi-Young; Jeong, Yong Kee; Lee, Jae-Dong; Yoo, Young Hyun; Choi, Yung Hyun

    2011-06-01

    Cordycepin (3'-deoxyadenosin), a specific polyadenylation inhibitor, is the main functional component in Cordyceps militaris, one of the top three renowned traditional Chinese medicines. Cordycepin has been shown to possess many pharmacological activities including immunological stimulation, and anti-bacterial, anti-viral, and anti-tumor effects. However, the mechanisms underlying its anti-cancer mechanisms are not yet understood. In this study, the apoptotic effects of cordycepin were investigated in human leukemia cells. Treatment with cordycepin significantly inhibited cell growth in a concentration-dependent manner by inducing apoptosis but not necrosis. This induction was associated with generation of reactive oxygen species (ROS), mitochondrial dysfunction, activation of caspases, and cleavage of poly(ADP-ribose) polymerase protein. However, apoptosis induced by cordycepin was attenuated by caspase inhibitors, indicating an important role for caspases in cordycepin responses. Administration of N-acetyl-l-cysteine, a scavenger of ROS, also significantly inhibited cordycepin-induced apoptosis and activation of caspases. These results support a mechanism whereby cordycepin induces apoptosis of human leukemia cells through a signaling cascade involving a ROS-mediated caspase pathway. PMID:21310227

  19. NF-?B Inhibitors from Brucea javanica Exhibiting Intracellular Effects on Reactive Oxygen Species

    PubMed Central

    Kim, Jeong-Ah; Lau, Edward K.; Pan, Li; Carcache de Blanco, Esperanza J.

    2010-01-01

    Aim Brucea javanica was studied to identify Nuclear Factor kappaB (NF-?B) inhibitors exhibiting Reactive Oxygen Species (ROS) intracellular amplification. Material and Methods Eight compounds were evaluated for selective cytotoxicity using HT-29, HeLa, and HL-60 cells, and in a NF-?B assay. Active compounds were then tested using ROS and Mitochondria Transmembrane Potential (MTP) assays. NF-?B and Nuclear Factor Activated T cell (NFAT) translocation were also assessed using their respective whole cell assays. Results Bruceajavanone B, bruceantin, bruceine A, (?)-hydnocarpin, and chrysoeriol exhibited cytotoxic potential and NF-?B p65 inhibition. Chrysoeriol exhibited selective cytotoxicity against leukemia cells with greater potency and also showed an ability to up-regulate NFAT transcriptional pathways through the amplification of intracellular ROS, in the presence of H2O2, to a greater degree than bruceantin and bruceine. Conclusion Chrysoeriol selectively kills leukemic cells and potentiates the amplification of ROS levels. Therefore, chrysoeriol could serve as a potential chemotherapeutic modifier for leukemia chemotherapy since leukemia cells have a higher susceptibility to elevated ROS levels. PMID:20944100

  20. Spin Biochemistry Modulates Reactive Oxygen Species (ROS) Production by Radio Frequency Magnetic Fields

    PubMed Central

    Usselman, Robert J.; Hill, Iain; Singel, David J.; Martino, Carlos F.

    2014-01-01

    The effects of weak magnetic fields on the biological production of reactive oxygen species (ROS) from intracellular superoxide (O2•?) and extracellular hydrogen peroxide (H2O2) were investigated in vitro with rat pulmonary arterial smooth muscle cells (rPASMC). A decrease in O2•? and an increase in H2O2 concentrations were observed in the presence of a 7 MHz radio frequency (RF) at 10 ?TRMS and static 45 ?T magnetic fields. We propose that O2•? and H2O2 production in some metabolic processes occur through singlet-triplet modulation of semiquinone flavin (FADH•) enzymes and O2•? spin-correlated radical pairs. Spin-radical pair products are modulated by the 7 MHz RF magnetic fields that presumably decouple flavin hyperfine interactions during spin coherence. RF flavin hyperfine decoupling results in an increase of H2O2 singlet state products, which creates cellular oxidative stress and acts as a secondary messenger that affects cellular proliferation. This study demonstrates the interplay between O2•? and H2O2 production when influenced by RF magnetic fields and underscores the subtle effects of low-frequency magnetic fields on oxidative metabolism, ROS signaling, and cellular growth. PMID:24681944

  1. Involvement of reactive oxygen species in cocaine-taking behaviors in rats.

    PubMed

    Jang, Eun Young; Ryu, Yeon-Hee; Lee, Bong Hyo; Chang, Su-Chan; Yeo, Mi Jin; Kim, Sang Hyun; Folsom, Ryan J; Schilaty, Nathan D; Kim, Kwang Joong; Yang, Chae Ha; Steffensen, Scott C; Kim, Hee Young

    2015-07-01

    Reactive oxygen species (ROS) have been implicated in the development of behavioral sensitization following repeated cocaine exposure. We hypothesized that increased ROS following cocaine exposure would act as signaling molecules in the mesolimbic dopamine (DA) system, which might play an important role in mediating the reinforcing effects of cocaine. The aim of this study was to evaluate cocaine enhancement of brain metabolic activity and the effects of ROS scavengers on cocaine self-administration behavior, cocaine-induced ROS production in the nucleus accumbens (NAc) and cocaine enhancement of DA release in the NAc. Metabolic neural activity monitored by temperature and oxidative stress were increased in NAc following cocaine exposure. Systemic administration of the ROS scavenger N-tert-butyl-?-phenylnitrone (PBN) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), either pre- or post-treatment, significantly decreased cocaine self-administration without affecting food intake. Infusion of TEMPOL into the NAc inhibited cocaine self-administration. Increased oxidative stress was found mainly on neurons, but not astrocytes, microglia or oligodendrocytes, in NAc of rats self-administering cocaine. TEMPOL significantly attenuated cocaine-induced enhancement of DA release in the NAc, compared to saline controls. TEMPOL had no effect on the enhancement of DA release produced by the DA transporter inhibitor GBR12909. Taken together, these findings suggest that enhancement of ROS production in NAc neurons contributes to the reinforcing effect of cocaine. PMID:24975938

  2. Antioxidant effects of antioxidant biofactor on reactive oxygen species in human gingival fibroblasts

    PubMed Central

    Matsui, Satoshi; Tsujimoto, Yasuhisa; Ozawa, Toshihiko; Matsushima, Kiyoshi

    2011-01-01

    The purpose of this study was to investigate the effects of antioxidant biofactor (AOB) on reactive oxygen species (ROS). Generation of superoxide radical (O2•?) and hydroxyl radical (•OH) was determined using an electron spin resonance (ESR) spin-trapping method. AOB was added at different concentrations to these free radical generating systems. The generation of both O2•? and •OH was scavenged by the addition of AOB in a dose-dependent manner. These results indicate that AOB has strong antioxidant properties against these radicals. We further investigated the anti-oxidative effect of AOB on human gingival fibroblasts (HGFs). HGFs were treated for 3 h with ?-MEM containing a combination of AOB and H2O2 (AOB + H2O2 group), containing H2O2 (H2O2 group), or containing AOB alone (AOB group). Non-stimulated HGFs were used as a control group. The number of surviving cells was in the order of the AOB group > control group > AOB + H2O2 group > H2O2 group. The level of expression of type I collagen mRNA and production of collagen were also in the order of the AOB group > control group > AOB + H2O2 group > H2O2 group. In conclusion, our results suggest that AOB may protect HGFs against oxidative stress by reducing stress-induced ROS. PMID:21562640

  3. Extracellular ultrathin fibers sensitive to intracellular reactive oxygen species: Formation of intercellular membrane bridges

    SciTech Connect

    Jung, Se-Hui; Park, Jin-Young; Joo, Jung-Hoon; Kim, Young-Myeong; Ha, Kwon-Soo, E-mail: ksha@kangwon.ac.kr

    2011-07-15

    Membrane bridges are key cellular structures involved in intercellular communication; however, dynamics for their formation are not well understood. We demonstrated the formation and regulation of novel extracellular ultrathin fibers in NIH3T3 cells using confocal and atomic force microscopy. At adjacent regions of neighboring cells, phorbol 12-myristate 13-acetate (PMA) and glucose oxidase induced ultrathin fiber formation, which was prevented by Trolox, a reactive oxygen species (ROS) scavenger. The height of ROS-sensitive ultrathin fibers ranged from 2 to 4 nm. PMA-induced formation of ultrathin fibers was inhibited by cytochalasin D, but not by Taxol or colchicine, indicating that ultrathin fibers mainly comprise microfilaments. PMA-induced ultrathin fibers underwent dynamic structural changes, resulting in formation of intercellular membrane bridges. Thus, these fibers are formed by a mechanism(s) involving ROS and involved in formation of intercellular membrane bridges. Furthermore, ultrastructural imaging of ultrathin fibers may contribute to understanding the diverse mechanisms of cell-to-cell communication and the intercellular transfer of biomolecules, including proteins and cell organelles.

  4. Cr speciation changes in the presence of ozone and reactive oxygen species at low relative humidity

    NASA Astrophysics Data System (ADS)

    Amouei Torkmahalleh, Mehdi; Lin, Lin; Holsen, Thomas M.; Rasmussen, Don H.; Hopke, Philip K.

    2013-06-01

    There is limited understanding of chromium chemistry in the atmosphere as well as after particles containing chromium are captured on filters during extended sampling intervals (24 h). Thus, experiments were conducted to investigate the role of ozone (4 ppm) and particle-bound reactive oxygen species (ROS) (>700 nM of equivalent H2O2) on chromium speciation. For Cr(VI) collected on a filter, reduction to Cr(III) at 24 °C, pH 4 and 10% RH decreased from 48 ± 3% to 26 ± 3% (p < 0.001) after 2 h of exposure, compared to the absence of added ozone (control experiments). Ozone and ROS led to some oxidation of Cr(III) to Cr(VI) (up to 7% for ozone at pH 4, up to 4.5 times for ROS and ozone at pH 9) with a steady-state concentration being reached after few hours. Ozone and ROS can compensate to some extent for Cr(VI) reduction occurring on PM-laden filters. Oxidation of Cr(III) by ozone slowed as the temperature decreased, implying that Cr(VI) sampling in a cool environment might be less likely biased by the oxidation of Cr(III) by atmospheric oxidants.

  5. Calcium and Reactive Oxygen Species in Acute Pancreatitis: Friend or Foe?

    PubMed Central

    Booth, David M.; Mukherjee, Rajarshi; Sutton, Robert

    2011-01-01

    Abstract Significance Acute pancreatitis (AP) is a debilitating and, at times, lethal inflammatory disease, the causes and progression of which are incompletely understood. Disruption of Ca2+ homeostasis in response to precipitants of AP leads to loss of mitochondrial integrity and cellular necrosis. Recent Advances While oxidative stress has been implicated as a major player in the pathogenesis of this disease, its precise roles remain to be defined. Recent developments are challenging the perception of reactive oxygen species (ROS) as nonspecific cytotoxic agents, suggesting that ROS promote apoptosis that may play a vital protective role in cellular stress since necrosis is avoided. Critical Issues Fresh clinical findings have indicated that antioxidant treatment does not ameliorate AP and may actually worsen the outcome. This review explores the complex links between cellular Ca2+ signaling and the intracellular redox environment, with particular relevance to AP. Future Directions Recent publications have underlined the importance of both Ca2+ and ROS within the pathogenesis of AP, particularly in the determination of cell fate. Future research should elucidate the subtle interplay between Ca2+ and redox mechanisms that operate to modulate mitochondrial function, with a view to devising strategies for the preservation of organellar function. Antioxid. Redox Signal. 15, 2683–2698. PMID:21861696

  6. The essential oil of bergamot stimulates reactive oxygen species production in human polymorphonuclear leukocytes.

    PubMed

    Cosentino, Marco; Luini, Alessandra; Bombelli, Raffaella; Corasaniti, Maria T; Bagetta, Giacinto; Marino, Franca

    2014-08-01

    Bergamot (Citrus aurantium L. subsp. bergamia) essential oil (BEO) is used in folk medicine as an antiseptic and anthelminthic and to facilitate wound healing. Evidence indicates that BEO has substantial antimicrobial activity; however its effects on immunity have never been examined. We studied the effects of BEO on reactive oxygen species (ROS) production in human polymorphonuclear leukocytes (PMN) and the role of Ca(2+) in the functional responses evoked by BEO in these cells. Results show that BEO increased intracellular ROS production in human PMN, an effect that required the contribution of extracellular (and, to a lesser extent, of intracellular) Ca(2+) . Bergamot essential oil also significantly increased ROS production induced by the chemotactic peptide N-formyl-Met-Leu-Phe and reduced the response to the protein kinase C activator phorbol myristate acetate. In conclusion, this is the first report showing the ability of BEO to increase ROS production in human PMN. This effect could both contribute to the activity of BEO in infections and in tissue healing as well as underlie an intrinsic proinflammatory potential. The relevance of these findings for the clinical uses of BEO needs careful consideration. PMID:24458921

  7. Ethylene Response Factor 6 Is a Regulator of Reactive Oxygen Species Signaling in Arabidopsis

    PubMed Central

    Sewelam, Nasser; Kazan, Kemal; Thomas-Hall, Skye R.; Kidd, Brendan N.; Manners, John M.; Schenk, Peer M.

    2013-01-01

    Reactive oxygen species (ROS) are produced in plant cells in response to diverse biotic and abiotic stresses as well as during normal growth and development. Although a large number of transcription factor (TF) genes are up- or down-regulated by ROS, currently very little is known about the functions of these TFs during oxidative stress. In this work, we examined the role of ERF6 (ETHYLENE RESPONSE FACTOR6), an AP2/ERF domain-containing TF, during oxidative stress responses in Arabidopsis. Mutant analyses showed that NADPH oxidase (RbohD) and calcium signaling are required for ROS-responsive expression of ERF6. erf6 insertion mutant plants showed reduced growth and increased H2O2 and anthocyanin levels. Expression analyses of selected ROS-responsive genes during oxidative stress identified several differentially expressed genes in the erf6 mutant. In particular, a number of ROS responsive genes, such as ZAT12, HSFs, WRKYs, MAPKs, RBOHs, DHAR1, APX4, and CAT1 were more strongly induced by H2O2 in erf6 plants than in wild-type. In contrast, MDAR3, CAT3, VTC2 and EX1 showed reduced expression levels in the erf6 mutant. Taken together, our results indicate that ERF6 plays an important role as a positive antioxidant regulator during plant growth and in response to biotic and abiotic stresses. PMID:23940555

  8. Aggregatibacter actinomycetemcomitans Invasion Induces Interleukin-1? Production Through Reactive Oxygen Species and Cathepsin B.

    PubMed

    Okinaga, Toshinori; Ariyoshi, Wataru; Nishihara, Tatsuji

    2015-06-01

    Interleukin-1 (IL-1) cytokines, IL-1?, IL-1?, and IL-18 play a crucial role in inflammatory responses in a variety of diseases including periodontitis. In this study, the periodontopathic bacterial pathogen, Aggregatibacter actinomycetemcomitans, induced cell death and cytokine release in macrophages. Cell viability was reduced by A. actinomycetemcomitans invasion using (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide assay. The production of IL-1? in A. actinomycetemcomitans-invaded macrophage cells was detected by real-time reverse transcriptase-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. Treatment with a caspase-1 inhibitor and silencing of the caspase-1 gene had no effect on IL-1? secretion induced by A. actinomycetemcomitans invasion. Pattern recognition receptor, NLRP3 was upregulated in A. actinomycetemcomitans-invaded macrophages. However, NLRP3 knockdown had no effect on the secretion of IL-1? in A. actinomycetemcomitans-invaded RAW 264 cells. In addition, A. actinomycetemcomitans invasion induced the generation of reactive oxygen species (ROS) and the release of cathepsin B in RAW 264 cells. Interestingly, CA074-Me, a cathepsin B inhibitor, and N-Acetyl-l-cysteine, a ROS inhibitor, prevented the production of IL-1? induced by A. actinomycetemcomitans. Taken together, these results suggest A. actinomycetemcomitans induce IL-1? production in RAW 264 cells through the production of ROS and cathepsin B, but not through the NLRP3/caspase-1 pathway. PMID:25789553

  9. Reactive Oxygen Species in the Signaling and Adaptation of Multicellular Microbial Communities

    PubMed Central

    ?áp, Michal; Váchová, Libuše; Palková, Zdena

    2012-01-01

    One of the universal traits of microorganisms is their ability to form multicellular structures, the cells of which differentiate and communicate via various signaling molecules. Reactive oxygen species (ROS), and hydrogen peroxide in particular, have recently become well-established signaling molecules in higher eukaryotes, but still little is known about the regulatory functions of ROS in microbial structures. Here we summarize current knowledge on the possible roles of ROS during the development of colonies and biofilms, representatives of microbial multicellularity. In Saccharomyces cerevisiae colonies, ROS are predicted to participate in regulatory events involved in the induction of ammonia signaling and later on in programmed cell death in the colony center. While the latter process seems to be induced by the total ROS, the former event is likely to be regulated by ROS-homeostasis, possibly H2O2-homeostasis between the cytosol and mitochondria. In Candida albicans biofilms, the predicted signaling role of ROS is linked with quorum sensing molecule farnesol that significantly affects biofilm formation. In bacterial biofilms, ROS induce genetic variability, promote cell death in specific biofilm regions, and possibly regulate biofilm development. Thus, the number of examples suggesting ROS as signaling molecules and effectors in the development of microbial multicellularity is rapidly increasing. PMID:22829965

  10. PKC? promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma.

    PubMed

    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

    2015-08-01

    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 (PKC?), a serine/threonine kinase among conventional PKC family, is recognized as a major player in signal transduction and tumor progression. Overexpression of PKC? is commonly observed in human HCC and associated with its poor prognosis. However, how PKC? is involved in hepatocellular carcinogenesis remains not fully understood. In this study, we found that among the members of conventional PKC family, PKC?, but not PKC?I or ?II, promoted ROS production in HCC cells. PKC? stimulated generation of ROS by up-regulating DUOX2 at post-transcriptional level. Depletion of DUOX2 abrogated PKC?-induced activation of AKT/MAPK pathways as well as cell proliferation, migration and invasion in HCC cells. Moreover, the expression of DUOX2 and PKC? was well positively correlated in both HCC cell lines and patient samples. Collectively, our findings demonstrate that PKC? plays a critical role in HCC development by inducing DUOX2 expression and ROS generation, and propose a strategy to target PKC?/DUOX2 as a potential adjuvant therapy for HCC treatment. PMID:26056003

  11. Activation of sperm EGFR by light irradiation is mediated by reactive oxygen species.

    PubMed

    Shahar, Shiran; Hillman, Pnina; Lubart, Rachel; Ickowicz, Debby; Breitbart, Haim

    2014-01-01

    To acquire fertilization competence, spermatozoa must undergo several biochemical and motility changes in the female reproductive tract, collectively called capacitation. Actin polymerization and the development of hyperactivated motility (HAM) are part of the capacitation process. In a recent study, we showed that irradiation of human sperm with visible light stimulates HAM through a mechanism involving reactive-oxygen-species (ROS), Ca(2+) influx, protein kinases A (PKA), and sarcoma protein kinase (Src). Here, we showed that this effect of light on HAM is mediated by ROS-dependent activation of the epidermal growth factor receptor (EGFR). Interestingly, ROS-mediated HAM even when the EGFR was activated by EGF, the physiological ligand of EGFR. Light irradiation stimulated ROS-dependent actin polymerization, and this effect was abrogated by PBP10, a peptide which activates the actin-severing protein, gelsolin, and causes actin-depolymerization in human sperm. Light-stimulated tyrosine phosphorylation of Src-dependent gelsolin, resulting in enhanced HAM. Thus, light irradiation stimulates HAM through a mechanism involving Src-mediated actin polymerization. Light-stimulated HAM and in vitro-fertilization (IVF) rate in mouse sperm, and these effects were mediated by ROS and EGFR. In conclusion, we show here that irradiation of sperm with visible light, enhances their fertilization capacity via a mechanism requiring ROS, EGFR and HAM. PMID:24724551

  12. Reactive Oxygen Species Hydrogen Peroxide Mediates Kaposi's Sarcoma-Associated Herpesvirus Reactivation from Latency

    PubMed Central

    Ye, Fengchun; Zhou, Fuchun; Bedolla, Roble G.; Jones, Tiffany; Lei, Xiufen; Kang, Tao; Guadalupe, Moraima; Gao, Shou-Jiang

    2011-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) establishes a latent infection in the host following an acute infection. Reactivation from latency contributes to the development of KSHV-induced malignancies, which include Kaposi's sarcoma (KS), the most common cancer in untreated AIDS patients, primary effusion lymphoma and multicentric Castleman's disease. However, the physiological cues that trigger KSHV reactivation remain unclear. Here, we show that the reactive oxygen species (ROS) hydrogen peroxide (H2O2) induces KSHV reactivation from latency through both autocrine and paracrine signaling. Furthermore, KSHV spontaneous lytic replication, and KSHV reactivation from latency induced by oxidative stress, hypoxia, and proinflammatory and proangiogenic cytokines are mediated by H2O2. Mechanistically, H2O2 induction of KSHV reactivation depends on the activation of mitogen-activated protein kinase ERK1/2, JNK, and p38 pathways. Significantly, H2O2 scavengers N-acetyl-L-cysteine (NAC), catalase and glutathione inhibit KSHV lytic replication in culture. In a mouse model of KSHV-induced lymphoma, NAC effectively inhibits KSHV lytic replication and significantly prolongs the lifespan of the mice. These results directly relate KSHV reactivation to oxidative stress and inflammation, which are physiological hallmarks of KS patients. The discovery of this novel mechanism of KSHV reactivation indicates that antioxidants and anti-inflammation drugs could be promising preventive and therapeutic agents for effectively targeting KSHV replication and KSHV-related malignancies. PMID:21625536

  13. Hydrolase stabilization via entanglement in poly(propylene sulfide) nanoparticles: stability towards reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Allen, Brett L.; Johnson, Jermaine D.; Walker, Jeremy P.

    2012-07-01

    In the advancement of green syntheses and sustainable reactions, enzymatic biocatalysis offers extremely high reaction rates and selectivity that goes far beyond the reach of chemical catalysts; however, these enzymes suffer from typical environmental constraints, e.g. operational temperature, pH and tolerance to oxidative environments. A common hydrolase enzyme, diisopropylfluorophosphatase (DFPase, EC 3.1.8.2), has demonstrated a pronounced efficacy for the hydrolysis of a variety of substrates for potential toxin remediation, but suffers from the aforementioned limitations. As a means to enhance DFPase’s stability in oxidative environments, enzymatic covalent immobilization within the polymeric matrix of poly(propylene sulfide) (PPS) nanoparticles was performed. By modifying the enzyme’s exposed lysine residues via thiolation, DFPase is utilized as a comonomer/crosslinker in a mild emulsion polymerization. The resultant polymeric polysulfide shell acts as a ‘sacrificial barrier’ by first oxidizing to polysulfoxides and polysulfones, rendering DFPase in an active state. DFPase-PPS nanoparticles thus retain activity upon exposure to as high as 50 parts per million (ppm) of hypochlorous acid (HOCl), while native DFPase is observed as inactive at 500 parts per billion (ppb). This trend is also confirmed by enzyme-generated (chloroperoxidase (CPO), EC 1.11.1.10) reactive oxygen species (ROS) including both HOCl (3 ppm) and ClO2 (100 ppm).

  14. Glucocorticoids: Dose-related effects on osteoclast formation and function via reactive oxygen species and autophagy.

    PubMed

    Shi, Jun; Wang, Long; Zhang, Hongyang; Jie, Qiang; Li, Xiaojie; Shi, Qiyue; Huang, Qiang; Gao, Bo; Han, Yuehu; Guo, Kai; Liu, Jian; Yang, Liu; Luo, Zhuojing

    2015-10-01

    Whether glucocorticoids directly enhance or interrupt osteoclastogenesis is still a controversial subject. In this study, we ascertained the dose-dependent positive effects of glucocorticoids on osteoclastogenesis in vivo and in vitro as well as investigated the mechanism in vitro. As the dose of glucocorticoids increased, osteoclastogenesis was stimulated at 0.1?M, a peak was achieved at 1?M and a corresponding decrease occurred at 10?M. Reactive oxygen species (ROS), which play a crucial role in osteoclastogenesis, and autophagy flux activity, a cellular recycling process, were consistently up-regulated along with the dose-dependent effects of the glucocorticoids on osteoclast formation and function. N-acetyl-cysteine (NAC), a ROS scavenger, abrogated the effects of the glucocorticoids on autophagy and osteoclastogenesis. Moreover, 3-methyladenine (3-MA), an autophagy inhibitor, interrupted osteoclastogenesis stimulation by the glucocorticoids. These results implied that with glucocorticoid administration, ROS and autophagy, as a downstream factor of ROS, played vital roles in osteoclast formation and function. 3-MA administration did not enhance ROS accumulation, so that autophagy had no effect on ROS induced by glucocorticoids. Our investigation demonstrated that glucocorticoids had dose-dependent positive effects on osteoclast formation and function via ROS and autophagy. These results provide support for ROS and autophagy as therapeutic targets in glucocorticoid-related bone loss diseases such as glucocorticoid-induced osteoporosis. PMID:26115910

  15. Reactive Oxygen Species Production and Brugia pahangi Survivorship in Aedes polynesiensis with Artificial Wolbachia Infection Types

    PubMed Central

    Andrews, Elizabeth S.; Crain, Philip R.; Fu, Yuqing; Howe, Daniel K.; Dobson, Stephen L.

    2012-01-01

    Heterologous transinfection with the endosymbiotic bacterium Wolbachia has been shown previously to induce pathogen interference phenotypes in mosquito hosts. Here we examine an artificially infected strain of Aedes polynesiensis, the primary vector of Wuchereria bancrofti, which is the causative agent of Lymphatic filariasis (LF) throughout much of the South Pacific. Embryonic microinjection was used to transfer the wAlbB infection from Aedes albopictus into an aposymbiotic strain of Ae. polynesiensis. The resulting strain (designated “MTB”) experiences a stable artificial infection with high maternal inheritance. Reciprocal crosses of MTB with naturally infected wild-type Ae. polynesiensis demonstrate strong bidirectional incompatibility. Levels of reactive oxygen species (ROS) in the MTB strain differ significantly relative to that of the wild-type, indicating an impaired ability to regulate oxidative stress. Following a challenge with Brugia pahangi, the number of filarial worms achieving the infective stage is significantly reduced in MTB as compared to the naturally infected and aposymbiotic strains. Survivorship of MTB differed significantly from that of the wild-type, with an interactive effect between survivorship and blood feeding. The results demonstrate a direct correlation between decreased ROS levels and decreased survival of adult female Aedes polynesiensis. The results are discussed in relation to the interaction of Wolbachia with ROS production and antioxidant expression, iron homeostasis and the insect immune system. We discuss the potential applied use of the MTB strain for impacting Ae. polynesiensis populations and strategies for reducing LF incidence in the South Pacific. PMID:23236284

  16. Role of extracellular calcium and mitochondrial oxygen species in psychosine-induced oligodendrocyte cell death.

    PubMed

    Voccoli, V; Tonazzini, I; Signore, G; Caleo, M; Cecchini, M

    2014-01-01

    Globoid cell leukodystrophy (GLD) is a metabolic disease caused by mutations in the galactocerebrosidase (GALC) gene. GALC is a lysosomal enzyme whose function is to degrade galacto-lipids, including galactosyl-ceramide and galactosyl-sphingosine (psychosine, PSY). GALC loss of function causes progressive intracellular accumulation of PSY. It is widely held that PSY is the main trigger for the degeneration of myelinating cells and progressive white-matter loss. However, still little is known about the molecular mechanisms by which PSY imparts toxicity. Here, we address the role of calcium dynamics during PSY-induced cell death. Using the human oligodendrocyte cell line MO3.13, we report that cell death by PSY is accompanied by robust cytosolic and mitochondrial calcium (Ca(2+)) elevations, and by mitochondrial reactive oxygen species (ROS) production. Importantly, we demonstrate that the reduction of extracellular calcium content by the chelating agent ethylenediaminetetraacetic acid can decrease intra-mitochondrial ROS production and enhance cell viability. Antioxidant administration also reduces mitochondrial ROS production and cell loss, but this treatment does not synergize with Ca(2+) chelation. Our results disclose novel intracellular pathways involved in PSY-induced death that may be exploited for therapeutic purposes to delay GLD onset and/or slow down its progression. PMID:25412308

  17. Role of extracellular calcium and mitochondrial oxygen species in psychosine-induced oligodendrocyte cell death

    PubMed Central

    Voccoli, V; Tonazzini, I; Signore, G; Caleo, M; Cecchini, M

    2014-01-01

    Globoid cell leukodystrophy (GLD) is a metabolic disease caused by mutations in the galactocerebrosidase (GALC) gene. GALC is a lysosomal enzyme whose function is to degrade galacto-lipids, including galactosyl-ceramide and galactosyl-sphingosine (psychosine, PSY). GALC loss of function causes progressive intracellular accumulation of PSY. It is widely held that PSY is the main trigger for the degeneration of myelinating cells and progressive white-matter loss. However, still little is known about the molecular mechanisms by which PSY imparts toxicity. Here, we address the role of calcium dynamics during PSY-induced cell death. Using the human oligodendrocyte cell line MO3.13, we report that cell death by PSY is accompanied by robust cytosolic and mitochondrial calcium (Ca2+) elevations, and by mitochondrial reactive oxygen species (ROS) production. Importantly, we demonstrate that the reduction of extracellular calcium content by the chelating agent ethylenediaminetetraacetic acid can decrease intra-mitochondrial ROS production and enhance cell viability. Antioxidant administration also reduces mitochondrial ROS production and cell loss, but this treatment does not synergize with Ca2+ chelation. Our results disclose novel intracellular pathways involved in PSY-induced death that may be exploited for therapeutic purposes to delay GLD onset and/or slow down its progression. PMID:25412308

  18. Targeting Cancer Cells with Reactive Oxygen and Nitrogen Species Generated by Atmospheric-Pressure Air Plasma

    PubMed Central

    Hoan, Nguyen Ngoc; Kim, Churl Ho; Moon, Eunpyo; Choi, Kyeong Sook; Yang, Sang Sik; Lee, Jong-Soo

    2014-01-01

    The plasma jet has been proposed as a novel therapeutic method for cancer. Anticancer activity of plasma has been reported to involve mitochondrial dysfunction. However, what constituents generated by plasma is linked to this anticancer process and its mechanism of action remain unclear. Here, we report that the therapeutic effects of air plasma result from generation of reactive oxygen/nitrogen species (ROS/RNS) including H2O2, Ox, OH?, •O2, NOx, leading to depolarization of mitochondrial membrane potential and mitochondrial ROS accumulation. Simultaneously, ROS/RNS activate c-Jun NH2-terminal kinase (JNK) and p38 kinase. As a consequence, treatment with air plasma jets induces apoptotic death in human cervical cancer HeLa cells. Pretreatment of the cells with antioxidants, JNK and p38 inhibitors, or JNK and p38 siRNA abrogates the depolarization of mitochondrial membrane potential and impairs the air plasma-induced apoptotic cell death, suggesting that the ROS/RNS generated by plasma trigger signaling pathways involving JNK and p38 and promote mitochondrial perturbation, leading to apoptosis. Therefore, administration of air plasma may be a feasible strategy to eliminate cancer cells. PMID:24465942

  19. Controllable generation of reactive oxygen species by femtosecond-laser irradiation

    NASA Astrophysics Data System (ADS)

    Yan, Wei; He, Hao; Wang, Yintao; Wang, Yisen; Hu, Minglie; Wang, Chingyue

    2014-02-01

    Femtosecond lasers have been advancing Biophotonics research in the past two decades with multiphoton microscopy, microsurgery, and photodynamic therapy. Nevertheless, laser irradiation is identified to bring photodamage to cells via reactive oxygen species (ROS) generation with unclear mechanism. Meanwhile, currently in biological researches, there is no effective method to provide controllable ROS production precisely, which originally is leaked from mitochondria during respiration and plays a key role in a lot of important cellular processes and cellular signaling pathways. In this study, we show the process of how the tightly focused femtosecond-laser induces ROS generation solely in mitochondria at the very beginning and then release to cytosol if the stimulus is intense enough. At certain weak power levels, the laser pulses induce merely moderate Ca2+ release but this is necessary for the laser to generate ROS in mitochondria. Cellular original ROS are also involved with a small contribution. When the power is above a threshold, ROS are then released to cytosol, indicating photodamage overwhelming cellular repair ability. The mechanisms in those two cases are quite different. Those results clarify parts of the mechanism in laser-induced ROS generation. Hence, it is possible to further this optical scheme to provide controllable ROS generation for ROS-related biological researches including mitochondrial diseases and aging.

  20. Mitochondria-Derived Reactive Oxygen Species Play an Important Role in Doxorubicin-Induced Platelet Apoptosis

    PubMed Central

    Wang, Zhicheng; Wang, Jie; Xie, Rufeng; Liu, Ruilai; Lu, Yuan

    2015-01-01

    Doxorubicin (DOX) is an effective chemotherapeutic agent; however; its use is limited by some side effects; such as cardiotoxicity and thrombocytopenia. DOX-induced cardiotoxicity has been intensively investigated; however; DOX-induced thrombocytopenia has not been clearly elucidated. Here we show that DOX-induced mitochondria-mediated intrinsic apoptosis and glycoprotein (GP)Ib? shedding in platelets. DOX did not induce platelet activation; whereas; DOX obviously reduced adenosine diphosphate (ADP)- and thrombin-induced platelet aggregation; and impaired platelet adhesion on the von Willebrand factor (vWF) surface. In addition; we also show that DOX induced intracellular reactive oxygen species (ROS) production and mitochondrial ROS generation in a dose-dependent manner. The mitochondria-targeted ROS scavenger Mito-TEMPO blocked intracellular ROS and mitochondrial ROS generation. Furthermore; Mito-TEMPO reduced DOX-induced platelet apoptosis and GPIb? shedding. These data indicate that DOX induces platelet apoptosis; and impairs platelet function. Mitochondrial ROS play a pivotal role in DOX-induced platelet apoptosis and GPIb? shedding. Therefore; DOX-induced platelet apoptosis might contribute to DOX-triggered thrombocytopenia; and mitochondria-targeted ROS scavenger would have potential clinical utility in platelet-associated disorders involving mitochondrial oxidative damage. PMID:25988386

  1. The phytotoxin coronatine induces light-dependent reactive oxygen species in tomato seedlings.

    PubMed

    Ishiga, Yasuhiro; Uppalapati, Srinivasa Rao; Ishiga, Takako; Elavarthi, Sathya; Martin, Bjorn; Bender, Carol L

    2009-01-01

    The phytotoxin coronatine (COR), which is produced by Pseudomonas syringae pv. tomato DC3000 (DC3000), has multiple roles in virulence that lead to chlorosis and a reduction in chlorophyll content. However, the physiological significance of COR-induced chlorosis in disease development is still largely unknown. Global expression analysis demonstrated that DC3000 and COR, but not the COR-defective mutant DB29, caused reduced expression of photosynthesis-related genes and result in a 1.5- to 2-fold reduction in maximum quantum efficiency of photosystem II (F(V)/F(M)). Tomato (Solanum lycopersicum) seedlings inoculated with DC3000 and incubated in a long daily photoperiod showed more necrosis than inoculated seedlings incubated in either dark or a short daily photoperiod. The accumulation of reactive oxygen species (ROS) was detected in cotyledons inoculated with either purified COR or DC3000 but not in tissues inoculated with DB29. Interestingly, COR-induced ROS accumulated only in light and was inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea and diphenylene iodonium, which function to inhibit electron transport from PSII. Furthermore, COR and DC3000 suppressed expression of the gene encoding the thylakoid Cu/Zn superoxide dismutase but not the cytosolic form of the same enzyme. In conclusion, these results demonstrate a role for COR-induced effects on photosynthetic machinery and ROS in modulating necrotic cell death during bacterial speck disease of tomato. PMID:18823314

  2. Demethyl fruticulin A (SCO-1) causes apoptosis by inducing reactive oxygen species in mitochondria.

    PubMed

    Monticone, Massimiliano; Bisio, Angela; Daga, Antonio; Giannoni, Paolo; Giaretti, Walter; Maffei, Massimo; Pfeffer, Ulrich; Romeo, Francesco; Quarto, Rodolfo; Romussi, Giovanni; Corte, Giorgio; Castagnola, Patrizio

    2010-12-01

    Demethyl fruticulin A (SCO-1) is a compound found in Salvia corrugata leaves. SCO-1 was reported to induce anoikis in cell lines via the membrane scavenging receptor CD36. However, experiments performed with cells lacking CD36 showed that SCO-1 was able to induce apoptosis also via alternative pathways. To gain some insight into the biological processes elicited by this compound, we undertook an unbiased genomic approach. Upon exposure of glioblastoma tumor initiating cells (GBM TICs) to SCO-1 for 24 h, we observed a deregulation of the genes belonging to the glutathione metabolism pathway and of those belonging to the biological processes related to the response to stress and to chemical stimulus. On this basis, we hypothesized that the SCO-1 killing effect could result from the induction of reactive oxygen species (ROS) in the mitochondria. This hypothesis was confirmed by flow cytometry using MitoSOX, a mitochondria-selective fluorescent reporter of ROS, and by the ability of N-acetyl cysteine (NAC) to inhibit apoptosis when co-administered with SOC-1 to the GBM TICs. We further show that NAC also protects other cell types such as HeLa, MG-63, and COS-7 from apoptosis. We therefore propose that ROS production is the major molecular mechanism responsible for the pro-apoptotic effect induced by SCO-1. Consequently, SCO-1 may have a potential therapeutic value, which deserves further investigation in animal models. PMID:20683904

  3. Apogossypolone induces reactive oxygen species accumulation and controls cell cycle progression in Raji Burkkit's lymphoma cells.

    PubMed

    Hu, Zhe-Yu; Xu, Fei; Sun, Rui; Chen, Yan-Feng; Zhang, Dong-Sheng; Fan, Yu-Hua; Sun, Jian

    2015-07-01

    Burkitt's lymphoma (BL) is a highly aggressive type of non-Hodgkin's lymphoma, with marked rates of proliferation and metabolism. The expression levels of the translocated cellular Myc (c-Myc) oncogene and Epstein-Barr virus infection have an oncogenic role in facilitating tumor progression and maintaining a malignant phenotype in BL Raji cells. The present study identified that more reactive oxygen species (ROS) were produced in Raji cells compared with other types of malignant B cells. Cells exhibiting higher ROS levels suggested facilitation of the induction of cell death by ROS-induction compounds. In the present study, apogossypolone (ApoG2) was observed to induce marked accumulation in the levels of ROS in the Raji cells, which damaged the cells and suppressed cell proliferation. Within 12 h following ApoG2 treatment, the Raji cells were prominently arrested in the G1 phase of the cell cycle. Immunoblotting analysis indicated that the chromodomain-helicase-DNA-binding protein 1, checkpoint kinase 1 and c-Myc proteins were significantly downregulated at 3, 6 and 12 h, respectively, following treatment. Following treatment with ApoG2 for 48 h, ApoG2 induced significant apoptosis in the Raji cells. This findings, together with our previous studies, which demonstrated ApoG2 as a potent inhibitor of anti-apoptotic B cell lymphoma 2 proteins, indicated that the ROS stimulatory effect of ApoG2 increased the antitumor activity of ApoG2. PMID:25738577

  4. Autophagy induction upon reactive oxygen species in Cd-stressed Arabidopsis thaliana

    NASA Astrophysics Data System (ADS)

    Zhang, WeiNa; Chen, WenLi

    2010-02-01

    Autophagy is a protein degradation process in which cells recycle cytoplasmic contents when subjected to environmental stress conditions or during certain stages of development. Upon the induction of autophagy, a double membrane autophagosome forms around cytoplasmic components and delivers them to the vacuole for degradation. In plants, autophagy has been shown previously to be induced during abiotic stresses including oxidative stress. Cd, as a toxicity heavy metal, resulted in the production of reactive oxygen species (ROS). In this paper, we demonstrated that ROS contributed to the induction of autophagy in Cd-stressed Arabidopsis thaliana. However, pre-incubation with ascorbic acid (AsA, antioxidant molecule) and catalase (CAT, a H2O2-specific scavenger) decreased the ROS production and the number of autolysosomal-like structures. Together our results indicated that the oxidative condition was essential for autophagy, as treatment with AsA and CAT abolished the formation of autophagosomes, and ROS may function as signal molecules to induce autophagy in abiotic stress.

  5. Asian Dust Particles Induce TGF-?1 via Reactive Oxygen Species in Bronchial Epithelial Cells

    PubMed Central

    Kyung, Sun Young; Yoon, Jin Young; Kim, Yu Jin; Lee, Sang Pyo; Park, Jeong-Woong

    2012-01-01

    Background Asian dust storms can be transported across eastern Asia. In vitro, Asian dust particle-induced inflammation and enhancement of the allergic reaction have been observed. However, the fibrotic effects of Asian dust particles are not clear. Production of transforming growth factor ?1 (TGF-?1) and fibronectin were investigated in the bronchial epithelial cells after exposure to Asian dust particulate matter (AD-PM10). Methods During Asian dust storm periods, air samples were collected. The bronchial epithelial cells were exposed to AD-PM10 with and without the antioxidant, N-acetyl-L-cysteine (NAC). Then TGF-?1 and fibronectin were detected by Western blotting. The reactive oxygen species (ROS) was detected by the measurement of dicholorodihydrofluorescin (DCF), using a FACScan, and visualized by a confocal microscopy. Results The expression of TGF-?1, fibronectin and ROS was high after being exposed to AD-PM10, compared to the control. NAC attenuated both TGF-?1 and fibronectin expression in the AD-PM10-exposed the bronchial epithelial cells. Conclusion AD-PM10 may have fibrotic potential in the bronchial epithelial cells and the possible mechanism is AD-PM10-induced intracellular ROS. PMID:23166540

  6. Behind the scenes: the roles of reactive oxygen species in guard cells.

    PubMed

    Song, Yuwei; Miao, Yuchen; Song, Chun-Peng

    2014-03-01

    Guard cells regulate stomatal pore size through integration of both endogenous and environmental signals; they are widely recognized as providing a key switching mechanism that maximizes both the efficient use of water and rates of CO? exchange for photosynthesis; this is essential for the adaptation of plants to water stress. Reactive oxygen species (ROS) are widely considered to be an important player in guard cell signalling. In this review, we focus on recent progress concerning the role of ROS as signal molecules in controlling stomatal movement, the interaction between ROS and intrinsic and environmental response pathways, the specificity of ROS signalling, and how ROS signals are sensed and relayed. However, the picture of ROS-mediated signalling is still fragmented and the issues of ROS sensing and the specificity of ROS signalling remain unclear. Here, we review some recent advances in our understanding of ROS signalling in guard cells, with an emphasis on the main players known to interact with abscisic acid signalling. PMID:24188383

  7. Piperlongumine induces pancreatic cancer cell death by enhancing reactive oxygen species and DNA damage

    PubMed Central

    Dhillon, Harsharan; Chikara, Shireen; Reindl, Katie M.

    2014-01-01

    Pancreatic cancer is one of the most deadly cancers with a nearly 95% mortality rate. The poor response of pancreatic cancer to currently available therapies and the extremely low survival rate of pancreatic cancer patients point to a critical need for alternative therapeutic strategies. The use of reactive oxygen species (ROS)-inducing agents has emerged as an innovative and effective strategy to treat various cancers. In this study, we investigated the potential of a known ROS inducer, piperlongumine (PPLGM), a bioactive agent found in long peppers, to induce pancreatic cancer cell death in cell culture and animal models. We found that PPLGM inhibited the growth of pancreatic cancer cell cultures by elevating ROS levels and causing DNA damage. PPLGM-induced DNA damage and pancreatic cancer cell death was reversed by treating the cells with an exogenous antioxidant. Similar to the in vitro studies, PPLGM caused a reduction in tumor growth in a xenograft mouse model of human pancreatic cancer. Tumors from the PPLGM-treated animals showed decreased Ki-67 and increased 8-OHdG expression, suggesting PPLGM inhibited tumor cell proliferation and enhanced oxidative stress. Taken together, our results show that PPLGM is an effective inhibitor for in vitro and in vivo growth of pancreatic cancer cells, and that it works through a ROS-mediated DNA damage pathway. These findings suggest that PPLGM has the potential to be used for treatment of pancreatic cancer. PMID:25530945

  8. Mitochondrial Respiratory Supercomplex Association Limits Production of Reactive Oxygen Species from Complex I

    PubMed Central

    Maranzana, Evelina; Barbero, Giovanna; Falasca, Anna Ida; Lenaz, Giorgio

    2013-01-01

    Abstract Aims: The mitochondrial respiratory chain is recognized today to be arranged in supramolecular assemblies (supercomplexes). Besides conferring a kinetic advantage (substrate channeling) and being required for the assembly and stability of Complex I, indirect considerations support the view that supercomplexes may also prevent excessive formation of reactive oxygen species (ROS) from the respiratory chain. In the present study, we have directly addressed this issue by testing the ROS generation by Complex I in two experimental systems in which the supramolecular organization of the respiratory assemblies is impaired by: (i) treatment either of bovine heart mitochondria or liposome-reconstituted supercomplex I-III with dodecyl maltoside; (ii) reconstitution of Complexes I and III at high phospholipids to protein ratio. Results: The results of our investigation provide experimental evidence that the production of ROS is strongly increased in either model, supporting the view that disruption or prevention of the association between Complex I and Complex III by different means enhances the generation of superoxide from Complex I. Innovation: Dissociation of supercomplexes may link oxidative stress and energy failure in a vicious circle. Conclusion: Our findings support a central role of mitochondrial supramolecular structure in the development of the aging process and in the etiology and pathogenesis of most major chronic diseases. Antioxid. Redox Signal. 19, 1469–1480. PMID:23581604

  9. Reactive oxygen species modulate HIF-1 mediated PAI-1 expression: involvement of the GTPase Rac1.

    PubMed

    Görlach, Agnes; Berchner-Pfannschmidt, Utta; Wotzlaw, Christoph; Cool, Robbert H; Fandrey, Joachim; Acker, Helmut; Jungermann, Kurt; Kietzmann, Thomas

    2003-05-01

    The hypoxia-inducible transcription factor HIF-1 mediates upregulation of plasminogen activator inhibitor-1 (PAI-1) expression under hypoxia. Reactive oxygen species (ROS) have also been implicated in PAI-1 gene expression. However, the role of ROS in HIF-1-mediated regulation of PAI-1 is not clear. We therefore investigated the role of the GTPase Rac1 which modulates ROS production in the pathway leading to HIF-1 and PAI-1 induction. Overexpression of constitutively activated (RacG12V) or dominant-negative (RacT17N) Rac1 increased or decreased, respectively, ROS production. In RacG12V-expressing cells, PAI-1 mRNA levels as well as HIF-alpha nuclear presence were reduced under normoxia and hypoxia whereas expression of RacT17N resulted in opposite effects. Treatment with the antioxidant pyr-rolidinedithiocarbamate or coexpression of the redox factor-1 restored HIF-1 and PAI-1 promoter activity in RacG12V-cells. In contrast, NFkappaB activation was enhanced in RacG12V-cells, but abolished by RacT17N. Thus, these findings suggest a mechanism explaining modified fibrinolysis and tissue remodeling in an oxidized environment. PMID:12719791

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

    SciTech Connect

    Perez-de-Arce, Karen [Departamento de Nutricion, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile); Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile); Foncea, Rocio [Departamento de Nutricion, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile)]. E-mail: rfoncea@med.puc.cl; Leighton, Federico [Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile)

    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.

  11. PKC? Regulates T-Cell Leukemia-Initiating Activity via Reactive Oxygen Species

    PubMed Central

    Giambra, Vincenzo; Jenkins, Christopher R.; Wang, Hongfang; Lam, Sonya H.; Shevchuk, Olena O.; Nemirovsky, Oksana; Wai, Carol; Gusscott, Sam; Chiang, Mark Y.; Aster, Jon C.; Humphries, R. Keith; Eaves, Connie; Weng, Andrew P.

    2013-01-01

    Reactive oxygen species (ROS), a by-product of cellular metabolism, damage intracellular macromolecules and, in excess, can promote normal hematopoietic stem cell differentiation and exhaustion1–3. However, mechanisms that regulate ROS levels in leukemia-initiating cells (LICs) and the biological role of ROS in these cells remain largely unknown. We show here the ROSlow subset of CD44+ cells in T-cell acute lymphoblastic leukemia (T-ALL), a malignancy of immature T-cell progenitors, to be highly enriched in the most aggressive LICs, and that ROS are maintained at low levels by downregulation of protein kinase C theta (PKC?). Strikingly, primary mouse T-ALLs lacking PKC? show improved LIC activity whereas enforced PKC? expression in both mouse and human primary T-ALLs compromised LIC activity. We also demonstrate that PKC? is positively regulated by RUNX1, and that NOTCH1, which is frequently activated by mutation in T-ALL4–6 and required for LIC activity in both mouse and human models7,8, downregulates PKC? and ROS via a novel pathway involving induction of RUNX3 and subsequent repression of RUNX1. These results reveal key functional roles for PKC? and ROS in T-ALL and suggest that aggressive biological behavior in vivo could be limited by therapeutic strategies that promote PKC? expression/activity or ROS accumulation. PMID:23086478

  12. Eriobotrya japonica counteracts reactive oxygen species and nitric oxide stimulated by chloramphenicol.

    PubMed

    Eraso, Alberto Jorge; Albesa, Inés

    2007-01-01

    Chloramphenicol is a toxic antibiotic used for certain infections, though aplastic anaemia is one of its side-effects. The results of our experiments showed that blood cells suffered oxidative stress in the presence of chloramphenicol, with a significant increase in reactive oxygen species (ROS) detected by luminol-chemiluminescence (CL). The extract of fruits of Eriobotrya japonica markedly decreased ROS in leukocytes and erythrocytes, the oxidative stress caused by this antibiotic. Nitro Blue Tetrazolium (NBT) assay with purified leukocytes demonstrated that the antioxidant action of E. japonica caused an intracellular reduction in ROS, and that the extracts decreased these promoters of oxidative stress to normal levels in the cytoplasm. Determinations of nitric oxide (NO) generation indicated that E. japonica extracts also inhibited the stimuli of NO provoked by chloramphenicol. This study showed that the immediate antioxidant effect of E. japonica could be associated with the action of vitamin A. The protective action of this fruit was seen on mature leukocytes and erythrocytes, beneficial effect on blood cells suggest that its extract could be used as an antioxidant agent complementing the administration of chloramphenicol, as a modern-day extension to its traditional use in Chinese medicine. PMID:17963326

  13. Bioconvertible vitamin antioxidants improve sunscreen photoprotection against UV-induced reactive oxygen species.

    PubMed

    Hanson, Kerry M; Clegg, Robert M

    2003-01-01

    The ability of sunscreens and antioxidants to deactivate highly destructive reactive oxygen species in human skin has remained inconclusive. Two-photon fluorescence imaging microscopy was used to determine the effect of sunscreen/antioxidant combinations upon UV-induced ROS generation in ex vivo human skin. A sunscreen combination containing octylmethoxycinnamate (Parsol MCX) and avobenzone (Parsol 1789) at SPF 8 and SPF 15 was tested for its ability to prevent UV radiation from generating ROS in the viable epidermal strata of ex vivo human skin. A UV dose equivalent to two hours of North American solar UV was used to irradiate the skin. Each sunscreen reduced the amount of ROS induced in the viable strata by a value consistent with the SPF level. UV photons that were not absorbed/scattered by the sunscreen formulations generated ROS within the viable epidermal layers. The addition of the bioconvertible antioxidants vitamin E acetate and sodium ascorbyl phosphate (STAY-C 50) improves photoprotection by converting to vitamins E and C, respectively, within the skin. The bioconversion forms an antioxidant reservoir that deactivates the ROS generated (within the strata granulosum, spinosum, and basale) by the UV photons that the sunscreens do not block in the stratum corneum. PMID:14730375

  14. Effects of Sanionia uncinata extracts in protecting against and inducing DNA cleavage by reactive oxygen species.

    PubMed

    Fernandes, Andréia da Silva; Mazzei, José Luiz; de Alencar, Alexandre Santos; Evangelista, Heitor; Felzenszwalb, Israel

    2011-01-01

    When mosses are exposed to increased quantities of ultraviolet (UV) radiation, they produce more secondary metabolites. Antarctica moss Sanionia uncinata (Hedw.) Loeske has presented high carotenoid contents in response to an increase in UVB radiation. This moss has been recommended as a potential source of antioxidants. In the present work, the protective and enhancing effects of aqueous (AE) and hydroalcoholic (HE) extracts of S. uncinata on the cleavage of supercoiled DNA were evaluated through topological modifications, quantified by densitometry after agarose gel electrophoresis. Total phenolic contents reached 5.89 mg/g. Our data demonstrated that the extract does not induce DNA cleavage. Furthermore, both extracts showed antioxidant activity that protected the DNA against cleavage induced by (i) O(2)(•-), 89% (AE) and 94% (HE) (P<0.05), and (ii) (.)OH, 17% (AE) and 18% (HE). However, the extracts intensified cleavage induced by Fenton-like reactions: (i) Cu(2+)/H(2)O(2), 94% (AE) and 100% (HE) (P<0.05), and (ii) SnCl(2), 62% (AE) and 56% (HE). DNA damages seem to follow different ways: (i) in the presence of Fenton-like reactions could be via reactive oxygen species generation and (ii) with HE/Cu(2+) could have also been triggered by other mechanisms. PMID:22005340

  15. Oxygen isotopic analyses of individual planktic foraminifera species: implications for seasonality in the western Arabian Sea

    NASA Astrophysics Data System (ADS)

    Naidu, P. D.; Niitsuma, N.; Naik, S.

    2014-09-01

    The variation of stable isotopes between individual shells of planktic foraminifera of a given species and size may provide short-term seasonal insight on Paleoceanography. In this context, oxygen isotope analyses of individual Globigerinoides sacculifer and Neogloboquadrina dutertrei were carried out from the Ocean Drilling Program Site 723A in the western Arabian Sea to unravel the seasonal changes for the last 22 kyr. ?18O values of single shells of G. sacculifer range from of 0.54 to 2.09‰ at various depths in the core which cover a time span of the last 22 kyr. Maximum inter-shell ?18O variability and high standard deviation is noticed from 20 to 10 kyr, whereas from 10 kyr onwards the inter shell ?18O variability decreased. The individual contribution of sea surface temperature (SST) and sea surface salinity (SSS) on the inter shell ?18O values of G. sacculifer were quantified. Maximum seasonal SST between 20 and 14 ka was caused due to weak summer monsoon upwelling and strong cold winter arid continental winds. Maximum SSS differences between 18 and 10 ka is attributed to the increase of net evaporation minus precipitation due to the shift of ITCZ further south. Overall, winter dominated SST signal in Greenland would be responsible to make a teleconnection between Indian monsoon and Greenland temperature. Thus the present study has wider implications in understanding wether the forcing mechanisms of tropical monsoon climate lies in high latitudes or in the tropics.

  16. 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

  17. Role of reactive oxygen species in the defective regeneration seen in aging muscle.

    PubMed

    Vasilaki, Aphrodite; Jackson, Malcolm J

    2013-12-01

    The ability of muscles to regenerate successfully following damage diminishes with age and this appears to be a major contributor to the development of muscle weakness and physical frailty. Successful muscle regeneration is dependent on appropriate reinnervation of regenerating muscle. Age-related changes in the interactions between nerve and muscle are poorly understood but may play a major role in the defective regeneration. During aging there is defective redox homeostasis and an accumulation of oxidative damage in nerve and muscle that may contribute to defective regeneration. The aim of this review is to summarise the evidence that abnormal reactive oxygen species (ROS) generation in nerve and/or muscle may be responsible for the defective regeneration that contributes to the degeneration of skeletal muscle observed during aging. Identifying the importance of ROS generation in skeletal muscle during aging could have fundamental implications for interventions to prevent muscle degeneration and treatments to reverse the age-related decline in muscle mass and function. PMID:23851030

  18. Anticancer activity of hispidin via reactive oxygen species-mediated apoptosis in colon cancer cells.

    PubMed

    Lim, Ji-Hong; Lee, Yoon-Mi; Park, Sa Ra; Kim, Da Hye; Lim, Beong Ou

    2014-08-01

    Few studies have been performed on the anticancer activity of hispidin, a phenolic compound produced from the medicinal mushroom Phellinus linteus. Herein, we studied hispidin-induced apoptosis, which is associated with the generation of reactive oxygen species (ROS) in colon cancer cells. Hispidin was found to reduce cell viability both in mouse and human colon cancer cells. Apoptotic cell morphological changes were observed by microscopy, and apoptosis was assessed in hispidin-treated cells using a biochemical method. The results showed accumulation of the sub-G1 cell population and increase in early apoptosis in a dose-dependent manner. In addition, hispidin induced apoptosis through up-regulation of both intrinsic and extrinsic apoptotic pathways. Although the molecular mechanism underlying hispidin-induced apoptosis is known to involve the generation of ROS, however hispidin did not show any apoptosis in the pre-treatment with a ROS scavenger, N-acetyl-L-cysteine. In conclusion, hispidin induces both intrinsic and extrinsic apoptotic pathways mediated by ROS in colon cancer cells, thereby suggesting that hispidin could be a promising new anticancer agent. PMID:25075033

  19. Oncogene-induced reactive oxygen species fuel hyperproliferation and DNA damage response activation

    PubMed Central

    Ogrunc, M; Di Micco, R; Liontos, M; Bombardelli, L; Mione, M; Fumagalli, M; Gorgoulis, V G; d'Adda di Fagagna, F

    2014-01-01

    Oncogene-induced reactive oxygen species (ROS) have been proposed to be signaling molecules that mediate proliferative cues. However, ROS may also cause DNA damage and proliferative arrest. How these apparently opposite roles can be reconciled, especially in the context of oncogene-induced cellular senescence, which is associated both with aberrant mitogenic signaling and DNA damage response (DDR)-mediated arrest, is unclear. Here, we show that ROS are indeed mitogenic signaling molecules that fuel oncogene-driven aberrant cell proliferation. However, by their very same ability to mediate cell hyperproliferation, ROS eventually cause DDR activation. We also show that oncogenic Ras-induced ROS are produced in a Rac1 and NADPH oxidase (Nox4)-dependent manner. In addition, we show that Ras-induced ROS can be detected and modulated in a living transparent animal: the zebrafish. Finally, in cancer we show that Nox4 is increased in both human tumors and a mouse model of pancreatic cancer and specific Nox4 small-molecule inhibitors act synergistically with existing chemotherapic agents. PMID:24583638

  20. Ultraviolet irradiation induces autofluorescence enhancement via production of reactive oxygen species and photodecomposition in erythrocytes

    SciTech Connect

    Wu, Xian [The Key Laboratory of Weak-Light Nonlinear Photonics, Ministry of Education, TEDA Applied Physics School and School of Physics, Nankai University, Tianjin 300457 (China)] [The Key Laboratory of Weak-Light Nonlinear Photonics, Ministry of Education, TEDA Applied Physics School and School of Physics, Nankai University, Tianjin 300457 (China); Pan, Leiting, E-mail: plt@nankai.edu.cn [The Key Laboratory of Weak-Light Nonlinear Photonics, Ministry of Education, TEDA Applied Physics School and School of Physics, Nankai University, Tianjin 300457 (China)] [The Key Laboratory of Weak-Light Nonlinear Photonics, Ministry of Education, TEDA Applied Physics School and School of Physics, Nankai University, Tianjin 300457 (China); Wang, Zhenhua; Liu, Xiaoli; Zhao, Dan; Zhang, Xinzheng; Rupp, Romano A. [The Key Laboratory of Weak-Light Nonlinear Photonics, Ministry of Education, TEDA Applied Physics School and School of Physics, Nankai University, Tianjin 300457 (China)] [The Key Laboratory of Weak-Light Nonlinear Photonics, Ministry of Education, TEDA Applied Physics School and School of Physics, Nankai University, Tianjin 300457 (China); Xu, Jingjun, E-mail: jjxu@nankai.edu.cn [The Key Laboratory of Weak-Light Nonlinear Photonics, Ministry of Education, TEDA Applied Physics School and School of Physics, Nankai University, Tianjin 300457 (China)] [The Key Laboratory of Weak-Light Nonlinear Photonics, Ministry of Education, TEDA Applied Physics School and School of Physics, Nankai University, Tianjin 300457 (China)

    2010-06-11

    Ultraviolet (UV) light has a significant influence on human health. In this study, human erythrocytes were exposed to UV light to investigate the effects of UV irradiation (UVI) on autofluorescence. Our results showed that high-dose continuous UVI enhanced erythrocyte autofluorescence, whereas low-dose pulsed UVI alone did not have this effect. Further, we found that H{sub 2}O{sub 2}, one type of reactive oxygen species (ROS), accelerated autofluorescence enhancement under both continuous and pulsed UVI. In contrast, continuous and pulsed visible light did not result in erythrocyte autofluorescence enhancement in the presence or absence of H{sub 2}O{sub 2}. Moreover, NAD(P)H had little effect on UVI-induced autofluorescence enhancement. From these studies, we conclude that UVI-induced erythrocyte autofluorescence enhancement via both UVI-dependent ROS production and photodecomposition. Finally, we present a theoretical study of this autofluorescence enhancement using a rate equation model. Notably, the results of this theoretical simulation agree well with the experimental data further supporting our conclusion that UVI plays two roles in the autofluorescence enhancement process.

  1. Reactive oxygen species production in mitochondria of human gingival fibroblast induced by blue light irradiation.

    PubMed

    Yoshida, Ayaka; Yoshino, Fumihiko; Makita, Tetsuya; Maehata, Yojiro; Higashi, Kazuyoshi; Miyamoto, Chihiro; Wada-Takahashi, Satoko; Takahashi, Shun-suke; Takahashi, Osamu; Lee, Masaichi Chang-il

    2013-12-01

    In recent years, it has become well known that the production of reactive oxygen species (ROS) induced by blue-light irradiation causes adverse effects of photo-aging, such as age-related macular degeneration of the retina. Thus, orange-tinted glasses are used to protect the retina during dental treatment involving blue-light irradiation (e.g., dental resin restorations or tooth bleaching treatments). However, there are few studies examining the effects of blue-light irradiation on oral tissue. For the first time, we report that blue-light irradiation by quartz tungsten halogen lamp (QTH) or light-emitting diode (LED) decreased cell proliferation activity of human gingival fibroblasts (HGFs) in a time-dependent manner (<5 min). Additionally, in a morphological study, the cytotoxic effect was observed in the cell organelles, especially the mitochondria. Furthermore, ROS generation induced by the blue-light irradiation was detected in mitochondria of HGFs using fluorimetry. In all analyses, the cytotoxicity was significantly higher after LED irradiation compared with cytotoxicity after QTH irradiation. These results suggest that blue light irradiation, especially by LED light sources used in dental aesthetic treatment, might have adverse effects on human gingival tissue. Hence, this necessitates the development of new dental aesthetic treatment methods and/or techniques to protect HGFs from blue light irradiation during dental therapy. PMID:24141287

  2. Helicobacter pylori protects oncogenically transformed cells from reactive oxygen species-mediated intercellular induction of apoptosis.

    PubMed

    Bauer, Georg; Bereswill, Stefan; Aichele, Peter; Glocker, Erik

    2014-07-01

    Malignant transformation of gastric epithelial cells by chronic Helicobacter pylori infection is caused by several mechanisms including attraction of reactive oxygen species (ROS)-producing neutrophils and cytotoxin-associated antigen A-mediated dysplastic alterations. Here we show that H.pylori protects transformed cells from ROS-mediated intercellular induction of apoptosis. This potential control step in oncogenesis depends on the HOCl and NO/peroxynitrite (PON) signaling pathways. Helicobacter pylori-associated catalase and superoxide dismutase (SOD) efficiently cooperate in the inhibition of HOCl and the NO/PON signaling pathways. Helicobacter pylori catalase prevents HOCl synthesis through decomposition of hydrogen peroxide. Helicobacter pylori-associated SOD interferes with the crucial interactions between superoxide anions and HOCl, as well as superoxide anions and NO. The ratio of bacteria to malignant cells is critical for sufficient protection of transformed cells. Low concentrations of H.pylori more efficiently inhibited ROS-mediated destruction of transformed cells when compared with high concentrations of bacteria. Our data demonstrate the critical role of H.pylori antioxidant enzymes in the survival of transformed cells, modulating an early step of oncogenesis that is distinct from the transformation process per se. PMID:24662971

  3. Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension.

    PubMed

    Cowley, Allen W; Abe, Michiaki; Mori, Takefumi; O'Connor, Paul M; Ohsaki, Yusuke; Zheleznova, Nadezhda N

    2015-02-01

    The physiological evidence linking the production of superoxide, hydrogen peroxide, and nitric oxide in the renal medullary thick ascending limb of Henle (mTAL) to regulation of medullary blood flow, sodium homeostasis, and long-term control of blood pressure is summarized in this review. Data obtained largely from rats indicate that experimentally induced elevations of either superoxide or hydrogen peroxide in the renal medulla result in reduction of medullary blood flow, enhanced Na(+) reabsorption, and hypertension. A shift in the redox balance between nitric oxide and reactive oxygen species (ROS) is found to occur naturally in the Dahl salt-sensitive (SS) rat model, where selective reduction of ROS production in the renal medulla reduces salt-induced hypertension. Excess medullary production of ROS in SS rats emanates from the medullary thick ascending limbs of Henle [from both the mitochondria and membrane NAD(P)H oxidases] in response to increased delivery and reabsorption of excess sodium and water. There is evidence that ROS and perhaps other mediators such as ATP diffuse from the mTAL to surrounding vasa recta capillaries, resulting in medullary ischemia, which thereby contributes to hypertension. PMID:25354941

  4. Nutritional Countermeasures Targeting Reactive Oxygen Species in Cancer: From Mechanisms to Biomarkers and Clinical Evidence

    PubMed Central

    Samoylenko, Anatoly; Hossain, Jubayer Al; Mennerich, Daniela; Kellokumpu, Sakari; Hiltunen, Jukka Kalervo

    2013-01-01

    Abstract Reactive oxygen species (ROS) exert various biological effects and contribute to signaling events during physiological and pathological processes. Enhanced levels of ROS are highly associated with different tumors, a Western lifestyle, and a nutritional regime. The supplementation of food with traditional antioxidants was shown to be protective against cancer in a number of studies both in vitro and in vivo. However, recent large-scale human trials in well-nourished populations did not confirm the beneficial role of antioxidants in cancer, whereas there is a well-established connection between longevity of several human populations and increased amount of antioxidants in their diets. Although our knowledge about ROS generators, ROS scavengers, and ROS signaling has improved, the knowledge about the direct link between nutrition, ROS levels, and cancer is limited. These limitations are partly due to lack of standardized reliable ROS measurement methods, easily usable biomarkers, knowledge of ROS action in cellular compartments, and individual genetic predispositions. The current review summarizes ROS formation due to nutrition with respect to macronutrients and antioxidant micronutrients in the context of cancer and discusses signaling mechanisms, used biomarkers, and its limitations along with large-scale human trials. Antioxid. Redox Signal. 19, 2157–2196. PMID:23458328

  5. Hyperthermia Induces Apoptosis through Endoplasmic Reticulum and Reactive Oxygen Species in Human Osteosarcoma Cells

    PubMed Central

    Hou, Chun-Han; Lin, Feng-Ling; Hou, Sheng-Mon; Liu, Ju-Fang

    2014-01-01

    Osteosarcoma (OS) is a relatively rare form of cancer, but OS is the most commonly diagnosed bone cancer in children and adolescents. Chemotherapy has side effects and induces drug resistance in OS. Since an effective adjuvant therapy was insufficient for treating OS, researching novel and adequate remedies is critical. Hyperthermia can induce cell death in various cancer cells, and thus, in this study, we investigated the anticancer method of hyperthermia in human OS (U-2 OS) cells. Treatment at 43 °C for 60 min induced apoptosis in human OS cell lines, but not in primary bone cells. Furthermore, hyperthermia was associated with increases of intracellular reactive oxygen species (ROS) and caspase-3 activation in U-2 OS cells. Mitochondrial dysfunction was followed by the release of cytochrome c from the mitochondria, and was accompanied by decreased anti-apoptotic Bcl-2 and Bcl-xL, and increased pro-apoptotic proteins Bak and Bax. Hyperthermia triggered endoplasmic reticulum (ER) stress, which was characterized by changes in cytosolic calcium levels, as well as increased calpain expression and activity. In addition, cells treated with calcium chelator (BAPTA-AM) blocked hyperthermia-induced cell apoptosis in U-2 OS cells. In conclusion, hyperthermia induced cell apoptosis substantially via the ROS, ER stress, mitochondria, and caspase pathways. Thus, hyperthermia may be a novel anticancer method for treating OS. PMID:25268613

  6. Effects of oxysterols on cell viability, inflammatory cytokines, VEGF and reactive oxygen species production on human retinal cells: cytoprotective effects and prevention of VEGF

    E-print Network

    Paris-Sud XI, Université de

    1 Effects of oxysterols on cell viability, inflammatory cytokines, VEGF and reactive oxygen species production on human retinal cells: cytoprotective effects and prevention of VEGF secretion by resveratrol B cytokines; oxysterols; phospholipidosis; resveratrol; reactive oxygen species; VEGF. hal-00514897,version1

  7. An example of molecular co-evolution: reactive oxygen species (ROS) and ROS scavenger levels in Schistosoma mansoni/Biomphalaria glabrata interactions

    E-print Network

    Paris-Sud XI, Université de

    An example of molecular co-evolution: reactive oxygen species (ROS) and ROS scavenger levels ROS scavengers in order to survive. In this context, ROS and ROS scavengers are involved in a co, Reactive oxygen species (ROS), ROS scavengers halsde-00580768,version1-29Mar2011 #12;1. Introduction44 45

  8. Studies on the inhibitory effects of curcumin and eugenol on the formation of reactive oxygen species and the oxidation of ferrous iron

    Microsoft Academic Search

    A. Ch. Pulla Reddy; Belur R. Lokesh

    1994-01-01

    The spice principles curcumin (from turmeric) and eugenol (from cloves) are good inhibitors of lipid peroxidation. Lipid peroxidation is known to be initiated by reactive oxygen species. The effect of curcumin and eugenol on the generation of reactive oxygen species in model systems were investigated. Both curcumin and eugenol inhibited superoxide anion generation in xanthine-xanthine oxidase system to an extent

  9. Growth of bulk AlN single crystals with low oxygen content taking into account thermal and kinetic effects of oxygen-related gaseous species

    NASA Astrophysics Data System (ADS)

    Guguschev, C.; Dittmar, A.; Moukhina, E.; Hartmann, C.; Golka, S.; Wollweber, J.; Bickermann, M.; Fornari, R.

    2012-12-01

    Kinetic models in the system Al-N-O-C-H are useful to predict the time- and temperature-dependent influences of oxygen related species on aluminum nitride (AlN) bulk crystal growth by the sublimation-recondensation (also known as physical vapor transport, PVT) method. The transient oxygen incorporation is modeled based on non-linear regression analyses of experimental mass spectrometric data performed at conditions comparable to those of PVT crystal growth, and can be calculated for any user-specified temperature program. The results are in good qualitative agreement with SIMS measurements taken at several positions along the growth direction of a seeded isometric aluminum nitride crystal. By optimizing growth set-up geometry, source purification process, and growth parameters, the impurity content for the grown crystals decreases significantly to values of 6 ppm, 15 ppm, and 30 ppm for O, Si, and C, respectively, 2.5 mm above the AlN seed-crystal interface.

  10. Mitochondrial Reactive Oxygen Species Production in Excitable Cells: Modulators of Mitochondrial and Cell Function

    PubMed Central

    Camara, Amadou K. S.

    2009-01-01

    Abstract The mitochondrion is a major source of reactive oxygen species (ROS). Superoxide (O2•?) is generated under specific bioenergetic conditions at several sites within the electron-transport system; most is converted to H2O2 inside and outside the mitochondrial matrix by superoxide dismutases. H2O2 is a major chemical messenger that, in low amounts and with its products, physiologically modulates cell function. The redox state and ROS scavengers largely control the emission (generation scavenging) of O2•?. Cell ischemia, hypoxia, or toxins can result in excess O2•? production when the redox state is altered and the ROS scavenger systems are overwhelmed. Too much H2O2 can combine with Fe2+ complexes to form reactive ferryl species (e.g., Fe(IV)?=?O•). In the presence of nitric oxide (NO•), O2•? forms the reactant peroxynitrite (ONOO?), and ONOOH-induced nitrosylation of proteins, DNA, and lipids can modify their structure and function. An initial increase in ROS can cause an even greater increase in ROS and allow excess mitochondrial Ca2+ entry, both of which are factors that induce cell apoptosis and necrosis. Approaches to reduce excess O2•? emission include selectively boosting the antioxidant capacity, uncoupling of oxidative phosphorylation to reduce generation of O2•? by inducing proton leak, and reversibly inhibiting electron transport. Mitochondrial cation channels and exchangers function to maintain matrix homeostasis and likely play a role in modulating mitochondrial function, in part by regulating O2•? generation. Cell-signaling pathways induced physiologically by ROS include effects on thiol groups and disulfide linkages to modify posttranslationally protein structure to activate/inactivate specific kinase/phosphatase pathways. Hypoxia-inducible factors that stimulate a cascade of gene transcription may be mediated physiologically by ROS. Our knowledge of the role played by ROS and their scavenging systems in modulation of cell function and cell death has grown exponentially over the past few years, but we are still limited in how to apply this knowledge to develop its full therapeutic potential. Antioxid. Redox Signal. 11, 1373–1414. PMID:19187004

  11. Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species.

    PubMed

    Ro, Seung-Hyun; Nam, Myeongjin; Jang, Insook; Park, Hwan-Woo; Park, Haeli; Semple, Ian A; Kim, Myungjin; Kim, Jeong Sig; Park, Haewon; Einat, Paz; Damari, Golda; Golikov, Maya; Feinstein, Elena; Lee, Jun Hee

    2014-05-27

    Uncoupling protein 1 (Ucp1), which is localized in the mitochondrial inner membrane of mammalian brown adipose tissue (BAT), generates heat by uncoupling oxidative phosphorylation. Upon cold exposure or nutritional abundance, sympathetic neurons stimulate BAT to express Ucp1 to induce energy dissipation and thermogenesis. Accordingly, increased Ucp1 expression reduces obesity in mice and is correlated with leanness in humans. Despite this significance, there is currently a limited understanding of how Ucp1 expression is physiologically regulated at the molecular level. Here, we describe the involvement of Sestrin2 and reactive oxygen species (ROS) in regulation of Ucp1 expression. Transgenic overexpression of Sestrin2 in adipose tissues inhibited both basal and cold-induced Ucp1 expression in interscapular BAT, culminating in decreased thermogenesis and increased fat accumulation. Endogenous Sestrin2 is also important for suppressing Ucp1 expression because BAT from Sestrin2(-/-) mice exhibited a highly elevated level of Ucp1 expression. The redox-inactive mutant of Sestrin2 was incapable of regulating Ucp1 expression, suggesting that Sestrin2 inhibits Ucp1 expression primarily through reducing ROS accumulation. Consistently, ROS-suppressing antioxidant chemicals, such as butylated hydroxyanisole and N-acetylcysteine, inhibited cold- or cAMP-induced Ucp1 expression as well. p38 MAPK, a signaling mediator required for cAMP-induced Ucp1 expression, was inhibited by either Sestrin2 overexpression or antioxidant treatments. Taken together, these results suggest that Sestrin2 and antioxidants inhibit Ucp1 expression through suppressing ROS-mediated p38 MAPK activation, implying a critical role of ROS in proper BAT metabolism. PMID:24825887

  12. Propylthiouracil prevents cutaneous and pulmonary fibrosis in the reactive oxygen species murine model of systemic sclerosis

    PubMed Central

    2013-01-01

    Introduction Recent advances suggest that the cellular redox state may play a significant role in the progression of fibrosis in systemic sclerosis (SSc). Another, and as yet poorly accounted for, feature of SSc is its overlap with thyroid abnormalities. Previous reports demonstrate that hypothyroidism reduces oxidant stress. The aim of this study was therefore to evaluate the effect of propylthiouracil (PTU), and of the hypothyroidism induced by it, on the development of cutaneous and pulmonary fibrosis in the oxidant stress murine model of SSc. Methods Chronic oxidant stress SSc was induced in BALB/c mice by daily subcutaneous injections of hypochlorous acid (HOCl) for 6 weeks. Mice (n = 25) were randomized into three arms: HOCl (n = 10), HOCl plus PTU (n = 10) or vehicle alone (n = 5). PTU administration was initiated 30 minutes after HOCl subcutaneous injection and continued daily for 6 weeks. Skin and lung fibrosis were evaluated by histologic methods. Immunohistochemical staining for alpha-smooth muscle actin (?-SMA) in cutaneous and pulmonary tissues was performed to evaluate myofibroblast differentiation. Lung and skin concentrations of vascular endothelial growth factor (VEGF), extracellular signal-related kinase (ERK), rat sarcoma protein (Ras), Ras homolog gene family (Rho), and transforming growth factor (TGF) ? were analyzed by Western blot. Results Injections of HOCl induced cutaneous and lung fibrosis in BALB/c mice. PTU treatment prevented both dermal and pulmonary fibrosis. Myofibroblast differentiation was also inhibited by PTU in the skin and lung. The increase in cutaneous and pulmonary expression of VEGF, ERK, Ras, and Rho in mice treated with HOCl was significantly prevented in mice co-administered ////with PTU. Conclusions PTU, probably through its direct effect on reactive oxygen species or indirectly through thyroid function inhibition, prevents the development of cutaneous and pulmonary fibrosis by blocking the activation of the Ras-ERK pathway in the oxidant-stress animal model of SSc. PMID:24286160

  13. Induction of reactive oxygen species and algal growth inhibition by tritiated water with or without copper.

    PubMed

    Réty, C; Gilbin, R; Gomez, E

    2012-03-01

    Tritium ((3) H) is a radioactive element of ecological concern because of its release into aquatic ecosystems from nuclear power plants. However, the acute and chronic effects of tritiated water (HTO) on aquatic organisms are poorly documented, as are its effects on oxidative stress. In addition, the effects of HTO in combination with other contaminants remain largely unexamined. Herein, we document the effect of HTO on a primary aquatic producer (Chlamydomonas reinhardtii) by measuring growth and oxidative stress using fluorimetric (H(2) DCF-DA) determination of Reactive Oxygen Species (ROS) production. The maximum cell density of the alga (1.65 × 10(6) cells mL(-1) ) was reduced by 23% (1.27 × 10(6) cells mL(-1) ) at the highest exposure tested (59 MBq mL(-1) HTO), whereas cells exposed to 0.9 MBq mL(-1) showed a significantly enhanced maximum cell density of 1.90 × 10(6) cells mL(-1) , an increase of 15%. With regard to oxidative stress, exposure to HTO (0.04, 0.16, and 2.8 MBq mL(-1) ) induced an early dose-dependent peak in ROS production after 14-15 min of exposure, followed by a slow decrease in ROS which stabilized after 60 min. Moreover, this study showed that the presence of HTO may influence the impact of other conventional, nonradioactive contaminants, such as copper, a well known oxidizing trace metal for aquatic organisms. A significant synergic effect of copper and HTO on ROS production was observed. This synergic effect on oxidative stress was shown to be linked to an enhanced copper uptake rate measured in the presence of HTO (> 4 times). We conclude that HTO should be considered as a sensitizer when in a mixture with other contaminants, especially through interactions on the antioxidant system of algae. PMID:20607814

  14. Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release

    PubMed Central

    Zorov, Dmitry B.; Juhaszova, Magdalena; Sollott, Steven J.

    2014-01-01

    Byproducts of normal mitochondrial metabolism and homeostasis include the buildup of potentially damaging levels of reactive oxygen species (ROS), Ca2+, etc., which must be normalized. Evidence suggests that brief mitochondrial permeability transition pore (mPTP) openings play an important physiological role maintaining healthy mitochondria homeostasis. Adaptive and maladaptive responses to redox stress may involve mitochondrial channels such as mPTP and inner membrane anion channel (IMAC). Their activation causes intra- and intermitochondrial redox-environment changes leading to ROS release. This regenerative cycle of mitochondrial ROS formation and release was named ROS-induced ROS release (RIRR). Brief, reversible mPTP opening-associated ROS release apparently constitutes an adaptive housekeeping function by the timely release from mitochondria of accumulated potentially toxic levels of ROS (and Ca2+). At higher ROS levels, longer mPTP openings may release a ROS burst leading to destruction of mitochondria, and if propagated from mitochondrion to mitochondrion, of the cell itself. The destructive function of RIRR may serve a physiological role by removal of unwanted cells or damaged mitochondria, or cause the pathological elimination of vital and essential mitochondria and cells. The adaptive release of sufficient ROS into the vicinity of mitochondria may also activate local pools of redox-sensitive enzymes involved in protective signaling pathways that limit ischemic damage to mitochondria and cells in that area. Maladaptive mPTP- or IMAC-related RIRR may also be playing a role in aging. Because the mechanism of mitochondrial RIRR highlights the central role of mitochondria-formed ROS, we discuss all of the known ROS-producing sites (shown in vitro) and their relevance to the mitochondrial ROS production in vivo. PMID:24987008

  15. Non-thermal Plasma Induces Apoptosis in Melanoma Cells via Production of Intracellular Reactive Oxygen Species

    PubMed Central

    Sensenig, Rachel; Kalghatgi, Sameer; Cerchar, Ekaterina; Fridman, Gregory; Shereshevsky, Alexey; Torabi, Behzad; Arjunan, Krishna Priya; Podolsky, Erica; Fridman, Alexander; Friedman, Gary; Azizkhan-Clifford, Jane; Brooks, Ari D.

    2012-01-01

    Non-thermal atmospheric pressure dielectric barrier discharge (DBD) plasma may provide a novel approach to treat malignancies via induction of apoptosis. The purpose of this study was to evaluate the potential of DBD plasma to induce apoptosis in melanoma cells. Melanoma cells were exposed to plasma at doses that did not induce necrosis, and cell viability and apoptotic activity were evaluated by Trypan blue exclusion test, Annexin-V/PI staining, caspase-3 cleavage, and TUNEL® analysis. Trypan blue staining revealed that non-thermal plasma treatment significantly decreased the viability of cells in a dose-dependent manner 3 and 24 h after plasma treatment. Annexin-V/PI staining revealed a significant increase in apoptosis in plasma-treated cells at 24, 48, and 72 h post-treatment (p<0.001). Caspase-3 cleavage was observed 48 h post-plasma treatment at a dose of 15 J/cm2. TUNEL® analysis of plasma-treated cells demonstrated an increase in apoptosis at 48 and 72 h post-treatment (p<0.001) at a dose of 15 J/cm2. Pre-treatment with N-acetyl-L-cysteine (NAC), an intracellular reactive oxygen species (ROS) scavenger, significantly decreased apoptosis in plasma-treated cells at 5 and 15 J/cm2. Plasma treatment induces apoptosis in melanoma cells through a pathway that appears to be dependent on production of intracellular ROS. DBD plasma production of intracellular ROS leads to dose-dependent DNA damage in melanoma cells, detected by ?-H2AX, which was completely abrogated by pre-treating cells with ROS scavenger, NAC. Plasma-induced DNA damage in turn may lead to the observed plasma-induced apoptosis. Since plasma is non-thermal, it may be used to selectively treat malignancies. PMID:21046465

  16. Inhibitors of phosphatidylinositide 3-kinase: effects on reactive oxygen species and platelet aggregation.

    PubMed

    Saeed, Sheikh Arshad; Connor, John Dennis; Imran; Quadri, Javeria; Tasneem, Shumaila; Ahmed, Sagheer; Mesaik, Muhammad Ahmed; Choudhary, Muhammad Iqbal

    2007-01-01

    Phosphoinositide 3-kinase (PI 3-kinase) exists in cells as a family of isoforms. The enzymes are important regulators of fundamental metabolic processes, such as energy utilization, growth, cell proliferation and survival. They are activated by cell surface receptors for hormones, and by G-protein coupled receptors. Enzyme p110 gamma, in particular, catalyzes production of second messengers from inositol phospholipids, including phosphoinositide (3,4,5) triphosphate or PtdIns (3,4,5) P3, PtdIns (3,4) P2 and Ptdins (3) P. The objective of this study was to corroborate the role of PI 3 kinase in ROS generation and in platelet aggregation through the use of four chemically unrelated inhibitors of PI 3 kinase: wortmannin, LY-294002, resveratrol and quercetin. In this study, we describe the effects of four PI 3-kinase inhibitors on the production of reactive oxygen species (ROS) and platelet aggregation induced by a diversity of agonists. Neutrophils and platelets were obtained from human blood and macrophages from mouse peritoneal cavity. ROS production was measured by a luminol-enhanced chemiluminescence assay; aggregation was measured in platelet-rich plasma (PRP) with a Chronolog Dual Channel Lumi-Aggregometer. Effects of graded concentrations of four enzyme inhibitors (wortmannin, LY-294002, resveratrol and quercetin) were evaluated. All inhibitors caused concentration-dependent depression of ROS generation and human platelet aggregation. They differed only in their potencies as revealed by concentration-response data. Moreover, inhibitors blocked activity of three chemically unrelated stimulants of aggregation: ADP, collagen and epinephrine. We conclude that inhibition of PI 3-kinase would appear to be a useful therapeutic goal in those conditions where the activities of platelets and/or phagocytes become aberrant. PMID:17556803

  17. GASA14 regulates leaf expansion and abiotic stress resistance by modulating reactive oxygen species accumulation.

    PubMed

    Sun, Shulan; Wang, Haoxiang; Yu, Hongmei; Zhong, Chunmei; Zhang, Xiaoxia; Peng, Jianzong; Wang, Xiaojing

    2013-04-01

    Gibberellic acid (GA) can regulate many plant developmental processes. GAST1 has been identified as a GA-stimulated transcript, and Arabidopsis GAST-like genes are known to constitute the GASA family. However, the functions of most GASA genes are not clear at present. In this study, the function of GASA14, a member of the GASA family, was investigated. GASA14 expression was upregulated by GA and downregulated by the transcriptional regulators that repress GA responses, the DELLA proteins GAI and RGA. Phenotypic analysis showed that growth of the GASA14 null mutant (gasa14-1) line was retarded, and the growth of the 35S::GASA14 lines were promoted in young plants. Furthermore, seed germination of the gasa14-1 plants showed more sensitivity to paclobutrazol (an inhibitor of GA biosynthesis) than Columbia (Col) plants, suggesting that GASA14 is required for GA-dependent responses. Analysis of the responses of the gasa14-1 and 35S::GASA14 lines to abscisic acid (ABA) and salt revealed that germination and seedling establishment of gasa14-1 were poorer than those of Col plants and that the 35S::GASA14 lines were more resistant to ABA and salt. Further analysis showed that overexpression of GASA14 could suppress reactive oxygen species (ROS) accumulation. Taken together, these results demonstrated that GASA14 regulates leaf expansion and abiotic stress resistance by modulating ROS accumulation. Because GASA14 contains both GASA (GA-stimulated in Arabidopsis) and PRP (proline-rich protein) domains, the PRP domain coding sequence was overexpressed in Col plants and it was found that the growth of the transgenic plants and the responses to ABA and salt were not altered. These results thus suggest that the GASA domain is necessary for the functions of GASA14. PMID:23378382

  18. Monitoring Cr Intermediates and Reactive Oxygen Species with Fluorescent Probes during Chromate Reduction

    PubMed Central

    2015-01-01

    Cr(VI) genotoxicity is caused by products of its reductive metabolism inside the cells. Reactive oxygen species (ROS) and Cr(V,IV) intermediates are potential sources of oxidative damage by Cr(VI). Here, we investigated seven fluorescent probes for the detection of ROS and non-ROS oxidants in Cr(VI) reactions with its main reducers. We found that Cr(V)-skipping metabolism of Cr(VI) by ascorbate in vitro gave no responses with all tested dyes, indicating nonreactivity of Cr(IV) and absence of ROS. Cr(VI) reduction with glutathione (GSH) or Cys strongly enhanced the fluorescence of dichlorofluorescein (DCF) and dihydrorhodamine 123 (DHR123) but produced minimal fluorescence with dihydroethidium and no increases with aminophenylfluorescein and CellRox Green, Orange, and Red. Several tests showed that Cr(VI)-thiol reactions lacked ROS and that Cr(V) caused oxidation of DCF and DHR123. DCF reacted only with free Cr(V), whereas DHR123 detected both the free Cr(V) and Cr(V)-GSH complex. We estimated that Cr(VI)-GSH reactions generated approximately 75% Cr(V)-GSH and 25% free Cr(V), whereas Cys reactions appeared to produce only free Cr(V). DHR123 measurements in H460 cells showed that reduction of Cr(VI) was complete within 20 min postexposure, but it lasted at least 1 h without GSH. Cells with restored ascorbate levels exhibited no DCF or DHR123 oxidation by Cr(VI). Overall, our results demonstrated that Cr(VI) metabolism with its biological reducers lacked ROS and that DHR123 and DCF responses were indicators of total and free Cr(V), respectively. CellRox dyes, dihydroethidium and aminophenylfluorescein, are insensitive to Cr(V,IV) and can be used for monitoring ROS during coexposure to Cr(VI) and oxidants. PMID:24646070

  19. 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

  20. Mercuric ions inhibit mitogen-activated protein kinase dephosphorylation by inducing reactive oxygen species

    SciTech Connect

    Haase, Hajo; Engelhardt, Gabriela; Hebel, Silke; Rink, Lothar, E-mail: LRink@ukaachen.de

    2011-01-01

    Mercury intoxication profoundly affects the immune system, in particular, signal transduction of immune cells. However, the mechanism of the interaction of mercury with cellular signaling pathways, such as mitogen activated protein kinases (MAPK), remains elusive. Therefore, the objective of this study is to investigate three potential ways in which Hg{sup 2+} ions could inhibit MAPK dephosphorylation in the human T-cell line Jurkat: (1) by direct binding to phosphatases; (2) by releasing cellular zinc (Zn{sup 2+}); and (3) by inducing reactive oxygen species (ROS). Hg{sup 2+} causes production of ROS, measured by dihydrorhodamine 123, and triggers ROS-mediated Zn{sup 2+} release, detected with FluoZin-3. Yet, phosphatase-inhibition is not mediated by binding of Zn{sup 2+} or Hg{sup 2+}. Rather, phosphatases are inactivated by at least two forms of thiol oxidation; initial inhibition is reversible with reducing agents such as Tris(2-carboxyethyl)phosphine. Prolonged inhibition leads to non-reversible phosphatase oxidation, presumably oxidizing the cysteine thiol to sulfinic- or sulfonic acid. Notably, phosphatases are a particularly sensitive target for Hg{sup 2+}-induced oxidation, because phosphatase activity is inhibited at concentrations of Hg{sup 2+} that have only minor impact on over all thiol oxidation. This phosphatase inhibition results in augmented, ROS-dependent MAPK phosphorylation. MAPK are important regulators of T-cell function, and MAPK-activation by inhibition of phosphatases seems to be one of the molecular mechanisms by which mercury affects the immune system.

  1. Reactive Oxygen Species Stimulate Insulin Secretion in Rat Pancreatic Islets: Studies Using Mono-Oleoyl-Glycerol

    PubMed Central

    Kane, Ada; Shirihai, Orian; Corkey, Barbara E.; Deeney, Jude T.

    2012-01-01

    Chronic exposure (24–72 hrs) of pancreatic islets to elevated glucose and fatty acid leads to glucolipoxicity characterized by basal insulin hypersecretion and impaired glucose-stimulated insulin secretion (GSIS). Our aim was to determine the mechanism for basal hypersecretion of insulin. We used mono-oleoyl-glycerol (MOG) as a tool to rapidly increase lipids in isolated rat pancreatic ß-cells and in the clonal pancreatic ß-cell line INS-1 832/13. MOG (25–400 µM) stimulated basal insulin secretion from ß-cells in a concentration dependent manner without increasing intracellular Ca2+ or O2 consumption. Like GSIS, MOG increased NAD(P)H and reactive oxygen species (ROS). The mitochondrial reductant ß-hydroxybutyrate (ß-OHB) also increased the redox state and ROS production, while ROS scavengers abrogated secretion. Diazoxide (0.4 mM) did not prevent the stimulatory effect of MOG, confirming that the effect was independent of the KATP-dependent pathway of secretion. MOG was metabolized to glycerol and long-chain acyl-CoA (LC-CoA), whereas, acute oleate did not similarly increase LC-CoA. Inhibition of diacylglycerol kinase (DGK) did not mimic the effect of MOG on insulin secretion, indicating that MOG did not act primarily by inhibiting DGK. Inhibition of acyl-CoA synthetase (ACS) reduced the stimulatory effect of MOG on basal insulin secretion by 30% indicating a role for LC-CoA. These data suggest that basal insulin secretion is stimulated by increased ROS production, due to an increase in the mitochondrial redox state independent of the established components of GSIS. PMID:22272304

  2. Reactive oxygen species stimulate insulin secretion in rat pancreatic islets: studies using mono-oleoyl-glycerol.

    PubMed

    Saadeh, Marylana; Ferrante, Thomas C; Kane, Ada; Shirihai, Orian; Corkey, Barbara E; Deeney, Jude T

    2012-01-01

    Chronic exposure (24-72 hrs) of pancreatic islets to elevated glucose and fatty acid leads to glucolipoxicity characterized by basal insulin hypersecretion and impaired glucose-stimulated insulin secretion (GSIS). Our aim was to determine the mechanism for basal hypersecretion of insulin. We used mono-oleoyl-glycerol (MOG) as a tool to rapidly increase lipids in isolated rat pancreatic ß-cells and in the clonal pancreatic ß-cell line INS-1 832/13. MOG (25-400 µM) stimulated basal insulin secretion from ß-cells in a concentration dependent manner without increasing intracellular Ca(2+) or O(2) consumption. Like GSIS, MOG increased NAD(P)H and reactive oxygen species (ROS). The mitochondrial reductant ß-hydroxybutyrate (ß-OHB) also increased the redox state and ROS production, while ROS scavengers abrogated secretion. Diazoxide (0.4 mM) did not prevent the stimulatory effect of MOG, confirming that the effect was independent of the K(ATP)-dependent pathway of secretion. MOG was metabolized to glycerol and long-chain acyl-CoA (LC-CoA), whereas, acute oleate did not similarly increase LC-CoA. Inhibition of diacylglycerol kinase (DGK) did not mimic the effect of MOG on insulin secretion, indicating that MOG did not act primarily by inhibiting DGK. Inhibition of acyl-CoA synthetase (ACS) reduced the stimulatory effect of MOG on basal insulin secretion by 30% indicating a role for LC-CoA. These data suggest that basal insulin secretion is stimulated by increased ROS production, due to an increase in the mitochondrial redox state independent of the established components of GSIS. PMID:22272304

  3. Antioxidant Enzymes Regulate Reactive Oxygen Species during Pod Elongation in Pisum sativum and Brassica chinensis

    PubMed Central

    Liu, Nan; Lin, Zhifang; Guan, Lanlan; Gaughan, Gerald; Lin, Guizhu

    2014-01-01

    Previous research has focused on the involvement of reactive oxygen species (ROS) in cell wall loosening and cell extension in plant vegetative growth, but few studies have investigated ROS functions specifically in plant reproductive organs. In this study, ROS levels and antioxidant enzyme activities were assessed in Pisum sativum and Brassica chinensis pods at five developmental stages. In juvenile pods, the high levels of O2.? and.OH indicates that they had functions in cell wall loosening and cell elongation. In later developmental stages, high levels of.OH were also related to increases in cell wall thickness in lignified tissues. Throughout pod development, most of the O2.? was detected on plasma membranes of parenchyma cells and outer epidermis cells of the mesocarp, while most of the H2O2 was detected on plasma membranes of most cells throughout the mesocarp. This suggests that these sites are presumably the locations of ROS generation. The antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) apparently contributed to ROS accumulation in pod wall tissues. Furthermore, specifically SOD and POD were found to be associated with pod growth through the regulation of ROS generation and transformation. Throughout pod development, O2.? decreases were associated with increased SOD activity, while changes in H2O2 accumulation were associated with changes in CAT and POD activities. Additionally, high POD activity may contribute to the generation of.OH in the early development of pods. It is concluded that the ROS are produced in different sites of plasma membranes with the regulation of antioxidant enzymes, and that substantial ROS generation and accumulation are evident in cell elongation and cell wall loosening in pod wall cells. PMID:24503564

  4. The role of mitochondria-derived reactive oxygen species in hyperthermia-induced platelet apoptosis.

    PubMed

    Wang, Zhicheng; Cai, Feng; Chen, Xiaoyu; Luo, Meihong; Hu, Lingling; Lu, Yuan

    2013-01-01

    A combination of hyperthermia with radiotherapy and chemotherapy for various solid tumors has been practiced clinically. However, hyperthermic therapy has side effects, such as thrombocytopenia. Up to now, the pathogenesis of hyperthermia-induced thrombocytopenia remains unclear. Previous studies have shown that hyperthermia induces platelet apoptosis. However, the signaling pathways and molecular mechanisms involved in hyperthermia-induced platelet apoptosis have not been determined. Here we show that hyperthermia induced intracellular reactive oxygen species (ROS) production and mitochondrial ROS generation in a time-dependent manner in platelets. The mitochondria-targeted ROS scavenger Mito-TEMPO blocked intracellular ROS and mitochondrial ROS generation. By contrast, inhibitors of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, nitric oxide synthase, cyclooxygenase and lipoxygenase did not. Furthermore, Mito-TEMPO inhibited hyperthermia-induced malonyldialdehyde production and cardiolipin peroxidation. We also showed that hyperthermia-triggered platelet apoptosis was inhibited by Mito-TEMPO. Furthermore, Mito-TEMPO ameliorated hyperthermia-impaired platelet aggregation and adhesion function. Lastly, hyperthermia decreased platelet manganese superoxide dismutase (MnSOD) protein levels and enzyme activity. These data indicate that mitochondrial ROS play a pivotal role in hyperthermia-induced platelet apoptosis, and decreased of MnSOD activity might, at least partially account for the enhanced ROS levels in hyperthermia-treated platelets. Therefore, determining the role of mitochondrial ROS as contributory factors in platelet apoptosis, is critical in providing a rational design of novel drugs aimed at targeting mitochondrial ROS. Such therapeutic approaches would have potential clinical utility in platelet-associated disorders involving oxidative damage. PMID:24023970

  5. Induction of reactive oxygen species-mediated autophagy by a novel microtubule-modulating agent.

    PubMed

    Karna, Prasanthi; Zughaier, Susu; Pannu, Vaishali; Simmons, Robert; Narayan, Satya; Aneja, Ritu

    2010-06-11

    Autophagy is being increasingly implicated in both cell survival and death. However, the intricate relationships between drug-induced autophagy and apoptosis remain elusive. Here we demonstrate that a tubulin-binding noscapine analog, (R)-9-bromo-5-((S)-4,5-dimethoxy-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]-di-oxolo[4,5-g]isoquinoline (Red-Br-nos), exerts a novel autophagic response followed by apoptotic cell death in human prostate cancer PC-3 cells. Red-Br-nos-induced autophagy was an early event detectable within 12 h that displayed a wide array of characteristic features including double membranous vacuoles with entrapped organelles, acidic vesicular organelles, and increased expression of LC3-II and beclin-1. Red-Br-nos-triggered release of reactive oxygen species (ROS) and attenuation of ROS by tiron, a ROS scavenger, reduced the sub-G(1) population suggesting ROS-dependent apoptosis. Abrogation of ROS also reduced autophagy indicating that ROS triggers autophagy. Pharmacological and genetic approaches to inhibit autophagy uncovered the protective role of Red-Br-nos-induced autophagy in PC-3 cells. Direct effects of the drug on mitochondria viz. disruption of normal cristae architecture and dissipation of mitochondrial transmembrane potential revealed a functional link between ROS generation, autophagy, and apoptosis induction. This is the first report to demonstrate the protective role of ROS-mediated autophagy and induction of caspase-independent ROS-dependent apoptosis in PC-3 cells by Red-Br-nos, a member of the noscapinoid family of microtubule-modulating anticancer agents. PMID:20404319

  6. The role of reactive oxygen species in Anopheles aquasalis response to Plasmodium vivax infection.

    PubMed

    Bahia, Ana C; Oliveira, José Henrique M; Kubota, Marina S; Araújo, Helena R C; Lima, José B P; Ríos-Velásquez, Claudia Maria; Lacerda, Marcus Vinícius G; Oliveira, Pedro L; Traub-Csekö, Yara M; Pimenta, Paulo F P

    2013-01-01

    Malaria affects millions of people worldwide and hundreds of thousands of people each year in Brazil. The mosquito Anopheles aquasalis is an important vector of Plasmodium vivax, the main human malaria parasite in the Americas. Reactive oxygen species (ROS) have been shown to have a role in insect innate immune responses as a potent pathogen-killing agent. We investigated the mechanisms of free radicals modulation after A. aquasalis infection with P. vivax. ROS metabolism was evaluated in the vector by studying expression and activity of three key detoxification enzymes, one catalase and two superoxide dismutases (SOD3A and SOD3B). Also, the involvement of free radicals in the mosquito immunity was measured by silencing the catalase gene followed by infection of A. aquasalis with P. vivax. Catalase, SOD3A and SOD3B expression in whole A. aquasalis were at the same levels of controls at 24 h and upregulated 36 h after ingestion of blood containing P. vivax. However, in the insect isolated midgut, the mRNA for these enzymes was not regulated by P. vivax infection, while catalase activity was reduced 24 h after the infectious meal. RNAi-mediated silencing of catalase reduced enzyme activity in the midgut, resulted in increased P. vivax infection and prevalence, and decreased bacterial load in the mosquito midgut. Our findings suggest that the interactions between A. aquasalis and P. vivax do not follow the model of ROS-induced parasite killing. It appears that P. vivax manipulates the mosquito detoxification system in order to allow its own development. This can be an indirect effect of fewer competitive bacteria present in the mosquito midgut caused by the increase of ROS after catalase silencing. These findings provide novel information on unique aspects of the main malaria parasite in the Americas interaction with one of its natural vectors. PMID:23441231

  7. The Role of Reactive Oxygen Species in Anopheles aquasalis Response to Plasmodium vivax Infection

    PubMed Central

    Bahia, Ana C.; Oliveira, José Henrique M.; Kubota, Marina S.; Araújo, Helena R. C.; Lima, José B. P.; Ríos-Velásquez, Claudia Maria; Lacerda, Marcus Vinícius G.; Oliveira, Pedro L.

    2013-01-01

    Malaria affects millions of people worldwide and hundreds of thousands of people each year in Brazil. The mosquito Anopheles aquasalis is an important vector of Plasmodium vivax, the main human malaria parasite in the Americas. Reactive oxygen species (ROS) have been shown to have a role in insect innate immune responses as a potent pathogen-killing agent. We investigated the mechanisms of free radicals modulation after A. aquasalis infection with P. vivax. ROS metabolism was evaluated in the vector by studying expression and activity of three key detoxification enzymes, one catalase and two superoxide dismutases (SOD3A and SOD3B). Also, the involvement of free radicals in the mosquito immunity was measured by silencing the catalase gene followed by infection of A. aquasalis with P. vivax. Catalase, SOD3A and SOD3B expression in whole A. aquasalis were at the same levels of controls at 24 h and upregulated 36 h after ingestion of blood containing P. vivax. However, in the insect isolated midgut, the mRNA for these enzymes was not regulated by P. vivax infection, while catalase activity was reduced 24 h after the infectious meal. RNAi-mediated silencing of catalase reduced enzyme activity in the midgut, resulted in increased P. vivax infection and prevalence, and decreased bacterial load in the mosquito midgut. Our findings suggest that the interactions between A. aquasalis and P. vivax do not follow the model of ROS-induced parasite killing. It appears that P. vivax manipulates the mosquito detoxification system in order to allow its own development. This can be an indirect effect of fewer competitive bacteria present in the mosquito midgut caused by the increase of ROS after catalase silencing. These findings provide novel information on unique aspects of the main malaria parasite in the Americas interaction with one of its natural vectors. PMID:23441231

  8. Smoke Extract Impairs Adenosine Wound Healing. Implications of Smoke-Generated Reactive Oxygen Species

    PubMed Central

    Zimmerman, Matthew C.; Zhang, Hui; Castellanos, Glenda; O’Malley, Jennifer K.; Alvarez-Ramirez, Horacio; Kharbanda, Kusum; Sisson, Joseph H.; Wyatt, Todd A.

    2013-01-01

    Adenosine concentrations are elevated in the lungs of patients with asthma and chronic obstructive pulmonary disease, where it balances between tissue repair and excessive airway remodeling. We previously demonstrated that the activation of the adenosine A2A receptor promotes epithelial wound closure. However, the mechanism by which adenosine-mediated wound healing occurs after cigarette smoke exposure has not been investigated. The present study investigates whether cigarette smoke exposure alters adenosine-mediated reparative properties via its ability to induce a shift in the oxidant/antioxidant balance. Using an in vitro wounding model, bronchial epithelial cells were exposed to 5% cigarette smoke extract, were wounded, and were then stimulated with either 10 ?M adenosine or the specific A2A receptor agonist, 5?-(N-cyclopropyl)–carboxamido–adenosine (CPCA; 10 ?M), and assessed for wound closure. In a subset of experiments, bronchial epithelial cells were infected with adenovirus vectors encoding human superoxide dismutase and/or catalase or control vector. In the presence of 5% smoke extract, significant delay was evident in both adenosine-mediated and CPCA-mediated wound closure. However, cells pretreated with N-acetylcysteine (NAC), a nonspecific antioxidant, reversed smoke extract–mediated inhibition. We found that cells overexpressing mitochondrial catalase repealed the smoke extract inhibition of CPCA-stimulated wound closure, whereas superoxide dismutase overexpression exerted no effect. Kinase experiments revealed that smoke extract significantly reduced the A2A-mediated activation of cyclic adenosine monophosphate–dependent protein kinase. However, pretreatment with NAC reversed this effect. In conclusion, our data suggest that cigarette smoke exposure impairs A2A-stimulated wound repair via a reactive oxygen species–dependent mechanism, thereby providing a better understanding of adenosine signaling that may direct the development of pharmacological tools for the treatment of chronic inflammatory lung disorders. PMID:23371060

  9. Platelet activation through interaction with hemodialysis membranes induces neutrophils to produce reactive oxygen species.

    PubMed

    Itoh, Saotomo; Susuki, Chie; Tsuji, Tsutomu

    2006-05-01

    The intradialytic activation of leukocytes is one of the major causes of hemodialysis-associated complications. During hemodialysis, the formation of microaggregates consisting of platelets and neutrophils has been observed to accompany the production of reactive oxygen species (ROS) by leukocytes. In this study, we investigated the interaction of platelets and neutrophils with hemodialysis membranes in vitro to elucidate the mechanism underlying microaggregate formation and its relevance to leukocyte activation. The production of ROS in neutrophils was induced by the coincubation of neutrophils with polysulfone (PS) membranes, and was increased when platelets were present in the neutrophil suspension. Neutrophils that were incubated with polymethylmethacrylate (PMMA) membranes in the presence of platelets also produced significant levels of ROS, suggesting that the presence of platelets augmented ROS production in neutrophils. Platelets adhered more firmly to hydrophobic membranes such as PS and PMMA membranes than to hydrophilic membranes, such as those composed of regenerated cellulose (RC) or ethylene vinylalcohol copolymer (EVAL). The adhesion of platelets to dialysis membranes composed of different materials was correlated with those membranes' ability to induce platelet activation as assessed by the cell surface expression of P-selectin. Moreover, coincubation of neutrophils with platelets that had been treated with hydrophobic membranes induced a higher level of superoxide anion relative to those treated with hydrophilic membranes in association with the P-selectin-mediated microaggregate formation. These results suggest that platelets activated through interaction with hemodialysis membranes stimulate neutrophils to produce ROS via P-selectin-mediated adhesion, and that this property of adhesion to platelets is critical for the biocompatibility of hemodialysis membranes. PMID:16400657

  10. Superparamagnetic iron oxide nanoparticles exacerbate the risks of reactive oxygen species-mediated external stresses.

    PubMed

    Luo, Cheng; Li, Yan; Yang, Liang; Wang, Xun; Long, Jiangang; Liu, Jiankang

    2015-03-01

    Superparamagnetic iron oxide nanoparticles (IONPs) have been widely applied in numerous biomedical fields. The evaluation of the toxicity of IONPs to the environment and human beings is indispensable to guide their applications. IONPs are usually considered to have good biocompatibility; however, some literatures have reported the toxicity of IONPs in vitro and in vivo. The controversy surrounding the biocompatibility of IONPs prompted us to carefully consider the biological effects of IONPs, especially under stress conditions. However, the potential risks of IONPs under stress conditions have not yet been evaluated in depth. Acrolein is widespread in the environment and modulates stress-induced gene activation and cell death in many organs and tissues. In this study, we assessed the sensitivity of H9c2 cardiomyocyte cells embedded with IONPs to acrolein and investigated the possible molecular mechanisms involved in this sensitivity. IONPs, which alone exhibited no toxicity, sensitized the H9c2 cardiomyocytes to acrolein-induced dysfunction. The IONP/acrolein treatment induced a loss of viability, membrane disruption, reactive oxygen species (ROS) generation, Erk activation, mitochondrial and lysosomal dysfunction, and necrosis in H9c2 cells. Treatment with an ROS generation inhibitor (diphenyleneiodonium) or an iron chelator (deferoxamine) prevented the IONP/acrolein-induced loss of viability, suggesting that ROS and IONP degradation facilitated the toxicity of the IONP/acrolein treatment in H9c2 cells. Our data suggest that cells embedded in IONPs are more vulnerable to oxidative stress, which confirms the hypothesis that nanoparticles can sensitize cells to the adverse effects of external stimulation. The present work provides a new perspective from which to evaluate the interactions between nanoparticles and cells. PMID:24847785

  11. Reactive Oxygen Species and Angiogenesis: NADPH Oxidase as Target for Cancer Therapy

    PubMed Central

    Ushio-Fukai, Masuko; Nakamura, Yoshimasa

    2009-01-01

    Angiogenesis is essential for tumor growth, metastasis, arteriosclerosis as well as embryonic development and wound healing. Its process is dependent on cell proliferation, migration and capillary tube formation in endothelia cells (ECs). High levels of reactive oxygen species (ROS) such as superoxide and H2O2 are observed in various cancer cells. Accumulating evidence suggests that ROS function as signaling molecules to mediate various growth-related responses including angiogenesis. ROS-dependent angiogenesis can be regulated by endogenous antioxidant enzymes such as SOD and thioredoxin. Vascular endothelial growth factor (VEGF), one of the major angiogenesis factor, is induced in growing tumors and stimulates EC proliferation and migration primarily through the VEGF receptor type2 (VEGFR2, Flk1/KDR). Major source of ROS in ECs is a NADPH oxidase which consists of Nox1, Nox2, Nox4, Nox5, p22phox, p47phox and the small G protein Rac1. NADPH oxidase is activated by various growth factors including VEGF and angiopoietin-1 as well as hypoxia and ischemia, and ROS derived from this oxidase are involved in VEGFR2 autophosphorylation, and diverse redox signaling pathways leading to induction of transcription factors and genes involved in angiogenesis. Dietary antioxidants appear to be effective for treatment of tumor angiogenesis. The aim of this review is to provide an overview of the recent progress on role of ROS derived from NADPH oxidase and redox signaling events involved in angiogenesis. Understanding these mechanisms may provide insight into the NADPH oxidase and redox signaling components as potential therapeutic targets for tumor angiogenesis. PMID:18406051

  12. Regulation of soybean seed germination through ethylene production in response to reactive oxygen species

    PubMed Central

    Ishibashi, Yushi; Koda, Yuka; Zheng, Shao-Hui; Yuasa, Takashi; Iwaya-Inoue, Mari

    2013-01-01

    Background and Aims Despite their toxicity, reactive oxygen species (ROS) play important roles in plant cell signalling pathways, such as mediating responses to stress or infection and in programmed cell death, at lower levels. Although studies have indicated that hydrogen peroxide (H2O2) promotes seed germination of several plants such as Arabidopsis, barley, wheat, rice and sunflower, the role of H2O2 in soybean seed germination is not well known. The aim of this study therefore was to investigate the relationships between ROS, plant hormones and soybean seed germination. Methods An examination was made of soybean seed germination, the expression of genes related to ethylene biosynthesis, endogenous ethylene contents, and the number and area of cells in the root tip, using N-acetylcysteine, an antioxidant, to counteract the effect of ROS. Key Results H2O2 promoted germination, which N-acetylcysteine suppressed, suggesting that ROS are involved in the regulation of soybean germination. H2O2 was produced in the embryonic axis after imbibition. N-Acetylcysteine suppressed the expression of genes related to ethylene biosynthesis and the production of endogenous ethylene. Interestingly, ethephon, which is converted to ethylene, and H2O2 reversed the suppression of seed germination by N-acetylcysteine. Furthermore, morphological analysis revealed that N-acetylcysteine suppressed cell elongation at the root tip, and this suppression was also reversed by ethephon or H2O2 treatments, as was the case in germination. Conclusions In soybean seeds, ROS produced in the embryonic axis after imbibition induce the production of endogenous ethylene, which promotes cell elongation in the root tip. This appears to be how ROS regulate soybean seed germination. PMID:23131300

  13. Hypothalamic Reactive Oxygen Species Are Required for Insulin-Induced Food Intake Inhibition

    PubMed Central

    Jaillard, Tristan; Roger, Michael; Galinier, Anne; Guillou, Pascale; Benani, Alexandre; Leloup, Corinne; Casteilla, Louis; Pénicaud, Luc; Lorsignol, Anne

    2009-01-01

    OBJECTIVE Insulin plays an important role in the hypothalamic control of energy balance, especially by reducing food intake. Emerging data point to a pivotal role of reactive oxygen species (ROS) in energy homeostasis regulation, but their involvement in the anorexigenic effect of insulin is unknown. Furthermore, ROS signal derived from NADPH oxidase activation is required for physiological insulin effects in peripheral cells. In this study, we investigated the involvement of hypothalamic ROS and NADPH oxidase in the feeding behavior regulation by insulin. RESEARCH DESIGN AND METHODS We first measured hypothalamic ROS levels and food intake after acute intracerebroventricular injection of insulin. Second, effect of pretreatment with a ROS scavenger or an NADPH oxidase inhibitor was evaluated. Third, we examined the consequences of two nutritional conditions of central insulin unresponsiveness (fasting or short-term high-fat diet) on the ability of insulin to modify ROS level and food intake. RESULTS In normal chow-fed mice, insulin inhibited food intake. At the same dose, insulin rapidly and transiently increased hypothalamic ROS levels by 36%. The pharmacological suppression of this insulin-stimulated ROS elevation, either by antioxidant or by an NADPH oxidase inhibitor, abolished the anorexigenic effect of insulin. Finally, in fasted and short-term high-fat diet–fed mice, insulin did not promote elevation of ROS level and food intake inhibition, likely because of an increase in hypothalamic diet-induced antioxidant defense systems. CONCLUSIONS A hypothalamic ROS increase through NADPH oxidase is required for the anorexigenic effect of insulin. PMID:19389827

  14. Mitochondrial Reactive Oxygen Species Are Obligatory Signals for Glucose-Induced Insulin Secretion

    PubMed Central

    Leloup, Corinne; Tourrel-Cuzin, Cécile; Magnan, Christophe; Karaca, Melis; Castel, Julien; Carneiro, Lionel; Colombani, Anne-Laure; Ktorza, Alain; Casteilla, Louis; Pénicaud, Luc

    2009-01-01

    OBJECTIVE—Insulin secretion involves complex events in which the mitochondria play a pivotal role in the generation of signals that couple glucose detection to insulin secretion. Studies on the mitochondrial generation of reactive oxygen species (ROS) generally focus on chronic nutrient exposure. Here, we investigate whether transient mitochondrial ROS production linked to glucose-induced increased respiration might act as a signal for monitoring insulin secretion. RESEARCH DESIGN AND METHODS—ROS production in response to glucose was investigated in freshly isolated rat islets. ROS effects were studied using a pharmacological approach and calcium imaging. RESULTS—Transient glucose increase from 5.5 to 16.7 mmol/l stimulated ROS generation, which was reversed by antioxidants. Insulin secretion was dose dependently blunted by antioxidants and highly correlated with ROS levels. The incapacity of ?-cells to secrete insulin in response to glucose with antioxidants was associated with a decrease in ROS production and in contrast to the maintenance of high levels of ATP and NADH. Then, we investigated the mitochondrial origin of ROS (mROS) as the triggering signal. Insulin release was mimicked by the mitochondrial-complex blockers, antimycin and rotenone, that generate mROS. The adding of antioxidants to mitochondrial blockers or to glucose was used to lower mROS reversed insulin secretion. Finally, calcium imaging on perifused islets using glucose stimulation or mitochondrial blockers revealed that calcium mobilization was completely reversed using the antioxidant trolox and that it was of extracellular origin. No toxic effects were present using these pharmacological approaches. CONCLUSIONS—Altogether, these complementary results demonstrate that mROS production is a necessary stimulus for glucose-induced insulin secretion. PMID:19073765

  15. Induction of heme oxygenase in mammalian cells by mineral fibers: distinctive effect of reactive oxygen species.

    PubMed

    Suzuki, K; Hei, T K

    1996-04-01

    Exponentially growing human-hamster hybrid [AL] cells treated with a 40 micrograms/ml (8 micrograms/cm2) dose of UICC standard reference chrysotile fibers induced heme oxygenase (HO) protein with a maximum expression level at 8 h post-treatment. While the constitutive HO expression was detectable in non-treated AL cells, the protein level was increased approximately 4.5-fold in fiber-treated cells. The induction was dose-dependent at fiber concentration between 2.5 micrograms/ml (0.5 microgram/cm2) and 40 micrograms/ml (8 micrograms/cm2) with the induced HO concentrated mostly in the cytoplasm as shown by immunostaining. Several other types of mineral fibers examined including crocidolites, tremolites, and erionites also induced HO synthesis with varying degree of efficiency. In general, chrysotile and crocidolite were more efficient inducers of HO than tremolite and erionite when compared at fiber doses that resulted in approximately 50% survival (LD50) level. The effects of antioxidant enzymes on HO induction were examined by concurrent treatment of fiber-exposed cultures with SOD and catalase. Although addition of superoxide dismutase (SOD) and catalase inhibited HO induction in a dose-dependent manner, they offered no protection on fiber-mediated clonogenic toxicity in the same population of treated cells. These results suggest that reactive oxygen species (ROS) produced by asbestos fibers play an essential role in the induction of HO and that different mineral fibers, when applied at equitoxic doses, often result in different oxidative stress status as determined by the induction of HO proteins. PMID:8625475

  16. Reactive oxygen species and IRF1 stimulate IFN? production by proximal tubules during ischemic AKI

    PubMed Central

    Winterberg, Pamela D.; Wang, Yanxia; Lin, Keng-Mean; Hartono, John R.; Nagami, Glenn T.; Zhou, Xin J.; Shelton, John M.; Richardson, James A.

    2013-01-01

    We previously reported that expression of the transcription factor interferon regulatory factor 1 (IRF1) is an early, critical maladaptive signal expressed by renal tubules during murine ischemic acute kidney injury (AKI). We now show that IRF1 mediates signals from reactive oxygen species (ROS) generated during ischemic AKI and that these signals ultimately result in production of ?-subtypes of type I interferons (IFN?s). We found that genetic knockout of the common type I IFN receptor (IFNARI?/?) improved kidney function and histology during AKI. There are major differences in the spatial-temporal production of the two major IFN subtypes, IFN? and IFN?s: IFN? expression peaks at 4 h, earlier than IFN?s, and continues at the same level at 24 h; expression of IFN?s also increases at 4 h but continues to increase through 24 h. The magnitude of the increase in IFN?s relative to baseline is much greater than that of IFN?. We show by immunohistology and study of isolated cells that IFN? is produced by renal leukocytes and IFN?s are produced by renal tubules. IRF1, IFN?s, and IFNARI were found on the same renal tubules during ischemic AKI. Furthermore, we found that ROS induced IFN? expression by renal tubules in vitro. This expression was inhibited by small interfering RNA knockdown of IRF1. Overexpression of IRF1 resulted in the production of IFN?s. Furthermore, we found that IFN? stimulated production of maladaptive proinflammatory CXCL2 by renal tubular cells. Altogether our data support the following autocrine pathway in renal tubular cells: ROS > IRF1 > IFN? > IFNARI > CXCL2. PMID:23657854

  17. Increased effectiveness of carbon ions in the production of reactive oxygen species in normal human fibroblasts.

    PubMed

    Dettmering, Till; Zahnreich, Sebastian; Colindres-Rojas, Miriam; Durante, Marco; Taucher-Scholz, Gisela; Fournier, Claudia

    2015-01-01

    The production of reactive oxygen species (ROS), especially superoxide anions (O2 (·-)), is enhanced in many normal and tumor cell types in response to ionizing radiation. The influence of ionizing radiation on the regulation of ROS production is considered as an important factor in the long-term effects of irradiation (such as genomic instability) that might contribute to the development of secondary cancers. In view of the increasing application of carbon ions in radiation therapy, we aimed to study the potential impact of ionizing density on the intracellular production of ROS, comparing photons (X-rays) with carbon ions. For this purpose, we used normal human cells as a model for irradiated tissue surrounding a tumor. By quantifying the oxidization of Dihydroethidium (DHE), a fluorescent probe sensitive to superoxide anions, we assessed the intracellular ROS status after radiation exposure in normal human fibroblasts, which do not show radiation-induced chromosomal instability. After 3-5 days post exposure to X-rays and carbon ions, the level of ROS increased to a maximum that was dose dependent. The maximum ROS level reached after irradiation was specific for the fibroblast type. However, carbon ions induced this maximum level at a lower dose compared with X-rays. Within ?1 week, ROS decreased to control levels. The time-course of decreasing ROS coincides with an increase in cell number and decreasing p21 protein levels, indicating a release from radiation-induced growth arrest. Interestingly, radiation did not act as a trigger for chronically enhanced levels of ROS months after radiation exposure. PMID:25304329

  18. Reactive oxygen species induce a procoagulant state in endothelial cells by inhibiting tissue factor pathway inhibitor.

    PubMed

    Cimmino, Giovanni; Cirillo, Plinio; Ragni, Massimo; Conte, Stefano; Uccello, Giuseppe; Golino, Paolo

    2015-08-01

    Tissue factor pathway inhibitor (TFPI) is a serine-protease inhibitor, which modulates coagulation tissue factor-dependent (TF). It binds directly and inhibits the TF-FVII/FVIIa complex as well as FXa. Time to reperfusion of acute ischemic myocardium is essential for tissue salvage. However, reperfusion also results in a unique form of myocardial damage, such as contractile dysfunction, decreased coronary flow and altered vascular reactivity. Oxidants and reactive oxygen species (ROS) formation is increased in the post-ischemic heart and is responsible of post-ischemic injury. It has been reported that ROS promote a procoagulant state via TF expression while no data are available on the effect on TFPI. Endothelial cells were incubated with two different ROS generating systems, xanthine (X)/xanthine oxidase (XO) for 5 min, or H2O2 (500 ?M) for 24 h. TFPI activity was measured in supernatants by chromogenic assay and TFPI-mRNA analyzed by RT-PCR 2 h after ROS exposure. Unstimulated cells and cells exposed to either X or XO served as controls. Western blot and ligand dot blot was performed to evaluate ROS effect on TFPI structure and binding to FXa. ROS generated by X/XO as well as H2O2 system resulted in decreased TFPI activity compared to unstimulated cells while X or XO alone had no effect. No differences in TFPI mRNA levels versus controls was observed. A significant degradation of TFPI was induced by ROS exposure, resulting in a decreased ability to bind FXa. ROS induce a procoagulant state in endothelial cells by altering TFPI structure, resulting in inhibition of TFPI binding to Factor Xa and loss of activity. This phenomenon might have important consequences during reperfusion of post-ischemic myocardium. PMID:25712553

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

    PubMed Central

    Endres, Lauren; Dziergowska, Agnieszka; Ma?kiewicz, 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

  20. A Porous Tissue Engineering Scaffold Selectively Degraded by Cell-Generated Reactive Oxygen Species

    PubMed Central

    Martin, John R.; Gupta, Mukesh K.; Page, Jonathan M.; Yu, Fang; Davidson, Jeffrey M.; Guelcher, Scott A.

    2014-01-01

    Biodegradable tissue engineering scaffolds are commonly fabricated from poly(lactide-co-glycolide) (PLGA) or similar polyesters that degrade by hydrolysis. PLGA hydrolysis generates acidic breakdown products that trigger an accelerated, autocatalytic degradation mechanism that can create mismatched rates of biomaterial breakdown and tissue formation. Reactive oxygen species (ROS) are key mediators of cell function in both health and disease, especially at sites of inflammation and tissue healing, and induction of inflammation and ROS are natural components of the in vivo response to biomaterial implantation. Thus, polymeric biomaterials that are selectively degraded by cell-generated ROS may have potential for creating tissue engineering scaffolds with better matched rates of tissue in-growth and cell-mediated scaffold biodegradation. To explore this approach, a series of poly(thioketal) (PTK) urethane (PTK-UR) biomaterial scaffolds were synthesized that degrade specifically by an ROS-dependent mechanism. PTK-UR scaffolds had significantly higher compressive moduli than analogous poly(ester urethane) (PEUR) scaffolds formed from hydrolytically-degradable ester-based diols (p < 0.05). Unlike PEUR scaffolds, the PTK-UR scaffolds were stable under aqueous conditions out to 25 weeks but were selectively degraded by ROS, indicating that their biodegradation would be exclusively cell-mediated. The in vitro oxidative degradation rates of the PTK-URs followed first-order degradation kinetics, were significantly dependent on PTK composition (p < 0.05), and correlated to ROS concentration. In subcutaneous rat wounds, PTK-UR scaffolds supported cellular infiltration and granulation tissue formation, followed first-order degradation kinetics over 7 weeks, and produced significantly greater stenting of subcutaneous wounds compared to PEUR scaffolds. These combined results indicate that ROS-degradable PTK-UR tissue engineering scaffolds have significant advantages over analogous polyester-based biomaterials and provide a robust, cell-degradable substrate for guiding new tissue formation. PMID:24491510

  1. Role of Glycocalyx in Flow-Induced Production of Nitric Oxide and Reactive Oxygen Species

    PubMed Central

    Kumagai, Robert; Lu, Xiao; Kassab, Ghassan S.

    2009-01-01

    Although the glycocalyx has been implicated in wall shear stress (WSS) mechanotransduction, the role of glycocalyx components in nitric oxide (NO*) and reactive oxygen species (ROS) production remains unclear. Here, we tested the hypothesis that glycocalyx is implicated in both endothelial NO* and O2- production. Specifically, we evaluated the role of hyaluronic acid (HA), heparan sulfate (HS), and sialic acid (SA) in NO* and O2- mechanotransduction. Twenty-seven ex-vivo porcine superficial femoral arteries were incubated with either heparinase III, hyaluronidase, or neuraminidase, to remove HS, HA, or SA, respectively, from the glycocalyx. The arteries were then subjected to steady state flow and the effluent solution was measured for nitrites and the vessel diameter was tracked to quantify the degree of vasodilation. Our results show that removal of HA decreased both nitrites and vasodilation, and tempol treatment had no reversing effect. Degradation of HS proteoglycans decreased NO* bioavailability through an increase in O2- production as indicated by fluorescent signals of dihydroethidium (DHE) and its area fraction (209±24% increase) and also removed extracellular O2- dismutase (ecSOD) (67±9% decrease). The removal of SA also increased O2- production as indicated by DHE fluorescent signals (86±17% increase) and the addition of tempol, a mimic O2- scavenger, restored both NO* availability and vasodilation in both heparinase and neuraminidase treated vessels. This implies that HS and SA are not directly involved in WSS mediated NO* production. This study implicates HA in WSS-mediated NO* mechanotransduction and underscores the role of HS and SA in ROS regulation in vessel wall in response to WSS stimulation. PMID:19500664

  2. Activated intrarenal reactive oxygen species and renin angiotensin system in IgA nephropathy

    PubMed Central

    OHASHI, N.; URUSHIHARA, M.; KOBORI, H.

    2009-01-01

    Immunoglobulin A (IgA) nephropathy is recognized worldwide as the most common primary glomerulopathy. Although the mechanisms underlying the development of IgA nephropathy are gradually being clarified, their details remain unclear, and a radical cure for this condition has not yet been established. It has been clinically demonstrated that the immunoreactivities of intrarenal heme oxygenase-1 (HO-1) and 4-hydroxy-2-nonenal (4-HNE) — markers of reactive oxygen species (ROS) — and those of intrarenal angiotensinogen (AGT) and angiotensin II (Ang II) — markers of renin angiotensin system (RAS) — in IgA nephropathy patients were significantly increased as compared to those of control subjects. In an animal study, high IgA of ddY (HIGA) mice were used as an IgA nephropathy model and compared with BALB/c mice, which served as the control. The levels of markers for ROS (urinary 8-isoprostane and intrarenal 4-HNE), RAS (intrarenal AGT and Ang II), and renal damage in the HIGA mice were significantly increased as compared to those in the BALB/c mice. Moreover, an interventional study using HIGA mice demonstrated that the expressions of 2 lines of intrarenal ROS markers (4-HNE and HO-1), 2 lines of intrarenal RAS markers (AGT and Ang II) and renal damage decreased significantly in HIGA mice receiving treatment with the Ang II receptor blocker olmesartan but not in HIGA mice receiving treatment with RAS-independent antihypertensive drugs (hydralazine, reserpine, and hydrochlorothiazide) when compared with HIGA mice that were not treated. These data suggest that intrarenal ROS and RAS activation plays a pivotal role in the development of IgA nephropathy. PMID:19417726

  3. 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

  4. Vanadium compounds discriminate hepatoma and normal hepatic cells by differential regulation of reactive oxygen species.

    PubMed

    Wang, Qin; Liu, Tong-Tong; Fu, Ying; Wang, Kui; Yang, Xiao-Gai

    2010-09-01

    Our previous study indicated that vanadium compounds can block cell cycle progression at the G1/S phase in human hepatoma HepG2 cells via a highly activated extracellular signal-regulated protein kinase (ERK) signal. To explore their differential action on normal cells, we investigated the response of an immortalized hepatic cell line, L02 cells. The results demonstrated that a higher concentration of vanadium compounds was needed to inhibit L02 proliferation, which was associated with S and G2/M cell cycle arrest. In addition, in contrast to insignificant reactive oxygen species (ROS) generation in HepG2 cells, all of the vanadium compounds resulted significant increases in both O2.- and H2O2 levels in L02 cells. At the same time, ERK and c-Jun N-terminal kinase (JNK) as well as cell division control protein 2 homolog (Cdc2) were found to be highly phosphorylated, which could be counteracted with the antioxidant N-acetylcysteine (NAC). The current study also demonstrated that both the ERK and the JNK pathways contributed to the cell cycle arrest induced by vanadium compounds in L02 cells. More importantly, it was found that although NAC can ameliorate the cytotoxicity of vanadium compounds in L02 cells, it did not decrease their cytotoxicity in HepG2 cells. It thus shed light on the potential therapeutic applications of vanadium compounds with antioxidants as synergistic agents to reduce their toxicities in human normal cells without affecting their antitumor activities in cancer cells. PMID:20443032

  5. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages

    SciTech Connect

    O'Toole, Timothy E. [Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, KY 40202 (United States)], E-mail: teotoo01@gwise.louisville.edu; Zheng Yuting; Hellmann, Jason; Conklin, Daniel J.; Barski, Oleg; Bhatnagar, Aruni [Institute of Molecular Cardiology, Department of Medicine, University of Louisville, Louisville, KY 40202 (United States)

    2009-04-15

    Acrolein is a ubiquitous component of environmental pollutants such as automobile exhaust, cigarette, wood, and coal smoke. It is also a natural constituent of several foods and is generated endogenously during inflammation or oxidation of unsaturated lipids. Because increased inflammation and episodic exposure to acrolein-rich pollutants such as traffic emissions or cigarette smoke have been linked to acute myocardial infarction, we examined the effects of acrolein on matrix metalloproteinases (MMPs), which destabilize atherosclerotic plaques. Our studies show that exposure to acrolein resulted in the secretion of MMP-9 from differentiated THP-1 macrophages. Acrolein-treatment of macrophages also led to an increase in reactive oxygen species (ROS), free intracellular calcium ([Ca{sup 2+}]{sub i}), and xanthine oxidase (XO) activity. ROS production was prevented by allopurinol, but not by rotenone or apocynin and by buffering changes in [Ca{sup 2+}]{sub I} with BAPTA-AM. The increase in MMP production was abolished by pre-treatment with the antioxidants Tiron and N-acetyl cysteine (NAC) or with the xanthine oxidase inhibitors allopurinol or oxypurinol. Finally, MMP activity was significantly stimulated in aortic sections from apoE-null mice containing advanced atherosclerotic lesions after exposure to acrolein ex vivo. These observations suggest that acrolein exposure results in MMP secretion from macrophages via a mechanism that involves an increase in [Ca{sup 2+}]{sub I}, leading to xanthine oxidase activation and an increase in ROS production. ROS-dependent activation of MMPs by acrolein could destabilize atherosclerotic lesions during brief episodes of inflammation or pollutant exposure.

  6. Reactive oxygen species produced by NAD(P)H oxidase inhibit apoptosis in pancreatic cancer cells.

    PubMed

    Vaquero, Eva C; Edderkaoui, Mouad; Pandol, Stephen J; Gukovsky, Ilya; Gukovskaya, Anna S

    2004-08-13

    One reason why pancreatic cancer is so aggressive and unresponsive to treatments is its resistance to apoptosis. We report here that reactive oxygen species (ROS) are a prosurvival, antiapoptotic factor in pancreatic cancer cells. Human pancreatic adenocarcinoma MIA PaCa-2 and PANC-1 cells generated ROS, which was stimulated by growth factors (serum, insulin-like growth factor I, or fibroblast growth factor-2). Growth factors also stimulated membrane NAD(P)H oxidase activity in these cells. Both intracellular ROS and NAD(P)H oxidase activity were inhibited by antioxidants tiron and N-acetylcysteine and the inhibitor of flavoprotein-dependent oxidases, diphenylene iodonium, but not by inhibitors of various other ROS-generating enzymes. Using Rho(0) cells deficient in mitochondrial DNA, we showed that a nonmitochondrial NAD(P)H oxidase is a major source of growth factor-induced ROS in pancreatic cancer cells. Among proteins that have been implicated in NAD(P)H oxidase activity, MIA PaCa-2 and PANC-1 cells do not express the phagocytic gp91(phox) subunit but express several nonphagocytic oxidase (NOX) isoforms. Transfection with Nox4 antisense oligonucleotide inhibited NAD(P)H oxidase activity and ROS production in MIA PaCa-2 and PANC-1 cells. Inhibiting ROS with the antioxidants, Nox4 antisense, or MnSOD overexpression all stimulated apoptosis in pancreatic cancer cells as measured by internucleosomal DNA fragmentation, phosphatidylserine externalization, cytochrome c release, and effector caspase activation. The results show that growth factor-induced ROS produced by NAD(P)H oxidase (probably Nox4) protect pancreatic cancer cells from apoptosis. This mechanism may play an important role in pancreatic cancer resistance to treatment and thus represent a novel therapeutic target. PMID:15155719

  7. Norepinephrine Reduces Reactive Oxygen Species (ROS) and DNA Damage in Ovarian Surface Epithelial Cells

    PubMed Central

    Patel, Pooja R; Hegde, Muralidhar L; Theruvathu, Jacob; Mitra, Sankar A; Boldogh, Istvan; Sowers, Lawrence

    2015-01-01

    Objective To determine the role of norepinephrine (NE) on DNA damage and reactive oxygen species (ROS) generation in ovarian surface epithelial cells. Method Non-tumorigenic, immortalized ovarian surface epithelial cells were treated with NE, bleomycin, and bleomycin followed by NE. The comet assay was performed on each treatment group to determine the amount of single and double-strand breaks induced by treatments. ROS levels for each treatment group were measured using the H2DCF-DA fluorescence assay. Finally, RNA transcripts were measured for each treatment group with regards to the expression of DNA repair and oxidative stress genes. Results The mean tail moment of untreated cells was significantly greater than that of cells treated with NE (p=0.02). The mean tail moment of cells treated with bleomycin was significantly greater than that of cells treated with bleomycin followed by NE (p<0.01). Treatment with NE resulted in significantly less ROS generation than in untreated cells (p<0.01). NE treatment after hydrogen peroxide treatment resulted in a noticeable decrease in ROS generation. Genes associated with oxidative stress were upregulated in cells treated with bleomycin, however this upregulation was blunted when bleomycin-treated cells were treated subsequently with NE. Conclusion NE is associated with decreased DNA damage and ROS production in ovarian surface epithelial cells. This effect is protective in the presence of the oxidative-damaging agent bleomycin. These results suggest an additional physiologic role for the stress hormone NE, in protecting ovarian surface epithelial cells from oxidative stress. PMID:26167254

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

    PubMed

    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

    2015-01-01

    Reactive oxygen species (ROS) can have divergent effects in cerebral and peripheral circulations. We found that Ca(2+)-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 Ca(2+) signals representing Ca(2+) 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. Ca(2+) entry during a single TRPA1 sparklet was twice that of a TRPV4 sparklet and ~200 times that of an L-type Ca(2+) 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, Ca(2+)-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 Ca(2+) influx through TRPA1 channels in the endothelium of cerebral arteries to cause dilation. PMID:25564678

  9. Effects of reactive oxygen species and neutrophils on endothelium-dependent relaxation of rat thoracic aorta.

    PubMed

    Bauer, Viktor; Sotníková, Ružena; Drábiková, Katarína

    2011-12-01

    Reactive oxygen species (ROS) are produced in different metabolic processes including the respiratory burst of neutrophils accompanying local inflammation. The aim of this study was to analyze the effects of N-formyl-methionyl-leucyl-phenylalanine (FMLP)-activated neutrophils, isolated from the guinea pig peritoneal cavity, on isolated rings of a large (conduit) artery, the rat thoracic aorta. FMLP-activated neutrophils enhanced the basal tension increased by ?(1)-adrenergic stimulation. In phenylephrine-precontracted aortae, they elicited marked contraction, while in noradrenaline-precontracted rat aortal rings they caused a biphasic response (contraction-relaxation). To eliminate interaction of activated neutrophils with catecholamines, in the subsequent experiments the basal tension was increased by KCl-induced depolarization. Activated neutrophils evoked a low-amplitude biphasic response (relaxation-contraction) on the KCl-induced contraction. Not only the acetylcholine- and A(23187)-induced relaxations but also the catalase sensitive hydrogen peroxide (H(2)O(2)) elicited contractions were endothelium-dependent. Even though the acetylcholine-induced relaxation was changed by activated neutrophils and by the ROS studied, their effects differed significantly, yet none of them did eliminate fully the endothelium-dependent acetylcholine relaxation. The effect of activated neutrophils resembled the effect of superoxide anion radical (O(2) (•-)) produced by xanthine/xanthine oxidase (X/XO) and differed from the inhibitory effects of Fe(2)SO(4)/H(2)O(2)-produced hydroxyl radical ((•)OH) and H(2)O(2). Thus O(2) (•-) produced either by activated neutrophils or X/XO affected much less the endothelium-dependent acetylcholine-activated relaxation mechanisms than did (•)OH and H(2)O(2). In the large (conduit) artery, the effects of activated neutrophils and various ROS (O(2) (•-), (•)OH and H(2)O(2)) seem to be more dependent on muscle tension than on endothelial mechanisms. PMID:22319253

  10. Measurement of reactive oxygen species in the culture media using Acridan Lumigen PS-3 assay.

    PubMed

    Uy, Benedict; McGlashan, Susan R; Shaikh, Shamim B

    2011-09-01

    Reactive oxygen species (ROS) are generated continuously during aerobic metabolism. ROS are highly reactive molecules and in excessive amounts, can lead to protein and DNA oxidation, protein cross-linking, and cell death. Cell-culture models provide a valuable tool in understanding the mechanisms that lead to cell death. Accumulation of ROS within cells and/or their release into the culture media are highly cell type-specific. The ability to estimate ROS levels in the culture media is an important step in understanding the mechanisms contributing to disease processes. In this paper, we describe the optimization of a simple method to estimate ROS levels in the culture media using the Acridan Lumigen PS-3 reagent provided in the Amersham ECL Plus kit (GE Healthcare, UK). We have shown that the Acridan Lumigen PS-3 assay generates ROS-specific chemiluminescence in fresh as well as media stored at -20°C, in as little as 10-20 ?l of samples. The method was able to detect the dose (of stimulants)- and time (acute and chronic)-dependent changes in ROS levels in media collected from various cell types. Our results suggest that the kit reagents, PBS buffer, and various media did not contribute significantly to the overall chemiluminescence generated in the assay; however, we suggest that the unused medium specific for each cell type should be used as blanks and final readings of test samples normalized against these readings. As this method uses commonly available laboratory equipment and commercially available reagents, we believe this assay is convenient, economical, and specific in estimating ROS released extracellularly into the culture media. PMID:21966257

  11. Naturally and stimulated levels of reactive oxygen species in cooled stallion semen destined for artificial insemination.

    PubMed

    Johannisson, A; Lundgren, A; Humblot, P; Morrell, J M

    2014-10-01

    The decrease in foaling rates after artificial insemination with cooled semen warrants the search for new predictors of fertility. The objectives were to investigate levels of naturally occurring reactive oxygen species (ROS) in cooled, stored stallion semen doses for artificial insemination (AI), and their relationship with parameters of semen quality and with pregnancy rate. Semen was collected from warmblood stallions (n=15) and used to prepare commercial semen doses for AI. Sperm quality was evaluated after cooled transport to the laboratory overnight. The results were correlated with observed foaling and pregnancy rates. Hydroethidine and dichlorodihydrofluorescein diacetate were used as indicators for the ROS superoxide and hydrogen peroxide, respectively. Sperm morphology, motility, plasma membrane integrity and chromatin integrity were also evaluated. These variables were correlated with each other and with pregnancy rates. We found a high inter-individual variation in the ROS levels between stallions. The proportion of live, hydrogen peroxide-negative spermatozoa was correlated with progressive motility, whereas live hydrogen peroxide-negative spermatozoa and chromatin damage were negatively correlated, indicating that low levels of hydrogen peroxide were correlated with good chromatin integrity. The percentage of dead hydrogen peroxide-positive sperm was negatively related to the foaling rate. The negative relationships were stronger when combining results from both assays for ROS. These results for stored semen samples indicate that high individual variation exists for superoxide and hydrogen peroxide measurements, and that ROS status can influence sperm quality. Thus, ROS may be some of the factors influencing fertility. Moreover, combinations of ROS variables improved the correlation with fertility, indicating the usefulness of including these variables in a future model for prediction of the fertility of a semen sample. PMID:24916995

  12. Reactive oxygen species in stallion semen can be affected by season and colloid centrifugation.

    PubMed

    Morrell, J M; Winblad, C; Georgakas, A; Stuhtmann, G; Humblot, P; Johannisson, A

    2013-07-01

    There are anecdotal reports that equine fertility may decline towards the end of the breeding season. Previous studies have examined differences in sperm quality between the breeding season and non-breeding season but few studies have investigated the proportions of superoxide or peroxide containing spermatozoa at different times during the breeding season. The purpose of this study was to measure the content of these reactive oxygen species (ROS) at the beginning and end of the Swedish breeding season, using flow cytometric analysis of the fluorescence produced after staining with hydroethidium and dichlorodihydrofluorescein diacetate. In addition, the effects of a new method of selecting good quality spermatozoa by colloid centrifugation, known as Single Layer Centrifugation (SLC), on ROS-content were investigated. Superoxide production by stallion spermatozoa was found to be higher at the start than at the end of the breeding season in Sweden (22±16% versus 9±6%, P<0.05), whereas sperm motility was lower (total motility 80±9% versus 90±6%, P<0.01; progressive motility 55±12% versus 60±8%, P<0.05, at the beginning and end of the breeding season respectively). The mean values of the other parameters of sperm quality measured did not differ with time within the breeding season although differences did occur for individual stallions. SLC was found to select motile spermatozoa that contained less superoxide (16±14% versus 23±18%, P<0.01) and less peroxide (0.3±0.8 versus 1±2%, P<0.01) than uncentrifuged controls, although they were capable of producing ROS when stimulated with menadione. This reduced peroxide production may contribute to the enhanced sperm survival (retention of motility) seen in the SLC samples during storage. PMID:23778304

  13. Impact of hypothalamic reactive oxygen species in the regulation of energy metabolism and food intake

    PubMed Central

    Drougard, Anne; Fournel, Audren; Valet, Philippe; Knauf, Claude

    2015-01-01

    Hypothalamus is a key area involved in the control of metabolism and food intake via the integrations of numerous signals (hormones, neurotransmitters, metabolites) from various origins. These factors modify hypothalamic neurons activity and generate adequate molecular and behavioral responses to control energy balance. In this complex integrative system, a new concept has been developed in recent years, that includes reactive oxygen species (ROS) as a critical player in energy balance. ROS are known to act in many signaling pathways in different peripheral organs, but also in hypothalamus where they regulate food intake and metabolism by acting on different types of neurons, including proopiomelanocortin (POMC) and agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons. Hypothalamic ROS release is under the influence of different factors such as pancreatic and gut hormones, adipokines (leptin, apelin,…), neurotransmitters and nutrients (glucose, lipids,…). The sources of ROS production are multiple including NADPH oxidase, but also the mitochondria which is considered as the main ROS producer in the brain. ROS are considered as signaling molecules, but conversely impairment of this neuronal signaling ROS pathway contributes to alterations of autonomic nervous system and neuroendocrine function, leading to metabolic diseases such as obesity and type 2 diabetes. In this review we focus our attention on factors that are able to modulate hypothalamic ROS release in order to control food intake and energy metabolism, and whose deregulations could participate to the development of pathological conditions. This novel insight reveals an original mechanism in the hypothalamus that controls energy balance and identify hypothalamic ROS signaling as a potential therapeutic strategy to treat metabolic disorders. PMID:25759638

  14. IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway

    SciTech Connect

    Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori; Iguchi, Genzo; Nishizawa, Hitoshi; Yamamoto, Masaaki; Suda, Kentaro [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)] [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Takahashi, Yutaka, E-mail: takahash@med.kobe-u.ac.jp [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)] [Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Cellular senescence plays an important role in tumorigenesis and aging process. Black-Right-Pointing-Pointer We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. Black-Right-Pointing-Pointer IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. Black-Right-Pointing-Pointer These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated {beta}-galactosidase (SA-{beta}-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the present study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, {gamma}H2AX, the increased levels of p53 and p21 proteins, and activated SA-{beta}-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-{beta}-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.

  15. A High Precision Method for Quantitative Measurements of Reactive Oxygen Species in Frozen Biopsies

    PubMed Central

    Lindgren, Mikael; Gustafsson, Håkan

    2014-01-01

    Objective An electron paramagnetic resonance (EPR) technique using the spin probe cyclic hydroxylamine 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH) was introduced as a versatile method for high precision quantification of reactive oxygen species, including the superoxide radical in frozen biological samples such as cell suspensions, blood or biopsies. Materials and Methods Loss of measurement precision and accuracy due to variations in sample size and shape were minimized by assembling the sample in a well-defined volume. Measurement was carried out at low temperature (150 K) using a nitrogen flow Dewar. The signal intensity was measured from the EPR 1st derivative amplitude, and related to a sample, 3-carboxy-proxyl (CP•) with known spin concentration. Results The absolute spin concentration could be quantified with a precision and accuracy better than ±10 µM (k?=?1). The spin concentration of samples stored at ?80°C could be reproduced after 6 months of storage well within the same error estimate. Conclusion The absolute spin concentration in wet biological samples such as biopsies, water solutions and cell cultures could be quantified with higher precision and accuracy than normally achievable using common techniques such as flat cells, tissue cells and various capillary tubes. In addition; biological samples could be collected and stored for future incubation with spin probe, and also further stored up to at least six months before EPR analysis, without loss of signal intensity. This opens for the possibility to store and transport incubated biological samples with known accuracy of the spin concentration over time. PMID:24603936

  16. Benzene's metabolites alter c-MYB activity via reactive oxygen species in HD3 cells

    SciTech Connect

    Wan, Joanne [Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario (Canada); Winn, Louise M. [Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario (Canada) and School of Environmental Studies, Queen's University, Kingston, Ontario (Canada)]. E-mail: winnl@queensu.ca

    2007-07-15

    Benzene is a known leukemogen that is metabolized to form reactive intermediates and reactive oxygen species (ROS). The c-Myb oncoprotein is a transcription factor that has a critical role in hematopoiesis. c-Myb transcript and protein have been overexpressed in a number of leukemias and cancers. Given c-Myb's role in hematopoiesis and leukemias, it is hypothesized that benzene interferes with the c-Myb signaling pathway and that this involves ROS. To investigate our hypothesis, we evaluated whether benzene, 1,4-benzoquinone, hydroquinone, phenol, and catechol generated ROS in chicken erythroblast HD3 cells, as measured by 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (DCFDA) and dihydrorhodamine-123 (DHR-123), and whether the addition of 100 U/ml of the antioxidating enzyme superoxide dismutase (SOD) could prevent ROS generation. Reduced to oxidized glutathione ratios (GSH:GSSG) were also assessed as well as hydroquinone and benzoquinone's effects on c-Myb protein levels and activation of a transiently transfected reporter construct. Finally we attempted to abrogate benzene metabolite mediated increases in c-Myb activity with the use of SOD. We found that benzoquinone, hydroquinone, and catechol increased DCFDA fluorescence, increased DHR-123 fluorescence, decreased GSH:GSSG ratios, and increased reporter construct expression after 24 h of exposure. SOD was able to prevent DCFDA fluorescence and c-Myb activity caused by benzoquinone and hydroquinone only. These results are consistent with other studies, which suggest metabolite differences in benzene-mediated toxicity. More importantly, this study supports the hypothesis that benzene may mediate its toxicity through ROS-mediated alterations in the c-Myb signaling pathway.

  17. Generation and function of reactive oxygen species in dendritic cells during antigen presentation.

    PubMed

    Matsue, Hiroyuki; Edelbaum, Dale; Shalhevet, David; Mizumoto, Norikatsu; Yang, Chendong; Mummert, Mark E; Oeda, Junichi; Masayasu, Hiroyuki; Takashima, Akira

    2003-09-15

    Although reactive oxygen species (ROS) have long been considered to play pathogenic roles in various disorders, this classic view is now being challenged by the recent discovery of their physiological roles in cellular signaling. To determine the immunological consequence of pharmacological disruption of endogenous redox regulation, we used a selenium-containing antioxidant compound ebselen known to modulate both thioredoxin and glutaredoxin pathways. Ebselen at 5-20 micro M inhibited Con A-induced proliferation and cytokine production by the HDK-1 T cell line as well as the LPS-triggered cytokine production by XS52 dendritic cell (DC) line. Working with the in vitro-reconstituted Ag presentation system composed of bone marrow-derived DC, CD4(+) T cells purified from DO11.10 TCR-transgenic mice and OVA peptide (serving as Ag), we observed that 1) both T cells and DC elevate intracellular oxidation states upon Ag-specific interaction; 2) ebselen significantly inhibits ROS production in both populations; and 3) ebselen at 5-20 micro M inhibits DC-induced proliferation and cytokine production by T cells as well as T cell-induced cytokine production by DC. Thus, Ag-specific, bidirectional DC-T cell communication can be blocked by interfering with the redox regulation pathways. Allergic contact hypersensitivity responses in BALB/c mice to oxazolone, but not irritant contact hypersensitivity responses to croton oil, were suppressed significantly by postchallenge treatment with oral administrations of ebselen (100 mg/kg per day). These results provide both conceptual and technical frameworks for studying ROS-dependent regulation of DC-T cell communication during Ag presentation and for testing the potential utility of antioxidants for the treatment of immunological disease. PMID:12960326

  18. Reactive oxygen species and x-ray disrupted spontaneous [Ca²?]I oscillation in alveolar macrophages.

    PubMed

    Chen, Hao; Ye, Hong; Meng, Da-Quan; Cai, Peng-Cheng; Chen, Feng; Zhu, Li-Ping; Tang, Qiu; Long, Zhi-Xiong; Zhou, Qiong; Jin, Yang; Xin, Jian-Bao; Tao, Xiao-Nan; Ma, Wan-Li

    2013-04-01

    Radiation leads to a rapid burst of reactive oxygen species (ROS), which is considered to be one of the major causes of radiation-induced injury. ROS have previously been shown to induce changes in cytosolic Ca²? ([Ca²?]i) including [Ca²?]i oscillation. However, the role of radiation in [Ca²?]i oscillation is poorly understood. The purpose of this study was to identify the effect of ROS and X ray on [Ca²?]i oscillation, as well as their role in radiation-induced lung injury. Alveolar macrophages were cultured in the absence and presence of different doses of hydrogen peroxide (H?O?) or exposed to X-ray irradiation with or without pretreatment of diphenyleneiodonium chloride (DPI, an inhibitor of NADPH oxidases) or tetrandrine (TET, a calcium entry blocker) and cytosolic Ca²? concentration was detected by fluorescent Ca²? indicator Fura-2. Rat radiation lung injury was induced in vivo by using 40 Gy X ray and DPI or TET was used to prevent radiation-induced lung injury. The results showed that there was spontaneous [Ca²?]i oscillation in alveolar macrophages under normal conditions, and treatment of H?O? (100-500 ?M) or 2 Gy X ray inhibited the spontaneous [Ca²?]i oscillation and induced [Ca²?]i rise. TET abolished H?O? or X ray induced [Ca²?]i rise in alveolar macrophages, and attenuated X ray- induced rat alveolitis in vivo. DPI prevented X-ray-induced inhibition of [Ca²?]i oscillation in alveolar macrophages and prevented X-ray-induced rat alveolitis. Taken together, the data suggest that the disruption of [Ca²?]i oscillation and induction of [Ca²?]i rise through ROS is involved in the mechanism of radiation-induced lung injury. PMID:23421826

  19. Mice producing less reactive oxygen species are relatively resistant to collagen glycopeptide vaccination against arthritis.

    PubMed

    Batsalova, Tsvetelina; Dzhambazov, Balik; Klaczkowska, Dorota; Holmdahl, Rikard

    2010-09-01

    The bottleneck for the induction of collagen-induced arthritis in mice is the recognition of immunodominant type II collagen (CII) peptide (CII259-273) bound to the MHC class II molecule A(q). We have shown previously that the posttranslationally glycosylated lysine at position 264 in this epitope is of great importance for T cell recognition and tolerance induction to CII as well as for arthritis development. The Ncf1 gene, controlling oxidative burst, has been shown to play an important role for immune tolerance to CII. To investigate the effect of oxidation on the efficiency of immune-specific vaccination with MHC class II/glycosylated-CII peptide complexes, we used Ncf1 mutated mice. We demonstrate that normal reactive oxygen species (ROS) levels contribute to the establishment of tolerance and arthritis protection, because only mice with a functional oxidative burst were completely protected from arthritis after administration of the glycosylated CII259-273 peptide in complex with MHC class II. Transfer of T cells from vaccinated mice with functional Ncf1 protein resulted in strong suppression of clinical signs of arthritis in B10.Q mice, whereas the Ncf1 mutated mice as recipients had a weaker suppressive effect, suggesting that ROS modified the secondary rather than the primary immune response. A milder but still significant effect was also observed in ROS deficient mice. During the primary vaccination response, regulatory T cells, upregulation of negative costimulatory molecules, and increased production of anti-inflammatory versus proinflammatory cytokines in both Ncf1 mutated and wild type B10.Q mice was observed, which could explain the vaccination effect independent of ROS. PMID:20686129

  20. The phytoalexin camalexin mediates cytotoxicity towards aggressive prostate cancer cells via reactive oxygen species

    PubMed Central

    Smith, Basil A.; Neal, Corey L.; Chetram, Mahandranauth; Vo, BaoHan; Mezencev, Roman; Hinton, Cimona

    2013-01-01

    Camalexin is a phytoalexin that accumulates in various cruciferous plants upon exposure to environmental stress and plant pathogens. Besides moderate antibacterial and antifungal activity, camalexin was reported to also exhibit antiproliferative and cancer chemopreventive effects in breast cancer and leukemia. We studied the cytotoxic effects of camalexin treatment on prostate cancer cell lines and whether this was mediated by reactive oxygen species (ROS) generation. As models, we utilized LNCaP and its aggressive subline, C4-2, as well as ARCaP cells stably transfected with empty vector (Neo) control or constitutively active Snail cDNA that represents an epithelial to mesenchymal transition (EMT) model and displays increased cell migration and tumorigenicity. We confirmed previous studies showing that C4-2 and ARCaP-Snail cells express more ROS than LNCaP and ARCaP-Neo, respectively. Camalexin increased ROS, decreased cell proliferation, and increased apoptosis more significantly in C4-2 and ARCaP-Snail cells as compared to LNCaP and ARCaP-Neo cells, respectively, while normal prostate epithelial cells (PrEC) were unaffected. Increased caspase-3/7 activity and increased cleaved PARP protein shown by Western blot analysis was suggestive of increased apoptosis. The ROS scavenger N-acetyl cysteine (NAC) antagonized the effects of camalexin, whereas the addition of exogenous hydrogen peroxide potentiated the effects of camalexin, showing that camalexin is mediating its effects through ROS. In conclusion, camalexin is more potent in aggressive prostate cancer cells that express high ROS levels, and this phytoalexin has a strong potential as a novel therapeutic agent for the treatment of especially metastatic prostate cancer. PMID:23179315

  1. Involvement of selective reactive oxygen species upstream of proapoptotic branches of unfolded protein response.

    PubMed

    Yokouchi, Makiko; Hiramatsu, Nobuhiko; Hayakawa, Kunihiro; Okamura, Maro; Du, Shuqi; Kasai, Ayumi; Takano, Yosuke; Shitamura, Akihiro; Shimada, Tsuyoshi; Yao, Jian; Kitamura, Masanori

    2008-02-15

    Cadmium triggers apoptosis of LLC-PK1 cells through induction of endoplasmic reticulum (ER) stress. We found that cadmium caused generation of reactive oxygen species (ROS) and that cadmium-induced ER stress was inhibited by antioxidants. In contrast, suppression of ER stress did not attenuate cadmium-triggered oxidative stress, suggesting that ER stress occurs downstream of oxidative stress. Exposure of the cells to either O(2)(*), H(2)O(2), or ONOO(-) caused apoptosis, whereas ER stress was induced only by O(2)(*) or ONOO(-). Transfection with manganese superoxide dismutase significantly attenuated cadmium-induced ER stress and apoptosis, whereas pharmacological inhibition of ONOO(-) was ineffective. Interestingly, transfection with catalase attenuated cadmium-induced apoptosis without affecting the level of ER stress. O(2)(*) caused activation of the activating transcription factor 6-CCAAT/enhancer-binding protein-homologous protein (CHOP) and the inositol-requiring ER-to-nucleus signal kinase 1-X-box-binding protein 1 (XBP1) proapoptotic cascades, and overexpression of manganese superoxide dismutase attenuated cadmium-triggered induction of both pathways. Furthermore, phosphorylation of proapoptotic c-Jun N-terminal kinase by O(2)(*) or cadmium was suppressed by dominant-negative inhibition of XBP1. These data elucidated 1) cadmium caused ER stress via generation of ROS, 2) O(2)(*) was selectively involved in cadmium-triggered, ER stress-mediated apoptosis through activation of the activating transcription factor 6-CHOP and inositol-requiring ER-to-nucleus signal kinase 1-XBP1 pathways, and 3) phosphorylation of JNK was caused by O(2)(*)-triggered activation of XBP1. PMID:18086661

  2. Measurements of UV-generated free radicals/reactive oxygen species (ROS) in skin

    NASA Astrophysics Data System (ADS)

    Herrling, Th.; Jung, K.; Fuchs, J.

    2006-03-01

    Free radicals/reactive oxygen species (ROS) generated in skin by UV irradiation were measured by electron spin resonance (ESR). To increase the sensitivity of measurement the short life free radicals/ROS were scavenged and accumulated by using the nitroxyl probe 3-carboxy-2,2,5,5-tetrametylpyrrolidine-1-oxyl (PCA). The spatial distribution of free radicals/ROS measured in pig skin biopsies with ESR imaging after UV irradiation corresponds to the intensity decay of irradiance in the depth of the skin. The main part of free radicals/ROS were generated by UVA (320-400 nm) so that the spatial distribution of free radicals reaches up to the lower side of the dermis. In vivo measurements on human skin were performed with a L-band ESR spectrometer and a surface coil integrating the signal intensities from all skin layers to get a sufficient signal amplitude. Using this experimental arrangement the protection of UVB and UVA/B filter against the generation of free radicals/ROS in skin were measured. The protection against ROS and the repair of damages caused by them can be realized with active antioxidants characterized by a high antioxidative power (AP). The effect of UV filter and antioxidants corresponding to their protection against free radicals/ROS in skin generated by UVAB irradiation can be quantified by the new radical sun protection factor (RSF). The RSF indicates the increase of time for staying in the sun to generate the same number of free radicals/ROS in the skin like for the unprotected skin. Regarding the amount of generated free radicals/ROS in skin as an biophysical endpoint the RSF characterizes both the protection against UVB and UVA radiation.

  3. Angiotensin-II-induced reactive oxygen species along the SFO-PVN-RVLM pathway: implications in neurogenic hypertension.

    PubMed

    Braga, V A; Medeiros, I A; Ribeiro, T P; França-Silva, M S; Botelho-Ono, M S; Guimarães, D D

    2011-09-01

    Neurogenic hypertension has been the subject of extensive research worldwide. This review is based on the premise that some forms of neurogenic hypertension are caused in part by the formation of angiotensin-II (Ang-II)-induced reactive oxygen species along the subfornical organ-paraventricular nucleus of the hypothalamus-rostral ventrolateral medulla pathway (SFO-PVN-RVLM pathway). We will discuss the recent contribution of our laboratory and others regarding the mechanisms by which neurons in the SFO (an important circumventricular organ) are activated by Ang-II, how the SFO communicates with two other important areas involved in sympathetic activity regulation (PVN and RVLM) and how Ang-II-induced reactive oxygen species participate along the SFO-PVN-RVLM pathway in the pathogenesis of neurogenic hypertension. PMID:21755262

  4. Effect of Electron-Transport Inhibitors on the Generation of Reactive Oxygen Species by Pea Mitochondria during Succinate Oxidation

    Microsoft Academic Search

    V. N. Popov; E. K. Ruuge; A. A. Starkov

    2003-01-01

    The effect of inhibitors of the cytochrome pathway and alternative oxidase on the rate of respiration and generation of reactive oxygen species by pea mitochondria was studied. Respiration of mitochondria from pea cotyledons was inhibited by 70-80% by salicylhydroxamate (SHAM). The rate of hydrogen peroxide production by pea cotyledon mitochondria during succinate oxidation was 0.15 nmol\\/min per mg protein. SHAM

  5. Resveratrol inhibits foam cell formation via NADPH oxidase 1-mediated reactive oxygen species and monocyte chemotactic protein-1

    Microsoft Academic Search

    Dae-Weon Park; Kheewoong Baek; Jae-Ryong Kim; Jae-Jin Lee; Sang-Ho Ryu; Byung-Rho Chin; Suk-Hwan Baek

    2009-01-01

    Resveratrol is a polyphenolic compound in red wine that has anti-oxidant and cardioprotective effects in animal models. Reactive oxygen species (ROS) and monocyte chemotactic protein-1 (MCP-1) play key roles in foam cell formation and atherosclerosis. We studied LPS-mediated foam cell formation and the ef- fect of resveratrol. Resveratrol pretreatment strongly suppressed LPS-induced foam cell formation. To de- termine if resveratrol

  6. Hyperosmotic stress-dependent NF?B activation is regulated by reactive oxygen species and IGF-1 in cultured cardiomyocytes

    Microsoft Academic Search

    Verónica Eisner; Alfredo Criollo; Clara Quiroga; Claudio Olea-Azar; Juan Francisco Santibañez; Rodrigo Troncoso; Mario Chiong; Guillermo Díaz-Araya; Rocío Foncea; Sergio Lavandero

    2006-01-01

    We have recently shown that hyperosmotic stress activates p65\\/RelB NF?B in cultured cardiomyocytes with dichotomic actions on caspase activation and cell death. It remains unexplored how NF?B is regulated in cultured rat cardiomyocytes exposed to hyperosmotic stress. We study here: (a) if hyperosmotic stress triggers reactive oxygen species (ROS) generation and in turn whether they regulate NF?B and (b) if

  7. The Effects of Lipopolysaccharide-Induced Reactive Oxygen Species Were Blunted by Calcium Oxalate in Renal Tubular Epithelial Cells

    Microsoft Academic Search

    F. T. Borges; A. S. Garofalo; M. A. Dalboni; N. P. Abreu; Y. M. Michelacci; N. Schor

    2008-01-01

    Background\\/Aim: Previously we demonstrated that calcium oxalate (CaOx) in LLC-PK1 cells and oxalate in MDCK cells induce tubular damage and greater glycosaminoglycan synthesis. We test the hypothesis that reactive oxygen species (ROS) and prostaglandins mediate these effects. Methods: LLC-PK1 and MDCK cells were exposed to graded concentrations of CaOx, oxalate or both. Glycosaminoglycan synthesis was analyzed through metabolic labeling and

  8. Sex as a response to oxidative stress: a twofold increase in cellular reactive oxygen species activates sex genes

    Microsoft Academic Search

    Aurora M. Nedelcu; Oana Marcu; Richard E. Michod

    2004-01-01

    Organisms are constantly subjected to factors that can alter the cellular redox balance and result in the formation of a series of highly reactive molecules known as reactive oxygen species (ROS). As ROS can be damaging to biological structures, cells evolved a series of mechanisms (e.g. cell-cycle arrest, pro- grammed cell death) to respond to high levels of ROS (i.e.

  9. Purification, crystallization and preliminary X-ray diffraction studies on goat (Capra hircus) hemoglobin - a low oxygen affinity species.

    PubMed

    Moorthy, Ponnuraj Sathya; Neelagandan, Kamariah; Balasubramanian, Moovarkumudalvan; Ponnuswamy, Mondikalipudur Nanjappa Gounder

    2009-01-01

    Hemoglobin is a vital protein present in almost all higher species. It is a transport protein involved in carrying oxygen from lungs to tissues and carbon dioxide back to lungs by an intrinsically coordinated manner. Even though a good amount of work has been carried out in this direction there exists scarcity of structural insight on low oxygen affinity species. Attempts are being made to unravel the structural insight of this low oxygen affinity species. Goat blood plasma was collected, treated with EDTA to avoid blood clotting and purification was accomplished using DEAE-anion chromatographic column. The goat hemoglobin was crystallized using 50mM of phosphate buffer at pH 6.7 with 1M NaCl and PEG 3350 as precipitant by hanging drop vapor diffusion method. Crystals obtained are screened and suitable crystals are taken for data collection using mar345dtb as image plate detector system. Goat hemoglobin crystal diffracted up to 2.61 A resolution. Goat hemoglobin crystallizes in orthorhombic space group P212(1)2(1) as a whole biological molecule in the asymmetric unit with cell dimensions a=53.568A, b=67.365A, c=154.183A. PMID:19356147

  10. Flow cytometric assessment of reactive oxygen species generations that are directly related to cellular ZnO nanoparticle uptake.

    PubMed

    Yoo, Hyun Ju; Yoon, Tae Hyun

    2014-07-01

    In this study, a simple flow cytometry protocol to evaluate nanoparticle associated biological response was proposed. Particularly, we have evaluated the effect of surface charge on the cellular nanoparticle associations and nanoparticle-induced apoptosis. Significant enhancement in side scattering intensity was observed for the HeLa cells treated with positively charged (PLL)ZnO nanoparticles, suggesting that the (PLL)ZnO nanoparticles may induce cell death via adsorption and endocytosis of the nanoparticles. On the other hand, the negatively charged (PAA)ZnO nanoparticle seems to cause cell death process indirectly via the released Zn ions, with less contribution from cellular association of nanoparticles. Time- and dose-dependent studies on cellular association of ZnO nanoparticles, and ZnO associated reactive oxygen species generation were also performed for the HeLa cells exposed to the (PLL)ZnO nanoparticle. For those cells associated with (PLL)ZnO nanoparticle, a significant enhancement in reactive oxygen species generation was observed even at a lower concentration (10 ppm), which was not observable for the results with the whole cell population. By using this approach, we are able to distinguish biological responses (e.g., reactive oxygen species (ROS) generation) directly related to the cellular associations of NPs from those indirectly related to the cellular associations of NPs, such as the cytotoxicity caused by the NP released metal ions. PMID:24758038

  11. Pretreatment of Parsley (Petroselinum crispum L.) Suspension Cultures with Methyl Jasmonate Enhances Elicitation of Activated Oxygen Species.

    PubMed

    Kauss, H.; Jeblick, W.; Ziegler, J.; Krabler, W.

    1994-05-01

    Suspension-cultured cells of parsley (Petroselinum crispum L.) were used to demonstrate an influence of jasmonic acid methyl ester (JAME) on the elicitation of activated oxygen species. Preincubation of the cell cultures for 1 d with JAME greatly enhanced the subsequent induction by an elicitor preparation from cell walls of Phytophtora megasperma f. sp. glycinea (Pmg elicitor) and by the polycation chitosan. Shorter preincubation times with JAME were less efficient, and the effect was saturated at about 5 [mu]M JAME. Treatment of the crude Pmg elicitor with trypsin abolished induction of activated oxygen species, an effect similar to that seen with elicitation of coumarin secretion. These results suggest that JAME conditioned the parsley suspension cells in a time-dependent manner to become more responsive to elicitation, reminiscent of developmental effects caused by JAME in whole plants. It is interesting that pretreatment of the parsley cultures with 2,6-dichloroisonicotinic and 5-chlorosalicylic acid only slightly enhanced the elicitation of activated oxygen species, whereas these substances greatly enhanced the elicitation of coumarin secretion. Therefore, these presumed inducers of systemic acquired resistance exhibit a specificity different from JAME. PMID:12232189

  12. Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma.

    PubMed

    Singer, E; Judkins, J; Salomonis, N; Matlaf, L; Soteropoulos, P; McAllister, S; Soroceanu, L

    2015-01-01

    Glioblastoma (GBM) resistance to therapy is the most common cause of tumor recurrence, which is ultimately fatal in 90% of the patients 5 years after initial diagnosis. A sub-population of tumor cells with stem-like properties, glioma stem cells (GSCs), is specifically endowed to resist or adapt to the standard therapies, leading to therapeutic resistance. Several anticancer agents, collectively termed redox therapeutics, act by increasing intracellular levels of reactive oxygen species (ROS). In this study, we investigated mechanisms underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non-psychoactive cannabinoid and redox modulator. Using primary GSCs, we showed that CBD induced a robust increase in ROS, which led to the inhibition of cell survival, phosphorylated (p)-AKT, self-renewal and a significant increase in the survival of GSC-bearing mice. Inhibition of self-renewal was mediated by the activation of the p-p38 pathway and downregulation of key stem cell regulators Sox2, Id1 and p-STAT3. Following CBD treatment, a subset of GSC successfully adapted, leading to tumor regrowth. Microarray, Taqman and functional assays revealed that therapeutic resistance was mediated by enhanced expression of the antioxidant response system Xc catalytic subunit xCT (SLC7A11 (solute carrier family 7 (anionic amino-acid transporter light chain), member 11)) and ROS-dependent upregulation of mesenchymal (MES) markers with concomitant downregulation of proneural (PN) markers, also known as PN-MES transition. This 'reprogramming' of GSCs occurred in culture and in vivo and was partially due to activation of the NFE2L2 (NRF2 (nuclear factor, erythroid 2-like)) transcriptional network. Using genetic knockdown and pharmacological inhibitors of SLC7A11, we demonstrated that combining CBD treatment with the inhibition of system Xc resulted in synergistic ROS increase leading to robust antitumor effects, that is, decreased GSC survival, self-renewal, and invasion. Our investigation provides novel mechanistic insights into the antitumor activity of redox therapeutics and suggests that combinatorial approaches using small molecule modulators of ROS offer therapeutic benefits in GBM. PMID:25590811

  13. Scavenging of reactive oxygen species induced by hyperthermia in biological fluid

    PubMed Central

    Ueno, Megumi; Nyui, Minako; Nakanishi, Ikuo; Anzai, Kazunori; Ozawa, Toshihiko; Matsumoto, Ken-ichiro; Uto, Yoshihiro

    2014-01-01

    The scavenging activity of rat plasma against hyperthermia-induced reactive oxygen species was tested. The glutathione-dependent reduction of a nitroxyl radical, 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, which was restricted by adding superoxide dismutase or by deoxygenating the reaction mixture, was applied to an index of superoxide (O2•?) generation. A reaction mixture containing 0.1 mM 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl and 1 mM glutathione was prepared using 100 mM phosphate buffer containing 0.05 mM diethylenetriaminepentaacetic acid. The reaction mixture was kept in a screw-top vial and incubated in a water bath at 37 or 44°C. The time course of the electron paramagnetic resonance signal of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl in the reaction mixture was measured by an X-band EPR spectrometer (JEOL, Tokyo, Japan). When the same experiment was performed using rat plasma instead of 100 mM PB, the glutathione-dependent reduction of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, i.e., generation of O2•?, was not obtained. Only the first-order decay reduction of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, which indicates direct reduction of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, was obtained in rat plasma. Adding 0.5% albumin to the phosphate buffer reaction mixture could almost completely inhibit O2•? generation at 37°C. However, addition of 0.5% albumin could not inhibit O2•? generation at 44°C, i.e., hyperthermic temperature. Ascorbic acid also showed inhibition of O2•? generation by 0.01 mM at 37°C, but 0.02 mM or more could inhibit O2•? generation at 44°C. A higher concentration of ascorbic acid showed first-order reduction, i.e., direct one-electron reduction, of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl. Hyperthermia-induced O2•? generation in rat plasma can be mostly inhibited by albumin and ascorbic acid in the plasma. PMID:24688214

  14. Reactive Oxygen Species Suppress Cardiac NaV1.5 Expression through Foxo1

    PubMed Central

    Ye, Bo; Li, Xiang; Dong, Henry H.; Hill, Joseph A.; Li, Faqian; Xu, Haodong

    2012-01-01

    NaV1.5 is a cardiac voltage-gated Na+ channel ?subunit and is encoded by the SCN5a gene. The activity of this channel determines cardiac depolarization and electrical conduction. Channel defects, including mutations and decrease of channel protein levels, have been linked to the development of cardiac arrhythmias. The molecular mechanisms underlying the regulation of NaV1.5 expression are largely unknown. Forkhead box O (Foxo) proteins are transcriptional factors that bind the consensus DNA sequences in their target gene promoters and regulate the expression of these genes. Comparative analysis revealed conserved DNA sequences, 5?-CAAAACA-3? (insulin responsive element, IRE), in rat, mouse and human SCN5a promoters with the latter two containing two overlapping Foxo protein binding IREs, 5?-CAAAACAAAACA-3?. This finding led us to hypothesize that Foxo1 regulates NaV1.5 expression by directly binding the SCN5a promoter and affecting its transcriptional activity. In the present study, we determined whether Foxo1 regulates NaV1.5 expression at the transcriptional level and also defined the role of Foxo1 in hydrogen peroxide (H2O2)-mediated NaV1.5 suppression in HL-1 cardiomyocytes using chromatin immunoprecipitation (ChIP), constitutively nuclear Foxo1 expression, and RNAi Foxo1 knockdown as well as whole cell voltage-clamp recordings. ChIP with anti-Foxo1 antibody and follow-up semi-quantitative PCR with primers flanking Foxo1 binding sites in the proximal SCN5a promoter region clearly demonstrated enrichment of DNA, confirming Foxo1 recruitment to this consensus sequence. Foxo1 mutant (T24A/S319A-GFP, Foxo1-AA-GFP) was retained in nuclei, leading to a decrease of NaV1.5 expression and Na+ current, while silencing of Foxo1 expression by RNAi resulted in the augmentation of NaV1.5 expression. H2O2 significantly reduced NaV1.5 expression by promoting Foxo1 nuclear localization and this reduction was prevented by RNAi silencing Foxo1 expression. These studies indicate that Foxo1 negatively regulates NaV1.5 expression in cardiomyocytes and reactive oxygen species suppress NaV1.5 expression through Foxo1. PMID:22400069

  15. HIV antiretroviral drug combination induces endothelial mitochondrial dysfunction and reactive oxygen species production, but not apoptosis

    SciTech Connect

    Jiang Bo; Hebert, Valeria Y. [Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71103 (United States); Li, Yuchi [Cardiopulmonary Research Institute, Winthrop University Hospital, State University of New York at Stony Brook School of Medicine, Mineola, NY 11501 (United States); Mathis, J. Michael [Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71103 (United States); Alexander, J. Steven [Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71103 (United States); Dugas, Tammy R. [Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71103 (United States)], E-mail: tdugas@lsuhsc.edu

    2007-10-01

    Numerous reports now indicate that HIV patients administered long-term antiretroviral therapy (ART) are at a greater risk for developing cardiovascular diseases. Endothelial dysfunction is an initiating event in atherogenesis and may contribute to HIV-associated atherosclerosis. We previously reported that ART induces direct endothelial dysfunction in rodents. In vitro treatment of human umbilical vein endothelial cells (HUVEC) with ART indicated endothelial mitochondrial dysfunction and a significant increase in the production of reactive oxygen species (ROS). In this study, we determined whether ART-induced endothelial dysfunction is mediated via mitochondria-derived ROS and whether this mitochondrial injury culminates in endothelial cell apoptosis. Two major components of ART combination therapy, a nucleoside reverse transcriptase inhibitor and a protease inhibitor, were tested, using AZT and indinavir as representatives for each. Microscopy utilizing fluorescent indicators of ROS and mitochondria demonstrated the mitochondrial localization of ART-induced ROS. MnTBAP, a cell-permeable metalloporphyrin antioxidant, abolished ART-induced ROS production. As a final step in confirming the mitochondrial origin of the ART-induced ROS, HUVEC were transduced with a cytosolic- compared to a mitochondria-targeted catalase. Transduction with the mitochondria-targeted catalase was more effective than cytoplasmic catalase in inhibiting the ROS and 8-isoprostane (8-iso-PGF{sub 2{alpha}}) produced after treatment with either AZT or indinavir. However, both mitochondrial and cytoplasmic catalase attenuated ROS and 8-iso-PGF{sub 2{alpha}} production induced by the combination treatment, suggesting that in this case, the formation of cytoplasmic ROS may also occur, and thus, that the mechanism of toxicity in the combination treatment group may be different compared to treatment with AZT or indinavir alone. Finally, to determine whether ART-induced mitochondrial dysfunction and ROS production culminate in apoptosis, we performed the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL), annexin V and 4',6-diamidino-2-phenylindole (DAPI) staining, and caspase-3 activity assays. However, none of these assays showed appreciable levels of ART-induced apoptosis. Our studies thus suggest that in endothelial cells, ART induces mitochondrial dysfunction with a concomitant increase in mitochondria-derived ROS. This compromised mitochondrial function may be one important factor culminating in endothelial dysfunction, without inducing an increase in apoptosis.

  16. Scavenging of reactive oxygen species induced by hyperthermia in biological fluid.

    PubMed

    Ueno, Megumi; Nyui, Minako; Nakanishi, Ikuo; Anzai, Kazunori; Ozawa, Toshihiko; Matsumoto, Ken-Ichiro; Uto, Yoshihiro

    2014-03-01

    The scavenging activity of rat plasma against hyperthermia-induced reactive oxygen species was tested. The glutathione-dependent reduction of a nitroxyl radical, 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, which was restricted by adding superoxide dismutase or by deoxygenating the reaction mixture, was applied to an index of superoxide (O2 (•-)) generation. A reaction mixture containing 0.1 mM 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl and 1 mM glutathione was prepared using 100 mM phosphate buffer containing 0.05 mM diethylenetriaminepentaacetic acid. The reaction mixture was kept in a screw-top vial and incubated in a water bath at 37 or 44°C. The time course of the electron paramagnetic resonance signal of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl in the reaction mixture was measured by an X-band EPR spectrometer (JEOL, Tokyo, Japan). When the same experiment was performed using rat plasma instead of 100 mM PB, the glutathione-dependent reduction of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, i.e., generation of O2 (•-), was not obtained. Only the first-order decay reduction of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, which indicates direct reduction of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl, was obtained in rat plasma. Adding 0.5% albumin to the phosphate buffer reaction mixture could almost completely inhibit O2 (•-) generation at 37°C. However, addition of 0.5% albumin could not inhibit O2 (•-) generation at 44°C, i.e., hyperthermic temperature. Ascorbic acid also showed inhibition of O2 (•-) generation by 0.01 mM at 37°C, but 0.02 mM or more could inhibit O2 (•-) generation at 44°C. A higher concentration of ascorbic acid showed first-order reduction, i.e., direct one-electron reduction, of 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl. Hyperthermia-induced O2 (•-) generation in rat plasma can be mostly inhibited by albumin and ascorbic acid in the plasma. PMID:24688214

  17. Reactive molecular dynamics simulations of oxygen species in a liquid water layer of interest for plasma medicine

    NASA Astrophysics Data System (ADS)

    Yusupov, M.; Neyts, E. C.; Simon, P.; Berdiyorov, G.; Snoeckx, R.; van Duin, A. C. T.; Bogaerts, A.

    2014-01-01

    The application of atmospheric pressure plasmas in medicine is increasingly gaining attention in recent years, although very little is currently known about the plasma-induced processes occurring on the surface of living organisms. It is known that most bio-organisms, including bacteria, are coated by a liquid film surrounding them, and there might be many interactions between plasma species and the liquid layer before the plasma species reach the surface of the bio-organisms. Therefore, it is essential to study the behaviour of the reactive species in a liquid film, in order to determine whether these species can travel through this layer and reach the biomolecules, or whether new species are formed along the way. In this work, we investigate the interaction of reactive oxygen species (i.e. O, OH, HO2 and H2O2) with water, which is assumed as a simple model system for the liquid layer surrounding biomolecules. Our computational investigations show that OH, HO2 and H2O2 can travel deep into the liquid layer and are hence in principle able to reach the bio-organism. Furthermore, O, OH and HO2 radicals react with water molecules through hydrogen-abstraction reactions, whereas no H-abstraction reaction takes place in the case of H2O2. This study is important to gain insight into the fundamental operating mechanisms in plasma medicine, in general, and the interaction mechanisms of plasma species with a liquid film, in particular.

  18. Interpreting species-specific variation in tree-ring oxygen isotope ratios among three temperate forest trees.

    PubMed

    Song, Xin; Clark, Kenneth S; Helliker, Brent R

    2014-09-01

    Although considerable variation has been documented in tree-ring cellulose oxygen isotope ratios (?(18)O(cell)) among co-occurring species, the underlying causes are unknown. Here, we used a combination of field measurements and modelling to investigate the mechanisms behind variations in late-wood ?(18) O(cell) (?(18)O(lc)) among three co-occurring species (chestnut oak, black oak and pitch pine) in a temperate forest. For two growing seasons, we quantified among-species variation in ?(18)O(lc), as well as several variables that could potentially cause the ?(18)O(lc) variation. Data analysis based on the ?(18) O(cell) model rules out leaf water enrichment (?(18)O(lw)) and tree-ring formation period (?t), but highlights source water ?(18) O (?(18) O(sw)) as an important driver for the measured difference in ?(18)O(lc) between black and chestnut oak. However, the enriched ?(18)O(lc) in pitch pine relative to the oaks could not be sufficiently explained by consideration of the above three variables only, but rather, we show that differences in the proportion of oxygen exchange during cellulose synthesis (p(ex)) is most likely a key mechanism. Our demonstration of the relevance of some species-specific features (or lack thereof) to ?(18)O(cell) has important implications for isotope based ecophysiological/paleoclimate studies. PMID:24588709

  19. The known and unknown sources of reactive oxygen and nitrogen species in haemocytes of marine bivalve molluscs.

    PubMed

    Donaghy, Ludovic; Hong, Hyun-Ki; Jauzein, Cécile; Choi, Kwang-Sik

    2015-01-01

    Reactive oxygen and nitrogen species (ROS and RNS) are naturally produced in all cells and organisms. Modifications of standard conditions alter reactive species generation and may result in oxidative stress. Because of the degradation of marine ecosystems, massive aquaculture productions, global change and pathogenic infections, oxidative stress is highly prevalent in marine bivalve molluscs. Haemocytes of bivalve molluscs produce ROS and RNS as part of their basal metabolism as well as in response to endogenous and exogenous stimuli. However, sources and pathways of reactive species production are currently poorly deciphered in marine bivalves, potentially leading to misinterpretations. Although sources and pathways of ROS and RNS productions are highly conserved between vertebrates and invertebrates, some uncommon pathways seem to only exist in marine bivalves. To understand the biology and pathobiology of ROS and RNS in haemocytes of marine bivalves, it is necessary to characterise their sources and pathways of production. The aims of the present review are to discuss the currently known and unknown intracellular sources of reactive oxygen and nitrogen species in marine bivalve molluscs, in light of terrestrial vertebrates, and to expose principal pitfalls usually encountered. PMID:25449373

  20. Coupling of oxygen, nitrogen, and hydrocarbon species in the photochemistry of Titan's atmosphere

    NASA Astrophysics Data System (ADS)

    Dobrijevic, M.; Hébrard, E.; Loison, J. C.; Hickson, K. M.

    2014-01-01

    Analysis of recent detections of water by Herschel/HIFI-PACS and Cassini/CIRS suggest for a steep gradient of the water profile in the lower stratosphere of Titan's atmosphere (Cottini, V., Nixon, C.A., Jennings, D.E., Anderson, C.M., Gorius, N., Bjoraker, G.L., Coustenis, A., Teanby, N.A., Achterberg, R.K., Béezard, B., de Kok, R., Lellouch, E., Irwin, P.G.J., Flasar, F.M., Bampasidis, G. [2012]. Icarus 220, 855-862; Moreno, R., Lellouch, E., Lara, L.M., Feuchtgruber, H., Rengel, M., Hartogh, P., Courtin, R. [2012]. Icarus 221, 753-767). This result provides a good opportunity to better understand the origin of oxygen compounds. However, the current photochemical models use an incomplete oxygen chemical scheme. In the present work, we improve the photochemistry of oxygen and introduce in particular a coupling between hydrocarbon, oxygen and nitrogen chemistries. Through the use of several different scenarios, we show that some oxygen compound abundances are sensitive to the nature of oxygen atoms (O+, OH and H2O) and the source of the flux (micrometeorites ablation or Enceladus' plume activity). Our model also predicts the presence of new and as yet undetected compounds such as NO (nitric oxide), HNO (nitrosyl hydride), HNCO (isocyanic acid) and N2O (nitrous oxide). Their future putative detection will give valuable constraints to discriminate between the different hypotheses for the nature and the source of oxygen compounds in the atmosphere of Titan. Through the use of a Monte Carlo-based uncertainty propagation study and global sensitivity analysis, we identify the key reactions that should be studied in priority to improve coupled photochemical models of Titan's atmosphere.

  1. Control of selectivity in allylic alcohol oxidation on gold surfaces: the role of oxygen adatoms and hydroxyl species.

    PubMed

    Mullen, Gregory M; Zhang, Liang; Evans, Edward J; Yan, Ting; Henkelman, Graeme; Mullins, C Buddie

    2015-02-14

    Gold catalysts display high activity and good selectivity for partial oxidation of a number of alcohol species. In this work, we discuss the effects of oxygen adatoms and surface hydroxyls on the selectivity for oxidation of allylic alcohols (allyl alcohol and crotyl alcohol) on gold surfaces. Utilizing temperature programmed desorption (TPD), reactive molecular beam scattering (RMBS), and density functional theory (DFT) techniques, we provide evidence to suggest that the selectivity displayed towards partial oxidation versus combustion pathways is dependent on the type of oxidant species present on the gold surface. TPD and RMBS results suggest that surface hydroxyls promote partial oxidation of allylic alcohols to their corresponding aldehydes with very high selectivity, while oxygen adatoms promote both partial oxidation and combustion pathways. DFT calculations indicate that oxygen adatoms can react with acrolein to promote the formation of a bidentate surface intermediate, similar to structures that have been shown to decompose to generate combustion products over other transition metal surfaces. Surface hydroxyls do not readily promote such a process. Our results help explain phenomena observed in previous studies and may prove useful in the design of future catalysts for partial oxidation of alcohols. PMID:25588689

  2. Photosensitization of CdSe/ZnS QDs and reliability of assays for reactive oxygen species production.

    SciTech Connect

    Cooper, D. R.; Dimitrijevic, N. M.; Nadeau, J. L.; McGill Univ.

    2010-01-01

    CdSe/ZnS quantum dots (QDs) conjugated to biomolecules that can act as electron donors are said to be 'photosensitized': that is, they are able to oxidize or reduce molecules whose redox potential lies inside their band edges, in particular molecular oxygen and water. This leads to the formation of reactive oxygen species (ROS) and phototoxicity. In this work, we quantify the generation of different forms of ROS from as-synthesized QDs in toluene; water-solubilized, unconjugated QDs; QDs conjugated to the neurotransmitter dopamine; and dopamine alone. Results of indirect fluorescent ROS assays, both in solution and inside cells, are compared with those of spin-trap electron paramagentic resonance spectroscopy (EPR). The effect of these particles on the metabolism of mammalian cells is shown to be dependent upon light exposure and proportional to the amount of ROS generated.

  3. Control of reactive oxygen species (ROS) production through histidine kinases in Aspergillus nidulans under different growth conditions?

    PubMed Central

    Hayashi, Saki; Yoshioka, Megumi; Matsui, Tetsuji; Kojima, Kensuke; Kato, Masashi; Kanamaru, Kyoko; Kobayashi, Tetsuo

    2014-01-01

    Sensor histidine kinases (HKs) are important factors that control cellular growth in response to environmental conditions. The expression of 15 HKs from Aspergillus nidulans was analyzed by quantitative real-time PCR under vegetative, asexual, and sexual growth conditions. Most HKs were highly expressed during asexual growth. All HK gene-disrupted strains produced reactive oxygen species (ROS). Three HKs are involved in the control of ROS: HysA was the most abundant under the restricted oxygen condition, NikA is involved in fungicide sensing, and FphA inhibits sexual development in response to red light. Phosphotransfer signal transduction via HysA is essential for ROS production control. PMID:24490133

  4. Effect of fructose 1,6-bisphosphate on the iron redox state relating to the generation of reactive oxygen species.

    PubMed

    Murakami, Keiko; Yoshino, Masataka

    2015-08-01

    Role of fructose 1,6-bisphosphate-mediated iron oxidation in the generation of reactive oxygen species was analyzed. Aconitase the most sensitive enzyme to oxidative stress was inactivated potently by fructose 1,6-bisphosphate in the presence of ferrous ion, and further by ADP and PEP to a lesser extent. The inactivation requires cyanide, suggesting that the superoxide radical is responsible for the inactivation. Addition of ascorbic acid and dithiothreitol prevented aconitase from the inactivation. Fructose 1,6-bisphosphate, ADP and PEP stimulated the oxidation of ferrous ion causing one-electron reduction of oxygen molecule. Superoxide radical formed with iron oxidation participates in the oxidative inactivation of aconitase and the citric acid cycle, resulting in the induction of the Crabtree effect, that is, high glucose-mediated inhibition of oxidative metabolism in mitochondria. PMID:25940829

  5. Hazardous components and health effects of atmospheric aerosol particles: reactive oxygen species, soot, polycyclic aromatic compounds and allergenic proteins.

    PubMed

    Shiraiwa, Manabu; Selzle, Kathrin; Pöschl, Ulrich

    2012-08-01

    This review outlines recent advances in the investigation of the chemical properties, molecular interactions and health effects of hazardous compounds in atmospheric aerosols, in particular reactive oxygen species (ROS), soot, polycyclic aromatic compounds (PACs) and allergenic proteins. Epidemiological studies show correlations between air particulate matter and adverse health effects of air pollution including allergy, asthma, cardiovascular and respiratory diseases, but the causative relations and mechanisms of interaction on the molecular level are still unclear. ROS generated by photochemical and heterogeneous reactions in the atmosphere seem to play a key role in aerosol health effects and provide a direct link between atmospheric and physiological multiphase processes. Soot and PACs can trigger formation of ROS in vivo, leading to inflammation and cellular damage. PACs as well as allergenic proteins are efficiently oxygenated and nitrated upon exposure to ozone and nitrogen dioxide, which leads to an enhancement of their toxicity and allergenicity. PMID:22300277

  6. Reactive oxygen species' role in endothelial dysfunction by electron paramagnetic resonance

    NASA Astrophysics Data System (ADS)

    Wassall, Cynthia D.

    The endothelium is a single layer of cells lining the arteries and is involved in many physiological reactions which are responsible for vascular tone. Free radicals are important participants in these chemical reactions in the endothelium. Here we quantify free radicals, ex vivo, in biological tissue with continuous wave electron paramagnetic resonance (EPR). In all of the experiments in this thesis, we use a novel EPR spin trapping technique that has been developed for tissue segments. EPR spin trapping is often considered the 'gold standard' in reactive oxygen species (ROS) detection because of its sensitivity and non-invasive nature. In all experiments, tissue was placed in physiological saline solution with 190-mM PBN (N-tert -butyl-?-phenylnitrone), 10% by volume dimethyl-sulphoxide (DMSO) for cryopreservation, and incubated in the dark for between 30 minutes up to 2 hours at 37°C while gently being stirred. Tissue and supernatant were then loaded into a syringe and frozen at -80°C until EPR analysis. In our experiments, the EPR spectra were normalized with respect to tissue volume. Conducting experiments at liquid nitrogen temperature leads to some experimental advantages. The freezing of the spin adducts renders them stable over a longer period, which allows ample time to analyze tissue samples for ROS. The dielectric constant of ice is greatly reduced over its liquid counterpart; this property of water enables larger sample volumes to be inserted into the EPR cavity without overloading it and leads to enhanced signal detection. Due to Maxwell-Boltzmann statistics, the population difference goes up as the temperature goes down, so this phenomenon enhances the signal intensity as well. With the 'gold standard' assertion in mind, we investigated whether slicing tissue to assay ROS that is commonly used in fluorescence experiments will show more free radical generation than tissue of a similar volume that remains unsliced. Sliced tissue exhibited a 76% increase in ROS generation; this implies that higher ROS concentrations in sliced tissue indicate extraneous ROS generation not associated with the ROS stimulus of interest. We also investigated the role of ROS in chronic flow overload (CFO). Elevation of shear stress that increases production of vascular ROS has not been well investigated. We hypothesize that CFO increases ROS production mediated in part by NADPH oxidase, which leads to endothelial dysfunction. ROS production increased threefold in response to CFO. The endothelium dependent vasorelaxation was compromised in the CFO group. Treatment with apocynin significantly reduced ROS production in the vessel wall, preserved endothelial function, and inhibited expressions of p22/p47phox and NOX2/NOX4. The present data implicate NADPH oxidase produced ROS and eNOS uncoupling in endothelial dysfunction at 1 wk of CFO. In further work, a swine right ventricular hypertrophy (RVH) model induced by pulmonary artery (PA) banding was used to study right coronary artery (RCA) endothelial function and ROS level. Endothelial function was compromised in RCA of RVH as attributed to insufficient endothelial nitric oxide synthase cofactor tetrahydrobiopterin. In conclusion, stretch due to outward remodeling of RCA during RVH (at constant wall shear stress), similar to vessel stretch in hypertension, appears to induce ROS elevation, endothelial dysfunction, and an increase in basal tone. Finally, although hypertension-induced vascular stiffness and dysfunction are well established in patients and animal models, we hypothesize that stretch or distension due to hypertension and outward expansion is the cause of endothelial dysfunction mediated by angiotensin II type 1 (AT1) receptor in coronary arteries. The expression and activation of AT1 receptor and the production of ROS were up regulated and endothelial function deteriorated in the RCA. The acute inhibition of AT1 receptor and NADPH oxidase partially restored the endothelial function. Stretch or distension activates the AT1 receptor which mediates ROS production; this colle

  7. Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation

    PubMed Central

    Yoo, Ki-Chun; Yoon, Chang-Hwan; Kwon, Dongwook; Hyun, Kyung-Hwan; Woo, Soo Jung; Kim, Rae-Kwon; Lim, Eun-Jung; Suh, Yongjoon; Kim, Min-Jung; Yoon, Tae Hyun; Lee, Su-Jae

    2012-01-01

    Background Titanium dioxide (TiO2) has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO2 particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO2 has yet to be defined. Methods and results In this study, we demonstrated that combined treatment with TiO2 nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO2 nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO2P25–70) together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO2-induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO2P25–70 and ultraviolet A irradiation. Conclusion These results indicate that sub-100 nm sized TiO2 treatment under ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-mediated upregulation of the death receptor, Fas, and activation of the preapoptotic protein, Bax. Elucidating the molecular mechanisms by which nanosized particles induce activation of cell death signaling pathways would be critical for the development of prevention strategies to minimize the cytotoxicity of nanomaterials. PMID:22419868

  8. Formation of Syncytial Knots is Increased by Hyperoxia, Hypoxia and Reactive Oxygen Species

    Microsoft Academic Search

    A. E. P. Heazell; S. J. Moll; C. J. P. Jones; P. N. Baker; I. P. Crocker

    2007-01-01

    The syncytiotrophoblast contains aggregates of nuclei termed syncytial knots. Increased numbers of syncytial knots have been reported in placentae of pregnancies complicated by pre-eclampsia and fetal growth restriction (FGR). As oxidative stress has been implicated in the pathophysiology of these disorders, we hypothesised that the formation of syncytial knots may be induced by exposure to hypoxia, hyperoxia or reactive oxygen

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

    Microsoft Academic Search

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

    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

  10. The effect of the copper chelator tetraethylenepentamine on reactive oxygen species generation by human hematopoietic progenitor cells.

    PubMed

    Prus, Eugenia; Fibach, Eitan

    2007-12-01

    Clinical observations suggest that copper (Cu) plays a role in regulating hematopoietic progenitor cell (HPC) development. Cu is known to generate oxidative stress in cells which in turn affects proliferation, differentiation and apoptosis. To study this role of Cu, we used double staining flow cytometry to measure reactive oxygen species (ROS) generation by neonatal cord blood-derived CD34(+)CD38(-) cells. ROS was increased by Cu and was decreased by the Cu chelator tetraethylenepentamine (TEPA). Previously, we showed that TEPA reduces the free Cu content of HPCs and stimulates their ex vivo expansion. The present results suggest that TEPA affects expansion of HPCs by lowering their oxidative stress. PMID:18047399

  11. Formation of reactive oxygen and nitrogen species by repetitive negatively pulsed helium atmospheric pressure plasma jets propagating into humid air

    NASA Astrophysics Data System (ADS)

    Norberg, Seth A.; Johnsen, Eric; Kushner, Mark J.

    2015-06-01

    Atmospheric pressure plasma jets have many beneficial effects in their use in surface treatment and, in particular, plasma medicine. One of these benefits is the controlled production of reactive oxygen and nitrogen species (RONS) in the active discharge through the molecular gases added to the primary noble gas in the input mixture, and through the interaction of reactive species in the plasma effluent with the ambient air. In this computational investigation, a parametric study was performed on the production of RONS in a multiply pulsed atmospheric pressure plasma jet sustained in a He/O2 mixture and flowing into ambient humid air. The consequences of flow rate, O2 fraction, voltage, and repetition rate on reactant densities after a single discharge pulse, after 30 pulses, and after the same total elapsed time were investigated. At the end of the first discharge pulse, voltage has the greatest influence on RONS production. However, the systematic trends for production of RONS depend on repetition rate and flow rate in large part due to the residence time of RONS in the plasma zone. Short residence times result in reactive species produced by the previous pulse still being in the discharge tube or in the path of the ionization wave at the next pulse. The RONS therefore accumulate in the tube and in the near effluent on a pulse-to-pulse basis. This accumulation enables species requiring multiple reactions among the primary RONS species to be produced in greater numbers.

  12. Challenges and advances in quantum dot fluorescent probes to detect reactive oxygen and nitrogen species: a review.

    PubMed

    Adegoke, Oluwasesan; Forbes, Patricia B C

    2015-03-01

    The pathological and physiological effects of reactive oxygen and nitrogen species (ROS/RNS) have instigated increasing awareness in the scientific field with respect to the development of suitable probes for their detection. Among the various probes developed to date, semiconductor quantum dots (QDs) fluorescent probes have attracted significant attention. The unfavourable properties of ROS/RNS with respect to their detection, such as their short lifetimes and the competitive presence of various endogenous reactive species, capable of interfering with the probe in biological matrices, have hindered the effective performance of most probes as well as complicating the design of suitable probes. The development of novel QD fluorescent probes capable of circumventing these problems is thus, of scientific interest. In this review, we highlight the challenges faced, pros and cons and published developments to date, with respect to QD fluorescent probes for ROS/RNS such as H2O2, O2(·-), ·OH, HOCl, NO and ONOO(-). PMID:25682423

  13. Phenylalanine hydroxylase: absolute configuration and source of oxygen of the 4a-hydroxytetrahydropterin species.

    PubMed

    Dix, T A; Bollag, G E; Domanico, P L; Benkovic, S J

    1985-06-01

    The formation of tyrosine from phenylalanine catalyzed by rat liver phenylalanine hydroxylase is coupled to the generation of a 4a-hydroxy adduct from the requisite tetrahydropterin cofactor. As indicated by its circular dichroism (CD) spectrum, the optical activity of the adduct generated from racemic 6-methyltetrahydropterin requires stereoselectivity of the oxygenation. The absolute configuration of this new stereocenter is 4a(S)-hydroxy-6(RS)-methyltetrahydropterin by analogy to the CD spectrum of one of the four stereoisomers of 5-deaza-4a-hydroxy-6-methyltetrahydropterin. The source of the 4a-hydroxy oxygen is O2, as demonstrated by the observation of a 18O-induced 13C shift in the 13C NMR spectrum of the adduct when generated from [4a-13C]-6-methyltetrahydropterin and 18O2. PMID:4016080

  14. Generation of Reactive Oxygen Species by Mitochondrial Complex I: Implications in Neurodegeneration

    Microsoft Academic Search

    Romana Fato; Christian Bergamini; Serena Leoni; Paola Strocchi; Giorgio Lenaz

    2008-01-01

    Mitochondrial Complex I [NADH Coenzyme Q (CoQ) oxidoreductase] is the least understood of respiratory complexes. In this review\\u000a we emphasize some novel findings on this enzyme that are of relevance to the pathogenesis of neurodegenerative diseases. Besides\\u000a CoQ, also oxygen may be an electron acceptor from the enzyme, with generation of superoxide radical in the mitochondrial matrix.\\u000a The site of

  15. Mitochondrial-derived reactive oxygen species (ROS) play a causal role in aging-related intervertebral disc degeneration

    PubMed Central

    Nasto, Luigi A.; Robinson, Andria R.; Ngo, Kevin; Clauson, Cheryl L.; Dong, Qing; St. Croix, Claudette; Sowa, Gwendolyn; Pola, Enrico; Robbins, Paul D.; Kang, James; Niedernhofer, Laura J.; Wipf, Peter; Vo, Nam V.

    2013-01-01

    Oxidative damage is a well-established driver of aging. Evidence of oxidative stress exists in aged and degenerated discs, but it is unclear how it affects disc metabolism. In this study, we first determined whether oxidative stress negatively impacts disc matrix metabolism using disc organotypic and cell cultures. Mouse disc organotypic culture grown at atmospheric oxygen (20% O2) exhibited perturbed disc matrix homeostasis, including reduced proteoglycan synthesis and enhanced expression of matrix metalloproteinases, compared to discs grown at low oxygen levels (5% O2). Human disc cells grown at 20% O2 showed increased levels of mitochondrial-derived superoxide anions and perturbed matrix homeostasis. Treatment of disc cells with the mitochondria-targeted reactive oxygen species (ROS) scavenger XJB-5-131 blunted the adverse effects caused by 20% O2. Importantly, we demonstrated that treatment of accelerated aging Ercc1?/?mice, previously established to be a useful in vivo model to study age-related intervertebral disc degeneration (IDD), also resulted in improved disc total glycosaminoglycan content and proteoglycan synthesis. This demonstrates that mitochondrial-derived ROS contributes to age-associated IDD in Ercc1?/?mice. Collectively, these data provide strong experimental evidence that mitochondrial-derived ROS play a causal role in driving changes linked to aging-related IDD and a potentially important role for radical scavengers in preventing IDD. PMID:23389888

  16. ARSENIC SPECIES THAT CAUSE RELEASE OF IRON FROM FERRITIN AND GENERATION OF ACTIVATED OXYGEN

    EPA Science Inventory

    ABSTRACT The in vitro effects of four different species of arsenic { arsenate, arsenite, monomethylarsonic acid and dimethylarsinic acid) in mobilizing iron from horse spleen ferritin under aerobic and anaerobic conditions were investigated. Dimethylarsinicacid {DMA(V...

  17. Reactive oxygen and nitrogen species in defense/stress responses activated by chitosan in sycamore cultured cells.

    PubMed

    Malerba, Massimo; Cerana, Raffaella

    2015-01-01

    Chitosan (CHT) is a non-toxic and inexpensive compound obtained by deacetylation of chitin, the main component of the exoskeleton of arthropods as well as of the cell walls of many fungi. In agriculture CHT is used to control numerous diseases on various horticultural commodities but, although different mechanisms have been proposed, the exact mode of action of CHT is still unknown. In sycamore (Acer pseudoplatanus L.) cultured cells, CHT induces a set of defense/stress responses that includes production of H2O2 and nitric oxide (NO). We investigated the possible signaling role of these reactive molecules in some CHT-induced responses by means of inhibitors of production and/or scavengers. The results show that both reactive nitrogen and oxygen species are not only a mere symptom of stress conditions but are involved in the responses induced by CHT in sycamore cells. In particular, NO appears to be involved in a cell death form induced by CHT that shows apoptotic features like DNA fragmentation, increase in caspase-3-like activity and release of cytochrome c from the mitochondrion. On the contrary, reactive oxygen species (ROS) appear involved in a cell death form induced by CHT that does not show these apoptotic features but presents increase in lipid peroxidation. PMID:25642757

  18. Insulin over expression induces heart abnormalities via reactive oxygen species regulation, might be step towards cardiac hypertrophy.

    PubMed

    Mushtaq, S; Ali, T; Gul, M; Javed, Q; Emanueli, C; Murtaza, I

    2015-01-01

    Insulin is known to regulate blood—glucose level and promote its utilization as an energy source in cardiac tissues under normal physiological conditions as well as stimulates signaling pathways that involved cell growth and proliferation. Although recently insulin generated free radicals via NAD(P)H has been documented but the molecular mechanism is still under investigation. The aim of present study is to elucidate the reactive oxygen species (ROS) dependent possible role of insulin in cardiac abnormalities, including hypertrophy by regulation of antioxidants enzyme (SOD) activity. In the current study, 60 cardiac patients and 50 healthy individuals as well as the rat model with insulin administration were under investigation. Oxidant, anti—oxidant biochemical assays, hypertrophic marker expression via immunobloting and histopathology were performed. We observed statistically significant elevation of the reactive oxygen species level in the serum of patients as well as in the insulin administrated rat model, a mild expression of cardiac marker in experimental models along with abnormal histopathology of hearts. However, super oxide dismutase free radical scavenger activity was down regulated upon insulin treatment compared to control rats. Conclusively, the present study showed that over expression of insulin might stimulate cardiac hypertrophic signal via up regulation of free radicals and down regulation of antioxidants enzymes including SOD activity. PMID:25817343

  19. Inorganic Polyphosphates Regulate Hexokinase Activity and Reactive Oxygen Species Generation in Mitochondria of Rhipicephalus (Boophilus) microplus Embryo

    PubMed Central

    Fraga, Amanda; Moraes, Jorge; da Silva, José Roberto; Costa, Evenilton P.; Menezes, Jackson; da Silva Vaz Jr, Itabajara; Logullo, Carlos; da Fonseca, Rodrigo Nunes; Campos, Eldo

    2013-01-01

    The physiological roles of polyphosphates (poly P) recently found in arthropod mitochondria remain obscure. Here, the possible involvement of poly P with reactive oxygen species generation in mitochondria of Rhipicephalus microplus embryos was investigated. Mitochondrial hexokinase and scavenger antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione reductase were assayed during embryogenesis of R. microplus. The influence of poly P3 and poly P15 were analyzed during the period of higher enzymatic activity during embryogenesis. Both poly Ps inhibited hexokinase activity by up to 90% and, interestingly, the mitochondrial membrane exopolyphosphatase activity was stimulated by the hexokinase reaction product, glucose-6-phosphate. Poly P increased hydrogen peroxide generation in mitochondria in a situation where mitochondrial hexokinase is also active. The superoxide dismutase, catalase and glutathione reductase activities were higher during embryo cellularization, at the end of embryogenesis and during embryo segmentation, respectively. All of the enzymes were stimulated by poly P3. However, superoxide dismutase was not affected by poly P15, catalase activity was stimulated only at high concentrations and glutathione reductase was the only enzyme that was stimulated in the same way by both poly Ps. Altogether, our results indicate that inorganic polyphosphate and mitochondrial membrane exopolyphosphatase regulation can be correlated with the generation of reactive oxygen species in the mitochondria of R. microplus embryos. PMID:23983617

  20. Preventive antioxidant responses to extreme oxygen level fluctuation in a subterranean crustacean.

    PubMed

    Lawniczak, M; Romestaing, C; Roussel, D; Maazouzi, C; Renault, D; Hervant, F

    2013-06-01

    The principal aim of this work was to explore the responses of the groundwater crustacean Niphargus rhenorhodanensis to oxidative stress caused by short- and long-term drastic variations in oxygen level. To this end, we investigated thiobarbituric acid reactive substances (TBARS) levels and anti-oxidative enzyme (SOD and GPx) activities during 24 h anoxia and post-anoxia recovery, and during 10 days of severe hypoxia and post-hypoxia recovery. We observed a decrease in TBARS amounts during recovery from severe hypoxia. Parallel to these results, we observed an overactivation of SOD activity after a 24 h anoxic stress. GPx activity measured at the end of anoxia or severe hypoxia and in the early hours of post-stress recovery also showed an overactivation compared to the control group. We can hypothesize that this overproduction of GPx corresponded to an anticipatory mechanism coping with the overproduction of reactive oxygen species (ROS) during the recovery phase in subterranean animals. This response could be considered as a major asset for life in alternately normoxic and hypoxic conditions, and therefore in extreme biotopes such as groundwaters. PMID:23545443

  1. The Effect of Cerium Oxide Nanoparticle Valence State on Reactive Oxygen Species and Toxicity.

    PubMed

    Dunnick, Katherine M; Pillai, Rajalekshmi; Pisane, Kelly L; Stefaniak, Aleksandr B; Sabolsky, Edward M; Leonard, Stephen S

    2015-07-01

    Cerium oxide (CeO2) nanoparticles, which are used in a variety of products including solar cells, gas sensors, and catalysts, are expected to increase in industrial use. This will subsequently lead to additional occupational exposures, making toxicology screenings crucial. Previous toxicology studies have presented conflicting results as to the extent of CeO2 toxicity, which is hypothesized to be due to the ability of Ce to exist in both a +3 and +4 valence state. Thus, to study whether valence state and oxygen vacancy concentration are important in CeO2 toxicity, CeO2 nanoparticles were doped with gadolinium to adjust the cation (Ce, Gd) and anion (O) defect states. The hypothesis that doping would increase toxicity and decrease antioxidant abilities as a result of increased oxygen vacancies and inhibition of +3 to +4 transition was tested. Differences in toxicity and reactivity based on valence state were determined in RLE-6TN rat alveolar epithelial and NR8383 rat alveolar macrophage cells using enhanced dark field microscopy, electron paramagnetic resonance (EPR), and annexin V/propidium iodide cell viability stain. Results from EPR indicated that as doping increased, antioxidant potential decreased. Alternatively, doping had no effect on toxicity at 24 h. The present results imply that as doping increases, thus subsequently increasing the Ce(3+)/Ce(4+) ratio, antioxidant potential decreases, suggesting that differences in reactivity of CeO2 are due to the ability of Ce to transition between the two valence states and the presence of increased oxygen vacancies, rather than dependent on a specific valence state. PMID:25778836

  2. Metallic species, oxygen and silicon in the lunar exosphere: Upper limits and prospects for LADEE measurements

    NASA Astrophysics Data System (ADS)

    Sarantos, Menelaos; Killen, Rosemary M.; Glenar, David A.; Benna, Mehdi; Stubbs, Timothy J.

    2012-03-01

    The only species that have been so far detected in the lunar exosphere are Na, K, Ar, and He. However, models for the production and loss of species derived from the lunar regolith through micrometeoroid impact vaporization, sputtering, and photon-stimulated desorption, predict that a host of other species should exist in the lunar exosphere. Assuming that loss processes are limited to ballistic escape, photoionization, and recycling to the surface, we have computed column abundances and compared them to published upper limits for the Moon. Only for Ca do modeled abundances clearly exceed the available measurements. This result suggests the relevance of some loss processes that were not included in the model, such as the possibility of gas-to-solid phase condensation during micrometeoroid impacts or the formation of stable metallic oxides. Our simulations and the recalculation of efficiencies for resonant light scattering show that models for other species studied are not well constrained by existing measurements. This fact underlines the need for improved remote and in situ measurements of the lunar exosphere such as those planned by the Lunar Atmosphere and Dust Environment Explorer (LADEE) spacecraft. Our simulations of the LADEE neutral mass spectrometer and visible/ultraviolet spectrometer indicate that LADEE measurements promise to provide definitive observations or set stringent upper limits for all regolith-driven exospheric species. We predict that observations by LADEE will constrain assumed model parameters for the exosphere of the Moon.

  3. Metallic Species, Oxygen and Silicon in the Lunar Exosphere: Upper Limits and Prospects for LADEE Measurements

    NASA Technical Reports Server (NTRS)

    Sarantos, Menelaos; Killen, Rosemary Margaret; Glenar, David A.; Benna, Mehdi; Stubbs, Timothy J.

    2012-01-01

    The only species that have been so far detected in the lunar exosphere are Na, K, Ar,and He. However, models for the production and loss of species derived from the lunarregolith through micrometeoroid impact vaporization, sputtering, and photon-stimulateddesorption, predict that a host of other species should exist in the lunar exosphere.Assuming that loss processes are limited to ballistic escape, photoionization, and recyclingto the surface, we have computed column abundances and compared them to publishedupper limits for the Moon. Only for Ca do modeled abundances clearly exceed theavailable measurements. This result suggests the relevance of some loss processes thatwere not included in the model, such as the possibility of gas-to-solid phasecondensation during micrometeoroid impacts or the formation of stable metallic oxides.Our simulations and the recalculation of efficiencies for resonant light scattering showthat models for other species studied are not well constrained by existingmeasurements. This fact underlines the need for improved remote and in situmeasurements of the lunar exosphere such as those planned by the Lunar Atmosphereand Dust Environment Explorer (LADEE) spacecraft. Our simulations of the LADEEneutral mass spectrometer and visibleultraviolet spectrometer indicate that LADEE measurements promise to provide definitive observations or set stringent upper limitsfor all regolith-driven exospheric species. We predict that observations by LADEE willconstrain assumed model parameters for the exosphere of the Moon.

  4. Novel ternary vanadium-betaine-peroxido species suppresses H-ras and matrix metalloproteinase-2 expression by increasing reactive oxygen species-mediated apoptosis in cancer cells.

    PubMed

    Petanidis, Savvas; Kioseoglou, Efrosini; Hadzopoulou-Cladaras, Margarita; Salifoglou, Athanasios

    2013-07-28

    Vanadium is known for its antitumorigenicity. Poised to investigate the impact of well-defined forms of vanadium on processes and specific biomolecules (oncogenes-proteins) involved in cancer cell physiology, a novel ternary V(V)-peroxido-betaine compound was employed in experiments targeting cell viability, apoptosis, reactive oxygen species (ROS) production, H-ras signaling, and matrix metalloproteinase-2 (MMP-2) expression in human breast cancer epithelial and lung adenocarcinoma cells. The results reveal that vanadium imparts a significant decrease in cancer cell viability, reducing H-ras and MMP-2 expression by increasing ROS-mediated apoptosis, distinctly emphasizing the nature, structure and properties of ternary ligands on vanadium anti-tumor activity and its future potential as a metallodrug. PMID:23474496

  5. A study of over-production and enhanced secretion of enzymes. Quarterly report 2

    SciTech Connect

    Dashek, W.V.

    1993-04-08

    This project is concerned with the over-production of ligno-cellulolytic enzymes which are relevant to the paper-pulp industry and agricultural community. Since ligno-cellulosics are components of wood, the project involves the forest, a renewable energy resource. Attention is focused on the following: over-production of polyphenol oxidase; establishment of the route of polyphenol oxidase secretion; regulation of polyphenol oxidase secretion; purification of extracellular oxidase.

  6. A field-derived oxygen isotope fractionation equation for Salvelinus species.

    PubMed

    Storm-Suke, Andrea; Dempson, J Brian; Reist, James D; Power, Michael

    2007-01-01

    Field-collected otolith samples of young-of the-year Arctic charr (Salvelinus alpinus) and brook charr (Salvelinus fontinalis) and monitored water temperatures were used to estimate a delta(18)O fractionation equation for the genus Salvelinus. When compared to literature reported equations, the developed fractionation equation had a statistically similar slope but dissimilar intercept. Statistical similarities among fractionation equation slope estimates suggest a common otolith delta(18)O incorporation response among fish species that may be interpreted as widespread equilibrium otolith delta(18)O deposition. Statistical dissimilarities among intercept estimates question broad applicability of any single fractionation equation to all fish species and were interpreted here to have biological meaning as a result of known differences in standard metabolic rates among species. Attempts to statistically cross-validate fractionation equations by prediction of water temperatures used in other fractionation studies indicated significant biases in the range of -7.9 to 6.7 degrees C that preclude the broad use of any single fractionation equation for accurate thermal reconstructions. Differences in equation intercepts and the prevalence of predictive biases do not support the conclusion of previous studies concerning the wide applicability and/or general accuracy of fractionation equations and suggest fractionation equations are best developed at the species- or taxon-specific (e.g., genus) level. PMID:18022960

  7. Up-Regulation of A1M/?1-Microglobulin in Skin by Heme and Reactive Oxygen Species Gives Protection from Oxidative Damage

    PubMed Central

    Olsson, Magnus G.; Allhorn, Maria; Larsson, Jörgen; Cederlund, Martin; Lundqvist, Katarina; Schmidtchen, Artur; Sørensen, Ole E.; Mörgelin, Matthias; Åkerström, Bo

    2011-01-01

    During bleeding the skin is subjected to oxidative insults from free heme and radicals, generated from extracellular hemoglobin. The lipocalin ?1-microglobulin (A1M) was recently shown to have reductase properties, reducing heme-proteins and other substrates, and to scavenge heme and radicals. We investigated the expression and localization of A1M in skin and the possible role of A1M in the protection of skin tissue from damage induced by heme and reactive oxygen species. Skin explants, keratinocyte cultures and purified collagen I were exposed to heme, reactive oxygen species, and/or A1M and investigated by biochemical methods and electron microscopy. The results demonstrate that A1M is localized ubiquitously in the dermal and epidermal layers, and that the A1M-gene is expressed in keratinocytes and up-regulated after exposure to heme and reactive oxygen species. A1M inhibited the heme- and reactive oxygen species-induced ultrastructural damage, up-regulation of antioxidation and cell cycle regulatory genes, and protein carbonyl formation in skin and keratinocytes. Finally, A1M bound to purified collagen I (Kd?=?0.96×10?6 M) and could inhibit and repair the destruction of collagen fibrils by heme and reactive oxygen species. The results suggest that A1M may have a physiological role in protection of skin cells and matrix against oxidative damage following bleeding. PMID:22096585

  8. Polyphenols prevent ageing-related impairment in skeletal muscle mitochondrial function through decreased reactive oxygen species production.

    PubMed

    Charles, Anne-Laure; Meyer, Alain; Dal-Ros, Stéphanie; Auger, Cyril; Keller, Nathalie; Ramamoorthy, Thanuja Gali; Zoll, Joffrey; Metzger, Daniel; Schini-Kerth, Valérie; Geny, Bernard

    2013-02-01

    Ageing is associated with skeletal muscle impairment. Changes in mitochondrial homeostasis are thought to play a key role in this process. This study examined whether chronic intake of polyphenols (PPs), which are known to be modulators of oxidative stress, might prevent the age-related decline of mitochondrial functions in skeletal muscle. Three groups of 10 Wistar rats were investigated. Rats aged 16 weeks were compared with rats aged 40 weeks that were given 75 mg kg(-1) day(-1) PPs or solvent in the drinking water starting at week 16. Mitochondrial respiratory chain complex activities were measured in saponin-skinned fibres of soleus muscles using glutamate-malate (V(max)), succinate (V(succ)) and N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride-ascorbate (V(TMPD)). Production of reactive oxygen species was assessed using dihydroethidium staining. Transcript levels of genes involved in antioxidant defence were determined using RT-PCR. Ageing reduced muscle V(max) (from 8.8 ± 0.45 to 6.17 ± 0.51 ?mol O(2) min(-1) g(-1), -30.5%, P < 0.01), V(TMPD) (from 20.67 ± 1.24 to 16.55 ± 1.16 ?mol O(2) min(-1) g(-1), -19.9%, P < 0.05), increased production of reactive oxygen species (from 100 ± 9.9 to 351.1 ± 31.7%) and decreased transcripts of mitochondrial superoxide dismutase 2 (-59.3%, P < 0.01), peroxisome proliferator-activated receptor ? coactivator-1? (PGC-1?; -61.5%, P < 0.05) and sirtuin 1 (-54.2%, P < 0.05). Chronic PP intake normalized V(max) (8.63 ± 0.63 ?mol O(2) min(-1) g(-1)), decreased production of reactive oxygen species (141.7 ± 16.7%, P < 0.001) and enhanced antioxidant defence (superoxide dismutase 2 expression, +151.3%, P < 0.05) and PGC-1? expression (+185.7%, P < 0.05) in comparison to age-matched untreated rats. The present data indicate that regular intake of PPs starting at a young age prevents age-related mitochondrial respiratory impairment in skeletal muscle, probably through decreased oxidative stress and enhancement of PGC-1? expression. PMID:22903980

  9. Gas-phase Reactive Oxygen and Nitrogen Species in Air Surface Dielectric Barrier Discharges by FTIR and UV spectroscopy

    NASA Astrophysics Data System (ADS)

    Chang, Hung-Wen; Sakiyama, Yukinori; Hsu, Cheng-Che; Graves, David B.

    2012-10-01

    Atmospheric pressure plasmas are considered promising for biomedical treatment purpose due to the production of reactive oxygen species and reactive nitrogen species during the discharge. In this study, a surface micro-discharge system which operates at 10 kHz, 0.01 -- 1 W/cm^2 in ambient air is used. FTIR and UV-absorbance are used to investigate the time-average gas phase composition and time-resolved ozone concentration, respectively. The results showed that the gas composition is greatly influenced by the power consumption in plasmas. At 0.3 W/cm^2, the gas phase is dominant by NOx species and nearly no ozone is observed while at 0.05 W/cm^2 the amount of NOx is less and the ozone is dominant. Also, time-resolved ozone measurement by means of UV (254 nm) absorbance shows that ozone concentration reaches higher than 1000 ppm in the first tens of seconds and quenched within 1 minutes at high power condition. However, at low power condition no obvious quench of ozone is observed and the ozone concentration attains a steady state in response to the equilibrium of ozone generation and diffusion loss

  10. Evidence of the production of hot hydrogen atoms in RF plasmas by catalytic reactions between hydrogen and oxygen species

    E-print Network

    Jonathan Phillips; Chun Ku Chen; Randell Mills

    2005-08-31

    Selective H-atom line broadening was found to be present throughout the volume (13.5 cm ID x 38 cm length) of RF generated H2O plasmas in a GEC cell. Notably, at low pressures (ca. hydrogen was 'hot' with energies greater than 40 eV with a pressure dependence, but only a weak power dependence. The degree of broadening was virtually independent of the position studied within the GEC cell, similar to the recent finding for He/H2 and Ar/H2 plasmas in the same GEC cell. In contrast to the atomic hydrogen lines, no broadening was observed in oxygen species lines at low pressures. Also, in control Xe/H2 plasmas run in the same cell at similar pressures and adsorbed power, no significant broadening of atomic hydrogen, Xe, or any other lines was observed. Stark broadening or acceleration of charged species due to high electric fields can not explain the results since (i) the electron density was insufficient by orders of magnitude, (ii) the RF field was essentially confined to the cathode fall region in contrast to the broadening that was independent of position, and (iii) only the atomic hydrogen lines were broadened. Rather, all of the data is consistent with a model that claims specific, predicted, species can act catalytically through a resonant energy transfer mechanism to create hot hydrogen atoms in plasmas.

  11. Passiflora manicata (Juss.) aqueous leaf extract protects against reactive oxygen species and protein glycation in vitro and ex vivo models.

    PubMed

    da Silva Morrone, Maurilio; de Assis, Adriano Martimbianco; da Rocha, Ricardo Fagundes; Gasparotto, Juciano; Gazola, Andressa Córneo; Costa, Geison Modesti; Zucolotto, Silvana Maria; Castellanos, Leonardo H; Ramos, Freddy A; Schenkel, Eloir Paulo; Reginatto, Flávio Henrique; Gelain, Daniel Pens; Moreira, José C F

    2013-10-01

    The leaf extracts of many species of genus Passiflora have been extensively investigated for their biological activities on several rat tissues, but mainly in the central nervous system and liver. They posses anxiolytic-like, sedative effects and antioxidant properties. Evidences suggest a key role of C-glycosylflavonoids in the biological activities of Passiflora extracts. Some species (such as P. manicata) of the genus are still poorly investigated for their chemical and biological activity. In this work, we aim to investigate both antioxidant and antiglycation properties of aqueous extract of P. manicata leaves (PMLE) in vitro and ex vivo models. Crude extract showed the C-glycosylflavonoid isovitexin as the major compound. Isoorientin and vitexin were also identified. In TRAP/TAR assay, PMLE showed a significant antioxidant activity. PMLE at concentrations of 10 and 100 ?g mL?¹ significantly decreasing LDH leakage in rat liver slices. Antioxidant effect also was observed by decreased in oxidative damage markers in slices hence hydrogen peroxide was added as oxidative stress inductor. PMLE inhibited protein glycation at all concentrations tested. In summary, P. manicata aqueous leaf extract possess protective properties against reactive oxygen species and also protein glycation, and could be considered a new source of natural antioxidants. PMID:23876820

  12. Ubiquity and dominance of oxygenated species in organic aerosols in anthropogenically-influenced Northern Hemisphere midlatitudes

    NASA Astrophysics Data System (ADS)

    Zhang, Q.; Jimenez, J. L.; Canagaratna, M. R.; Allan, J. D.; Coe, H.; Ulbrich, I.; Alfarra, M. R.; Takami, A.; Middlebrook, A. M.; Sun, Y. L.; Dzepina, K.; Dunlea, E.; Docherty, K.; DeCarlo, P. F.; Salcedo, D.; Onasch, T.; Jayne, J. T.; Miyoshi, T.; Shimono, A.; Hatakeyama, S.; Takegawa, N.; Kondo, Y.; Schneider, J.; Drewnick, F.; Borrmann, S.; Weimer, S.; Demerjian, K.; Williams, P.; Bower, K.; Bahreini, R.; Cottrell, L.; Griffin, R. J.; Rautiainen, J.; Sun, J. Y.; Zhang, Y. M.; Worsnop, D. R.

    2007-07-01

    Organic aerosol (OA) data acquired by the Aerosol Mass Spectrometer (AMS) in 37 field campaigns were deconvolved into hydrocarbon-like OA (HOA) and several types of oxygenated OA (OOA) components. HOA has been linked to primary combustion emissions (mainly from fossil fuel) and other primary sources such as meat cooking. OOA is ubiquitous in various atmospheric environments, on average accounting for 64%, 83% and 95% of the total OA in urban, urban downwind, and rural/remote sites, respectively. A case study analysis of a rural site shows that the OOA concentration is much greater than the advected HOA, indicating that HOA oxidation is not an important source of OOA, and that OOA increases are mainly due to SOA. Most global models lack an explicit representation of SOA which may lead to significant biases in the magnitude, spatial and temporal distributions of OA, and in aerosol hygroscopic properties.

  13. Oxygen isotope exchange between carbonic acid, bicarbonate, carbonate, and water: A re-examination of the data of McCrea (1950) and an expression for the overall partitioning of oxygen isotopes between the carbonate species and water

    SciTech Connect

    Usdowski, E.; Hoefs, J. (Geochemisches Institut der Universitaet, Goettingen (Germany))

    1993-08-01

    An examination of McCrea's work (1950) shows that the [sup 18]O/[sup 16]O ratio of rapidly precipitated calcium carbonate depends upon the pH value of the solution and discloses that the oxygen isotope equilibrium fractionation between the sum of the dissolved carbonate species and water is linearly related to the equilibrium between the carbonate species. This relation permits the calculation of fractionation factors for the individual carbonate species and the expression of an overall fractionation factor in terms of individual factors and the oxygen proportions of the carbonate species. The fractionation factors aH[sub 2]CO[sub 3]-H[sub 2]O = 1.0396, aHCO[sub 3][sup [minus

  14. The novel magnecular species of hydrogen and oxygen with increased specific weight and energy content

    Microsoft Academic Search

    Ruggero Maria Santilli

    2003-01-01

    In this paper we review the new chemical species of magnecules introduced in preceding works (see monograph, R.M. Santilli, Foundations of hadronic chemistry with applications to new clean energies and fuels. Boston-Dordrecht-London: Kluwer Academic Publisher, 2001 for a general review), which consist of individual atoms, radicals and ordinary molecules bonded together into stable clusters under a new internal attractive force

  15. Farnesol-induced generation of reactive oxygen species dependent on mitochondrial transmembrane potential hyperpolarization mediated by F 0F 1ATPase in yeast

    Microsoft Academic Search

    Kiyotaka Machida; Toshio Tanaka

    1999-01-01

    An isoprenoid farnesol (FOH) inhibited cellular oxygen consumption and induced mitochondrial generation of reactive oxygen species (ROS) in cells of Saccharomyces cerevisiae in correlation with hyperpolarization of the mitochondrial transmembrane potential (mt??). The FOH-induced events were coordinately abolished with the F1-ATPase inhibitor sodium azide as well as the F0F1-ATPase inhibitor oligomycin, suggesting the dependence of ROS generation on mt?? hyperpolarization

  16. Reactive Oxygen Species and Mitochondrial KATP Channels Mediate Helium-Induced Preconditioning Against Myocardial Infarction In Vivo

    PubMed Central

    Pagel, Paul S.; Krolikowski, John G.; Pratt, Phillip F.; Shim, Yon Hee; Amour, Julien; Warltier, David C.; Weihrauch, Dorothee

    2008-01-01

    Objectives Helium produces preconditioning by activating prosurvival kinases, but the roles of reactive oxygen species (ROS) or mitochondrial KATP channels in this process are unknown. We tested the hypothesis that ROS and mitochondrial KATP channels mediate helium-induced preconditioning in vivo. Design Randomized, prospective study. Setting University research laboratory. Participants Male New Zealand white rabbits. Interventions Rabbits (n=64) were instrumented for measurement of systemic hemodynamics and subjected to a 30 min left anterior descending coronary artery (LAD) occlusion and 3 h reperfusion. In separate experimental groups, rabbits (n=7 or 8 per group) were randomly assigned to receive 0.9% saline (control) or three cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture before LAD occlusion with or without the ROS scavengers N-acetylcysteine (NAC; 150 mg/kg) or N-2-mercaptoproprionyl glycine (2-MPG; 75 mg/kg), or the mitochondrial KATP antagonist 5-hydroxydecanoate (5-HD; 5 mg/kg). Statistical analysis of data was performed with analysis of variance for repeated measures followed by Bonferroni's modification of Student's t test. Measurements and Main Results Myocardial infarct size was determined using triphenyltetrazolium chloride staining and presented as a percentage of the left ventricular area at risk. Helium significantly (P<0.05) reduced infarct size (23±4% of the area at risk; mean±SD) compared with control (46±3%). NAC, 2-MPG, and 5-HD did not affect irreversible ischemic injury when administered alone (49±5, 45±6, and 45±3%), but these drugs blocked reductions in infarct size produced by helium (45±4, 45±2, and 44±3%). Conclusions The results suggest that ROS and mitochondrial KATP channels mediate helium-induced preconditioning in vivo. PMID:18662630

  17. Effect of electron-transport inhibitors on the generation of reactive oxygen species by pea mitochondria during succinate oxidation.

    PubMed

    Popov, V N; Ruuge, E K; Starkov, A A

    2003-07-01

    The effect of inhibitors of the cytochrome pathway and alternative oxidase on the rate of respiration and generation of reactive oxygen species by pea mitochondria was studied. Respiration of mitochondria from pea cotyledons was inhibited by 70-80% by salicylhydroxamate (SHAM). The rate of hydrogen peroxide production by pea cotyledon mitochondria during succinate oxidation was 0.15 nmol/min per mg protein. SHAM considerably accelerated the hydrogen peroxide production. The SHAM-dependent H2O2 production was stimulated by 2 micro M antimycin A and inhibited by 5 mM KCN and 1 micro M myxothiazol. The study of the rate of O2*- generation by pea mitochondria using EPR spin traps and epinephrine oxidation showed that H2O2 accumulation can be accounted for by a significant increase in the rate of O2*- production. PMID:12946256

  18. HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species

    PubMed Central

    Capasso, Melania; Bhamrah, Mandeep K; Henley, Tom; Boyd, Robert S; Langlais, Claudia; Cain, Kelvin; Dinsdale, David; Pulford, Karen; Kan, Mahmood; Musset, Boris; Cherny, Vladimir V; Morgan, Deri; Gascoyne, Randy D; Vigorito, Elena; DeCoursey, Thomas E; MacLennan, Ian C M; Dyer, Martin J S

    2011-01-01

    Voltage-gated proton currents regulate generation of reactive oxygen species (ROS) in phagocytic cells. In B cells, stimulation of the B cell antigen receptor (BCR) results in the production of ROS that participate in B cell activation, but the involvement of proton channels is unknown. We report here that the voltage-gated proton channel HVCN1 associated with the BCR complex and was internalized together with the BCR after activation. BCR-induced generation of ROS was lower in HVCN1-deficient B cells, which resulted in attenuated BCR signaling via impaired BCR-dependent oxidation of the tyrosine phosphatase SHP-1. This resulted in less activation of the kinases Syk and Akt, impaired mitochondrial respiration and glycolysis, and diminished antibody responses in vivo. Our findings identify unanticipated functions for proton channels in B cells and demonstrate the importance of ROS in BCR signaling and downstream metabolism. PMID:20139987

  19. Mountain cedar pollen induces IgE-independent mast cell degranulation, IL-4 production, and intracellular reactive oxygen species generation

    PubMed Central

    Endo, Shuichiro; Hochman, Daniel J.; Midoro-Horiuti, Terumi; Goldblum, Randall M.; Brooks, Edward G.

    2011-01-01

    Cedar pollens cause severe allergic disease throughout the world. We have previously characterized allergenic pollen glycoproteins from mountain cedar (Juniperus ashei) that bind to allergen-specific immunoglobulin E (IgE). In the present report, we investigated an alternative pathway of mast cell activation by mountain cedar pollen extract through IgE-independent mechanisms. We show that mountain cedar pollen directly induces mast cell serotonin and IL-4 release and enhances release induced by IgE cross-linking. Concomitant with mediator release, high levels of intracellular reactive oxygen species (ROS) were generated, and both ROS and serotonin release were inhibited by anti-oxidants. These findings suggest that alternative mechanisms exist whereby pollen exposure enhances allergic inflammatory mediator release through mechanisms that involve ROS. These mechanisms have the potential for enhancing the allergenic potency of pollens. PMID:21944563

  20. TDAG51 deficiency promotes oxidative stress-induced apoptosis through the generation of reactive oxygen species in mouse embryonic fibroblasts

    PubMed Central

    Park, Eui-Soon; Kim, Juhyeok; Ha, Tae-uk; Choi, Jong-Soon; Soo Hong, Kwan; Rho, Jaerang

    2013-01-01

    Apoptosis has an important role in maintaining tissue homeostasis in cellular stress responses such as inflammation, endoplasmic reticulum stress, and oxidative stress. T-cell death-associated gene 51 (TDAG51) is a member of the pleckstrin homology-like domain family and was first identified as a pro-apoptotic gene in T-cell receptor-mediated cell death. However, its pro-apoptotic function remains controversial. In this study, we investigated the role of TDAG51 in oxidative stress-induced apoptotic cell death in mouse embryonic fibroblasts (MEFs). TDAG51 expression was highly increased by oxidative stress responses. In response to oxidative stress, the production of intracellular reactive oxygen species was significantly enhanced in TDAG51-deficient MEFs, resulting in the activation of caspase-3. Thus, TDAG51 deficiency promotes apoptotic cell death in MEFs, and these results indicate that TDAG51 has a protective role in oxidative stress-induced cell death in MEFs. PMID:23928855

  1. Enhancement of the acrolein-induced production of reactive oxygen species and lung injury by GADD34.

    PubMed

    Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Liu, Lintao; Isobe, Ken-ichi

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS). Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2? in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury. PMID:25821552

  2. Enhancement of the Acrolein-Induced Production of Reactive Oxygen Species and Lung Injury by GADD34

    PubMed Central

    Sun, Yang; Ito, Sachiko; Nishio, Naomi; Tanaka, Yuriko; Chen, Nana; Isobe, Ken-ichi

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by lung destruction and inflammation. As a major compound of cigarette smoke, acrolein plays a critical role in the induction of respiratory diseases. GADD34 is known as a growth arrest and DNA damage-related gene, which can be overexpressed in adverse environmental conditions. Here we investigated the effects of GADD34 on acrolein-induced lung injury. The intranasal exposure of acrolein induced the expression of GADD34, developing the pulmonary damage with inflammation and increase of reactive oxygen species (ROS). Conversely, the integrality of pulmonary structure was preserved and the generation of ROS was reduced in GADD34-knockout mice. Acrolein-induced phosphorylation of eIF2? in GADD34-knockout epithelial cells by shRNA protected cell death by reducing misfolded protein-caused oxidative stress. These data indicate that GADD34 participates in the development of acrolein-induced lung injury. PMID:25821552

  3. Preliminary in vitro and ex vivo evaluation of afzelin, kaempferitrin and pterogynoside action over free radicals and reactive oxygen species.

    PubMed

    Vellosa, José Carlos Rebuglio; Regasini, Luis Octávio; Belló, Caroline; Schemberger, Josiane Aparecida; Khalil, Najeh Maissar; de Araújo Morandim-Giannetti, Andreia; da Silva Bolzani, Vanderlan; Brunetti, Iguatemy Lourenço; de Faria Oliveira, Olga Maria Mascarenhas

    2015-06-01

    Biological activities of flavonoids have been extensively reviewed in literature. The biochemical profile of afzelin, kaempferitrin, and pterogynoside acting on reactive oxygen species was investigated in this paper. The flavonoids were able to act as scavengers of the superoxide anion, hypochlorous acid and taurine chloramine. Although flavonoids are naturally occurring substances in plants which antioxidant activities have been widely advertised as beneficial, afzelin, kaempferitrin, and pterogynoside were able to promote cytotoxic effect. In red blood cells this toxicity was enhanced, depending on flavonoids concentration, in the presence of hypochlorous acid, but reduced in the presence of 2,2'-azo-bis(2-amidinopropane) free radical. These flavonoids had also promoted the death of neutrophils, which was exacerbated when the oxidative burst was initiated by phorbol miristate acetate. Therefore, despite their well-known scavenging action toward free radicals and oxidants, these compounds could be very harmful to living organisms through their action over erythrocytes and neutrophils. PMID:25315635

  4. Reactive oxygen species formation and apoptosis in human peripheral blood mononuclear cell induced by 900 MHz mobile phone radiation.

    PubMed

    Lu, Yao-Sheng; Huang, Bao-Tian; Huang, Yao-Xiong

    2012-01-01

    We demonstrate that reactive oxygen species (ROS) plays an important role in the process of apoptosis in human peripheral blood mononuclear cell (PBMC) which is induced by the radiation of 900 MHz radiofrequency electromagnetic field (RFEMF) at a specific absorption rate (SAR) of ~0.4 W/kg when the exposure lasts longer than two hours. The apoptosis is induced through the mitochondrial pathway and mediated by activating ROS and caspase-3, and decreasing the mitochondrial potential. The activation of ROS is triggered by the conformation disturbance of lipids, protein, and DNA induced by the exposure of GSM RFEMF. Although human PBMC was found to have a self-protection mechanism of releasing carotenoid in response to oxidative stress to lessen the further increase of ROS, the imbalance between the antioxidant defenses and ROS formation still results in an increase of cell death with the exposure time and can cause about 37% human PBMC death in eight hours. PMID:22778799

  5. New insights into the functional roles of reactive oxygen species during embryo sac development and fertilization in Arabidopsis thaliana.

    PubMed

    Martin, María Victoria; Distéfano, Ayelén Mariana; Zabaleta, Eduardo Julián; Pagnussat, Gabriela Carolina

    2013-10-01

    Previously considered as toxic by-products of aerobic metabolism, reactive oxygen species (ROS) are emerging as essential signaling molecules in eukaryotes. Recent evidence showed that maintenance of ROS homeostasis during female gametophyte development is crucial for embryo sac patterning and fertilization. Although ROS are exclusively detected in the central cell of mature embryo sacs, the study of mutants deficient in ROS homeostasis suggests that controlled oxidative bursts might take place earlier during gametophyte development. Also, a ROS burst that depends on pollination takes place inside the embryo sac. This oxidative response might be required for pollen tube growth arrest and for sperm cell release. In this mini-review, we will focus on new insights into the role of ROS during female gametophyte development and fertilization. Special focus will be made on the mitochondrial Mn-Superoxide dismutase (MSD1), which has been recently reported to be essential for maintaining ROS homeostasis during embryo sac formation. PMID:23887494

  6. Antioxidant defence systems and generation of reactive oxygen species in osteosarcoma cells with defective mitochondria: effect of selenium.

    PubMed

    Wojewoda, Marta; Duszy?ski, Jerzy; Szczepanowska, Joanna

    2010-01-01

    Mitochondrial diseases originate from mutations in mitochondrial or nuclear genes encoding for mitochondrial proteome. Neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP) syndrome is associated with the T8993G transversion in ATP6 gene which results in substitution at the very conservative site in the subunit 6 of mitochondrial ATP synthase. Defects in the mitochondrial respiratory chain and the ATPase are considered to be accompanied by changes in the generation of reactive oxygen species (ROS). This study aimed to elucidate effects of selenium on ROS and antioxidant system of NARP cybrid cells with 98% of T8993G mutation load. We found that selenium decreased ROS generation and increased the level and activity of antioxidant enzymes such as glutathione peroxidase (GPx) and thioredoxin reductase (TrxR). Therefore, we propose selenium to be a promising therapeutic agent not only in the case of NARP syndrome but also other diseases associated with mitochondrial dysfunctions and oxidative stress. PMID:20138159

  7. Reactive Oxygen Species Formation and Apoptosis in Human Peripheral Blood Mononuclear Cell Induced by 900?MHz Mobile Phone Radiation

    PubMed Central

    Lu, Yao-Sheng; Huang, Bao-Tian; Huang, Yao-Xiong

    2012-01-01

    We demonstrate that reactive oxygen species (ROS) plays an important role in the process of apoptosis in human peripheral blood mononuclear cell (PBMC) which is induced by the radiation of 900?MHz radiofrequency electromagnetic field (RFEMF) at a specific absorption rate (SAR) of ~0.4?W/kg when the exposure lasts longer than two hours. The apoptosis is induced through the mitochondrial pathway and mediated by activating ROS and caspase-3, and decreasing the mitochondrial potential. The activation of ROS is triggered by the conformation disturbance of lipids, protein, and DNA induced by the exposure of GSM RFEMF. Although human PBMC was found to have a self-protection mechanism of releasing carotenoid in response to oxidative stress to lessen the further increase of ROS, the imbalance between the antioxidant defenses and ROS formation still results in an increase of cell death with the exposure time and can cause about 37% human PBMC death in eight hours. PMID:22778799

  8. Reactive Oxygen Species Modulation of Na/K-ATPase Regulates Fibrosis and Renal Proximal Tubular Sodium Handling

    PubMed Central

    Liu, Jiang; Kennedy, David J.; Yan, Yanling; Shapiro, Joseph I.

    2012-01-01

    The Na/K-ATPase is the primary force regulating renal sodium handling and plays a key role in both ion homeostasis and blood pressure regulation. Recently, cardiotonic steroids (CTS)-mediated Na/K-ATPase signaling has been shown to regulate fibrosis, renal proximal tubule (RPT) sodium reabsorption, and experimental Dahl salt-sensitive hypertension in response to a high-salt diet. Reactive oxygen species (ROS) are an important modulator of nephron ion transport. As there is limited knowledge regarding the role of ROS-mediated fibrosis and RPT sodium reabsorption through the Na/K-ATPase, the focus of this review is to examine the possible role of ROS in the regulation of Na/K-ATPase activity, its signaling, fibrosis, and RPT sodium reabsorption. PMID:22518311

  9. Defining the mechanisms by which the reactive oxygen species by-product, 4-hydroxynonenal, affects human sperm cell function.

    PubMed

    Baker, Mark A; Weinberg, Anita; Hetherington, Louise; Villaverde, Ana-Izabel; Velkov, Tony; Baell, Jonathan; Gordon, Christopher P

    2015-04-01

    Lipid peroxidation products such as the naturally occurring aldehyde 4-hydroxynonenal (4-HNE) are known to be cytotoxic toward different cell types, including spermatozoa. In order to understand this at the molecular level, we have employed a proteomic approach to characterize direct 4-HNE adducts on human spermatozoa. Several proteins were identified to be of particular interest, including aldehyde labeling of histone methyltransferase and dynein heavy chain. In addition, we found that 4-HNE bound to part of the activation segment, cysteine residue 199, of protein kinase A (PKA). Interestingly, at low levels, addition of 4-HNE had a stimulatory effect on PKA. However, this did not correlate to increased phosphotyrosine levels during capacitation. This data explains the link between reactive oxygen species and sperm toxicity. Given that epigenetic regulation is likely affected in oxidative-stressed spermatozoa, this data show that spermatozoa appear to shut down under these conditions before reaching the egg. PMID:25673561

  10. High levels of reactive oxygen species in gold nanoparticle-targeted cancer cells following femtosecond pulse irradiation

    PubMed Central

    Minai, Limor; Yeheskely-Hayon, Daniella; Yelin, Dvir

    2013-01-01

    Cancer cells could be locally damaged using specifically targeted gold nanoparticles and laser pulse irradiation, while maintaining minimum damage to nearby, particle-free tissue. Here, we show that in addition to the immediate photothermal cell damage, high concentrations of reactive oxygen species (ROS) are formed within the irradiated cells. Burkitt lymphoma B cells and epithelial breast cancer cells were targeted by antibody-coated gold nanospheres and irradiated by a few resonant femtosecond pulses, resulting in significant elevation of intracellular ROS which was characterized and quantified using time-lapse microscopy of different fluorescent markers. The results suggest that techniques that involve targeting of various malignancies using gold nanoparticles and ultrashort pulses may be more effective and versatile than previously anticipated, allowing diverse, highly specific set of tools for local cancer therapy. PMID:23828378

  11. Examination of the mechanism of phenanthrenequinone toxicity to Vibrio fischeri: evidence for a reactive oxygen species-mediated toxicity mechanism.

    PubMed

    Wang, Wenxi; Nykamp, Julie; Huang, Xiao-Dong; Gerhardt, Karen; Dixon, D George; Greenberg, Bruce M

    2009-08-01

    Phenanthrenequinone (PHQ) is a photoproduct of phenanthrene, one of the most prevalent polycyclic aromatic hydrocarbons in the environment. Phenanthrenequinone is a compound of substantial interest, because its toxicity can be much greater than its parent chemical to aquatic organisms. The toxicity mechanisms of PHQ to the luminescent marine bacterium Vibrio fischeri were examined in the present study. Phenanthrenequinone can redox cycle in bacterial cells and transfer electrons to O2, enhancing the production of superoxide (O*2-), hydrogen peroxide (H2O2), and other reactive oxygen species (ROS). Exposure of cells to PHQ increased activity of superoxide dismutase (SOD), which detoxifies the ROS superoxide. Concentrations of PHQ that induced the production of H2O2 and other ROS, as well as the elevated levels of Fe-SOD, were correlated with its toxicity as measured by luminescence. Furthermore, toxicity of PHQ to V. fischeri was lowered under the anaerobic conditions, suggesting that the absence of oxygen, which would limit the production of ROS, alleviated toxicity of PHQ. Thus, a ROS-mediated toxicity mechanism of PHQ is highly implicated by in the present study. PMID:19265456

  12. Chemiluminescence assay for quinones based on generation of reactive oxygen species through the redox cycle of quinone.

    PubMed

    Kishikawa, Naoya; Ohkubo, Nobuhiro; Ohyama, Kaname; Nakashima, Kenichiro; Kuroda, Naotaka

    2009-02-01

    A sensitive and selective chemiluminescence assay for the determination of quinones was developed. The method was based on generation of reactive oxygen species through the redox reaction between quinone and dithiothreitol as reductant, and then the generated reactive oxygen was detected by luminol chemiluminescence. The chemiluminescence was intense, long-lived, and proportional to quinone concentration. It is concluded that superoxide anion was involved in the proposed chemiluminescence reaction because the chemiluminescence intensity was decreased only in the presence of superoxide dismutase. Among the tested quinones, the chemiluminescence was observed from 9,10-phenanthrenequinone, 1,2-naphthoquinone, and 1,4-naphthoquinone, whereas it was not observed from 9,10-anthraquinone and 1,4-benzoquinone. The chemiluminescence property was greatly different according to the structure of quinones. The chemiluminescence was also observed for biologically important quinones such as ubiquinone. Therefore, a simple and rapid assay for ubiquinone in pharmaceutical preparation was developed based on the proposed chemiluminescence reaction. The detection limit (blank + 3SD) of ubiquinone was 0.05 microM (9 ng/assay) with an analysis time of 30 s per sample. The developed assay allowed the direct determination of ubiquinone in pharmaceutical preparation without any purification procedure. PMID:19066858

  13. Blue-light dependent reactive oxygen species formation by Arabidopsis cryptochrome may define a novel evolutionarily conserved signaling mechanism.

    PubMed

    Consentino, Laurent; Lambert, Stefan; Martino, Carlos; Jourdan, Nathalie; Bouchet, Pierre-Etienne; Witczak, Jacques; Castello, Pablo; El-Esawi, Mohamed; Corbineau, Francoise; d'Harlingue, Alain; Ahmad, Margaret

    2015-06-01

    Cryptochromes are widespread blue-light absorbing flavoproteins with important signaling roles. In plants they mediate de-etiolation, developmental and stress responses resulting from interaction with downstream signaling partners such as transcription factors and components of the proteasome. Recently, it has been shown that Arabidopsis cry1 activation by blue light also results in direct enzymatic conversion of molecular oxygen (O2 ) to reactive oxygen species (ROS) and hydrogen peroxide (H2 O2 ) in vitro. Here we explored whether direct enzymatic synthesis of ROS by Arabidopsis cry1 can play a physiological role in vivo. ROS formation resulting from cry1 expression was measured by fluorescence assay in insect cell cultures and in Arabidopsis protoplasts from cryptochrome mutant seedlings. Cell death was determined by colorimetric assay. We found that ROS formation results from cry1 activation and induces cell death in insect cell cultures. In plant protoplasts, cryptochrome activation results in rapid increase in ROS formation and cell death. We conclude that ROS formation by cryptochromes may indeed be of physiological relevance and could represent a novel paradigm for cryptochrome signaling. PMID:25728686

  14. Mutational spectrum of bleomycin in lacZ mouse kidney: a possible model for mutational spectrum of reactive oxygen species.

    PubMed

    Guttenplan, Joseph B; Khmelnitsky, Michael; Haesevoets, Roderick; Kosinska, Wieslawa

    2004-10-01

    The mutational spectrum of bleomycin was compared with the spontaneous mutational spectrum in lacZ mouse kidney. Mice were treated with four 20 mg/kg of doses of bleomycin over a two-week period, leading to a mutant fraction several times greater than that of controls. The major class of bleomycin-induced mutations consisted of small deletions, in particular -1 deletions at AT base pairs and hot spots for deletions at 5'-GTC-3' sequences. Smaller, but significant fractions of GC > AT followed by GC > TA substitutions were also observed. In untreated mice, the major class of mutations consisted of GC > AT substitutions followed by GC > TA mutations, and a much smaller fraction of deletions. Other than the specificity of bleomycin for AT base pairs and the 5'-GTC-3' hotspots, the mutational spectrum of bleomycin in mice is similar to that reported for ionizing radiation. However, bleomycin initially mediates the formation of oxidized DNA via reduction of molecular oxygen, as opposed to the radiolysis of water. In this respect mutagenesis induced by bleomycin may be more similar to that induced by endogenous reactive oxygen species (ROS) than mutagenesis induced by ionizing radiation. If bleomycin-induced mutagenesis is an appropriate model for mutagenesis induced by ROS, then, based on the difference between the mutational spectrum of bleomycin and spontaneous mutagenesis, the latter appears not to result predominantly from ROS, at least in mouse kidney. PMID:15450417

  15. Reactive Oxygen Species-Mediated Mitochondria-to-Nucleus Signaling: A Key to Aging and Radical-Caused Diseases

    NSDL National Science Digital Library

    Peter Storz (Mayo Clinic Comprehensive Cancer Center; Department of Cancer Biology REV)

    2006-04-25

    The mitochondrial respiratory chain generates reactive oxygen species (ROS), oxygen-containing molecules that are chemically reactive because they contain unpaired electrons, as a by-product of aerobic metabolism. These ROS are rapidly detoxified by antioxidant proteins. The failure of effective detoxification of cells from mROS contributes to aging and has been implicated in the development and progression of age-related diseases. ROS can be decreased by dietary antioxidants or by antioxidant proteins, which are encoded by nuclear genes. Because the source of ROS and the location of gene regulation are separated, mitochondria-to-nucleus signaling is thought to regulate cellular detoxification. Notable advances have been made in identifying the protective signaling pathways that are activated by increased intracellular oxidant levels. There is increasing evidence that protein oxidation directly regulates phosphatases and kinases. Some of these signaling molecules appear to function as ROS sensors that initiate signaling from the mitochondria to the nucleus. Understanding how the mitochondrion signals to the nucleus to regulate antioxidant proteins might be useful in efforts to extend life span in humans or to improve treatments for neurodegenerative or other diseases influenced by ROS.

  16. A heteroplasmic, not homoplasmic, mitochondrial DNA mutation promotes tumorigenesis via alteration in reactive oxygen species generation and apoptosis

    PubMed Central

    Park, Jeong Soon; Sharma, Lokendra Kumar; Li, Hongzhi; Xiang, Ruihua; Holstein, Deborah; Wu, Jun; Lechleiter, James; Naylor, Susan L.; Deng, Janice J.; Lu, Jianxin; Bai, Yidong

    2009-01-01

    Mitochondrial alteration has been long proposed to play a major role in tumorigenesis. Recently, mitochondrial DNA (mtDNA) mutations have been found in a variety of cancer cells. In this study, we examined the contribution of mtDNA mutation and mitochondrial dysfunction in tumorigenesis first using human cell lines carrying a frame-shift at NADH dehydrogenase (respiratory complex I) subunit 5 gene (ND5); the same homoplasmic mutation was also identified in a human colorectal cancer cell line earlier. With increasing mutant ND5 mtDNA content, respiratory function including oxygen consumption and ATP generation through oxidative phosphorylation declined progressively, while lactate production and dependence on glucose increased. Interestingly, the reactive oxygen species (ROS) levels and apoptosis exhibited antagonistic pleiotropy associated with mitochondrial defects. Furthermore, the anchorage-dependence phenotype and tumor-forming capacity of cells carrying wild-type and mutant mtDNA were tested by growth assay in soft agar and subcutaneous implantation of the cells in nude mice. Surprisingly, the cell line carrying the heteroplasmic ND5 mtDNA mutation showed significantly enhanced tumor growth, while cells with homoplasmic form of the same mutation inhibited tumor formation. Similar results were obtained from the analysis of a series of mouse cell lines carrying a nonsense mutation at ND5 gene. Our results indicate that the mtDNA mutations might play an important role in the early stage of cancer development, possibly through alteration of ROS generation and apoptosis. PMID:19208652

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

    PubMed

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

    2014-12-12

    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. PMID:25446085

  18. Physicochemical mechanism of the interaction between cobalt metal and carbide particles to generate toxic activated oxygen species.

    PubMed

    Lison, D; Carbonnelle, P; Mollo, L; Lauwerys, R; Fubini, B

    1995-06-01

    Hard metal alloys (or cemented carbides) are made of a mixture of tungsten carbide particles (WC, more than 80%) cemented in cobalt metal powder (Co, 5-10%). The inhalation of hard metal particles may cause an interstitial pulmonary disease, the mechanism of which involves an interaction between Co and WC particles. Some epidemiological data also suggest that hard metal dust can induce lung cancer in workers. In a macrophage culture model, butylated hydroxytoluene (1 mM) protected from the cytotoxicity of hard metal particles, suggesting a possible involvement of lipid peroxidation in the toxicity of these powders. In a biochemical system, a mixture of Co and WC particles, but not Co or WC alone, stimulated the production of thiobarbituric acid-reactive substances from arachidonic acid. Using a spin trapping system applied to aqueous particulate suspensions and electrochemical techniques, we present experimental evidence that the association of Co and carbide particles represents a specific toxic entity producing large amounts of activated oxygen species. The mechanism of this interaction proceeds through the oxidation of cobalt metal catalyzed at the surface of carbide particles and resulting in the reduction of dissolved oxygen. This physicochemical property of hard metal particles provides a new basis for interpreting their inflammatory action and their possible carcinogenic effect on the lung. PMID:7548741

  19. Donor ligand effect on the nature of the oxygenating species in Mn(III)(salen)-catalyzed epoxidation of olefins: experimental evidence for multiple active oxidants.

    PubMed

    Collman, James P; Zeng, Li; Brauman, John I

    2004-04-19

    The stereoselectivity of olefin epoxidation catalyzed by Mn(III)(salen)X (1a, X = Cl(-); 1b, X = BF(4)(-)) complexes is examined in the presence of neutral donor ligands, employing various iodosylarenes (ArIO: PhIO, C(6)F(5)IO, and MesIO) as the oxygen atom source. The cis/trans ratios of stilbene oxides and the enantiomeric excesses of styrene oxide and 1,2-dihydronaphthalene oxide are found to be strongly dependent on the nature of the iodosylarenes under certain conditions. In other cases, olefin epoxidation is shown to proceed with essentially identical diastereoselectivities or enantioselectivities, regardless of the oxygen atom source used. We propose that a Mn(V)(salen)-oxo intermediate and a complex between the catalyst and the terminal oxidant competitively effect the epoxidation when the stereoselectivities are markedly dependent on the oxygen atom source. A single Mn(V)(salen)-oxo species is considered to be the sole oxygenating intermediate when the terminal oxidants do not exert a notable influence on the product selectivities. Our results clearly demonstrate the existence of multiple oxidizing species and the conditions in which only a single oxygenating intermediate is involved. The axial donor ligands (both anionic ligands and neutral ligands) are shown to strongly influence both the identity and the reactivity of the oxygenating species. PMID:15074985

  20. Glutathione prevents preterm parturition and fetal death by targeting macrophage-induced reactive oxygen species production in the myometrium.

    PubMed

    Hadi, Tarik; Bardou, Marc; Mace, Guillaume; Sicard, Pierre; Wendremaire, Maeva; Barrichon, Marina; Richaud, Sarah; Demidov, Oleg; Sagot, Paul; Garrido, Carmen; Lirussi, Frédéric

    2015-06-01

    Preterm birth is an inflammatory process resulting from the massive infiltration of innate immune cells and the production of proinflammatory cytokines in the myometrium. However, proinflammatory cytokines, which induce labor in vivo, fail to induce labor-associated features in human myometrial cells (MCs). We thus aimed to investigate if reactive oxygen species (ROS) production could be the missing step between immune cell activation and MC response. Indeed, we found that ROS production is increased in the human preterm laboring myometrium (27% ROS producing cells, respectively, versus 2% in nonlaboring controls), with 90% ROS production in macrophages. Using LPS-stimulated myometrial samples and cell coculture experiments, we demonstrated that ROS production is required for labor onset. Furthermore, we showed that ROS are required first in the NADPH oxidase (NADPHox)-2/NF-?B-dependent macrophage response to inflammatory stimuli but, more importantly, to trigger macrophage-induced MCs transactivation. Remarkably, in a murine model of LPS-induced preterm labor (inducing delivery within 17 hours, with no pup survival), cotreatment with glutathione delayed labor onset up to 94 hours and prevented in utero fetal distress, allowing 46% pups to survive. These results suggest that targeting ROS production with the macrophage-permeable antioxidant glutathione could constitute a promising strategy to prevent preterm birth.- Hadi, T., Bardou, M., Mace, G., Sicard, P., Wendremaire, M., Barrichon, M., Richaud, S., Demidov, O., Sagot, P., Garrido, C., Lirussi, F. Glutathione prevents preterm parturition and fetal death by targeting macrophage-induced reactive oxygen species production in the myometrium. PMID:25757563

  1. Thrombospondin-1 Activation of Signal-Regulatory Protein-? Stimulates Reactive Oxygen Species Production and Promotes Renal Ischemia Reperfusion Injury

    PubMed Central

    Yao, Mingyi; Rogers, Natasha M.; Csányi, Gábor; Rodriguez, Andres I.; Ross, Mark A.; St. Croix, Claudette; Knupp, Heather; Novelli, Enrico M.; Thomson, Angus W.; Pagano, Patrick J.

    2014-01-01

    Ischemia reperfusion injury (IRI) causes tissue and organ injury, in part, through alterations in tissue blood flow and the production of reactive oxygen species. The cell surface receptor signal-regulatory protein-? (SIRP-?) is expressed on inflammatory cells and suppresses phagocytosis, but the function of SIRP-? in IRI has not been determined. We reported previously that the matricellular protein thrombospondin-1 is upregulated in IRI. Here, we report a novel interaction between thrombospondin-1 and SIRP-? on nonphagocytic cells. In cell-free experiments, thrombospondin-1 bound SIRP-?. In vascular smooth muscle cells and renal tubular epithelial cells, treatment with thrombospondin-1 led to phosphorylation of SIRP-? and downstream activation of Src homology domain 2–containing phosphatase-1. Thrombospondin-1 also stimulated phosphorylation of p47phox (an organizer subunit for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1/2) and increased production of superoxide, both of which were abrogated by knockdown or antibody blockade of SIRP-?. In rodent aortic rings, treatment with thrombospondin-1 increased the production of superoxide and inhibited nitric oxide–mediated vasodilation in a SIRP-?–dependent manner. Renal IRI upregulated the thrombospondin-1–SIRP-? signaling axis and was associated with increased superoxide production and cell death. A SIRP-? antibody that blocks thrombospondin-1 activation of SIRP-? mitigated the effects of renal IRI, increasing blood flow, suppressing production of reactive oxygen species, and preserving cellular architecture. A role for CD47 in SIRP-? activation in these pathways is also described. Overall, these results suggest that thrombospondin-1 binding to SIRP-? on nonphagocytic cells activates NADPH oxidase, limits vasodilation, and promotes renal IRI. PMID:24511121

  2. Reactive oxygen species and oxidative DNA damage mediate the cytotoxicity of tungsten-nickel-cobalt alloys in vitro

    SciTech Connect

    Harris, R.M.; Williams, T.D.; Hodges, N.J.; Waring, R.H., E-mail: R.H.Waring@bham.ac.uk

    2011-01-01

    Tungsten alloys (WA) have been introduced in an attempt to find safer alternatives to depleted uranium and lead munitions. However, it is known that at least one alloy, 91% tungsten-6% nickel-3% cobalt (WNC-91-6-3), causes rhabdomyosarcomas when fragments are implanted in rat muscle. This raises concerns that shrapnel, if not surgically removable, may result in similar tumours in humans. There is therefore a clear need to develop rapid and robust in vitro methods to characterise the toxicity of different WAs in order to identify those that are most likely to be harmful to human health and to guide development of new materials in the future. In the current study we have developed a rapid visual in vitro assay to detect toxicity mediated by individual WA particles in cultured L6-C11 rat muscle cells. Using a variety of techniques (histology, comet assay, caspase-3 activity, oxidation of 2'7'-dichlorofluorescin to measure the production of reactive oxygen species and whole-genome microarrays) we show that, in agreement with the in vivo rat carcinogenicity studies, WNC-91-6-3 was the most toxic of the alloys tested. On dissolution, it produces large amounts of reactive oxygen species, causes significant amounts of DNA damage, inhibits caspase-3, triggers a severe hypoxic response and kills the cells in the immediate vicinity of the alloy particles within 24 h. By combining these in vitro data we offer a mechanistic explanation of the effect of this alloy in vivo and show that in vitro tests are a viable alternative for assessing new alloys in the future.

  3. Reactive oxygen species and oxidative DNA damage mediate the cytotoxicity of tungsten-nickel-cobalt alloys in vitro.

    PubMed

    Harris, R M; Williams, T D; Hodges, N J; Waring, R H

    2011-01-01

    Tungsten alloys (WA) have been introduced in an attempt to find safer alternatives to depleted uranium and lead munitions. However, it is known that at least one alloy, 91% tungsten-6% nickel-3% cobalt (WNC-91-6-3), causes rhabdomyosarcomas when fragments are implanted in rat muscle. This raises concerns that shrapnel, if not surgically removable, may result in similar tumours in humans. There is therefore a clear need to develop rapid and robust in vitro methods to characterise the toxicity of different WAs in order to identify those that are most likely to be harmful to human health and to guide development of new materials in the future. In the current study we have developed a rapid visual in vitro assay to detect toxicity mediated by individual WA particles in cultured L6-C11 rat muscle cells. Using a variety of techniques (histology, comet assay, caspase-3 activity, oxidation of 2'7'-dichlorofluorescin to measure the production of reactive oxygen species and whole-genome microarrays) we show that, in agreement with the in vivo rat carcinogenicity studies, WNC-91-6-3 was the most toxic of the alloys tested. On dissolution, it produces large amounts of reactive oxygen species, causes significant amounts of DNA damage, inhibits caspase-3, triggers a severe hypoxic response and kills the cells in the immediate vicinity of the alloy particles within 24h. By combining these in vitro data we offer a mechanistic explanation of the effect of this alloy in vivo and show that in vitro tests are a viable alternative for assessing new alloys in the future. PMID:20934443

  4. The SUMO E3-ligase PIAS1 couples reactive oxygen species-dependent JNK activation to oxidative cell death

    PubMed Central

    Leitao, Beatriz B.; Jones, Marius C.; Brosens, Jan J.

    2011-01-01

    Human endometrial stromal cells (HESCs) exposed to reactive oxygen species (ROS) mount a hypersumoylation response in a c-Jun N-terminal kinase (JNK)-dependent manner. The mechanism that couples JNK signaling to the small ubiquitin-related modifier (SUMO) pathway and its functional consequences are not understood. We show that ROS-dependent JNK activation converges on the SUMO pathway via PIAS1 (protein inhibitor of activated STAT1). Unexpectedly, PIAS1 knockdown not only prevented ROS-dependent hypersumoylation but also enhanced JNK signaling in HESCs. Conversely, PIAS overexpression increased sumoylation of various substrates, including c-Jun, yet inhibited basal and ROS-dependent JNK activity independently of its SUMO ligase function. Expression profiling demonstrated that PIAS1 knockdown enhances and profoundly modifies the transcriptional response to oxidative stress signals. Using a cutoff of 2-fold change or more, a total of 250 ROS-sensitive genes were identified, 97 of which were not dependent on PIAS1. PIAS1 knockdown abolished the regulation of 43 genes but also sensitized 110 other genes to ROS. Importantly, PIAS1 silencing was obligatory for the induction of several cellular defense genes in response to oxidative stress. In agreement, PIAS1 knockdown attenuated ROS-dependent caspase-3/7 activation and subsequent apoptosis. Thus, PIAS1 determines the level of JNK activity in HESCs, couples ROS signaling to the SUMO pathway, and promotes oxidative cell death.—Leitao, B. B., Jones, M. C., Brosens, J. J. The SUMO E3-ligase PIAS1 couples reactive oxygen species-dependent JNK activation to oxidative cell death. PMID:21676946

  5. Overproduction of lignin peroxidase by Phanerochaete chrysosporium (BKM-F-1767) under nonlimiting nutrient conditions.

    PubMed

    Dosoretz, C G; Rothschild, N; Hadar, Y

    1993-06-01

    The ligninolytic enzymes synthesized by Phanerochaete chrysosporium BKM-F-1767 immobilized on polyurethane foam were characterized under limiting, sufficient, and excess nutrient conditions. The fungus was grown in a nonimmersed liquid culture system under conditions close to those occurring in nature, with nitrogen concentrations ranging from 2.4 to 60 mM. This nonimmersed liquid culture system consisted of fungal mycelium immobilized on porous pieces of polyurethane foam saturated with liquid medium and highly exposed to gaseous oxygen. Lignin peroxidase (LIP) activity decreased to almost undetectable levels as the initial NH4+ levels were increased over the range from 2.4 to 14 mM and then increased with additional increases in initial NH4+ concentration. At 45 mM NH4+, LIP was overproduced, reaching levels of 800 U/liter. In addition, almost simultaneous secretion of LIP and secretion of manganese-dependent lignin peroxidase were observed on the third day of incubation. Manganese-dependent lignin peroxidase activity was maximal under nitrogen limitation conditions (2.4 mM NH4+) and then decreased to 40 to 50% of the maximal level in the presence of sufficient or excess initial NH4+ concentrations. Overproduction of LIP in the presence of a sufficient nitrogen level (24 mM NH4+) and excess nitrogen levels (45 to 60 mM NH4+) seemed to occur as a response to carbon starvation after rapid glucose depletion. The NH4+ in the extracellular fluid reappeared as soon as glucose was depleted, and an almost complete loss of CO2 was observed, suggesting that an alternative energy source was generated by self-proteolysis of cell proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8328807

  6. Psidium cattleianum fruit extracts are efficient in vitro scavengers of physiologically relevant reactive oxygen and nitrogen species.

    PubMed

    Ribeiro, Alessandra Braga; Chisté, Renan Campos; Freitas, Marisa; da Silva, Alex Fiori; Visentainer, Jesuí Vergílio; Fernandes, Eduarda

    2014-12-15

    Psidium cattleianum, an unexploited Brazilian native fruit, is considered a potential source of bioactive compounds. In the present study, the in vitro scavenging capacity of skin and pulp extracts from P. cattleianum fruits against reactive oxygen species (ROS) and reactive nitrogen species (RNS) was evaluated by in vitro screening assays. Additionally, the composition of phenolic compounds and carotenoids in both extracts was determined by LC-MS/MS. The major phenolic compounds identified and quantified (dry matter) in the skin and pulp extracts of P. cattleianum were ellagic acid (2213-3818 ?g/g extracts), ellagic acid deoxyhexoside (1475-2,070 ?g/g extracts) and epicatechin gallate (885-1,603 ?g/g extracts); while all-trans-lutein (2-10 ?g/g extracts), all-trans-antheraxanthin (1.6-9 ?g/g extracts) and all-trans-?-carotene (4-6 ?g/g extracts) were the major carotenoids identified in both extracts. P. cattleianum pulp extract showed higher scavenging capacity than skin extract for all tested ROS and RNS. Considering the potential beneficial effects to human health, P. cattleianum may be considered as a good source of natural antioxidants and may be useful for the food and phytopharmaceutical industry. PMID:25038660

  7. The ubiquitin–proteasome pathway protects Chlamydomonas reinhardtii against selenite toxicity, but is impaired as reactive oxygen species accumulate

    PubMed Central

    Vallentine, Patrick; Hung, Chiu-Yueh; Xie, Jiahua; Van Hoewyk, Doug

    2014-01-01

    The ubiquitin–proteasome pathway (UPP) coordinates a myriad of physiological processes in higher plants, including abiotic stress responses, but it is less well characterized in algal species. In this study, the green alga Chlamydomonas reinhardtii was used to gain insights into the role of the UPP during moderate and severe selenite stress at three different time points. The data indicate that activity of the UPP in response to selenium (Se) stress was both time and dose dependent. Moderate selenite stress increased proteasome activity, protein ubiquitination and the proteasomal removal of malformed selenoproteins. However, severe Se stress caused by prolonged selenite treatment or high selenite concentration decreased proteasome activity, inhibited protein ubiquitination and prevented the proteasomal removal of selenoproteins. The UPP impairment during severe Se stress was associated with the observed accumulation of reactive oxygen species (ROS), including mitochondrial superoxide. Additionally, proteasomal inhibition decreased the concentration of chlorophyll in cultures challenged with Se. Therefore, although the UPP protects Chlamydomonas against Se stress, severe oxidative stress induced by selenite toxicity likely hinders the UPP's capacity to mediate a stress response. The possibility that stress tolerance in plants is dependent upon optimal UPP activity and maintenance is discussed. PMID:25301821

  8. Cadmium generates reactive oxygen- and carbon-centered radical species in rats: insights from in vivo spin-trapping studies.

    PubMed

    Liu, Jie; Qian, Steven Y; Guo, Qiong; Jiang, JinJie; Waalkes, Michael P; Mason, Ronald P; Kadiiska, Maria B

    2008-08-15

    Cadmium (Cd) is a known industrial and environmental pollutant. In the present work, an in vivo spin-trapping technique was used in conjunction with electron spin resonance (ESR) spectroscopy to investigate free radical generation in rats following administration of cadmium chloride (CdCl2, 40 micromol/kg) and the spin trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN, 1 g/kg). In Cd-treated rats, POBN radical adducts were formed in the liver, were excreted into the bile, and exhibited an ESR spectrum consistent with a carbon-centered radical species probably derived from endogenous lipids. Isotope substitution of dimethyl sulfoxide [(CH3)2SO] with 13C demonstrated methyl radical formation (POBN/*13CH3). This adduct indicated the production of hydroxyl radical, which reacted with [(13CH3)2SO] to form *13CH3, which then reacted with POBN to form POBN/*13CH3. Depletion of hepatic glutathione by diethyl maleate significantly increased free radical production, whereas inactivation of Kupffer cells by gadolinium chloride and chelation of iron by desferal inhibited it. Treatment with the xanthine oxidase inhibitor allopurinol, the catalase inhibitor aminobenzotriazole, or the cytochrome P450 inhibitor 3-amino-1,2,4-triazole had no effect. This is the first study to show Cd generation of reactive oxygen- and carbon-centered radical species by involvement of both iron mediation through iron-catalyzed reactions and activation of Kupffer cells, the resident liver macrophages. PMID:18501199

  9. Reactive oxygen species alter gene expression in podocytes: induction of granulocyte macrophage-colony-stimulating factor.

    PubMed

    Greiber, Stefan; Müller, Barbara; Daemisch, Petra; Pavenstädt, Hermann

    2002-01-01

    It has been suggested that reactive oxygen radicals (ROS) play a crucial role in the pathogenesis of proteinuria and podocyte injury. It was investigated whether changes in gene expression might account for ROS-induced podocyte dysfunction. Differentiated podocytes were incubated with control media or with exogenous ROS from the xanthine/xanthine-oxidase reaction for 4 h. A PCR-based suppressive subtractive hybridization assay was applied to isolate and clone mRNAs that were differentially expressed by exogenous ROS. One differentially expressed clone was identified as the proinflammatory cytokine granulocyte macrophage-colony-stimulating factor (GM-CSF). Regulation of GM-CSF in podocytes was further studied by Northern analysis and enzyme-linked immunosorbent assay. Exogenous ROS caused a concentration-dependent, >10-fold induction of GM-CSF mRNA after 4 h. A >50-fold increase in GM-CSF protein release in podocytes that had been stimulated with ROS could be detected. Induction of GM-CSF protein was inhibited by actinomycin D, which indicated that increased mRNA transcription was involved. The ROS scavengers dimethyl-thio-urea and pyrrolidone-dithio-carbamate strongly inhibited increased GM-CSF production induced by ROS. GM-CSF release was also induced when internal ROS production was triggered with NADH, whereas H2O2 had only a small effect. GM-CSF release by podocytes was also stimulated by lipopolysaccharide (LPS), interleukin-1 (IL-1), and phorbolester (PMA). Dimethyl-thio-urea significantly inhibited the LPS-, IL-1-, and PMA-induced GM-CSF production. Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) but not activator protein-1 was involved in the upregulation of ROS-induced GM-CSF production. The data indicate that GM-CSF is differentially expressed by ROS in podocytes. ROS also partially mediate the effects of PMA and IL-1 on podocyte GM-CSF production. Because GM-CSF can enhance glomerular inflammation and induces mesangial proliferation, these data might provide further insight into the mechanisms of ROS-induced glomerular injury. PMID:11752025

  10. H2S Inhibits Hyperglycemia-Induced Intrarenal Renin-Angiotensin System Activation via Attenuation of Reactive Oxygen Species Generation

    PubMed Central

    Ni, Jun; Li, Chen; Shao, Decui; Liu, Jia; Shen, Yang; Wang, Zhen; Zhou, Li; Zhang, Wei; Huang, Yu; Yu, Chen; Wang, Rui; Lu, Limin

    2013-01-01

    Decrease in endogenous hydrogen sulfide (H2S) was reported to participate in the pathogenesis of diabetic nephropathy (DN). This study is aimed at exploring the relationship between the abnormalities in H2S metabolism, hyperglycemia-induced oxidative stress and the activation of intrarenal renin-angiotensin system (RAS). Cultured renal mesangial cells (MCs) and streptozotocin (STZ) induced diabetic rats were used for the studies. The expressions of angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin II (Ang II) type I receptor (AT1), transforming growth factor-?1 (TGF-?1) and collagen IV were measured by real time PCR and Western blot. Reactive oxygen species (ROS) production was assessed by fluorescent probe assays. Cell proliferation was analyzed by 5'-bromo-2'-deoxyuridine incorporation assay. Ang II concentration was measured by an enzyme immunoassay. AGT, ACE and AT1 receptor mRNA levels and Ang II concentration were increased in high glucose (HG) -treated MCs, the cell proliferation rate and the production of TGF-?1 and of collagen IV productions were also increased. The NADPH oxidase inhibitor diphenylenechloride iodonium (DPI) was able to reverse the HG-induced RAS activation and the changes in cell proliferation and collagen synthesis. Supplementation of H2S attenuated HG-induced elevations in ROS and RAS activation. Blockade on H2S biosynthesis from cystathione-?-lyase (CSE) by DL-propargylglycine (PPG) resulted in effects similar to that of HG treatment. In STZ-induced diabetic rats, the changes in RAS were also reversed by H2S supplementation without affecting blood glucose concentration. These data suggested that the decrease in H2S under hyperglycemic condition leads to an imbalance between oxidative and reductive species. The increased oxidative species results in intrarenal RAS activation, which, in turn, contributes to the pathogenesis of renal dysfunction. PMID:24058553

  11. Reactions of iron clusters with oxygen and ethylene: Observation of particularly stable species

    NASA Astrophysics Data System (ADS)

    Huisken, F.; Kohn, B.; Alexandrescu, R.; Morjan, I.

    2000-10-01

    Iron clusters have been produced by CO2-laser-induced decomposition of iron pentacarbonyl in a flow reactor. The absorption of CO2 laser photons was achieved by using SF6 as a sensitizer. By adding an oxidizing gas, N2O, or a hydrocarbon, C2H4, molecules which are also dissociated in the laser field, the iron clusters may react with several radicals. The as-synthesized species are extracted from the reaction zone by a conical nozzle and expanded into the source chamber of a cluster beam apparatus where they are analyzed with a time-of-flight mass spectrometer. In the experiment with N2O, we observe a magic peak at m=856 amu which can be readily assigned to the particularly stable Fe13O8 cluster. If C2H4 is added to the reactant gas, the mass spectrum reveals a magic peak at mass m=884 amu. Using deuterated ethylene, the magic peak shifts by 12 amu to larger masses, indicating that the magic cluster contains 12 hydrogen atoms. With the given restrictions, we readily derive the molecular formula Fe13C12H12. Chemical stability and symmetry considerations suggest that the detailed chemical formula of the magic cluster is Fe13(C2H2)6 and that its structure corresponds to a Fe13 icosahedron with six HC=CH or C=CH2 groups bound to six pairs of the 12 iron surface atoms.

  12. Reactive oxygen species regulated mitochondria-mediated apoptosis in PC12 cells exposed to chlorpyrifos

    SciTech Connect

    Lee, Jeong Eun [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of) [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Park, Jae Hyeon [Hanyang Biomedical Research Institute, Seoul (Korea, Republic of) [Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Shin, In Chul [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of)] [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Koh, Hyun Chul, E-mail: hckoh@hanyang.ac.kr [Department of Pharmacology, College of Medicine, Hanyang University, Seoul (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of)

    2012-09-01

    Reactive oxidative species (ROS) generated by environmental toxicants including pesticides could be one of the factors underlying the neuronal cell damage in neurodegenerative diseases. In this study we found that chlorpyrifos (CPF) induced apoptosis in dopaminergic neuronal components of PC12 cells as demonstrated by the activation of caspases and nuclear condensation. Furthermore, CPF also reduced the tyrosine hydroxylase-positive immunoreactivity in substantia nigra of the rat. In addition, CPF induced inhibition of mitochondrial complex I activity. Importantly, N-acetyl cysteine (NAC) treatment effectively blocked apoptosis via the caspase-9 and caspase-3 pathways while NAC attenuated the inhibition of mitochondrial complex I activity as well as the oxidative metabolism of dopamine (DA). These results demonstrated that CPF-induced apoptosis was involved in mitochondrial dysfunction through the production of ROS. In the response of cellular antioxidant systems to CPF, we found that CPF treatment increased HO-1 expression while the expression of CuZnSOD and MnSOD was reduced. In addition, we found that CPF treatment activated MAPK pathways, including ERK 1/2, the JNK, and the p38 MAP kinase in a time-dependent manner. NAC treatment abolished MAPK phosphorylation caused by CPF, indicating that ROS are upstream signals of MAPK. Interestingly, MAPK inhibitors abolished cytotoxicity and reduced ROS generation by CPF treatment. Our results demonstrate that CPF induced neuronal cell death in part through MAPK activation via ROS generation, suggesting its potential to generate oxidative stress via mitochondrial damage and its involvement in oxidative stress-related neurodegenerative disease. -- Highlights: ? Chlorpyrifos induces apoptosis. ? Chlorpyrifos inhibits mitochondrial complex I activity. ? ROS is involved in chlorpyrifos-induced apoptosis. ? Chlorpyrifos affects cellular antioxidant systems. ? Chlorpyrifos-induced apoptosis mediates activation of MAPK.

  13. MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo

    PubMed Central

    Mattox, Taylor A.; Young, Martin E.; Rubel, Carrie E.; Spaniel, Carolyn; Rodríguez, Jessica E.; Grevengoed, Trisha J.; Gautel, Mathias; Xu, Zhelong; Anderson, Ethan J.; Willis, Monte S.

    2014-01-01

    MuRF1 is a previously reported ubiquitin-ligase found in striated muscle that targets troponin I and myosin heavy chain for degradation. While MuRF1 has been reported to interact with mitochondrial substrates in yeast two-hybrid studies, no studies have identified MuRF1’s role in regulating mitochondrial function to date. In the present study, we measured cardiac mitochondrial function from isolated permeabilized muscle fibers in previously phenotyped MuRF1 transgenic and MuRF1?/? mouse models to determine the role of MuRF1 in intermediate energy metabolism and ROS production. We identified a significant decrease in reactive oxygen species production in cardiac muscle fibers from MuRF1 transgenic mice with increased alpha-MHC driven MuRF1 expression. Increased MuRF1 expression in ex vivo and in vitro experiments revealed no alterations in the respiratory chain complex I and II function. Working perfusion experiments on MuRF1 transgenic hearts demonstrated significant changes in glucose or oleate oxidation; however, total oxygen consumption was decreased. This data provides evidence for MuRF1 as a novel regulator of cardiac ROS, offering another mechanism by which increased MuRF1 expression may be cardioprotective in ischemia reperfusion injury, in addition to its inhibition of apoptosis via proteasome-mediate degradation of c-Jun. The lack of mitochondrial function phenotype identified in MuRF1?/? hearts may be due to the overlapping interactions of MuRF1 and MuRF2 with energy regulating proteins found by yeast two-hybrid studies reported here, implying a duplicity in MuRF1 and MuRF2’s regulation of mitochondrial function. PMID:24733503

  14. Dissolved oxygen fluctuations in karst spring flow and implications for endemic species: Barton Springs, Edwards aquifer, Texas, USA

    USGS Publications Warehouse

    Mahler, Barbara J.; Bourgeais, Renan

    2013-01-01

    Karst aquifers and springs provide the dissolved oxygen critical for survival of endemic stygophiles worldwide, but little is known about fluctuations of dissolved oxygen concentrations (DO) and factors that control those concentrations. We investigated temporal variation in DO at Barton Springs, Austin, Texas, USA. During 2006–2012, DO fluctuated by as much as a factor of 2, and at some periods decreased to concentrations that adversely affect the Barton Springs salamander (Eurycea sorosum) (?4.4 mg/L), a federally listed endangered species endemic to Barton Springs. DO was lowest (?4.4 mg/L) when discharge was low (?1 m3/s) and spring water temperature was >21 °C, although not at a maximum; the minimum DO recorded was 4.0 mg/L. Relatively low DO (3/s) and maximum T (22.2 °C). A four-segment linear regression model with daily data for discharge and spring water temperature as explanatory variables provided an excellent fit for mean daily DO (Nash–Sutcliffe coefficient for the validation period of 0.90). DO also fluctuated at short-term timescales in response to storms, and DO measured at 15-min intervals could be simulated with a combination of discharge, spring temperature, and specific conductance as explanatory variables. On the basis of the daily-data regression model, we hypothesize that more frequent low DO corresponding to salamander mortality could result from (i) lower discharge from Barton Springs resulting from increased groundwater withdrawals or decreased recharge as a result of climate change, and (or) (ii) higher groundwater temperature as a result of climate change.

  15. Heat-induced formation of reactive oxygen species and 8-oxoguanine, a biomarker of damage to DNA

    PubMed Central

    Bruskov, Vadim I.; Malakhova, Lyudmila V.; Masalimov, Zhaksylyk K.; Chernikov, Anatoly V.

    2002-01-01

    Heat-induced formation of 8-oxoguanine was demonstrated in DNA solutions in 10–3 M phosphate buffer, pH 6.8, by enzyme-linked immunosorbent assays using monoclonal antibodies against 8-oxoguanine. A radiation-chemical yield of 3.7 × 10–2 µmol J–1 for 8-oxoguanine production in DNA upon ?-irradiation was used as an adequate standard for quantitation of 8-oxoguanine in whole DNA. The initial yield of heat-induced 8-oxoguanine exhibits first order kinetics. The rate constants for 8-oxoguanine formation were determined at elevated temperatures; the activation energy was found to be 27 ± 2 kcal/mol. Extrapolation to 37°C gave a value of k37 = 4.7 × 10–10 s–1. Heat-induced 8-oxoguanine formation and depurination of guanine and adenine show similarities of the processes, which implies that heat-mediated generation of reactive oxygen species (ROS) should occur. Heat-induced production of H2O2 in phosphate buffer was shown. The sequence of reactions of thermally mediated ROS formation have been established: activation of dissolved oxygen to the singlet state, generation of superoxide radicals and their dismutation to H2O2. Gas saturation (O2, N2 and Ar), D2O, scavengers of 1O2, O2–• and OH• radicals and metal chelators influenced heat-induced 8-oxoguanine formation as they affected thermal ROS generation. These findings imply that heat acts via ROS attack leading to oxidative damage to DNA. PMID:11884633

  16. Rutin inhibits hydrogen peroxide-induced apoptosis through regulating reactive oxygen species mediated mitochondrial dysfunction pathway in human umbilical vein endothelial cells

    Microsoft Academic Search

    Guohua Gong; Yuan Qin; Wen Huang; Shu Zhou; Xiaohua Yang; Dan Li

    2010-01-01

    Apoptosis of human vein endothelium cell caused by reactive oxygen species is implicated in the pathogenesis of cardiovascular diseases. Rutin, an active flavonoid compound, is well known to possess potent antioxidant properties against oxidative stress insults through undefined mechanism(s). In this study, we first investigated the possible protective effects of rutin against apoptosis of human umbilical vein endothelial cells (HUVECs)

  17. Effects of hypothermic storage of striped bass (Morone saxatilis) sperm on intracellular calcium, reactive oxygen species formation, mitochondrial function, motility, and viability

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Experiments were conducted to determine the effect of hypothermic 24 h storage of striped bass sperm cells on viability, intracellular Ca2+ ([Ca2+]i), mitochondrial membrane potential (D'm), and reactive oxygen species (ROS) formation (oxidation of hydroethidine to ethidium) as determined by flow cy...

  18. Effects of hypothermic storage of striped bass (Morone saxatilis) sperm on intracellular calcium, reactive oxygen species formation, mitochondrial function, motility, and viability

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Experiments were conducted to determine the effect of hypothermic 24 h storage of striped bass sperm cells (Morone saxatilis) on viability, intracellular Ca2+ [Ca2+]i, mitochondrial membrane potential (''m), and reactive oxygen species (ROS) formation as determined by flow cytometry; motion activati...

  19. Changes in susceptibility of bovine sperm to in situ DNA denaturation during prolonged incubation at ambient temperature under conditions of exposure to reactive oxygen species and nuclease inhibitor

    Microsoft Academic Search

    Jacek Krzyzosiak; Donald Evenson; Colin Pitt; Lorna Jost; Peter Molan; Ramakrishnan Vishwanath

    2000-01-01

    Sperm were incubated for up to 9 days in the presence or absence of exogenous hydrogen peroxide, phenylalanine, catalase and aurintricarboxylic acid to assess the influence of reactive oxygen species and inhibition of deoxyribonucleases on sperm chromatin stability. The assessment of sperm DNA susceptibility to in situ acid denaturation by the sperm chromatin structure assay did not detect any difference

  20. Hydroxytyrosol reduces intracellular reactive oxygen species levels in vascular endothelial cells by upregulating catalase expression through the AMPK-FOXO3a pathway.

    PubMed

    Zrelli, Houda; Matsuoka, Mieko; Kitazaki, Shiho; Zarrouk, Mokhtar; Miyazaki, Hitoshi

    2011-06-25

    Reactive oxygen species are critically involved in the endothelial dysfunction that contributes to atherosclerosis development. Hydroxytyrosol (HT), a main phenolic compound in olive oil and leaves from Olea europaea L., has antiatherogenic properties with powerful antioxidant activity. The present study verifies the antioxidant activity of HT on H2O2-induced intracellular reactive oxygen species in porcine pulmonary artery endothelial cells (VECs) and the involved molecular mechanisms. Incubation of VECs with HT prevented the increase in intracellular reactive oxygen species levels in the presence of H2O2. HT increased catalase mRNA, protein and activity. Catalase siRNA suppressed HT-dependent reduction of intracellular reactive oxygen species. HT increased both cytosolic and nuclear protein levels of forkhead transcription factor 3a (FOXO3a), as well as the phosphorylation of AMP-activated protein kinase (AMPK) that translocates FOXO3a to the nucleus. AMPK siRNA and a specific inhibitor suppressed HT-induced FOXO3a upregulation and catalase expression. Moreover, FOXO3a siRNA blocked HT-dependent increase in catalase expression. Taken together, our findings strongly demonstrate that HT positively regulates the antioxidant defense system in VECs by inducing the phosphorylation of AMPK with subsequent activation of FOXO3a and catalase expression, and provides a molecular basis for the prevention of cardiovascular diseases by HT. PMID:21497591

  1. Development of Normal Reference Values for Seminal Reactive Oxygen Species and Their Correlation with Leukocytes and Semen Parameters in a Fertile Population

    Microsoft Academic Search

    Kelly S. Athayde; Marcello Cocuzza; Ashok Agarwal; Natalie Krajcir; Antonio M. Lucon; Miguel Srougi; Jorge Hallak

    2007-01-01

    Although reactive oxygen species (ROSs) are clearly implicated in the pathogenesis of male infertility, few studies have attempted to define the basal levels of ROSs in fertile men. Levels of ROSs are highly influenced by the presence of leukocytes and are associated with decreased seminal parameters. The objective of our study was to determine the normal ROS reference values in

  2. Rehydration of the Lichen Ramalina lacera Results in Production of Reactive Oxygen Species and Nitric Oxide and a Decrease in Antioxidants

    PubMed Central

    Weissman, Lior; Garty, Jacob; Hochman, Ayala

    2005-01-01

    Lichens are slow-growing associations of fungi and unicellular green algae or cyanobacteria. They are poikilohydric organisms whose lifestyle in many cases consists of alternating periods of desiccation, with low metabolic activity, and hydration, which induces increase in their metabolism. Lichens have apparently adapted to such extreme transitions between desiccation and rehydration, but the mechanisms that govern these adaptations are still poorly understood. In this study, the effect of rehydration on the production of reactive oxygen species and nitric oxide as well as low-molecular-weight antioxidants was investigated with the lichen Ramalina lacera. Rehydration of R. lacera resulted in the initiation of and a rapid increase in photosynthetic activity. Recovery of photosynthesis was accompanied by bursts of intracellular production of reactive oxygen species and nitric oxide. Laser-scanning confocal microscopy using dichlorofluorescein fluorescence revealed that formation of reactive oxygen species following rehydration was associated with both symbiotic partners of the lichen. The rate and extent of reactive oxygen species production were similar in the light and in the dark, suggesting a minor contribution of photosynthesis. Diaminofluorescein fluorescence, indicating nitric oxide formation, was detected only in fungal hyphae. Activities associated with rehydration did not have a deleterious effect on membrane integrity as assessed by measurement of electrolyte leakage, but water-soluble low-molecular-weight antioxidants decreased significantly. PMID:15812046

  3. In utero and in vitro effects of benzene and its metabolites on erythroid differentiation and the role of reactive oxygen species

    Microsoft Academic Search

    Helen J. Badham; Louise M. Winn

    2010-01-01

    Benzene is a ubiquitous occupational and environmental toxicant. Exposures to benzene both prenatally and during adulthood are associated with the development of disorders such as aplastic anemia and leukemia. Mechanisms of benzene toxicity are unknown; however, generation of reactive oxygen species (ROS) by benzene metabolites may play a role. Little is known regarding the effects of benzene metabolites on erythropoiesis.

  4. Cell uptake, intracellular distribution, fate and reactive oxygen species generation of polymer brush engineered CeO2-x NPs

    NASA Astrophysics Data System (ADS)

    Qiu, Yuan; Rojas, Elena; Murray, Richard A.; Irigoyen, Joseba; Gregurec, Danijela; Castro-Hartmann, Pablo; Fledderman, Jana; Estrela-Lopis, Irina; Donath, Edwin; Moya, Sergio E.

    2015-04-01

    Cerium Oxide nanoparticles (CeO2-x NPs) are modified with polymer brushes of negatively charged poly (3-sulfopropylmethacrylate) (PSPM) and positively charged poly (2-(methacryloyloxy)ethyl-trimethylammonium chloride) (PMETAC) by Atom Transfer Radical Polymerisation (ATRP). CeO2-x NPs are fluorescently labelled by covalently attaching Alexa Fluor® 488/Fluorescein isothiocyanate to the NP surface prior to polymerisation. Cell uptake, intracellular distribution and the impact on the generation of intracellular Reactive Oxygen Species (ROS) with respect to CeO2-x NPs are studied by means of Raman Confocal Microscopy (CRM), Transmission Electron Microscopy (TEM) and Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). PSPM and PMETAC coated CeO2-x NPs show slower and less uptake compared to uncoated Brush modified NPs display a higher degree of co-localisation with cell endosomes and lysosomes after 24 h of incubation. They also show higher co-localisation with lipid bodies when compared to unmodified CeO2-x NPs. The brush coating does not prevent CeO2-x NPs from displaying antioxidant properties.Cerium Oxide nanoparticles (CeO2-x NPs) are modified with polymer brushes of negatively charged poly (3-sulfopropylmethacrylate) (PSPM) and positively charged poly (2-(methacryloyloxy)ethyl-trimethylammonium chloride) (PMETAC) by Atom Transfer Radical Polymerisation (ATRP). CeO2-x NPs are fluorescently labelled by covalently attaching Alexa Fluor® 488/Fluorescein isothiocyanate to the NP surface prior to polymerisation. Cell uptake, intracellular distribution and the impact on the generation of intracellular Reactive Oxygen Species (ROS) with respect to CeO2-x NPs are studied by means of Raman Confocal Microscopy (CRM), Transmission Electron Microscopy (TEM) and Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). PSPM and PMETAC coated CeO2-x NPs show slower and less uptake compared to uncoated Brush modified NPs display a higher degree of co-localisation with cell endosomes and lysosomes after 24 h of incubation. They also show higher co-localisation with lipid bodies when compared to unmodified CeO2-x NPs. The brush coating does not prevent CeO2-x NPs from displaying antioxidant properties. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr00884k

  5. Horseradish peroxidase-immobilized magnetic mesoporous silica nanoparticles as a potential candidate to eliminate intracellular reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Shen, Yajing; Zhang, Ye; Zhang, Xiang; Zhou, Xiuhong; Teng, Xiyao; Yan, Manqing; Bi, Hong

    2015-02-01

    Horseradish peroxidase-immobilized magnetic mesoporous silica nanoparticles (MMSNs-HRP) have been synthesized by a NHS/EDC coupling between the amino groups of horseradish peroxidase (HRP) and the carboxyl groups on the MMSNs surface. It is found that the immobilized HRP on MMSNs still retain high activity and the MMSNs-HRP can eliminate the reactive oxygen species (ROS) in Chinese hamster ovary (CHO) cells induced by the addition of H2O2 aqueous solution. Further, the fluorescent MMSN-HRP-CD nanoparticles have been prepared by attaching biocompatible, fluorescent carbon dots (CDs) to MMSNs-HRP. We have also investigated the effect of an applied magnetic field on cellular uptake of MMSNs-HRP-CDs and found that the internalization of MMSNs-HRP-CDs by CHO cells could be enhanced within 2 hours under the magnetic field. This work provides us with a novel and efficient method to eliminate ROS in living cells by using HRP-immobilized nanoparticles.Horseradish peroxidase-immobilized magnetic mesoporous silica nanoparticles (MMSNs-HRP) have been synthesized by a NHS/EDC coupling between the amino groups of horseradish peroxidase (HRP) and the carboxyl groups on the MMSNs surface. It is found that the immobilized HRP on MMSNs still retain high activity and the MMSNs-HRP can eliminate the reactive oxygen species (ROS) in Chinese hamster ovary (CHO) cells induced by the addition of H2O2 aqueous solution. Further, the fluorescent MMSN-HRP-CD nanoparticles have been prepared by attaching biocompatible, fluorescent carbon dots (CDs) to MMSNs-HRP. We have also investigated the effect of an applied magnetic field on cellular uptake of MMSNs-HRP-CDs and found that the internalization of MMSNs-HRP-CDs by CHO cells could be enhanced within 2 hours under the magnetic field. This work provides us with a novel and efficient method to eliminate ROS in living cells by using HRP-immobilized nanoparticles. Electronic supplementary information (ESI) available: TEM image of CDs, BET XRD patterns of Fe3O4 nanoparticles and MMSNs; N2 adsorption/desorption isotherms of MMSNs; FT-IR spectra of Fe3O4 nanoparticles, MMSNs and MMSNs-NH2 the fluorescent microscopy images of CHO cells co-incubated with MMSNs-HRP PL emission spectra of CDs conjugation with HRP and MMSNs-HRP in aqueous solution, respectively; and the fluorescent microscopy images of CHO cells co-incubated with MMSNs-HRP at different concentrations. See DOI: 10.1039/c4nr06269h

  6. Reactive oxygen species on bone mineral density and mechanics in Cu,Zn superoxide dismutase (Sod1) knockout mice

    SciTech Connect

    Smietana, Michael J. [Biomedical Engineering, University of Michigan, 2025 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200 (United States)] [Biomedical Engineering, University of Michigan, 2025 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200 (United States); Arruda, Ellen M. [Biomedical Engineering, University of Michigan, 2025 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200 (United States) [Biomedical Engineering, University of Michigan, 2025 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200 (United States); Mechanical Engineering, University of Michigan, 2250 GG Brown, 2350 Hayward, Ann Arbor, MI 48109 (United States); Program in Macromolecular Science and Engineering, University of Michigan, 2250 GG Brown, 2350 Hayward, Ann Arbor, MI 48109 (United States); Faulkner, John A.; Brooks, Susan V. [Biomedical Engineering, University of Michigan, 2025 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200 (United States) [Biomedical Engineering, University of Michigan, 2025 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200 (United States); Molecular and Integrative Physiology, University of Michigan, 2025 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200 (United States); Larkin, Lisa M., E-mail: llarkin@umich.edu [Biomedical Engineering, University of Michigan, 2025 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200 (United States); Molecular and Integrative Physiology, University of Michigan, 2025 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-2200 (United States)

    2010-12-03

    Research highlights: {yields} Reactive oxygen species (ROS) are considered to be a factor in the onset of a number of age-associated conditions, including loss of BMD. {yields} Cu,Zn-superoxide dismutase (Sod1) deficient mice have increased ROS, reduced bone mineral density, decreased bending stiffness, and decreased strength compared to WT controls. {yields} Increased ROS caused by the deficiency of Sod1, may be responsible for the changes in BMD and bone mechanics and therefore represent an appropriate model for studying mechanisms of age-associated bone loss. -- Abstract: Reactive oxygen species (ROS) play a role in a number of degenerative conditions including osteoporosis. Mice deficient in Cu,Zn-superoxide dismutase (Sod1) (Sod1{sup -/-} mice) have elevated oxidative stress and decreased muscle mass and strength compared to wild-type mice (WT) and appear to have an accelerated muscular aging phenotype. Thus, Sod1{sup -/-} mice may be a good model for evaluating the effects of free radical generation on diseases associated with aging. In this experiment, we tested the hypothesis that the structural integrity of bone as measured by bending stiffness (EI; N/mm{sup 2}) and strength (MPa) is diminished in Sod1{sup -/-} compared to WT mice. Femurs were obtained from male and female WT and Sod1{sup -/-} mice at 8 months of age and three-point bending tests were used to determine bending stiffness and strength. Bones were also analyzed for bone mineral density (BMD; mg/cc) using micro-computed tomography. Femurs were approximately equal in length across all groups, and there were no significant differences in BMD or EI with respect to gender in either genotype. Although male and female mice demonstrated similar properties within each genotype, Sod1{sup -/-} mice exhibited lower BMD and EI of femurs from both males and females compared with gender matched WT mice. Strength of femurs was also lower in Sod1{sup -/-} mice compared to WT as well as between genders. These data indicate that increased oxidative stress, due to the deficiency of Sod1 is associated with decreased bone stiffness and strength and Sod1{sup -/-} mice may represent an appropriate model for studying disease processes in aging bone.

  7. Chlamydia muridarum Infection of Macrophages Elicits Bactericidal Nitric Oxide Production via Reactive Oxygen Species and Cathepsin B.