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Sample records for resistance oxidative stress

  1. Oxidative Stress and Insulin Resistance

    PubMed Central

    Park, Kyong; Gross, Myron; Lee, Duk-Hee; Holvoet, Paul; Himes, John H.; Shikany, James M.; Jacobs, David R.

    2009-01-01

    OBJECTIVE Although cumulative evidence suggests that increased oxidative stress may lead to insulin resistance in vivo or in vitro, community-based studies are scarce. This study examined the longitudinal relationships of oxidative stress biomarkers with the development of insulin resistance and whether these relationships were independent of obesity in nondiabetic young adults. RESEARCH DESIGN AND METHODS Biomarkers of oxidative stress (F2-isoprostanes [F2Isop] and oxidized LDL [oxLDL]), insulin resistance (the homeostasis model assessment of insulin resistance [HOMA-IR]), and various fatness measures (BMI, waist circumference, and estimated percent fat) were obtained in a population-based observational study (Coronary Artery Risk Development in Young Adults) and its ancillary study (Young Adult Longitudinal Trends in Antioxidants) during 2000–2006. RESULTS There were substantial increases in estimated mean HOMA-IR over time. OxLDL and F2Isop showed little association with each other. Mean evolving HOMA-IR increased with increasing levels of oxidative stress markers (P < 0.001 for oxLDL and P = 0.06 for F2Isop), measured in 2000–2001. After additional adjustment for adiposity, a positive association between oxLDL and HOMA-IR was strongly evident, whereas the association between F2Isop and HOMA-IR was not. CONCLUSIONS We observed positive associations between each of two oxidative stress markers and insulin resistance. The association with oxidized LDL was independent of obesity, but that with F2Isop was not. PMID:19389821

  2. Oxidative Stress Resistance in Deinococcus radiodurans†

    PubMed Central

    Slade, Dea; Radman, Miroslav

    2011-01-01

    Summary: Deinococcus radiodurans is a robust bacterium best known for its capacity to repair massive DNA damage efficiently and accurately. It is extremely resistant to many DNA-damaging agents, including ionizing radiation and UV radiation (100 to 295 nm), desiccation, and mitomycin C, which induce oxidative damage not only to DNA but also to all cellular macromolecules via the production of reactive oxygen species. The extreme resilience of D. radiodurans to oxidative stress is imparted synergistically by an efficient protection of proteins against oxidative stress and an efficient DNA repair mechanism, enhanced by functional redundancies in both systems. D. radiodurans assets for the prevention of and recovery from oxidative stress are extensively reviewed here. Radiation- and desiccation-resistant bacteria such as D. radiodurans have substantially lower protein oxidation levels than do sensitive bacteria but have similar yields of DNA double-strand breaks. These findings challenge the concept of DNA as the primary target of radiation toxicity while advancing protein damage, and the protection of proteins against oxidative damage, as a new paradigm of radiation toxicity and survival. The protection of DNA repair and other proteins against oxidative damage is imparted by enzymatic and nonenzymatic antioxidant defense systems dominated by divalent manganese complexes. Given that oxidative stress caused by the accumulation of reactive oxygen species is associated with aging and cancer, a comprehensive outlook on D. radiodurans strategies of combating oxidative stress may open new avenues for antiaging and anticancer treatments. The study of the antioxidation protection in D. radiodurans is therefore of considerable potential interest for medicine and public health. PMID:21372322

  3. Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus

    PubMed Central

    Tangvarasittichai, Surapon

    2015-01-01

    Oxidative stress is increased in metabolic syndrome and type 2 diabetes mellitus (T2DM) and this appears to underlie the development of cardiovascular disease, T2DM and diabetic complications. Increased oxidative stress appears to be a deleterious factor leading to insulin resistance, dyslipidemia, β-cell dysfunction, impaired glucose tolerance and ultimately leading to T2DM. Chronic oxidative stress, hyperglycemia and dyslipidemia are particularly dangerous for β-cells from lowest levels of antioxidant, have high oxidative energy requirements, decrease the gene expression of key β-cell genes and induce cell death. If β-cell functioning is impaired, it results in an under production of insulin, impairs glucose stimulated insulin secretion, fasting hyperglycemia and eventually the development of T2DM. PMID:25897356

  4. Reduced resistance to oxidative stress during reproduction as a cost of early-life stress.

    PubMed

    Zimmer, Cédric; Spencer, Karen A

    2015-05-01

    Stress exposure during early-life development can have long-term consequences for a variety of biological functions including oxidative stress. The link between early-life stress and oxidative balance is beginning to be explored and previous studies have focused on this link in adult non-breeding or immature individuals. However, as oxidative stress is considered as the main physiological mechanism underlying the trade-off between self-maintenance and investment in reproduction, it is necessary to look at the consequences of early-life stress on oxidative status during reproduction. Here, we investigated the effects of exposure to pre- and/or post-natal stress on oxidative balance during reproduction under benign or stressful environmental conditions in an avian model species, the Japanese quail. We determined total antioxidant status (TAS), total oxidant status (TOS) and resistance to a free-radical attack in individual exposed to pre-natal stress, post-natal stress or both and in control individuals exposed to none of the stressors. TAS levels decreased over time in all females that reproduced under stressful conditions. TOS decreased between the beginning and the end of reproductive period in pre-natal control females. In all females, resistance to a free-radical attack decreased over the reproductive event but this decrease was more pronounced in females from a pre-natal stress development. Our results suggest that pre-natal stress may be associated with a higher cost of reproduction in terms of oxidative stress. These results also confirm that early-life stress can be associated with both benefits and costs depending of the life-history stage or environmental context. PMID:25542633

  5. Higher in vitro resistance to oxidative stress in extra-pair offspring.

    PubMed

    Losdat, S; Helfenstein, F; Saladin, V; Richner, H

    2011-11-01

    Oxidative stress is considered to act as a universal physiological constraint in life-history evolution of animals. This should be of interest for extra-pair paternity behaviour, and we tested here the prediction that offspring arising from extra-pair matings of female great tits show higher resistance to oxidative stress than within-pair offspring. Resistance to oxidative stress, measured as the whole blood resistance to a controlled free-radical attack, was significantly higher for extra-pair offspring as predicted although these were not heavier or in better body condition than within-pair offspring. Since resistance to oxidative stress has been suggested to enhance survival and reproductive rates, extra-pair offspring with superior resistance to oxidative stress, be it through maternal effects or paternal inheritance, may achieve higher fitness and thus provide significant indirect fitness benefits to their mothers. In addition, because oxidative stress affects colour signals and sperm traits, females may also gain fitness benefits by producing sons that are more attractive (sexy-sons hypothesis) and have sperm of superior quality (sexy-sperm hypothesis). Heritability of resistance to oxidative stress as well as maternal effects may both act as proximate mechanisms for the observed result. Disentangling these two mechanisms would require an experimental approach. Future long-term studies should also aim at experimentally testing whether higher resistance to oxidative stress of EP nestlings indeed translates into fitness benefits to females. PMID:21899636

  6. Tellurite: history, oxidative stress, and molecular mechanisms of resistance.

    PubMed

    Chasteen, Thomas Girard; Fuentes, Derie Esteban; Tantaleán, Juan Carlos; Vásquez, Claudio Christian

    2009-07-01

    The perceived importance of tellurium (Te) in biological systems has lagged behind selenium (Se), its lighter sister in the Group 16 chalcogens, because of tellurium's lower crustal abundance, lower oxyanion solubility and biospheric mobility and the fact that, unlike Se, Te has yet to be found to be an essential trace element. Te applications in electronics, optics, batteries and mining industries have expanded during the last few years, leading to an increase in environmental Te contamination, thus renewing biological interest in Te toxicity. This chalcogen is rarely found in the nontoxic, elemental state (Te(0)), but its soluble oxyanions, tellurite (TeO(3)(2-)) and tellurate (TeO(4)(2-)), are toxic for most forms of life even at very low concentrations. Although a number of Te resistance determinants (Tel) have been identified in plasmids or in the bacterial chromosome of different species of bacteria, the genetic and/or biochemical basis underlying bacterial TeO(3)(2-) toxicity is still poorly understood. This review traces the history of Te in its biological interactions, its enigmatic toxicity, importance in cellular oxidative stress, and interaction in cysteine metabolism. PMID:19368559

  7. Genome-Wide Association Analysis of Oxidative Stress Resistance in Drosophila melanogaster

    PubMed Central

    Weber, Allison L.; Khan, George F.; Magwire, Michael M.; Tabor, Crystal L.; Mackay, Trudy F. C.; Anholt, Robert R. H.

    2012-01-01

    Background Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress. Methods and Findings We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genome-wide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs) associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67–79% and 56–66% of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis. Conclusions We identified novel candidate genes associated with variation in resistance to oxidative stress that have context-dependent effects. These results form the basis for future translational studies to identify oxidative stress susceptibility/resistance genes that are evolutionary conserved and might play a role in human disease. PMID:22496853

  8. Enhanced oxidative stress resistance through activation of a zinc deficiency transcription factor in Brachypodium distachyon.

    PubMed

    Glover-Cutter, Kira M; Alderman, Stephen; Dombrowski, James E; Martin, Ruth C

    2014-11-01

    Identification of viable strategies to increase stress resistance of crops will become increasingly important for the goal of global food security as our population increases and our climate changes. Considering that resistance to oxidative stress is oftentimes an indicator of health and longevity in animal systems, characterizing conserved pathways known to increase oxidative stress resistance could prove fruitful for crop improvement strategies. This report argues for the usefulness and practicality of the model organism Brachypodium distachyon for identifying and validating stress resistance factors. Specifically, we focus on a zinc deficiency B. distachyon basic leucine zipper transcription factor, BdbZIP10, and its role in oxidative stress in the model organism B. distachyon. When overexpressed, BdbZIP10 protects plants and callus tissue from oxidative stress insults, most likely through distinct and direct activation of protective oxidative stress genes. Increased oxidative stress resistance and cell viability through the overexpression of BdbZIP10 highlight the utility of investigating conserved stress responses between plant and animal systems. PMID:25228396

  9. Enhanced oxidative stress resistance through activation of a zinc deficiency transcription factor in Brachypodium distachyon

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Identification of viable strategies to increase stress resistance of crops will become increasingly important for the goal of global food security as our population increases and our climate changes. Considering that resistance to oxidative stress is oftentimes an indicator of health and longevity i...

  10. Measuring oxidative stress resistance of Caenorhabditis elegans in 96-well microtiter plates.

    PubMed

    Possik, Elite; Pause, Arnim

    2015-01-01

    Oxidative stress, which is the result of an imbalance between production and detoxification of reactive oxygen species, is a major contributor to chronic human disorders, including cardiovascular and neurodegenerative diseases, diabetes, aging, and cancer. Therefore, it is important to study oxidative stress not only in cell systems but also using whole organisms. C. elegans is an attractive model organism to study the genetics of oxidative stress signal transduction pathways, which are highly evolutionarily conserved. Here, we provide a protocol to measure oxidative stress resistance in C. elegans in liquid. Briefly, ROS-inducing reagents such as paraquat (PQ) and H2O2 are dissolved in M9 buffer, and solutions are aliquoted in the wells of a 96 well microtiter plate. Synchronized L4/young adult C. elegans animals are transferred to the wells (5-8 animals/well) and survival is measured every hour until most worms are dead. When performing an oxidative stress resistance assay using a low concentration of stressors in plates, aging might influence the behavior of animals upon oxidative stress, which could lead to an incorrect interpretation of the data. However, in the assay described herein, this problem is unlikely to occur since only L4/young adult animals are being used. Moreover, this protocol is inexpensive and results are obtained in one day, which renders this technique attractive for genetic screens. Overall, this will help to understand oxidative stress signal transduction pathways, which could be translated into better characterization of oxidative stress-associated human disorders. PMID:25993260

  11. Manganese regulation of virulence factors and oxidative stress resistance in Neisseria gonorrhoeae

    PubMed Central

    Wu, Hsing-Ju; Seib, Kate L.; Srikhanta, Yogitha N.; Edwards, Jennifer; Kidd, Stephen P.; Maguire, Tina L .; Hamilton, Amanda; Pan, Kuan-Tin; Hsiao, He-Hsuan; Yao, Chen-Wen; Grimmond, Sean M.; Apicella, Michael A.; McEwan, Alastair G.; Wang, Andrew H-J.; Jennings, Michael P.

    2014-01-01

    Neisseria gonorrhoeae has evolved a complex and novel network of oxidative stress responses, including defense mechanisms that are dependent on manganese (Mn). We performed systematic analyses at the transcriptomic and proteomic (1D SDS-PAGE and Isotope-Coded Affinity Tag [ICAT]) levels to investigate the global expression changes that take place in a high Mn environment, which results in a Mn-dependent oxidative stress resistance phenotype. These studies revealed that 97 proteins are regulated at the post-transcriptional level under conditions of increased Mn concentration, including proteins involved in virulence (eg. Pilin, a key adhesin), oxidative stress defence (eg. superoxide dismutase), cellular metabolism, protein synthesis, RNA processing and cell division. Mn regulation of inorganic pyrophosphatase (Ppa) indicated the potential involvement of phosphate metabolism in the Mn-dependent oxidative stress defense. A detailed analysis of the role of Ppa and polyphosphate kinase (Ppk) in the gonococcal oxidative stress response revealed that ppk and ppa mutant strains showed increased resistance to oxidative stress. Investigation of these mutants grown with high Mn suggests that phosphate and pyrophosphate are involved in Mn-dependent oxidative stress resistance. PMID:20004262

  12. Eumelanin- and pheomelanin-based colour advertise resistance to oxidative stress in opposite ways.

    PubMed

    Roulin, A; Almasi, B; Meichtry-Stier, K S; Jenni, L

    2011-10-01

    The control mechanisms and information content of melanin-based colourations are still debated among evolutionary biologists. Recent hypotheses contend that molecules involved in melanogenesis alter other physiological processes, thereby generating covariation between melanin-based colouration and other phenotypic attributes. Interestingly, several molecules such as agouti and glutathione that trigger the production of reddish-brown pheomelanin have an inhibitory effect on the production of black/grey eumelanin, whereas other hormones, such as melanocortins, have the opposite effect. We therefore propose the hypothesis that phenotypic traits positively correlated with the degree of eumelanin-based colouration may be negatively correlated with the degree of pheomelanin-based colouration, or vice versa. Given the role played by the melanocortin system and glutathione on melanogenesis and resistance to oxidative stress, we examined the prediction that resistance to oxidative stress is positively correlated with the degree of black colouration but negatively with the degree of reddish colouration. Using the barn owl (Tyto alba) as a model organism, we swapped eggs between randomly chosen nests to allocate genotypes randomly among environments and then we measured resistance to oxidative stress using the KRL assay in nestlings raised by foster parents. As predicted, the degree of black and reddish pigmentations was positively and negatively correlated, respectively, with resistance to oxidative stress. Our results reveal that eumelanin- and pheomelanin-based colourations can be redundant signals of resistance to oxidative stress. PMID:21745253

  13. Failure of Elevating Calcium Induces Oxidative Stress Tolerance and Imparts Cisplatin Resistance in Ovarian Cancer Cells

    PubMed Central

    Ma, Liwei; Wang, Hongjun; Wang, Chunyan; Su, Jing; Xie, Qi; Xu, Lu; Yu, Yang; Liu, Shibing; Li, Songyan; Xu, Ye; Li, Zhixin

    2016-01-01

    Cisplatin is a commonly used chemotherapeutic drug, used for the treatment of malignant ovarian cancer, but acquired resistance limits its application. There is therefore an overwhelming need to understand the mechanism of cisplatin resistance in ovarian cancer, that is, ovarian cancer cells are insensitive to cisplatin treatment. Here, we show that failure of elevating calcium and oxidative stress tolerance play key roles in cisplatin resistance in ovarian cancer cell lines. Cisplatin induces an increase in oxidative stress and alters intracellular Ca2+ concentration, including cytosolic and mitochondrial Ca2+ in cisplatin-sensitive SKOV3 cells, but not in cisplatin-resistant SKOV3/DDP cells. Cisplatin induces mitochondrial damage and triggers the mitochondrial apoptotic pathway in cisplatin-sensitive SKOV3 cells, but rarely in cisplatin-resistant SKOV3/DDP cells. Inhibition of calcium signaling attenuates cisplatin-induced oxidative stress and intracellular Ca2+ overload in cisplatin-sensitive SKOV3 cells. Moreover, in vivo xenograft models of nude mouse, cisplatin significantly reduced the growth rates of tumors originating from SKOV3 cells, but not that of SKOV3/DDP cells. Collectively, our data indicate that failure of calcium up-regulation mediates cisplatin resistance by alleviating oxidative stress in ovarian cancer cells. Our results highlight potential therapeutic strategies to improve cisplatin resistance. PMID:27330840

  14. Proline Metabolism Increases katG Expression and Oxidative Stress Resistance in Escherichia coli

    PubMed Central

    Zhang, Lu; Alfano, James R.

    2014-01-01

    The oxidation of l-proline to glutamate in Gram-negative bacteria is catalyzed by the proline utilization A (PutA) flavoenzyme, which contains proline dehydrogenase (PRODH) and Δ1-pyrroline-5-carboxylate (P5C) dehydrogenase domains in a single polypeptide. Previous studies have suggested that aside from providing energy, proline metabolism influences oxidative stress resistance in different organisms. To explore this potential role and the mechanism, we characterized the oxidative stress resistance of wild-type and putA mutant strains of Escherichia coli. Initial stress assays revealed that the putA mutant strain was significantly more sensitive to oxidative stress than the parental wild-type strain. Expression of PutA in the putA mutant strain restored oxidative stress resistance, confirming that depletion of PutA was responsible for the oxidative stress phenotype. Treatment of wild-type cells with proline significantly increased hydroperoxidase I (encoded by katG) expression and activity. Furthermore, the ΔkatG strain failed to respond to proline, indicating a critical role for hydroperoxidase I in the mechanism of proline protection. The global regulator OxyR activates the expression of katG along with several other genes involved in oxidative stress defense. In addition to katG, proline increased the expression of grxA (glutaredoxin 1) and trxC (thioredoxin 2) of the OxyR regulon, implicating OxyR in proline protection. Proline oxidative metabolism was shown to generate hydrogen peroxide, indicating that proline increases oxidative stress tolerance in E. coli via a preadaptive effect involving endogenous hydrogen peroxide production and enhanced catalase-peroxidase activity. PMID:25384482

  15. Isocitrate Dehydrogenase Is Important for Nitrosative Stress Resistance in Cryptococcus neoformans, but Oxidative Stress Resistance Is Not Dependent on Glucose-6-Phosphate Dehydrogenase▿

    PubMed Central

    Brown, Sarah M.; Upadhya, Rajendra; Shoemaker, James D.; Lodge, Jennifer K.

    2010-01-01

    The opportunistic intracellular fungal pathogen Cryptococcus neoformans depends on many antioxidant and denitrosylating proteins and pathways for virulence in the immunocompromised host. These include the glutathione and thioredoxin pathways, thiol peroxidase, cytochrome c peroxidase, and flavohemoglobin denitrosylase. All of these ultimately depend on NADPH for either catalytic activity or maintenance of a reduced, functional form. The need for NADPH during oxidative stress is well established in many systems, but a role in resistance to nitrosative stress has not been as well characterized. In this study we investigated the roles of two sources of NADPH, glucose-6-phosphate dehydrogenase (Zwf1) and NADP+-dependent isocitrate dehydrogenase (Idp1), in production of NADPH and resistance to oxidative and nitrosative stress. Deletion of ZWF1 in C. neoformans did not result in an oxidative stress sensitivity phenotype or changes in the amount of NADPH produced during oxidative stress compared to those for the wild type. Deletion of IDP1 resulted in greater sensitivity to nitrosative stress than to oxidative stress. The amount of NADPH increased 2-fold over that in the wild type during nitrosative stress, and yet the idp1Δ strain accumulated more mitochondrial damage than the wild type during nitrosative stress. This is the first report of the importance of Idp1 and NADPH for nitrosative stress resistance. PMID:20400467

  16. Exhaustive submaximal endurance and resistance exercises induce temporary immunosuppression via physical and oxidative stress

    PubMed Central

    Jin, Chan-Ho; Paik, Il-Young; Kwak, Yi-Sub; Jee, Yong-Seok; Kim, Joo-Young

    2015-01-01

    Regular running and strength training are the best ways to improve aerobic capacity and develop the size of skeletal muscles. However, uncontrolled physical activities can often lead to an undertraining or over-training syndrome. In particular, overtraining causes persistent fatigue and reduces physical performance due to changes in the various physiological and immunological factors. In this study, we gave an exhaustive submaximal endurance or resistance exercise to participants and investigated the relationship between physical stress (cortisol level in blood), oxidative stress (intracellular ROS accumulation), and adaptive immune response (CD4:CD8 ratio). Materials and Methods Ten male volunteers were recruited, and performed a submaximal endurance or resistance exercise with 85% of VO2max or 1-repetition maximum until exhaustion. Blood samples were collected at rest, and at 0 and 30 min after the exercise. Cortisol levels, oxidative stress, and immune cell phenotypes in peripheral blood were evaluated. Cortisol levels in the sera increased after the exhaustive endurance and resistance exercises and such increments were maintained through the recovery. Intra-cellular ROS levels also increased after the exhaustive endurance and resistance exercises. The ratio of CD4+ T cells to CD8+ T cells after each type of submaximal exercise decreased compared with that at the resting stage, and returned to the resting level at 30 min after the exercise. In this study, an exhaustive endurance or a resistance exercise with submaximal intensity caused excessive physical stress, intra-cellular oxidative stress, and post-exercise immunosuppression. This result suggests that excessive physical stress induced temporary immune dysfunction via physical and oxidative stress. PMID:26331134

  17. Differential response of DDT susceptible and resistant Drosophila melanogaster strains to DDT and oxidative stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Metabolic DDT resistance in Drosophila melanogaster is associated with increased cytochrome P450 expression. Increased P450 activity is also associated with increased oxidative stress. In contrast, increased glutathione S transferase (GST) expression has been associated with a greater ability of o...

  18. [Oxidative stress in adipose tissue as a primary link in pathogenesis of insulin resistance].

    PubMed

    Kuzmenko, D I; Udintsev, S N; Klimentyeva, T K; Serebrov, V Yu

    2016-01-01

    Obesity is a leading risk factor of diabetes mellitus type 2, impairments of lipid metabolism and cardiovascular diseases. Dysfunctions of the accumulating weight of the visceral fat are primarily linked to pathogenesis of systemic insulin resistance. The review considers modern views about biochemical mechanisms underlying formation of oxidative stress in adipocytes at obesity, as one of key elements of impairments of their metabolism triggering formation of systemic insulin resistance. PMID:26973182

  19. Regulation of oxidative stress resistance in Campylobacter jejuni, a microaerophilic foodborne pathogen

    PubMed Central

    Kim, Jong-Chul; Oh, Euna; Kim, Jinyong; Jeon, Byeonghwa

    2015-01-01

    Campylobacter jejuni is one of the leading bacterial causes of human gastroenteritis. Due to the increasing rates of human campylobacteriosis, C. jejuni is considered as a serious public health concern worldwide. C. jejuni is a microaerophilic, fastidious bacterium. C. jejuni must overcome a wide range of stress conditions during foodborne transmission to humans, such as food preservation and processing conditions, and even in infection of the gastrointestinal tracts of humans. Particularly, this microaerophilic foodborne pathogen must survive in the atmospheric conditions prior to the initiation of infection. C. jejuni possesses unique regulatory mechanisms for oxidative stress resistance. Lacking OxyR and SoxRS that are highly conserved in other Gram-negative foodborne pathogens, C. jejuni modulates the expression of genes involved in oxidative stress resistance mainly via the peroxide resistance regulator and Campylobacter oxidative stress regulator. Based on recent findings of ours and others, in this review, we described how C. jejuni regulates the expression of oxidative stress defense. PMID:26284041

  20. Effect of myricetin, pyrogallol, and phloroglucinol on yeast resistance to oxidative stress.

    PubMed

    Mendes, Vanda; Vilaça, Rita; de Freitas, Victor; Ferreira, Pedro Moradas; Mateus, Nuno; Costa, Vítor

    2015-01-01

    The health beneficial effects of dietary polyphenols have been attributed to their intrinsic antioxidant activity, which depends on the structure of the compound and number of hydroxyl groups. In this study, the protective effects of pyrogallol, phloroglucinol, and myricetin on the yeast Saccharomyces cerevisiae were investigated. Pyrogallol and myricetin, which have a pyrogallol structure in the B ring, increased H2O2 resistance associated with a reduction in intracellular oxidation and protein carbonylation, whereas phloroglucinol did not exert protective effects. The acquisition of oxidative stress resistance in cells pretreated with pyrogallol and myricetin was not associated with an induction of endogenous antioxidant defences as assessed by the analysis of superoxide dismutase and catalase activities. However, myricetin, which provided greater stress resistance, prevented H2O2-induced glutathione oxidation. Moreover, myricetin increased the chronological lifespan of yeast lacking the mitochondrial superoxide dismutase (Sod2p), which exhibited a premature aging phenotype and oxidative stress sensitivity. These findings show that the presence of hydroxyl groups in the ortho position of the B ring in pyrogallol and myricetin contributes to the antioxidant protection afforded by these compounds. In addition, myricetin may alleviate aging-induced oxidative stress, particularly when redox homeostasis is compromised due to downregulation of endogenous defences present in mitochondria. PMID:26000072

  1. Mitochondrial oxidative stress is the achille's heel of melanoma cells resistant to Braf-mutant inhibitor

    PubMed Central

    André, Fanny; Jonneaux, Aurélie; Scalbert, Camille; Garçon, Guillaume; Malet-Martino, Myriam; Balayssac, Stéphane; Rocchi, Stephane; Savina, Ariel; Formstecher, Pierre; Mortier, Laurent; Kluza, Jérome; Marchetti, Philippe

    2013-01-01

    Vemurafenib/PLX4032, a selective inhibitor of mutant BRAFV600E, constitutes a paradigm shift in melanoma therapy. Unfortunately, acquired resistance, which unavoidably occurs, represents one major limitation to clinical responses. Recent studies have highlighted that vemurafenib activated oxidative metabolism in BRAFV600E melanomas expressing PGC1α. However, the oxidative state of melanoma resistant to BRAF inhibitors is unknown. We established representative in vitro and in vivo models of human melanoma resistant to vemurafenib including primary specimens derived from melanoma patients. Firstly, our study reveals that vemurafenib increased mitochondrial respiration and ROS production in BRAFV600E melanoma cell lines regardless the expression of PGC1α. Secondly, melanoma cells that have acquired resistance to vemurafenib displayed intrinsically high rates of mitochondrial respiration associated with elevated mitochondrial oxidative stress irrespective of the presence of vemurafenib. Thirdly, the elevated ROS level rendered vemurafenib-resistant melanoma cells prone to cell death induced by pro-oxidants including the clinical trial drug, elesclomol. Based on these observations, we propose that the mitochondrial oxidative signature of resistant melanoma constitutes a novel opportunity to overcome resistance to BRAF inhibition. PMID:24161908

  2. The role of D-GADD45 in oxidative, thermal and genotoxic stress resistance.

    PubMed

    Moskalev, Alexey; Plyusnina, Ekaterina; Shaposhnikov, Mikhail; Shilova, Lyubov; Kazachenok, Alexey; Zhavoronkov, Alexander

    2012-11-15

    There is a relationship between various cellular stress factors and aging. In earlier studies, we demonstrated that overexpression of the D-GADD45 gene increases the life span of Drosophila melanogaster. In this study, we investigate the relationship between D-GADD45 activity and resistance to oxidative, genotoxic and thermal stresses as well as starvation. In most cases, flies with constitutive and conditional D-GADD45 overexpression in the nervous system were more stress-resistant than ones without overexpression. At the same time, most of the studied stress factors increased D-GADD45 expression in the wild-type strain. The lifespan-extending effect of D-GADD45 overexpression was also retained after exposure to chronic and acute gamma-irradiation, with doses of 40 сGy and 30 Gy, respectively. However, knocking out D-GADD45 resulted in a significant reduction in lifespan, lack of radiation hormesis and radioadaptive response. A dramatic decrease in the spontaneous level of D-GADD45 expression was observed in the nervous system as age progressed, which may be one of the causes of the age-related deterioration of organismal stress resistance. Thus, D-GADD45 expression is activated by most of the studied stress factors, and D-GADD45 overexpression resulted in an increase of stress resistance. PMID:23095639

  3. Methionine Metabolism Alters Oxidative Stress Resistance via the Pentose Phosphate Pathway.

    PubMed

    Campbell, Kate; Vowinckel, Jakob; Keller, Markus A; Ralser, Markus

    2016-04-01

    Nutrient uptake and metabolism have a significant impact on the way cells respond to stress. The amino acid methionine is, in particular, a key player in the oxidative stress response, and acting as a reactive oxygen species scavenger, methionine is implicated in caloric restriction phenotypes and aging. We here provide evidence that some effects of methionine in stress situations are indirect and caused by altered activity of the nicotinamide adenine dinucleotide phosphate (NADPH) producing oxidative part of the pentose phosphate pathway (PPP). In Saccharomyces cerevisiae, both methionine prototrophic (MET15) and auxotrophic (met15Δ) cells supplemented with methionine showed an increase in PPP metabolite concentrations downstream of the NADPH producing enzyme, 6-phosphogluconate dehydrogenase. Proteomics revealed this enzyme to also increase in expression compared to methionine self-synthesizing cells. Oxidant tolerance was increased in cells preincubated with methionine; however, this effect was abolished when flux through the oxidative PPP was prevented by deletion of its rate limiting enzyme, ZWF1. Stress resistance phenotypes that follow methionine supplementation hence involve the oxidative PPP. Effects of methionine on oxidative metabolism, stress signaling, and aging have thus to be seen in the context of an altered activity of this NADP reducing pathway. Antioxid. Redox Signal. 24, 543-547. PMID:26596469

  4. Methionine Metabolism Alters Oxidative Stress Resistance via the Pentose Phosphate Pathway

    PubMed Central

    Campbell, Kate; Vowinckel, Jakob; Keller, Markus A.

    2016-01-01

    Abstract Nutrient uptake and metabolism have a significant impact on the way cells respond to stress. The amino acid methionine is, in particular, a key player in the oxidative stress response, and acting as a reactive oxygen species scavenger, methionine is implicated in caloric restriction phenotypes and aging. We here provide evidence that some effects of methionine in stress situations are indirect and caused by altered activity of the nicotinamide adenine dinucleotide phosphate (NADPH) producing oxidative part of the pentose phosphate pathway (PPP). In Saccharomyces cerevisiae, both methionine prototrophic (MET15) and auxotrophic (met15Δ) cells supplemented with methionine showed an increase in PPP metabolite concentrations downstream of the NADPH producing enzyme, 6-phosphogluconate dehydrogenase. Proteomics revealed this enzyme to also increase in expression compared to methionine self-synthesizing cells. Oxidant tolerance was increased in cells preincubated with methionine; however, this effect was abolished when flux through the oxidative PPP was prevented by deletion of its rate limiting enzyme, ZWF1. Stress resistance phenotypes that follow methionine supplementation hence involve the oxidative PPP. Effects of methionine on oxidative metabolism, stress signaling, and aging have thus to be seen in the context of an altered activity of this NADP reducing pathway. Antioxid. Redox Signal. 24, 543–547. PMID:26596469

  5. Constitutively Elevated Levels of Putrescine and Putrescine-Generating Enzymes Correlated with Oxidant Stress Resistance in Conyza bonariensis and Wheat.

    PubMed Central

    Ye, B.; Muller, H. H.; Zhang, J.; Gressel, J.

    1997-01-01

    Oxidant stress resistance in Conyza bonariensis and wheat (Triticum aestivum) has been correlated with high levels of antioxidant enzyme activities. Additionally, external oxidant stresses can increase a plant's levels of the enzymes of polyamine biosynthesis and polyamines, especially putrescine. We investigated the constitutive relationships between putrescine, putrescine-generating enzymes, and oxidant stress resistance in wheat and C. bonariensis. Putrescine was Constitutively elevated (2.5- to 5.7-fold) in 2-week-old-resistant wheat and C. bonariensis biotypes, which correlated with a 10- to 15-fold increase in paraquat oxidant resistance. Arginine and ornithine decarboxylase activities doubled, along with higher putrescine levels in resistant C. bonariensis. The variations in levels of putrescine and arginine and ornithine decarboxylase activities paralleled the constitutive variation of antioxidant enzymes, as well as oxidant resistance. Higher levels of both putrescine and antioxidant enzyme activities occurred during a peak of oxidant resistance at 10 weeks, when paraquat resistance in C. bonariensis plants is >50-fold greater than in the sensitive biotype. Application of 100 [mu]M putrescine can double oxidant-stress resistance in the resistant C. bonariensis. Putrescine may play an important role in contributing to the base level of oxidant resistance found at the nonpeak period. PMID:12223875

  6. Constitutively Elevated Levels of Putrescine and Putrescine-Generating Enzymes Correlated with Oxidant Stress Resistance in Conyza bonariensis and Wheat.

    PubMed

    Ye, B.; Muller, H. H.; Zhang, J.; Gressel, J.

    1997-12-01

    Oxidant stress resistance in Conyza bonariensis and wheat (Triticum aestivum) has been correlated with high levels of antioxidant enzyme activities. Additionally, external oxidant stresses can increase a plant's levels of the enzymes of polyamine biosynthesis and polyamines, especially putrescine. We investigated the constitutive relationships between putrescine, putrescine-generating enzymes, and oxidant stress resistance in wheat and C. bonariensis. Putrescine was Constitutively elevated (2.5- to 5.7-fold) in 2-week-old-resistant wheat and C. bonariensis biotypes, which correlated with a 10- to 15-fold increase in paraquat oxidant resistance. Arginine and ornithine decarboxylase activities doubled, along with higher putrescine levels in resistant C. bonariensis. The variations in levels of putrescine and arginine and ornithine decarboxylase activities paralleled the constitutive variation of antioxidant enzymes, as well as oxidant resistance. Higher levels of both putrescine and antioxidant enzyme activities occurred during a peak of oxidant resistance at 10 weeks, when paraquat resistance in C. bonariensis plants is >50-fold greater than in the sensitive biotype. Application of 100 [mu]M putrescine can double oxidant-stress resistance in the resistant C. bonariensis. Putrescine may play an important role in contributing to the base level of oxidant resistance found at the nonpeak period. PMID:12223875

  7. Oxidative stress and antioxidant responses to progressive resistance exercise intensity in trained and untrained males

    PubMed Central

    Özdemir, F; Çolak, R

    2015-01-01

    The relationship between oxidative stress and some exercise components of resistance exercise (e.g. intensity, exercise volume) has not been clearly defined. Additionally, the oxidative stress markers may respond differently in various conditions. This study aims to determine the effects of progressive intensity of resistance exercise (RE) on oxidative stress and antioxidants in trained and untrained men, and also to investigate the possible threshold intensity required to evoke oxidative stress. RE trained (N=8) and untrained (N=8) men performed the leg extension RE at progressive intensities standardized for total volume: 1x17 reps at 50% of one-repetition maximum (1RM); 1x14 reps at 60% of 1RM; 1x12 reps at 70% of 1RM; 2x5 reps at 80% of 1RM; and 3x3 reps at 90% of 1RM. Blood samples were drawn before (PRE) and immediately after each intensity, and after 30 minutes, 60 minutes and 24 hours following the RE. Lipid-hydroperoxide (LHP) significantly increased during the test and then decreased during the recovery in both groups (p<0.05); the POST-24 h LHP level was lower than PRE-LHP. Protein carbonyl (PCO) and superoxide dismutase (SOD) significantly increased (p<0.05); however, 8-hydroxy-2’-deoxyguanosine (8-OHdG) and glutathione (GSH) were not affected by the RE (p > 0.05). The results indicated that there was no significant training status x intensity interaction for examined variables (p > 0.05). Standardized volume of RE increased oxidative stress responses. Our study suggests that lower intensity (50%) is enough to increase LHP, whereas higher intensity (more than 80%) is required to evoke protein oxidation. PMID:26681835

  8. Genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction.

    PubMed

    Guan, Lili; Feng, Haiyan; Gong, Dezheng; Zhao, Xu; Cai, Li; Wu, Qiong; Yuan, Bo; Yang, Mei; Zhao, Jie; Zou, Yuan

    2013-12-01

    Insulin resistance (IR) increases with age and plays a key role in the pathogenesis of type 2 diabetes mellitus. Oxidative stress and mitochondrial dysfunction are supposed to be major factors leading to age-related IR. Genipin, an extract from Gardenia jasminoides Ellis fruit, has been reported to stimulate insulin secretion in pancreatic islet cells by regulating mitochondrial function. In this study, we first investigated the effects of genipin on insulin sensitivity and the potential mitochondrial mechanisms in the liver of aging rats. The rats were randomly assigned to receive intraperitoneal injections of either 25mg/kg genipin or vehicle once daily for 12days. The aging rats showed hyperinsulinemia and hyperlipidemia, and insulin resistance as examined by the decreased glucose decay constant rate during insulin tolerance test (kITT). The hepatic tissues showed steatosis and reduced glycogen content. Hepatic malondialdehyde level and mitochondrial reactive oxygen species (ROS) were higher, and levels of mitochondrial membrane potential (MMP) and ATP were lower as compared with the normal control rats. Administration of genipin ameliorated systemic and hepatic insulin resistance, alleviated hyperinsulinemia, hyperglyceridemia and hepatic steatosis, relieved hepatic oxidative stress and mitochondrial dysfunction in aging rats. Furthermore, genipin not only improved insulin sensitivity by promoting insulin-stimulated glucose consumption and glycogen synthesis, inhibited cellular ROS overproduction and alleviated the reduction of levels of MMP and ATP, but also reversed oxidative stress-associated JNK hyperactivation and reduced Akt phosphorylation in palmitate-treated L02 hepatocytes. In conclusion, genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction. PMID:24041487

  9. Enhanced Oxidative Stress Resistance through Activation of a Zinc Deficiency Transcription Factor in Brachypodium distachyon1[W][OPEN

    PubMed Central

    Glover-Cutter, Kira M.; Alderman, Stephen; Dombrowski, James E.; Martin, Ruth C.

    2014-01-01

    Identification of viable strategies to increase stress resistance of crops will become increasingly important for the goal of global food security as our population increases and our climate changes. Considering that resistance to oxidative stress is oftentimes an indicator of health and longevity in animal systems, characterizing conserved pathways known to increase oxidative stress resistance could prove fruitful for crop improvement strategies. This report argues for the usefulness and practicality of the model organism Brachypodium distachyon for identifying and validating stress resistance factors. Specifically, we focus on a zinc deficiency B. distachyon basic leucine zipper transcription factor, BdbZIP10, and its role in oxidative stress in the model organism B. distachyon. When overexpressed, BdbZIP10 protects plants and callus tissue from oxidative stress insults, most likely through distinct and direct activation of protective oxidative stress genes. Increased oxidative stress resistance and cell viability through the overexpression of BdbZIP10 highlight the utility of investigating conserved stress responses between plant and animal systems. PMID:25228396

  10. Anr, the anaerobic global regulator, modulates the redox state and oxidative stress resistance in Pseudomonas extremaustralis.

    PubMed

    Tribelli, Paula M; Nikel, Pablo I; Oppezzo, Oscar J; López, Nancy I

    2013-02-01

    The role of Anr in oxidative stress resistance was investigated in Pseudomonas extremaustralis, a polyhydroxybutyrate-producing Antarctic bacterium. The absence of Anr caused increased sensitivity to hydrogen peroxide under low oxygen tension. This phenomenon was associated with a decrease in the redox ratio, higher oxygen consumption and higher reactive oxygen species production. Physiological responses of the mutant to the oxidized state included an increase in NADP(H) content, catalase activity and exopolysaccharide production. The wild-type strain showed a sharp decrease in the reduced thiol pool when exposed to hydrogen peroxide, not observed in the mutant strain. In silico analysis of the genome sequence of P. extremaustralis revealed putative Anr binding sites upstream from genes related to oxidative stress. Genes encoding several chaperones and cold shock proteins, a glutathione synthase, a sulfate transporter and a thiol peroxidase were identified as potential targets for Anr regulation. Our results suggest a novel role for Anr in oxidative stress resistance and in redox balance maintenance under conditions of restricted oxygen supply. PMID:23223440

  11. The Cytochrome bd Oxidase of Porphyromonas gingivalis Contributes to Oxidative Stress Resistance and Dioxygen Tolerance

    PubMed Central

    Leclerc, Julia; Rosenfeld, Eric; Trainini, Mathieu; Martin, Bénédicte; Meuric, Vincent; Bonnaure-Mallet, Martine; Baysse, Christine

    2015-01-01

    Porphyromonas gingivalis is an etiologic agent of periodontal disease in humans. The disease is associated with the formation of a mixed oral biofilm which is exposed to oxygen and environmental stress, such as oxidative stress. To investigate possible roles for cytochrome bd oxidase in the growth and persistence of this anaerobic bacterium inside the oral biofilm, mutant strains deficient in cytochrome bd oxidase activity were characterized. This study demonstrated that the cytochrome bd oxidase of Porphyromonas gingivalis, encoded by cydAB, was able to catalyse O2 consumption and was involved in peroxide and superoxide resistance, and dioxygen tolerance. PMID:26629705

  12. Selection of insulin-producing rat insulinoma (RINm) cells with improved resistance to oxidative stress.

    PubMed

    Bloch, Konstantin O; Vorobeychik, Marina; Yavrians, Karina; Vardi, Pnina

    2003-06-01

    The defense system against reactive oxygen species is believed to be crucial for the survival of insulin-producing cells after various injuries. The aim of our study was to select a subpopulation of insulin-producing RINm cells with higher resistance to oxidative stress. The cells resistant to hydrogen peroxide (RINmHP) were obtained by repeated exposure of parental RINm cells to 100 and 200 microM hydrogen peroxide (HP). The increased resistance of RINmHP cells to HP was confirmed by three different cytotoxicity assays. In addition, the selected cells also were resistant to the cytotoxic effect of activated rat splenocytes compared to parental cells. The half-life of HP in the RINmHP cell culture medium was about 2.5 times lower than that of the parental cells, corresponding to the increased level of catalase expression and activity in selected cells. The increased defense property of the selected cells was not associated with any significant changes in insulin content and insulin response to a mixture of glucose with isobutyl methyl xanthine or potassium chloride. In conclusion, repeated exposure to HP induces selection of RINm cells with improved resistance to oxidative stress. This improved defense characteristic probably is due to an increased level of catalase expression and activity in the selected cells. PMID:12781331

  13. 25-Hydroxyvitamin D3-Deficiency Enhances Oxidative Stress and Corticosteroid Resistance in Severe Asthma Exacerbation

    PubMed Central

    Yang, Xiaoqiong; Cheng, Yuanyuan; zhang, Yun; Wang, Xiaoyun; Wang, Xing; Xie, Tao; Li, Guoping; Liu, Zhigang; Zhong, Nanshan

    2014-01-01

    Oxidative stress plays a significant role in exacerbation of asthma. The role of vitamin D in oxidative stress and asthma exacerbation remains unclear. We aimed to determine the relationship between vitamin D status and oxidative stress in asthma exacerbation. Severe asthma exacerbation patients with 25-hydroxyvitamin D3-deficiency (V-D deficiency) or 25-hydroxyvitamin D-sufficiency (V-D sufficiency) were enrolled. Severe asthma exacerbation with V-D-deficiency showed lower forced expiratory volume in one second (FEV1) compared to that with V-D-sufficiency. V-D-deficiency intensified ROS release and DNA damage and increased TNF-α, OGG1 and NFκB expression and NFκB phosphorylation in severe asthma exacerbation. Supplemental vitamin D3 significantly increased the rates of FEV1 change and decreased ROS and DNA damage in V-D-deficiency. Vitamin D3 inhibited LPS-induced ROS and DNA damage and were associated with a decline in TNF-α and NFκB in epithelial cells. H2O2 reduces nuclear translocation of glucocorticoid receptors in airway epithelial cell lines. V-D pretreatment enhanced the dexamethasone-induced nuclear translocation of glucocorticoid receptors in airway epithelial cell lines and monocytes from 25-hydroxyvitamin D3-deficiency asthma patients. These findings indicate that V-D deficiency aggravates oxidative stress and DNA damage, suggesting a possible mechanism for corticosteroid resistance in severe asthma exacerbation. PMID:25380286

  14. A putative TetR regulator is involved in nitric oxide stress resistance in Porphyromonas gingivalis.

    PubMed

    Boutrin, M-C; Yu, Y; Wang, C; Aruni, W; Dou, Y; Shi, L; Fletcher, H M

    2016-08-01

    To survive in the periodontal pocket, Porphyromonas gingivalis, the main causative agent of periodontal disease, must overcome oxidative and nitric oxide (NO) stress. Previously, we reported that, in the presence of NO comparable to stress conditions, the transcriptome of P. gingivalis was differentially expressed, and genes belonging to the PG1178-81 cluster were significantly upregulated. To further evaluate their role(s) in NO stress resistance, these genes were inactivated by allelic exchange mutagenesis. Isogenic mutants P. gingivalis FLL460 (ΔPG1181::ermF) and FLL461 (ΔPG1178-81::ermF) were black-pigmented, with gingipain and hemolytic activities comparable to that of the wild-type strain. Whereas the recovery of these isogenic mutants from NO stress was comparable to the wild-type, there was increased sensitivity to hydrogen peroxide-induced stress. RNA-Seq analysis under conditions of NO stress showed that approximately 5 and 8% of the genome was modulated in P. gingivalis FLL460 and FLL461, respectively. The PG1178-81 gene cluster was shown to be part of the same transcriptional unit and is inducible in response to NO stress. In the presence of NO, PG1181, a putative transcriptional regulator, was shown to bind to its own promoter region and that of several other NO responsive genes including PG0214 an extracytoplasmic function σ factor, PG0893 and PG1236. Taken together, the data suggest that PG1181 is a NO responsive transcriptional regulator that may play an important role in the NO stress resistance regulatory network in P. gingivalis. PMID:26332057

  15. Protective effects of coenzyme q(10) on decreased oxidative stress resistance induced by simvastatin.

    PubMed

    Kettawan, Aikkarach; Takahashi, Takayuki; Kongkachuichai, Ratchanee; Charoenkiatkul, Somsri; Kishi, Takeo; Okamoto, Tadashi

    2007-05-01

    The effects of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase), on oxidative stress resistance and the protective effects of coenzyme Q (CoQ) were investigated. When simvastatin was administered orally to mice, the levels of oxidized and reduced CoQ(9) and CoQ(10) in serum, liver, and heart, decreased significantly when compared to those of control. The levels of thiobarbituric acid reactive substances induced by Fe(2+)-ascorbate in liver and heart mitochondria also increased significantly with simvastatin. Furthermore, cultured cardiac myocytes treated with simvastatin exhibited less resistance to oxidative stress, decreased time to the cessation of spontaneous beating in response to H(2)O(2) addition, and decreased responsiveness to electrical field stimulation. These results suggested that oral administration of simvastatin suppresses the biosynthesis of CoQ, which shares the same biosynthesis pathway as cholesterol up to farnesyl pyrophosphate, thus compromising the physiological function of reduced CoQ, which possesses antioxidant activity. However, these undesirable effects induced by simvastatin were alleviated by coadministering CoQ(10) with simvastatin to mice. Simvastatin also reduced the activity of NADPH-CoQ reductase, a biological enzyme that converts oxidized CoQ to the corresponding reduced CoQ, while CoQ(10) administration improved it. These findings may also support the efficacy of coadministering CoQ(10) with statins. PMID:18398496

  16. Cryptococcus neoformans Yap1 is required for normal fluconazole and oxidative stress resistance

    PubMed Central

    Paul, Sanjoy; Doering, Tamara L.; Moye-Rowley, W. Scott

    2014-01-01

    Cryptococcus neoformans is a pathogen that is the most common cause of fungal meningitis. As with most fungal pathogens, the most prevalent clinical antifungal used to treat Cryptococcosis is orally administered fluconazole. Resistance to this antifungal is an increasing concern in treatment of fungal disease in general. Our knowledge of the specific determinants involved in fluconazole resistance in Cryptococcus is limited. Here we report the identification of an important genetic determinant of fluconazole resistance in Cryptococcus neoformans that encodes a basic region-leucine zipper transcription factor homologous to Saccharomyces cerevisiae Yap1. Expression of a codon-optimized form of the Cn YAP1 cDNA in S. cerevisiae complemented defects caused by loss of the endogenous S. cerevisiae YAP1 gene and activated transcription from a reporter gene construct. Mutant strains of C. neoformans lacking YAP1 were hypersensitive to a range of oxidative stress agents but importantly also to fluconazole. Loss of Yap1 homologues from other fungal pathogens like Candida albicans or Aspergillus fumigatus was previously found to cause oxidant hypersensitivity but had no detectable effect on fluconazole resistance. Our data provide evidence for a unique biological role of Yap1 in wild-type fluconazole resistance in C. neoformans. PMID:25445311

  17. Saccharomyces cerevisiae: Population Divergence and Resistance to Oxidative Stress in Clinical, Domesticated and Wild Isolates

    PubMed Central

    Diezmann, Stephanie; Dietrich, Fred S.

    2009-01-01

    Background Saccharomyces cerevisiae has been associated with human life for millennia in the brewery and bakery. Recently it has been recognized as an emerging opportunistic pathogen. To study the evolutionary history of S. cerevisiae, the origin of clinical isolates and the importance of a virulence-associated trait, population genetics and phenotypic assays have been applied to an ecologically diverse set of 103 strains isolated from clinics, breweries, vineyards, fruits, soil, commercial supplements and insect guts. Methodology/Principal Findings DNA sequence data from five nuclear DNA loci were analyzed for population structure and haplotype distribution. Additionally, all strains were tested for survival of oxidative stress, a trait associated with microbial pathogenicity. DNA sequence analyses identified three genetic subgroups within the recombining S. cerevisiae strains that are associated with ecology, geography and virulence. Shared alleles suggest that the clinical isolates contain genetic contribution from the fruit isolates. Clinical and fruit isolates exhibit high levels of recombination, unlike the genetically homogenous soil isolates in which no recombination was detected. However, clinical and soil isolates were more resistant to oxidative stress than any other population, suggesting a correlation between survival in oxidative stress and yeast pathogenicity. Conclusions/Significance Population genetic analyses of S. cerevisiae delineated three distinct groups, comprising primarily the (i) human-associated brewery and vineyard strains, (ii) clinical and fruit isolates (iii) and wild soil isolates from eastern U.S. The interactions between S. cerevisiae and humans potentiate yeast evolution and the development of genetically, ecologically and geographically divergent groups. PMID:19390633

  18. Staphylococcus aureus CymR Is a New Thiol-based Oxidation-sensing Regulator of Stress Resistance and Oxidative Response

    SciTech Connect

    Ji, Quanjiang; Zhang, Liang; Sun, Fei; Deng, Xin; Liang, Haihua; Bae, Taeok; He, Chuan

    2014-10-02

    As a human pathogen, Staphylococcus aureus must cope with oxidative stress generated by the human immune system. Here, we report that CymR utilizes its sole Cys-25 to sense oxidative stress. Oxidation followed by thiolation of this cysteine residue leads to dissociation of CymR from its cognate promoter DNA. In contrast, the DNA binding of the CymRC25S mutant was insensitive to oxidation and thiolation, suggesting that CymR senses oxidative stress through oxidation of its sole cysteine to form a mixed disulfide with low molecular weight thiols. The determined crystal structures of the reduced and oxidized forms of CymR revealed that Cys-25 is oxidized to Cys-25-SOH in the presence of H{sub 2}O{sub 2}. Deletion of cymR reduced the resistance of S. aureus to oxidative stresses, and the resistance was restored by expressing a C25S mutant copy of cymR. In a C25S substitution mutant, the expression of two genes, tcyP and mccB, was constitutively repressed and did not respond to hydrogen peroxide stress, whereas the expression of the genes were highly induced under oxidative stress in a wild-type strain, indicating the critical role of Cys-25 in redox signaling in vivo. Thus, CymR is another master regulator that senses oxidative stress and connects stress responses to virulence regulation in S. aureus.

  19. Effect of zinc supplementation on resistance of cultured human skin fibroblasts toward oxidant stress.

    PubMed

    Richard, M J; Guiraud, P; Leccia, M T; Beani, J C; Favier, A

    1993-01-01

    In purified system zinc has been shown to have an antioxidant role. Its effects on the resistance of cultured cells towards oxidative stress in vitro were examined. Diploid human skin fibroblasts were grown for 21 d in culture media (RPMI 1640 containing 15% fetal calf serum) added with different zinc (Zn) concentrations (100, 125, and 150 microM as Zinc chlorur ZnCl2). In comparison, cell controls were grown in standard culture media (6.5 microM Zn). The intracellular zinc levels of treated fibroblasts increased from 3- to 7-fold (2330 +/- 120 ng/mg protein in 150-microM Zn-treated cells versus 331 +/- 21 ng/mg protein in control cells). The intracellular copper increased 3- fold whereas the iron content slightly but not significantly decreased. The index of basal lipid peroxidation measured as thiobarbituric acid reactants (TBARs) of zinc-supplemented cells was lower than that of non zinc supplemented controls (0.89 mumol/g protein in 150 microM Zn-treated cells versus 1.59 mumol/g protein in controls). At these high doses of zinc, fibroblasts expressed lower antioxidant metalloenzymes activities. Diminished TBARs in Zn treated cells tends to support that Zn acts protectively against free radical mediated damage. However when the cells were challenged with extracellular oxidant stresses mediated by hypoxanthine/xanthine oxidase or hydrogen peroxide (H2O2), an increased toxicity in Zn-supplemented cells was observed. When we applied an intracellular oxidative stress as UV-B or UV-A radiation, Zn-treated fibroblasts were more resistant than cells grown in normal medium. If Zn has shown antioxidant effect in some in vitro or in vivo systems our observations clearly demonstrate that this role is not mediated by antioxidant metalloenzymes. PMID:7688532

  20. A polyphenolic flavonoid glabridin: Oxidative stress response in multidrug-resistant Staphylococcus aureus.

    PubMed

    Singh, Vigyasa; Pal, Anirban; Darokar, Mahendra P

    2015-10-01

    Glabridin a polyphenolic flavonoid from Glycyrrhiza glabra is known to possess several therapeutic properties. In the present study, we report for the first time the in vitro antibacterial activity (MIC values ranging from 3.12 to 25 μg/mL) of glabridin against multidrug-resistant clinical isolates of S. aureus by inducing oxidative stress. Increased levels of H2O2 and NO were observed in a dose-dependent manner after treatment of glabridin that further affected macromolecules such as DNA, lipids, and proteins. Surprisingly, glabridin was found to possess antioxidant properties when used at lower concentrations using three different methods including DPPH, FRAP, and SOD assays. These observations were further validated through the expression analysis of oxidative stress-responsive genes using qRT-PCR wherein glabridin was observed to up- and down-regulate these genes at lower and higher concentrations, respectively. In in vitro combination experiments, glabridin was found to reduce the MIC of different antibiotics such as norfloxacin, oxacillin, and vancomycin by up to 4-fold, while the MIC of glabridin itself was found to be reduced by up to 8-fold in the presence of antibiotics. A synergistic interaction was observed between norfloxacin and glabridin when used in combination against multidrug-resistant clinical isolate SA 4627 of Staphylococcus aureus at much lower concentrations, indicating the suitability of glabridin in combination therapy. PMID:26117328

  1. Increased resistance to oxidative stress in transgenic plants by targeting mannitol biosynthesis to chloroplasts

    SciTech Connect

    Shen, B.; Jensen, R.G.; Bohnert, H.J.

    1997-04-01

    To investigate the potential role of a polyol, mannitol, in oxidative stress protection, a bacterial mannitol-1-phosphate dehydrogenase gene was targeted to chloroplasts by the addition of an aminoterminal transit peptide. Transgenic tobacco (Nicotiana tabacum) lines accumulate mannitol at concentrations ranging from 2.5 to 7 {mu}mol/g fresh weight. Line BS1-31 accumulated approximately 100 mm mannitol in chloroplasts and was identical to the wild type in phenotype and photosynthetic performance. The presence of mannitol in chloroplasts resulted in an increased resistance to methyl viologen (MV)-induced oxidative stress, documented by the increased retention of chlorophyll in transgenic leaf tissue following MV treatment. In the presence of MV, isolated mesophyll cells of BS1-31 exhibited higher CO{sub 2} fixation than the wild type. When the hydroxyl radical probe dimethyl sulfoxide was introduced into cells, the initial formation rate of methane sulfinic acid was significantly lower in cells containing mannitol in the chloroplast compartment than in wild-type cells, indicating an increased hydroxyl radical-scavenging capacity in BS1-31 tobacco. We suggest that the chloroplast location of mannitol can supplement endogenous radical-scavenging mechanisms and reduce oxidative damage of cells by hydroxyl radicals. 43 refs., 5 figs., 1 tab.

  2. Diethylhexyl Phthalates Is Associated with Insulin Resistance via Oxidative Stress in the Elderly: A Panel Study

    PubMed Central

    Kim, Jin Hee; Park, Hye Yin; Bae, Sanghyuk; Lim, Youn-Hee; Hong, Yun-Chul

    2013-01-01

    Background Insulin resistance (IR) is believed to be the underlying mechanism of metabolic syndrome and type 2 diabetes mellitus (DM). Recently, a few studies have demonstrated that phthalates could cause oxidative stress which would contribute to the development of IR. Therefore, we evaluated whether exposure to phthalates affects IR, and oxidative stress is involved in the phthalates-IR pathway. Methods We recruited 560 elderly participants, and obtained blood and urine samples during repeated medical examinations. For the determination of phthalate exposure, we measured urinary levels of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) as metabolites of diethylhexyl phthalates (DEHP), and mono-n-butyl phthalate (MnBP) as a metabolite of di-butyl phthalate (DBP). Malondialdehyde (MDA), an oxidative stress biomarker, was also measured in urine samples. We measured serum levels of fasting glucose and insulin, and derived the homeostatic model assessment (HOMA) index to assess IR. A mixed-effect model and penalized regression spline were used to estimate the associations among phthalate metabolites, MDA, and IR. Results The molar sum of MEHHP and MEOHP (∑DEHP) were significantly associated with HOMA (β = 0.26, P = 0.040), and the association was apparent among participants with a history of DM (β = 0.88, P = 0.037) and among females (β = 0.30, P = 0.022). However, the relation between MnBP and HOMA was not found. When we evaluated whether oxidative stress is involved in increases of HOMA by ∑DEHP, MDA levels were significantly associated with increases of ∑DEHP (β = 0.11, P<0.001) and HOMA (β = 0.49, P = 0.049). Conclusions Our study results suggest that exposure to DEHP in the elderly population increases IR, which is related with oxidative stress, and that participants with a history of DM and females are more susceptible to DEHP exposure. PMID:23977034

  3. Adriamycin resistance in Chinese hamster fibroblasts following oxidative stress induced by photodynamic therapy.

    PubMed

    Fisher, A M; Ferrario, A; Gomer, C J

    1993-10-01

    Photodynamic therapy (PDT) generates reactive oxygen species that are responsible for the initial cytotoxic events produced by this treatment. An extended (16 h) porphyrin incubation prior to light irradiation increased expression of the 75, 78 and 94 kDa glucose-regulated stress proteins (GRP), as well as the cognate form of the 70 kDa heat shock protein. However, these stress proteins were not induced following isoeffective PDT doses using a short (1 h) porphyrin incubation protocol. In the current study, Chinese hamster fibroblasts were used to examine sensitivity to adjunctive PDT and adriamycin as previous reports indicate a correlation between stress protein synthesis and a decrease in adriamycin cytotoxicity. Treatments that either induced GRP (i.e. PDT with an extended porphyrin incubation or exposure to the calcium ionophore A23187) or did not induce GRP (i.e. PDT with a short porphyrin incubation or UV irradiation) were followed at increasing time intervals with a 1 h adriamycin incubation. A time-dependent decrease in adriamycin cytotoxicity was observed when cells were first exposed to either of the PDT protocols or to A23187. Alterations in intracellular drug levels did not account for the change in adriamycin sensitivity. Likewise, intracellular glutathione concentrations and antioxidant enzyme activities were not significantly altered following PDT or A23187. Parameters associated with altered adriamycin sensitivity included a decrease in the percentage of S phase cells following PDT and A23187 as well as a depletion of intracellular ATP after PDT using the extended porphyrin incubation. These results demonstrate that PDT can be added to the growing list of diverse stresses producing transient resistance to adriamycin and that stress protein induction is not universally associated with all oxidative treatments inducing this resistance. PMID:8248335

  4. MACROAUTOPHAGY AND CHAPERONE-MEDIATED AUTOPHAGY ARE REQUIRED FOR HEPATOCYTE RESISTANCE TO OXIDANT STRESS

    PubMed Central

    Wang, Yongjun; Singh, Rajat; Xiang, Youqing; Czaja, Mark J.

    2010-01-01

    The function of the lysosomal degradative pathway of autophagy in cellular injury is unclear as findings in nonhepatic cells have implicated autophagy as both a mediator of cell death and as a survival response. Autophagic function is impaired in steatotic and aged hepatocytes, suggesting that in these settings hepatocellular injury may be altered by the decrease in autophagy. To delineate the specific function of autophagy in the hepatocyte injury response, the effects of menadione-induced oxidative stress were examined in the RALA255-10G rat hepatocyte line when macroautophagy was inhibited by an shRNA-mediated knockdown of the autophagy gene atg5. Inhibition of macroautophagy sensitized cells to apoptotic and necrotic death from normally nontoxic concentrations of menadione. Inhibition of macroautophagy led to overactivation of the c-Jun N-terminal kinase (JNK)/c-Jun signaling pathway that induced cell death. Death occurred from activation of the mitochondrial death pathway with cellular ATP depletion, mitochondrial cytochrome c release and caspase activation. Sensitization to death from menadione occurred despite up regulation of other forms of autophagy in compensation for the loss of macroautophagy. Chaperone-mediated autophagy (CMA) also mediated resistance to menadione as CMA inhibition sensitized cells to death from menadione through a mechanism different from that of a loss of macroautophagy as death occurred in the absence of JNK/c-Jun overactivation or ATP depletion. Conclusion Hepatocyte resistance to injury from menadione-induced oxidative stress is mediated by distinct functions of both macroautophagy and CMA, indicating that impaired function of either form of autophagy may promote oxidant-induced liver injury. PMID:20578144

  5. Endurance training improves the resistance of rat diaphragm to exercise-induced oxidative stress.

    PubMed

    Oh-ishi, S; Kizaki, T; Ookawara, T; Sakurai, T; Izawa, T; Nagata, N; Ohno, H

    1997-11-01

    The current study was designed to test the hypothesis that endurance training improves the ability of the diaphragm muscle to resist exercise-induced oxidative stress. Twenty-eight male Wistar rats were assigned to either untrained or trained groups. Trained rats were treadmill-trained for 9 wk. Each group was subdivided into acutely exercised or nonexercised groups. Diaphragm muscle from each rat was analyzed to determine the levels of certain antioxidant enzymes: Mn-superoxide dismutase (Mn-SOD), Cu,Zn-superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase, and catalase. In addition, interleukin-1 and myeloperoxidase levels were determined. Endurance training upregulated all of the antioxidant enzymes. Conversely, acute exercise increased glutathione peroxidase and catalase in untrained rats, while it had no overt effect on any antioxidant enzymes in trained rats. Both Mn-SOD and Cu,Zn-SOD contents and activities were increased with endurance training. However, the mRNA expressions of both forms of SOD did not show any significant change with endurance training. Acute exercise also increased the levels of interleukin-1 and myeloperoxidase in untrained rats but not in trained rats. Moreover, acute exercise significantly increased the ability of neutrophils to produce superoxide, especially in untrained rats. The results from this study demonstrate that endurance training can upregulate certain antioxidant enzyme activities in rat diaphragm muscle, indicating the potential for improvement of the resistance to intracellular reactive oxygen species. The results of this study also suggest that acute exercise may cause oxidative damage in rat diaphragm through the activation of the inflammatory pathway and that endurance training may minimize such an extracellular oxidative stress by acute exercise. PMID:9372679

  6. AsrR Is an Oxidative Stress Sensing Regulator Modulating Enterococcus faecium Opportunistic Traits, Antimicrobial Resistance, and Pathogenicity

    PubMed Central

    Lebreton, François; van Schaik, Willem; Sanguinetti, Maurizio; Posteraro, Brunella; Torelli, Riccardo; Le Bras, Florian; Verneuil, Nicolas; Zhang, Xinglin; Giard, Jean-Christophe; Dhalluin, Anne; Willems, Rob J. L.; Leclercq, Roland; Cattoir, Vincent

    2012-01-01

    Oxidative stress serves as an important host/environmental signal that triggers a wide range of responses in microorganisms. Here, we identified an oxidative stress sensor and response regulator in the important multidrug-resistant nosocomial pathogen Enterococcus faecium belonging to the MarR family and called AsrR (antibiotic and stress response regulator). The AsrR regulator used cysteine oxidation to sense the hydrogen peroxide which results in its dissociation to promoter DNA. Transcriptome analysis showed that the AsrR regulon was composed of 181 genes, including representing functionally diverse groups involved in pathogenesis, antibiotic and antimicrobial peptide resistance, oxidative stress, and adaptive responses. Consistent with the upregulated expression of the pbp5 gene, encoding a low-affinity penicillin-binding protein, the asrR null mutant was found to be more resistant to β-lactam antibiotics. Deletion of asrR markedly decreased the bactericidal activity of ampicillin and vancomycin, which are both commonly used to treat infections due to enterococci, and also led to over-expression of two major adhesins, acm and ecbA, which resulted in enhanced in vitro adhesion to human intestinal cells. Additional pathogenic traits were also reinforced in the asrR null mutant including greater capacity than the parental strain to form biofilm in vitro and greater persistance in Galleria mellonella colonization and mouse systemic infection models. Despite overexpression of oxidative stress-response genes, deletion of asrR was associated with a decreased oxidative stress resistance in vitro, which correlated with a reduced resistance to phagocytic killing by murine macrophages. Interestingly, both strains showed similar amounts of intracellular reactive oxygen species. Finally, we observed a mutator phenotype and enhanced DNA transfer frequencies in the asrR deleted strain. These data indicate that AsrR plays a major role in antimicrobial resistance and

  7. Manganese Complexes: Diverse Metabolic Routes to Oxidative Stress Resistance in Prokaryotes and Yeast

    PubMed Central

    2013-01-01

    Abstract Significance: Antioxidant enzymes are thought to provide critical protection to cells against reactive oxygen species (ROS). However, many organisms can fully compensate for the loss of such enzymatic defenses by accumulating metabolites and Mn2+, which can form catalytic Mn-antioxidants. Accumulated metabolites can direct reactivity of Mn2+ with superoxide and specifically shield proteins from oxidative damage. Recent Advances: There is mounting evidence that Mn-Pi (orthophosphate) complexes act as potent scavengers of superoxide in all three branches of life. Moreover, it is evident that Mn2+ in complexes with carbonates, peptides, nucleosides, and organic acids can also form catalytic Mn-antioxidants, pointing to diverse metabolic routes to oxidative stress resistance. Critical Issues: What conditions favor utility of Mn-metabolites versus enzymatic means for removing ROS? Mn2+-metabolite defenses are critical for preserving the activity of repair enzymes in Deinococcus radiodurans exposed to intense radiation stress, and in Lactobacillus plantarum, which lacks antioxidant enzymes. In other microorganisms, Mn-antioxidants can serve as an auxiliary protection when enzymatic antioxidants are insufficient or fail. These findings of a critical role of Mn-antioxidants in the survival of prokaryotes under oxidative stress parallel the trends developing for the simple eukaryote Saccharomyces cerevisiae. Future Directions: Phosphates, peptides and organic acids are just a snapshot of the types of anionic metabolites that promote such reactivity of Mn2+. Their probable roles in pathogen defense against the host immune response and in ROS-mediated signaling pathways are also areas that are worthy of serious investigation. Moreover, it is clear that these protective chemical processes can be harnessed for practical purposes. Antioxid. Redox Signal. 19, 933–944. PMID:23249283

  8. Maternal Fructose Intake Induces Insulin Resistance and Oxidative Stress in Male, but Not Female, Offspring

    PubMed Central

    Rodríguez, Lourdes; Otero, Paola; Panadero, María I.; Rodrigo, Silvia; Álvarez-Millán, Juan J.; Bocos, Carlos

    2015-01-01

    Objective. Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and cardiovascular diseases. However, consumption of beverages containing fructose is allowed during gestation. Recently, we found that an intake of fructose (10% wt/vol) throughout gestation produces an impaired fetal leptin signalling. Therefore, we have investigated whether maternal fructose intake produces subsequent changes in their progeny. Methods. Blood samples from fed and 24 h fasted female and male 90-day-old rats born from fructose-fed, glucose-fed, or control mothers were used. Results. After fasting, HOMA-IR and ISI (estimates of insulin sensitivity) were worse in male descendents from fructose-fed mothers in comparison to the other two groups, and these findings were also accompanied by a higher leptinemia. Interestingly, plasma AOPP and uricemia (oxidative stress markers) were augmented in male rats from fructose-fed mothers compared to the animals from control or glucose-fed mothers. In contrast, female rats did not show any differences in leptinemia between the three groups. Further, insulin sensitivity was significantly improved in fasted female rats from carbohydrate-fed mothers. In addition, plasma AOPP levels tended to be diminished in female rats from carbohydrate-fed mothers. Conclusion. Maternal fructose intake induces insulin resistance, hyperleptinemia, and plasma oxidative stress in male, but not female, progeny. PMID:25763281

  9. Impact of Acinetobacter baumannii Superoxide Dismutase on Motility, Virulence, Oxidative Stress Resistance and Susceptibility to Antibiotics

    PubMed Central

    Heider, Christine; Skiebe, Evelyn; Wilharm, Gottfried

    2014-01-01

    Acinetobacter baumannii is a Gram-negative bacterium appearing as an opportunistic pathogen in hospital settings. Superoxide dismutase (SOD) contributes to virulence in several pathogenic bacteria by detoxifying reactive oxygen species released in the course of host defense reactions. However, the biological role of SODs in A. baumannii has not yet been elucidated. Here, we inactivated in A. baumannii ATCC 17978 gene A1S_2343, encoding a putative SOD of the Fe-Mn type by transposon insertion, resulting in mutant ATCC 17978 sod2343::Km. The mutation was also introduced in two naturally competent A. baumannii isolates by transformation with chromosomal DNA derived from mutant ATCC 17978 sod2343::Km. We demonstrate that inactivation of sod2343 leads to significant motility defects in all three A. baumannii strains. The mutant strains were more susceptible to oxidative stress compared to their parental strains. Susceptibility to colistin and tetracycline was increased in all mutant strains while susceptibility of the mutants to gentamicin, levofloxacin and imipenem was strain-dependent. In the Galleria mellonella infection model the mutant strains were significantly attenuated. In conclusion, sod2343 plays an important role in motility, resistance to oxidative stress, susceptibility to antibiotics and virulence in A. baumannii. PMID:25000585

  10. Maternal fructose intake induces insulin resistance and oxidative stress in male, but not female, offspring.

    PubMed

    Rodríguez, Lourdes; Otero, Paola; Panadero, María I; Rodrigo, Silvia; Álvarez-Millán, Juan J; Bocos, Carlos

    2015-01-01

    Objective. Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and cardiovascular diseases. However, consumption of beverages containing fructose is allowed during gestation. Recently, we found that an intake of fructose (10% wt/vol) throughout gestation produces an impaired fetal leptin signalling. Therefore, we have investigated whether maternal fructose intake produces subsequent changes in their progeny. Methods. Blood samples from fed and 24 h fasted female and male 90-day-old rats born from fructose-fed, glucose-fed, or control mothers were used. Results. After fasting, HOMA-IR and ISI (estimates of insulin sensitivity) were worse in male descendents from fructose-fed mothers in comparison to the other two groups, and these findings were also accompanied by a higher leptinemia. Interestingly, plasma AOPP and uricemia (oxidative stress markers) were augmented in male rats from fructose-fed mothers compared to the animals from control or glucose-fed mothers. In contrast, female rats did not show any differences in leptinemia between the three groups. Further, insulin sensitivity was significantly improved in fasted female rats from carbohydrate-fed mothers. In addition, plasma AOPP levels tended to be diminished in female rats from carbohydrate-fed mothers. Conclusion. Maternal fructose intake induces insulin resistance, hyperleptinemia, and plasma oxidative stress in male, but not female, progeny. PMID:25763281

  11. Inactivation of the organic hydroperoxide stress resistance regulator OhrR enhances resistance to oxidative stress and isoniazid in Mycobacterium smegmatis.

    PubMed

    Saikolappan, Sankaralingam; Das, Kishore; Dhandayuthapani, Subramanian

    2015-01-01

    The organic hydroperoxide stress resistance regulator (OhrR) is a MarR type of transcriptional regulator that primarily regulates the expression of organic hydroperoxide reductase (Ohr) in bacteria. In mycobacteria, the genes encoding these proteins exist in only a few species, which include the fast-growing organism Mycobacterium smegmatis. To delineate the roles of Ohr and OhrR in defense against oxidative stress in M. smegmatis, strains lacking the expression of these proteins were constructed by deleting the ohrR and ohr genes, independently and together, through homologous recombination. The OhrR mutant strain (MSΔohrR) showed severalfold upregulation of Ohr expression, which could be observed at both the transcript and protein levels. Similar upregulation of Ohr expression was also noticed in an M. smegmatis wild-type strain (MSWt) induced with cumene hydroperoxide (CHP) and t-butyl hydroperoxide (t-BHP). The elevated Ohr expression in MSΔohrR correlated with heightened resistance to oxidative stress due to CHP and t-BHP and to inhibitory effects due to the antituberculosis drug isoniazid (INH). Further, this mutant strain exhibited significantly enhanced survival in the intracellular compartments of macrophages. In contrast, the strains lacking either Ohr alone (MSΔohr) or both Ohr and OhrR (MSΔohr-ohrR) displayed limited or no resistance to hydroperoxides and INH. Additionally, these strains showed no significant differences in intracellular survival from the wild type. Electrophoretic mobility shift assays (EMSAs) revealed that the overexpressed and purified OhrR interacts with the ohr-ohrR intergenic region with a greater affinity and this interaction is contingent upon the redox state of the OhrR. These findings suggest that Ohr-OhrR is an important peroxide stress response system in M. smegmatis. PMID:25313389

  12. Inactivation of the Organic Hydroperoxide Stress Resistance Regulator OhrR Enhances Resistance to Oxidative Stress and Isoniazid in Mycobacterium smegmatis

    PubMed Central

    Saikolappan, Sankaralingam; Das, Kishore

    2014-01-01

    The organic hydroperoxide stress resistance regulator (OhrR) is a MarR type of transcriptional regulator that primarily regulates the expression of organic hydroperoxide reductase (Ohr) in bacteria. In mycobacteria, the genes encoding these proteins exist in only a few species, which include the fast-growing organism Mycobacterium smegmatis. To delineate the roles of Ohr and OhrR in defense against oxidative stress in M. smegmatis, strains lacking the expression of these proteins were constructed by deleting the ohrR and ohr genes, independently and together, through homologous recombination. The OhrR mutant strain (MSΔohrR) showed severalfold upregulation of Ohr expression, which could be observed at both the transcript and protein levels. Similar upregulation of Ohr expression was also noticed in an M. smegmatis wild-type strain (MSWt) induced with cumene hydroperoxide (CHP) and t-butyl hydroperoxide (t-BHP). The elevated Ohr expression in MSΔohrR correlated with heightened resistance to oxidative stress due to CHP and t-BHP and to inhibitory effects due to the antituberculosis drug isoniazid (INH). Further, this mutant strain exhibited significantly enhanced survival in the intracellular compartments of macrophages. In contrast, the strains lacking either Ohr alone (MSΔohr) or both Ohr and OhrR (MSΔohr-ohrR) displayed limited or no resistance to hydroperoxides and INH. Additionally, these strains showed no significant differences in intracellular survival from the wild type. Electrophoretic mobility shift assays (EMSAs) revealed that the overexpressed and purified OhrR interacts with the ohr-ohrR intergenic region with a greater affinity and this interaction is contingent upon the redox state of the OhrR. These findings suggest that Ohr-OhrR is an important peroxide stress response system in M. smegmatis. PMID:25313389

  13. Macronutrient intake induces oxidative and inflammatory stress: potential relevance to atherosclerosis and insulin resistance

    PubMed Central

    Ghanim, Husam; Chaudhuri, Ajay; Dhindsa, Sandeep; Kim, Sung Soo

    2010-01-01

    With the global increase in the epidemic of obesity and type 2 diabetes with a concomitant increase in atherosclerotic disease, an investigation into the effects of various macronutrients and food products has become necessary. Such investigation will allow us to better understand the relationship between the intake of various macronutrients and the pathogenesis of mechanisms underlying the regulation of insulin sensitivity and resistance, oxidative stress and inflammation, the regulation of hunger and satiety and atherogenesis. This review covers the first decade of work in this area relating the intake of usual foods and diets to their immediate and long term outcomes. The review also covers the exciting novel area of anti-inflammatory effects of certain foods. Hopefully, a comprehensive understanding of these actions of macronutrients and their long term effects will allow us to formulate food combinations which will lead to healthy eating habits and improvement in our overall health status. PMID:20200475

  14. Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer's Disease

    PubMed Central

    Verdile, Giuseppe; Keane, Kevin N.; Cruzat, Vinicius F.; Medic, Sandra; Sabale, Miheer; Rowles, Joanne; Wijesekara, Nadeeja; Martins, Ralph N.; Fraser, Paul E.; Newsholme, Philip

    2015-01-01

    Type 2 diabetes (T2DM), Alzheimer's disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer's disease (AD) is the most common subtype of dementia. Reduced release (for T2DM) and decreased action of insulin are central to the development and progression of both T2DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance affects many tissues and organs, either through impaired insulin signalling or through aberrant changes in both glucose and lipid (cholesterol and triacylglycerol) metabolism and concentrations in the blood. Although epidemiological and biological evidence has highlighted an increased incidence of cognitive decline and AD in patients with T2DM, the common molecular basis of cell and tissue dysfunction is rapidly gaining recognition. As a cause or consequence, the chronic inflammatory response and oxidative stress associated with T2DM, amyloid-β (Aβ) protein accumulation, and mitochondrial dysfunction link T2DM and AD. PMID:26693205

  15. Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer's Disease.

    PubMed

    Verdile, Giuseppe; Keane, Kevin N; Cruzat, Vinicius F; Medic, Sandra; Sabale, Miheer; Rowles, Joanne; Wijesekara, Nadeeja; Martins, Ralph N; Fraser, Paul E; Newsholme, Philip

    2015-01-01

    Type 2 diabetes (T2DM), Alzheimer's disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer's disease (AD) is the most common subtype of dementia. Reduced release (for T2DM) and decreased action of insulin are central to the development and progression of both T2DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance affects many tissues and organs, either through impaired insulin signalling or through aberrant changes in both glucose and lipid (cholesterol and triacylglycerol) metabolism and concentrations in the blood. Although epidemiological and biological evidence has highlighted an increased incidence of cognitive decline and AD in patients with T2DM, the common molecular basis of cell and tissue dysfunction is rapidly gaining recognition. As a cause or consequence, the chronic inflammatory response and oxidative stress associated with T2DM, amyloid-β (Aβ) protein accumulation, and mitochondrial dysfunction link T2DM and AD. PMID:26693205

  16. Açaí (Euterpe oleracea Mart.) modulates oxidative stress resistance in Caenorhabditis elegans by direct and indirect mechanisms.

    PubMed

    Bonomo, Larissa de Freitas; Silva, David Nunes; Boasquivis, Patrícia Ferreira; Paiva, Franciny Aparecida; Guerra, Joyce Ferreira da Costa; Martins, Talita Alves Faria; de Jesus Torres, Álvaro Gustavo; de Paula, Igor Thadeu Borges Raposo; Caneschi, Washington Luiz; Jacolot, Philippe; Grossin, Nicolas; Tessier, Frederic J; Boulanger, Eric; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia; Oliveira, Riva de Paula

    2014-01-01

    Açaí (Euterpe oleracea Mart.) has recently emerged as a promising source of natural antioxidants. Despite its claimed pharmacological and nutraceutical value, studies regarding the effects of açaí in vivo are limited. In this study, we use the Caenorhabditis elegans model to evaluate the in vivo antioxidant properties of açaí on an organismal level and to examine its mechanism of action. Supplementation with açaí aqueous extract (AAE) increased both oxidative and osmotic stress resistance independently of any effect on reproduction and development. AAE suppressed bacterial growth, but this antimicrobial property did not influence stress resistance. AAE-increased stress resistance was correlated with reduced ROS production, the prevention of sulfhydryl (SH) level reduction and gcs-1 activation under oxidative stress conditions. Our mechanistic studies indicated that AAE promotes oxidative stress resistance by acting through DAF-16 and the osmotic stress response pathway OSR-1/UNC-43/SEK-1. Finally, AAE increased polyglutamine protein aggregation and decreased proteasome activity. Our findings suggest that natural compounds available in AAE can improve the antioxidant status of a whole organism under certain conditions by direct and indirect mechanisms. PMID:24594796

  17. Açaí (Euterpe oleracea Mart.) Modulates Oxidative Stress Resistance in Caenorhabditis elegans by Direct and Indirect Mechanisms

    PubMed Central

    Bonomo, Larissa de Freitas; Silva, David Nunes; Boasquivis, Patrícia Ferreira; Paiva, Franciny Aparecida; Guerra, Joyce Ferreira da Costa; Martins, Talita Alves Faria; de Jesus Torres, Álvaro Gustavo; de Paula, Igor Thadeu Borges Raposo; Caneschi, Washington Luiz; Jacolot, Philippe; Grossin, Nicolas; Tessier, Frederic J.; Boulanger, Eric; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia; de Paula Oliveira, Riva

    2014-01-01

    Açaí (Euterpe oleracea Mart.) has recently emerged as a promising source of natural antioxidants. Despite its claimed pharmacological and nutraceutical value, studies regarding the effects of açaí in vivo are limited. In this study, we use the Caenorhabditis elegans model to evaluate the in vivo antioxidant properties of açaí on an organismal level and to examine its mechanism of action. Supplementation with açaí aqueous extract (AAE) increased both oxidative and osmotic stress resistance independently of any effect on reproduction and development. AAE suppressed bacterial growth, but this antimicrobial property did not influence stress resistance. AAE-increased stress resistance was correlated with reduced ROS production, the prevention of sulfhydryl (SH) level reduction and gcs-1 activation under oxidative stress conditions. Our mechanistic studies indicated that AAE promotes oxidative stress resistance by acting through DAF-16 and the osmotic stress response pathway OSR-1/UNC-43/SEK-1. Finally, AAE increased polyglutamine protein aggregation and decreased proteasome activity. Our findings suggest that natural compounds available in AAE can improve the antioxidant status of a whole organism under certain conditions by direct and indirect mechanisms. PMID:24594796

  18. Manganese Homeostasis in Group A Streptococcus Is Critical for Resistance to Oxidative Stress and Virulence

    PubMed Central

    Turner, Andrew G.; Ong, Cheryl-lynn Y.; Gillen, Christine M.; Davies, Mark R.; West, Nicholas P.; McEwan, Alastair G.

    2015-01-01

    ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]) is an obligate human pathogen responsible for a spectrum of human disease states. Metallobiology of human pathogens is revealing the fundamental role of metals in both nutritional immunity leading to pathogen starvation and metal poisoning of pathogens by innate immune cells. Spy0980 (MntE) is a paralog of the GAS zinc efflux pump CzcD. Through use of an isogenic mntE deletion mutant in the GAS serotype M1T1 strain 5448, we have elucidated that MntE is a manganese-specific efflux pump required for GAS virulence. The 5448ΔmntE mutant had significantly lower survival following infection of human neutrophils than did the 5448 wild type and the complemented mutant (5448ΔmntE::mntE). Manganese homeostasis may provide protection against oxidative stress, explaining the observed ex vivo reduction in virulence. In the presence of manganese and hydrogen peroxide, 5448ΔmntE mutant exhibits significantly lower survival than wild-type 5448 and the complemented mutant. We hypothesize that MntE, by maintaining homeostatic control of cytoplasmic manganese, ensures that the peroxide response repressor PerR is optimally poised to respond to hydrogen peroxide stress. Creation of a 5448ΔmntE-ΔperR double mutant rescued the oxidative stress resistance of the double mutant to wild-type levels in the presence of manganese and hydrogen peroxide. This work elucidates the mechanism for manganese toxicity within GAS and the crucial role of manganese homeostasis in maintaining GAS virulence. PMID:25805729

  19. [Enhanced Resistance of Pea Plants to Oxidative: Stress Caused by Paraquat during Colonization by Aerobic Methylobacteria].

    PubMed

    Agafonova, N V; Doronina, N Y; Trotsenko, Yu A

    2016-01-01

    The influence of colonization of the pea (Pisum sativum L.) by aerobic methylobacteria of five different species (Methylophilus flavus Ship, Methylobacterium extorquens G10, Methylobacillus arboreus Iva, Methylopila musalis MUSA, Methylopila turkiensis Sidel) on plant resistance to paraquat-induced stresses has been studied. The normal conditions of pea colonization by methylobacteria were characterized by a decrease in the activity of antioxidant enzymes (superoxide dismutase, catalase, and peroxidases) and in the concentrations of endogenous H2O2, proline, and malonic dialdehyde, which is a product of lipid peroxidation and indicator of damage to plant cell membranes, and an increase in the activity of the photosynthetic apparatus (the content of chlorophylls a, b and carotenoids). In the presence of paraquat, the colonized plants had higher activities of antioxidant enzymes, stable photosynthetic indices, and a less intensive accumulation of the products of lipid peroxidation as compared to noncolonized plants. Thus, colonization by methylobacteria considerably increased the adaptive protection of pea plants to the paraquat-induced oxidative stress. PMID:27266250

  20. A Novel Peptide from Soybean Protein Isolate Significantly Enhances Resistance of the Organism under Oxidative Stress.

    PubMed

    Ma, Heran; Liu, Rui; Zhao, Ziyuan; Zhang, Zhixian; Cao, Yue; Ma, Yudan; Guo, Yi; Xu, Li

    2016-01-01

    Recent studies have indicated that protein hydrolysates have broad biological effects. In the current study we describe a novel antioxidative peptide, FDPAL, from soybean protein isolate (SPI). The aim of this study was to purify and characterize an antioxidative peptide from SPI and determine its antioxidative mechanism. LC-MS/MS was used to isolate and identify the peptide from SPI. The sequence of the peptide was determined to be Phe-Asp-Pro-Ala-Leu (FDPAL, 561 Da). FDPAL can cause significant enhancement of resistance to oxidative stress both in cells as well as simple organisms. In Caenorhabditis elegans (C. elegans), FDPAL can up-regulate the expression of certain genes associated with resistance. The antioxidant activity of this peptide can be attributed to the presence of a specific amino acid sequence. Results from our work suggest that FDPAL can facilitate potential applications of proteins carrying this sequence in the nutraceutical, bioactive material and clinical medicine areas, as well as in cosmetics and health care products. PMID:27455060

  1. A Novel Peptide from Soybean Protein Isolate Significantly Enhances Resistance of the Organism under Oxidative Stress

    PubMed Central

    Ma, Heran; Liu, Rui; Zhao, Ziyuan; Zhang, Zhixian; Cao, Yue; Ma, Yudan; Guo, Yi; Xu, Li

    2016-01-01

    Recent studies have indicated that protein hydrolysates have broad biological effects. In the current study we describe a novel antioxidative peptide, FDPAL, from soybean protein isolate (SPI). The aim of this study was to purify and characterize an antioxidative peptide from SPI and determine its antioxidative mechanism. LC–MS/MS was used to isolate and identify the peptide from SPI. The sequence of the peptide was determined to be Phe-Asp-Pro-Ala-Leu (FDPAL, 561 Da). FDPAL can cause significant enhancement of resistance to oxidative stress both in cells as well as simple organisms. In Caenorhabditis elegans (C. elegans), FDPAL can up-regulate the expression of certain genes associated with resistance. The antioxidant activity of this peptide can be attributed to the presence of a specific amino acid sequence. Results from our work suggest that FDPAL can facilitate potential applications of proteins carrying this sequence in the nutraceutical, bioactive material and clinical medicine areas, as well as in cosmetics and health care products. PMID:27455060

  2. Eel green fluorescent protein is associated with resistance to oxidative stress.

    PubMed

    Funahashi, Aki; Komatsu, Masaharu; Furukawa, Tatsuhiko; Yoshizono, Yuki; Yoshizono, Hikari; Orikawa, Yasuhiro; Takumi, Shota; Shiozaki, Kazuhiro; Hayashi, Seiichi; Kaminishi, Yoshio; Itakura, Takao

    2016-01-01

    Green fluorescent protein (GFP) from eel (Anguilla japonica) muscle (eelGFP) is unique in the vertebrates and requires bilirubin as a ligand to emit fluorescence. This study was performed to clarify the physiological function of the unique GFP. Investigation of susceptibility to oxidative stress was carried out using three types of cell lines including jellyfish (Aequorea coerulescens) GFP (jfGFP)-, or eel GFP (eelGFP)-expressing HEK293 cells, and control vector-transfected HEK293 cells. Binding of eelGFP to bilirubin was confirmed by the observation of green fluorescence in HEK293-eelGFP cells. The growth rate was compared with the three types of cells in the presence or absence of phenol red which possessed antioxidant activity. The growth rates of HEK293-CV and HEK293-jfGFP under phenol red-free conditions were reduced to 52 and 31% of those under phenol red. Under the phenol red-free condition, HEK293-eelGFP had a growth rate of approximately 70% of the phenol red-containing condition. The eelGFP-expressing cells were approximately 2-fold resistant to oxidative stress such as H2O2 exposure. The fluorescence intensity partially decreased or disappeared after exposure to H2O2, and heterogeneous intensity of fluorescence was also observed in isolated eel skeletal muscle cells. These results suggested eelGFP, but not jfGFP, coupled with bilirubin provided the antioxidant activity to the cells as compared to non-bound free bilirubin. PMID:26746389

  3. Green Tea Extract Induces the Resistance of Caenorhabditis elegans against Oxidative Stress

    PubMed Central

    Abbas, Sami; Wink, Michael

    2014-01-01

    Epidemiological studies on the effects of green tea consumption (Camellia sinensis) have demonstrated a reduction for the risk of age-related diseases. The investigation of the in vivo and in vitro antioxidant properties of an aqueous extract of green tea (GTE) was the aim of the current study. 2,2-Diphenyl-1-picrylhydrazyl (DPPH•) and superoxide anion radical (O2•−) assays were used to estimate the GTE antioxidant activity. To investigate the protective effects of GTE against oxidative stress, wild-type N2 and transgenic strains (TJ374, hsp-16.2/GFP) of the model organism, Caenorhabditis elegans (C. elegans), were chosen. In the current study, the following catechins were identified by LC/ESI-MS: catechin, epicatechin, epicatechin gallate, gallocatechin, epigallocatechin and epigallocatechin gallate. GTE exhibited a free radical scavenging activity of DPPH• and O2•− with IC50 8.37 and 91.34 µg/mL, respectively. In the C. elegans strain (TJ374, hsp-16.2/GFP), the expression of hsp-16.2/GFP was induced by a nonlethal dose of juglone, and the fluorescence density of hsp-16.2/GFP was measured. The hsp-16.2/GFP was reduced by 68.43% in the worms pretreated with 100 µg/mL GTE. N2 worms pretreated with 100 µg/mL GTE exhibited an increased survival rate of 48.31% after a lethal dose application of juglone. The results suggest that some green tea constituents are absorbed by the worms and play a substantial role to enhance oxidative stress resistance in C. elegans. PMID:26784668

  4. Insulin Resistance in PCOS Patients Enhances Oxidative Stress and Leukocyte Adhesion: Role of Myeloperoxidase

    PubMed Central

    Victor, Victor M.; Rovira-Llopis, Susana; Bañuls, Celia; Diaz-Morales, Noelia; Martinez de Marañon, Arantxa; Rios-Navarro, Cesar; Alvarez, Angeles; Gomez, Marcelino; Rocha, Milagros; Hernández-Mijares, Antonio

    2016-01-01

    Cardiovascular diseases and oxidative stress are related to polycystic ovary syndrome (PCOS) and insulin resistance (IR). We have evaluated the relationship between myeloperoxidase (MPO) and leukocyte activation in PCOS patients according to homeostatic model assessment of IR (HOMA-IR), and have explored a possible correlation between these factors and endocrine and inflammatory parameters. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 101 PCOS subjects and 105 control subjects. We divided PCOS subjects into PCOS non-IR (HOMA-IR<2.5) and PCOS IR (HOMA-IR>2.5). Metabolic and anthropometric parameters, total and mitochondrial reactive oxygen species (ROS) production, MPO levels, interactions between human umbilical vein endothelial cells and leukocytes, adhesion molecules (E-selectin, ICAM-1 and VCAM-1) and proinflammatory cytokines (IL-6 and TNF-α) were evaluated. Oxidative stress was observed in PCOS patients, in whom there was an increase in total and mitochondrial ROS production and MPO levels. Enhanced rolling flux and adhesion, and a decrease in polymorphonuclear cell rolling velocity were also detected in PCOS subjects. Increases in IL-6 and TNF-α and adhesion molecules (E-selectin, ICAM-1 and VCAM-1) were also observed, particularly in the PCOS IR group, providing evidence that inflammation and oxidative stress are related in PCOS patients. HOMA-IR was positively correlated with hsCRP (p<0.001, r = 0.304), ROS production (p<0.01, r = 0.593), leukocyte rolling flux (p<0.05, r = 0.446), E-selectin (p<0.01, r = 0.436) and IL-6 (p<0.001, r = 0.443). The results show an increase in the rate of ROS and MPO levels in PCOS patients in general, and particularly in those with IR. Inflammation in PCOS induces leukocyte-endothelium interactions and a simultaneous increase in IL-6, TNF-α, E-selectin, ICAM-1 and VCAM-1. These conditions are aggravated by the presence of IR. PMID:27007571

  5. Aflatoxin production and environmental oxidative stress in Aspergillus flavus: Implications forhost resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The contamination of maize kernel tissues with aflatoxin is of major concern in global food production, particularly in developing countries. Resistance to aflatoxin is negatively influenced by environmental stress, namely drought stress. Given that reactive oxygen species (ROS) are known to accumul...

  6. Green Synthesis of Oxovanadium(IV)/chitosan Nanocomposites and Its Ameliorative Effect on Hyperglycemia, Insulin Resistance, and Oxidative Stress.

    PubMed

    Liu, Yanjun; Jie, Xu; Guo, Yongli; Zhang, Xin; Wang, Jingfeng; Xue, Changhu

    2016-02-01

    In this paper, the preparation, characterization, and ameliorative effect on high-fat high-sucrose diet-induced hyperglycemia, insulin resistance, oxidative stress in mice of novel oxovanadium(IV)/chitosan (OV/CS) nanocomposites were investigated. The nanobiocomposite was produced by chemical reduction by chitosan and L-ascorbic acid using microwave heating, under environment-friendly conditions, using aqueous solutions, and notably, by using both mediators as reducing and stabilizing agents. In addition, OV/CS nanocomposites were characterized by transmission electron microscopy, energy dispersive spectroscopy, particle size, and zeta potential measurements. In vivo experiments were designed to examine whether the OV/CS nanocomposites would provide additional benefits on oxidative stress, hyperglycemia, and insulin resistance in mice with type 2 diabetes. The results rendered insulin resistant by treating with OV/CS nanocomposites alleviate insulin resistance and improve oxidative stress. Such nanocomposite seem to be a valuable therapy to achieve and/or maintain glycemic control and therapeutic agents in the treatment arsenal for insulin resistance and type 2 diabetes. PMID:26144273

  7. Paraoxonase-1 is not affected in polycystic ovary syndrome without metabolic syndrome and insulin resistance, but oxidative stress is altered.

    PubMed

    Torun, Ayse Nur; Vural, Mehmet; Cece, Hasan; Camuzcuoglu, Hakan; Toy, Harun; Aksoy, Nurten

    2011-12-01

    Paraoxonase-1 (PON1) activity is decreased in polycystic ovary syndrome (PCOS) having metabolic syndrome (MetS) or insulin resistance (IR). We aimed to assess PON1 activity and oxidative stress in PCOS without MetS or IR. Metabolic and hormonal parameters, high-sensitive C-reactive protein (hs-CRP), oxidative stress parameters (total antioxidant status (TAS), total oxidative stress (TOS), oxidative stress index (OSI), lipid hydroperoxide (LOOH), total free sulfhydryl (--SH) groups), PON and arylesterase were analyzed in 30 normal weighed patients with PCOS without MetS or IR and 20 normal controls. Hs-CRP, PON, arylesterase, and TAS levels of PCOS and control groups were similar. LOOH, TOS, and OSI of PCOS group were higher than in the controls (p < 0.05; p < 0.001, and p < 0.001, respectively). - SH group levels showed a positive correlation with free testosterone (fT). TOS positively correlated with free androgen index (FAI), body mass index (BMI), waist-to-hip ratio (WHR), LOOH, and OSI. This study showed that oxidative stress is increased in PCOS even in the absence of MetS or IR. PON1 activity appears not to be affected in PCOS without MetS and IR. Several metabolic and antropometric risk factors may aggravate this altered oxidative state in PCOS. PMID:21557696

  8. Mechanisms of Oxidative Stress Resistance in The Brain: Lessons Learned From Hypoxia Tolerant Extremophilic Vertebrates

    PubMed Central

    Garbarino, Valentina R.; Orr, Miranda E.; Rodriguez, Karl A.; Buffenstein, Rochelle

    2016-01-01

    The Oxidative Stress Theory of Aging has had tremendous impact in research involving aging and age-associated diseases including those that affect the nervous system. With over half a century of accrued data showing both strong support for and against this theory, there is a need to critically evaluate the data acquired from common biomedical research models, and to also diversify the species used in studies involving this proximate theory. One approach is to follow Orgel’s second axiom that “evolution is smarter than we are” and judiciously choose species that may have evolved to live with chronic or seasonal oxidative stressors. Vertebrates that have naturally evolved to live under extreme conditions (e.g., anoxia or hypoxia), as well as those that undergo daily or seasonal torpor encounter both decreased oxygen availability and subsequent reoxygenation, with concomitant increased oxidative stress. Due to its high metabolic activity, the brain may be particularly vulnerable to oxidative stress. Here, we focus on oxidative stress responses in the brains of certain mouse models as well as extremophilic vertebrates. Exploring the naturally evolved biological tools utilized to cope with seasonal or environmentally variable oxygen availability may yield key information pertinent for how to deal with oxidative stress and thereby mitigate its propagation of age-associated diseases. PMID:25841340

  9. Reprogramming to a pluripotent state modifies mesenchymal stem cell resistance to oxidative stress

    PubMed Central

    Asensi, Karina D; Fortunato, Rodrigo S; dos Santos, Danúbia S; Pacheco, Thaísa S; de Rezende, Danielle F; Rodrigues, Deivid C; Mesquita, Fernanda C P; Kasai-Brunswick, Tais H; de Carvalho, Antonio C Campos; Carvalho, Denise P; Carvalho, Adriana B; Goldenberg, Regina C dos S

    2014-01-01

    Properties of induced pluripotent stem cells (iPSC) have been extensively studied since their first derivation in 2006. However, the modification in reactive oxygen species (ROS) production and detoxification caused by reprogramming still needs to be further elucidated. The objective of this study was to compare the response of iPSC generated from menstrual blood–derived mesenchymal stem cells (mb-iPSC), embryonic stem cells (H9) and adult menstrual blood–derived mesenchymal stem cells (mbMSC) to ROS exposure and investigate the effects of reprogramming on cellular oxidative stress (OS). mbMSC were extremely resistant to ROS exposure, however, mb-iPSC were 10-fold less resistant to H2O2, which was very similar to embryonic stem cell sensitivity. Extracellular production of ROS was also similar in mb-iPSC and H9 and almost threefold lower than in mbMSC. Furthermore, intracellular amounts of ROS were higher in mb-iPSC and H9 when compared with mbMSC. As the ability to metabolize ROS is related to antioxidant enzymes, we analysed enzyme activities in these cell types. Catalase and superoxide dismutase activities were reduced in mb-iPSC and H9 when compared with mbMSC. Finally, cell adhesion under OS conditions was impaired in mb-iPSC when compared with mbMSC, albeit similar to H9. Thus, reprogramming leads to profound modifications in extracellular ROS production accompanied by loss of the ability to handle OS. PMID:24528612

  10. Pinewood nematode-associated bacteria contribute to oxidative stress resistance of Bursaphelenchus xylophilus

    PubMed Central

    2013-01-01

    Background Pine wilt disease (PWD) caused by the pinewood nematode Bursaphelenchus xylophilus is one of the most serious forest diseases in the world. The role of B. xylophilus-associated bacteria in PWD and their interaction with the nematode, have recently been under substantial investigation. Several studies report a potential contribution of the bacteria for the PWD development, either as a helper to enhance the pathogenicity of the nematode or as a pathogenic agent expressing interesting traits related to lifestyle host-adaptation. Results We investigated the nematode-bacteria interaction under a severe oxidative stress (OS) condition using a pro-oxidant hydrogen peroxide and explored the adhesion ability of these bacteria to the cuticle surface of the nematodes. Our results clearly demonstrated a beneficial effect of the Serratia spp. (isolates LCN-4, LCN-16 and PWN-146) to B. xylophilus under the OS condition. Serratia spp. was found to be extremely OS-resistant, and promote survival of B. xylophilus and down-regulate two B. xylophilus catalase genes (Bxy-ctl-1 and Bxy-ctl-2). In addition, we show that the virulent isolate (Ka4) of B. xylophilus survives better than the avirulent (C14-5) isolate under the OS condition. The bacterial effect was transverse for both B. xylophilus isolates. We could not observe a strong and specific adhesion of these bacteria on the B. xylophilus cuticle surface. Conclusions We report, for the first time, that B. xylophilus associated bacteria may assist the nematode opportunistically in the disease, and that a virulent B. xylophilus isolate displayed a higher tolerance towards the OS conditions than an avirulent isolate. PMID:24365493

  11. Tartary buckwheat flavonoids protect hepatic cells against high glucose-induced oxidative stress and insulin resistance via MAPK signaling pathways.

    PubMed

    Hu, Yuanyuan; Hou, Zuoxu; Liu, Dongyang; Yang, Xingbin

    2016-03-01

    Oxidative stress plays a crucial role in chronic complication of diabetes. In this study, the protective effect of purified tartary buckwheat flavonoids (TBF) fraction against oxidative stress induced by a high-glucose challenge, which causes insulin resistance, was investigated on hepatic HepG2 cells. Oxidative status, phosphorylated mitogen-activated protein kinases (MAPKs), nuclear factor E2 related factor 2 (Nrf2) and p-(Ser307)-IRS-1 expression, and glucose uptake were evaluated. Results suggest that treatment of HepG2 cells with TBF alone improved glucose uptake and antioxidant enzymes, and activated Nrf2, and attenuated the IRS-1 Ser307 phosphorylation, and enhanced total levels of IRS-1. Furthermore, the high glucose-induced changes in antioxidant defences, Nrf2, p-MAPKs, p-IRS1 Ser307, and IRS-1 levels, and glucose uptake were also significantly inhibited by pre-treatment with TBF. Interestingly, the selective MAPK inhibitors significantly enhanced the TBF-mediated protection by inducing changes in the redox status, glucose uptake, p-(Ser307) and total IRS-1 levels. This report firstly showed that TBF could recover the redox status of insulin-resistant HepG2 cells, suggesting that TBF significantly protected the cells against high glucose-induced oxidative stress, and these beneficial effects of TBF on redox balance and insulin resistance were mediated by targeting MAPKs. PMID:26899161

  12. The Role of Oxidative Stress in the Longevity and Insecticide Resistance Phenotype of the Major Malaria Vectors Anopheles arabiensis and Anopheles funestus.

    PubMed

    Oliver, Shüné V; Brooke, Basil D

    2016-01-01

    Oxidative stress plays numerous biological roles, both functional and pathological. The role of oxidative stress in various epidemiologically relevant biological traits in Anopheles mosquitoes is not well established. In this study, the effects of oxidative stress on the longevity and insecticide resistance phenotype in the major malaria vector species An. arabiensis and An. funestus were examined. Responses to dietary copper sulphate and hydrogen peroxide were used as proxies for the oxidative stress phenotype by determining the effect of copper on longevity and hydrogen peroxide lethal dose. Glutathione peroxidase and catalase activities were determined colorimetrically. Oxidative burden was quantified as protein carbonyl content. Changes in insecticide resistance phenotype were monitored by WHO bioassay. Insecticide resistant individuals showed an increased capacity for coping with oxidative stress, mediated by increased glutathione peroxidase and catalase activity. This effect was observed in both species, as well as in laboratory strains and F1 individuals derived from wild-caught An. funestus mothers. Phenotypic capacity for coping with oxidative stress was greatest in strains with elevated Cytochrome P450 activity. Synergism of oxidative stress defence enzymes by dietary supplementation with haematin, 3-Amino-1, 2, 4-triazole and Sodium diethyldithiocarbamate significantly increased pyrethroid-induced mortality in An. arabiensis and An. funestus. It is therefore concluded that defence against oxidative stress underlies the augmentation of the insecticide resistance phenotype associated with multiple blood-feeding. This is because multiple blood-feeding ultimately leads to a reduction of oxidative stress in insecticide resistant females, and also reduces the oxidative burden induced by DDT and pyrethroids, by inducing increased glutathione peroxidase activity. This study highlights the importance of oxidative stress in the longevity and insecticide resistance

  13. The Role of Oxidative Stress in the Longevity and Insecticide Resistance Phenotype of the Major Malaria Vectors Anopheles arabiensis and Anopheles funestus

    PubMed Central

    Oliver, Shüné V.; Brooke, Basil D.

    2016-01-01

    Oxidative stress plays numerous biological roles, both functional and pathological. The role of oxidative stress in various epidemiologically relevant biological traits in Anopheles mosquitoes is not well established. In this study, the effects of oxidative stress on the longevity and insecticide resistance phenotype in the major malaria vector species An. arabiensis and An. funestus were examined. Responses to dietary copper sulphate and hydrogen peroxide were used as proxies for the oxidative stress phenotype by determining the effect of copper on longevity and hydrogen peroxide lethal dose. Glutathione peroxidase and catalase activities were determined colorimetrically. Oxidative burden was quantified as protein carbonyl content. Changes in insecticide resistance phenotype were monitored by WHO bioassay. Insecticide resistant individuals showed an increased capacity for coping with oxidative stress, mediated by increased glutathione peroxidase and catalase activity. This effect was observed in both species, as well as in laboratory strains and F1 individuals derived from wild-caught An. funestus mothers. Phenotypic capacity for coping with oxidative stress was greatest in strains with elevated Cytochrome P450 activity. Synergism of oxidative stress defence enzymes by dietary supplementation with haematin, 3-Amino-1, 2, 4-triazole and Sodium diethyldithiocarbamate significantly increased pyrethroid-induced mortality in An. arabiensis and An. funestus. It is therefore concluded that defence against oxidative stress underlies the augmentation of the insecticide resistance phenotype associated with multiple blood-feeding. This is because multiple blood-feeding ultimately leads to a reduction of oxidative stress in insecticide resistant females, and also reduces the oxidative burden induced by DDT and pyrethroids, by inducing increased glutathione peroxidase activity. This study highlights the importance of oxidative stress in the longevity and insecticide resistance

  14. FFA-induced hepatic insulin resistance in vivo is mediated by PKCδ, NADPH oxidase, and oxidative stress.

    PubMed

    Pereira, Sandra; Park, Edward; Mori, Yusaku; Haber, C Andrew; Han, Ping; Uchida, Toyoyoshi; Stavar, Laura; Oprescu, Andrei I; Koulajian, Khajag; Ivovic, Alexander; Yu, Zhiwen; Li, Deling; Bowman, Thomas A; Dewald, Jay; El-Benna, Jamel; Brindley, David N; Gutierrez-Juarez, Roger; Lam, Tony K T; Najjar, Sonia M; McKay, Robert A; Bhanot, Sanjay; Fantus, I George; Giacca, Adria

    2014-07-01

    Fat-induced hepatic insulin resistance plays a key role in the pathogenesis of type 2 diabetes in obese individuals. Although PKC and inflammatory pathways have been implicated in fat-induced hepatic insulin resistance, the sequence of events leading to impaired insulin signaling is unknown. We used Wistar rats to investigate whether PKCδ and oxidative stress play causal roles in this process and whether this occurs via IKKβ- and JNK-dependent pathways. Rats received a 7-h infusion of Intralipid plus heparin (IH) to elevate circulating free fatty acids (FFA). During the last 2 h of the infusion, a hyperinsulinemic-euglycemic clamp with tracer was performed to assess hepatic and peripheral insulin sensitivity. An antioxidant, N-acetyl-L-cysteine (NAC), prevented IH-induced hepatic insulin resistance in parallel with prevention of decreased IκBα content, increased JNK phosphorylation (markers of IKKβ and JNK activation, respectively), increased serine phosphorylation of IRS-1 and IRS-2, and impaired insulin signaling in the liver without affecting IH-induced hepatic PKCδ activation. Furthermore, an antisense oligonucleotide against PKCδ prevented IH-induced phosphorylation of p47(phox) (marker of NADPH oxidase activation) and hepatic insulin resistance. Apocynin, an NADPH oxidase inhibitor, prevented IH-induced hepatic and peripheral insulin resistance similarly to NAC. These results demonstrate that PKCδ, NADPH oxidase, and oxidative stress play a causal role in FFA-induced hepatic insulin resistance in vivo and suggest that the pathway of FFA-induced hepatic insulin resistance is FFA → PKCδ → NADPH oxidase and oxidative stress → IKKβ/JNK → impaired hepatic insulin signaling. PMID:24824652

  15. Whole Body Vibration Improves Insulin Resistance in db/db Mice: Amelioration of Lipid Accumulation and Oxidative Stress.

    PubMed

    Liu, Ying; Zhai, Mingming; Guo, Fan; Shi, Tengrui; Liu, Jiangzheng; Wang, Xin; Zhang, Xiaodi; Jing, Da; Hai, Chunxu

    2016-07-01

    Insulin resistance (IR) is the hallmark of type 2 diabetes mellitus (T2DM), which is one of the most important chronic noncommunicable diseases. Effective and feasible strategies to treat IR are still urgently needed. Previous research studies reported that whole body vibration (WBV) was beneficial for IR in clinical; however, its underlying mechanisms remains unknown. In the present study, db/db mice were treated with WBV administration 60 min/day for 12 weeks and the impaired insulin sensitivity was improved. Besides, liver steatosis was also ameliorated. Further explorations revealed that WBV could reduce the expression of SREBP1c and increase the expression of GSH-Px and consequently suppress oxidative stress. In conclusion, WBV attenuates oxidative stress to ameliorate liver steatosis and thus improves insulin resistance in db/db mice. Therefore, WBV administration is a promising treatment for individuals who suffered from central obesity and IR. PMID:26945578

  16. Modulation of Cell Metabolic Pathways and Oxidative Stress Signaling Contribute to Acquired Melphalan Resistance in Multiple Myeloma Cells

    PubMed Central

    Zub, Kamila Anna; de Sousa, Mirta Mittelstedt Leal; Sarno, Antonio; Sharma, Animesh; Demirovic, Aida; Rao, Shalini; Young, Clifford; Aas, Per Arne; Ericsson, Ida; Sundan, Anders; Jensen, Ole Nørregaard; Slupphaug, Geir

    2015-01-01

    Alkylating agents are widely used chemotherapeutics in the treatment of many cancers, including leukemia, lymphoma, multiple myeloma, sarcoma, lung, breast and ovarian cancer. Melphalan is the most commonly used chemotherapeutic agent against multiple myeloma. However, despite a 70–80% initial response rate, virtually all patients eventually relapse due to the emergence of drug-resistant tumour cells. By using global proteomic and transcriptomic profiling on melphalan sensitive and resistant RPMI8226 cell lines followed by functional assays, we discovered changes in cellular processes and pathways not previously associated with melphalan resistance in multiple myeloma cells, including a metabolic switch conforming to the Warburg effect (aerobic glycolysis), and an elevated oxidative stress response mediated by VEGF/IL8-signaling. In addition, up-regulated aldo-keto reductase levels of the AKR1C family involved in prostaglandin synthesis contribute to the resistant phenotype. Finally, selected metabolic and oxidative stress response enzymes were targeted by inhibitors, several of which displayed a selective cytotoxicity against the melphalan-resistant cells and should be further explored to elucidate their potential to overcome melphalan resistance. PMID:25769101

  17. A novel mitochondrial membrane protein, Ohmm, limits fungal oxidative stress resistance and virulence in the insect fungal pathogen Beauveria bassiana.

    PubMed

    He, Zhangjiang; Zhang, Suhong; Keyhani, Nemat O; Song, Yulin; Huang, Shuaishuai; Pei, Yan; Zhang, Yongjun

    2015-11-01

    The Hog1 mitogen-activated protein (MAP) kinase regulates environmental stress responses and virulence in the entomopathogenic fungus Beauveria bassiana. To further characterize this pathway, we constructed a subtraction library enriched for genes regulated by Hog1. One targeted gene, encoding a novel membrane protein, Ohmm (oxidative homeostasis membrane-protein-mitochondria), was uniquely identified as being downregulated in the ΔHog1 background during growth under non-stress and osmotic stress conditions, but upregulated under oxidative stress. Ohmm was an experimentally validated flavin-binding protein and targeted to the mitochondria. Deletion of Ohmm resulted in increased oxidative stress resistance, whereas overexpression caused an opposite phenotype. The ΔOhmm showed accumulation of reactive oxygen species with alterations in cell wall composition and compatible solute accumulation evident as compared with the wild type parent. Conidiation was reduced > 80%; however, conidia produced by the ΔOhmm strain germinated significantly faster than wild type cells. Insect bioassays using the greater wax moth revealed increased virulence for the ΔOhmm strain in both topical and intrahemocoel injection assays, indicating a negative effect of the presence of Ohmm with respect to pathogenesis. As predicted from our characterization, deletion of Ohmm in a ΔHog1 background rescued its oxidative sensitivity phenotype, confirming that Ohmm acts downstream of the Hog1 MAP-kinase. PMID:25403093

  18. Multiple transport systems mediate virus-induced acquired resistance to oxidative stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this paper, we report the phenomenon of acquired cross-tolerance to oxidative (UV-C and H2O2) stress in Nicotiana benthamiana plants infected with Potato virus X (PVX) and investigate the functional expression of transport systems in mediating this phenomenon. By combining multiple approaches, we...

  19. Mechanism of Different Stereoisomeric Astaxanthin in Resistance to Oxidative Stress in Caenorhabditis elegans.

    PubMed

    Liu, Xiaojuan; Luo, Qingxin; Cao, Yong; Goulette, Timothy; Liu, Xin; Xiao, Hang

    2016-09-01

    As a potent antioxidant in human diet, astaxanthin (AST) may play important roles in alleviating oxidative stress-driven adverse physiological effects. This study examined the effects of different stereoisomers of AST in protecting Caenorhabditis elegans from chemically induced oxidative stress. Three stereoisomers of AST investigated herein included 3S,3´S (S) AST, 3R,3´R (R) AST, and a statistical mixture (S: meso: R = 1:2:1) (M) AST. Under paraquat-induced oxidative conditions, all three types of AST significantly enhanced survival rate of C. elegans. The accumulation levels of ROS in the worms were reduced by 40.12%, 30.05%, and 22.04% by S, R, and M AST, respectively (P < 0.05). Compared with R and M AST, S significantly enhanced the expression levels of SOD-3. The results of RNA-Seq analysis demonstrated that AST protected C. elegans from oxidative damage potentially by modulating genes involved in the insulin/insulin-like growth factor (IGF) signaling (IIS) pathway and the oxidoreductase system. It is noteworthy that different stereoisomers of AST showed different effects on the expression levels of various genes related with oxidative stress. This study revealed important information on the in vivo antioxidative effects of AST stereoisomers, which might provide useful information for better utilization of AST. PMID:27527357

  20. Role of K(ATP) channels in β-cell resistance to oxidative stress.

    PubMed

    Drews, G; Düfer, M

    2012-10-01

    The importance of K(ATP) channels in stimulus-secretion coupling of β-cells is well established, although they are not indispensable for the maintenance of glycaemic control. This review article depicts a new role for K(ATP) channels by showing that genetic or pharmacological ablation of these channels protects β-cells against oxidative stress. Increased production of oxidants is a crucial factor in the pathogenesis of type 2 diabetes mellitus (T2DM). T2DM develops when β-cells can no longer compensate for the high demand of insulin resulting from excess fuel intake. Instead β-cells start to secrete less insulin and β-cell mass is diminished by apoptosis. Both, reduction of insulin secretion and β-cell mass induced by oxidative stress, are prevented by deletion or inhibition of K(ATP) channels. These findings may open up new insights into the early treatment of T2DM. PMID:22928572

  1. The association of oxidative stress with arterial compliance and vascular resistance in a bi-ethnic population: the SABPA study.

    PubMed

    Mokhaneli, Maserame Cleopatra; Fourie, Carla Maria T; Botha, Shani; Mels, Catharina Martha C

    2016-08-01

    A loss of arterial elasticity increases the risk for cardiovascular events. Oxidative injury to the vessel wall may be one of the underlying mechanisms influencing arterial elasticity. We compared markers of oxidative stress, antioxidant capacity, inflammation, windkessel compliance (Cwk), and total peripheral resistance (TPR) in black and white South Africans. Associations of arterial compliance and vascular resistance (as indicated by TPR) with oxidative stress, antioxidant capacity and inflammatory markers were also investigated. We included 146 black and 181 white men and women. Measurements from the Finometer device were used to calculate Cwk and TPR while thiobarbituric acids reactive substances (TBARS), glutathione peroxidase (GPx), C-reactive protein (CRP), and interleukin-6 (IL-6) were analyzed in serum or urine samples. Black participants had higher TPR, TBARS, GPx, CRP, and IL-6 levels (all p ≤ 0.018) and lower Cwk (both p ≤ 0.013) compared to white participants. Multiple regression analyses revealed independent associations of Cwk (β = -0.27, p = 0.015) and TPR (β = 0.18, p = 0.018) with TBARS in black participants, while Cwk (β = -0.10; p = 0.019) and TPR (β = 0.13, p = 0.047) were independently associated with GPx in white participants. Decreased arterial compliance and increased vascular resistance associated with increased oxidative damage independent of hypertensive status in black participants. These results suggest that oxidative stress plays a role in early vascular changes in a black population prone to the development of cardiovascular disease. PMID:27297811

  2. Enhanced Nox1 expression and oxidative stress resistance in c-kit-positive hematopoietic stem/progenitor cells.

    PubMed

    Urata, Yoshishige; Goto, Shinji; Luo, Lan; Doi, Hanako; Kitajima, Yuriko; Masuda, Shinya; Ono, Yusuke; Li, Tao-Sheng

    2014-10-24

    Although stem cells are generally thought to be resistant to oxidative stress, the fact and in detail molecular mechanism are still to be clearly identified. We herein tried to understand the overall characterization of redox regulatory signaling in hematopoietic stem cells. We purified c-kit-positive hematopoietic stem/progenitor cells from the bone marrow of healthy mice, and then evaluated their redox regulatory property. Compared to the c-kit-negative matured mononuclear cells, c-kit-positive stem/progenitor cells showed lower basic levels of intracellular reactive oxygen species, faster clearance of the accumulated intracellular reactive oxygen species, and higher resistant to oxidative stress. An overall view on the gene expression profile associated with redox regulation showed to be widely differed between cell types. We confirmed that the c-kit-positive stem/progenitor cells expressed significantly higher of Nox1 and catalase, but less of lactoperoxidase than these matured mononuclear cells. Our data suggests that stem cells keep specific redox regulatory property for defensing against oxidative stress. PMID:25451257

  3. Roles of thioredoxin and thioredoxin reductase in the resistance to oxidative stress in Lactobacillus casei.

    PubMed

    Serata, Masaki; Iino, Tohru; Yasuda, Emi; Sako, Tomoyuki

    2012-04-01

    The Lactobacillus casei strain Shirota used in this study has in the genome four putative thioredoxin genes designated trxA1, trxA2, trxA3 and trxA4, and one putative thioredoxin reductase gene designated trxB. To elucidate the roles of the thioredoxins and the thioredoxin reductase against oxidative stress in L. casei, we constructed gene disruption mutants, in which each of the genes trxA1, trxA2 and trxB, or both trxA1 and trxA2 were disrupted, and we characterized their growth and response to oxidative stresses. In aerobic conditions, the trxA1 (MS108) and the trxA2 (MS109) mutants had moderate growth defects, and the trxA1 trxA2 double mutant (MS110) had a severe growth defect, which was characterized by elongation of doubling time and a lower final turbidity level. Furthermore, the trxB mutant (MS111), which is defective in thioredoxin reductase, lost the ability to grow under aerobic conditions, although it grew partially under anaerobic conditions. The growth of these mutants, however, could be substantially restored by the addition of dithiothreitol or reduced glutathione. In addition, MS110 and MS111 were more sensitive to hydrogen peroxide and disulfide stress than the wild-type. In particular, the stress sensitivity of MS111 was significantly increased. On the other hand, transcription of all these genes was only weakly affected by these oxidative stresses. Taken together, these results suggest that the thioredoxin-thioredoxin reductase system is the major thiol/disulfide redox system and is essential to allow the facultative anaerobe L. casei to grow under aerobic conditions. PMID:22301908

  4. Mitochondrial oxidative stress as a novel therapeutic target to overcome intrinsic drug resistance in melanoma cell subpopulations

    PubMed Central

    Cierlitza, Monika; Chauvistré, Heike; Bogeski, Ivan; Zhang, Xin; Hauschild, Axel; Herlyn, Meenhard; Schadendorf, Dirk; Vogt, Thomas; Roesch, Alexander

    2015-01-01

    Despite recent success in melanoma therapy, most patients with metastatic disease still undergo deadly progression. We have identified a novel mechanism of multidrug resistance allowing a small subpopulation of slow-cycling melanoma cells to survive based on elevated oxidative bioenergy metabolism. In this study, we asked whether such slow-cycling cells could be eliminated by co-treatment with the copper-chelator elesclomol. Elesclomol–copper complexes can cause oxidative stress by disruption of the mitochondrial respiration chain or by indirect non-mitochondrial induction of reactive oxygen species. We have found that elesclomol effectively kills the slow-cycling subpopulation and prevents the selective enrichment for slow-cycling cells, which usually results after monotreatment. We hypothesize that elesclomol could overcome the multidrug resistance of slow-cycling melanoma cells and prevent tumor repopulation in melanoma patients in future. PMID:25453510

  5. Mitochondrial oxidative stress as a novel therapeutic target to overcome intrinsic drug resistance in melanoma cell subpopulations.

    PubMed

    Cierlitza, Monika; Chauvistré, Heike; Bogeski, Ivan; Zhang, Xin; Hauschild, Axel; Herlyn, Meenhard; Schadendorf, Dirk; Vogt, Thomas; Roesch, Alexander

    2015-02-01

    Despite recent success in melanoma therapy, most patients with metastatic disease still undergo deadly progression. We have identified a novel mechanism of multidrug resistance allowing a small subpopulation of slow-cycling melanoma cells to survive based on elevated oxidative bioenergy metabolism. In this study, we asked whether such slow-cycling cells could be eliminated by co-treatment with the copper-chelator elesclomol. Elesclomol-copper complexes can cause oxidative stress by disruption of the mitochondrial respiration chain or by indirect non-mitochondrial induction of reactive oxygen species. We have found that elesclomol effectively kills the slow-cycling subpopulation and prevents the selective enrichment for slow-cycling cells, which usually results after monotreatment. We hypothesize that elesclomol could overcome the multidrug resistance of slow-cycling melanoma cells and prevent tumor repopulation in melanoma patients in future. PMID:25453510

  6. Oxidation-resistant cermet

    NASA Technical Reports Server (NTRS)

    Phillips, W. M.

    1977-01-01

    Chromium metal alloys and chromium oxide ceramic are combined to produce cermets with oxidation-resistant properties. Application of cermets includes use in hot corrosive environments requiring strong resistive materials.

  7. Folic acid supplementation at lower doses increases oxidative stress resistance and longevity in Caenorhabditis elegans.

    PubMed

    Rathor, Laxmi; Akhoon, Bashir Akhlaq; Pandey, Swapnil; Srivastava, Swati; Pandey, Rakesh

    2015-12-01

    Folic acid (FA) is an essential nutrient that the human body needs but cannot be synthesized on its own. Fortified foods and plant food sources such as green leafy vegetables, beans, fruits, and juices are good sources of FA to meet the daily requirements of the body. The aim was to evaluate the effect of dietary FA levels on the longevity of well-known experimental aging model Caenorhabditis elegans. Here, we show for first time that FA extends organism life span and causes a delay in aging. We observed that FA inhibits mechanistic target of rapamycin (mTOR) and insulin/insulin growth factor 1 (IGF-1) signaling pathways to control both oxidative stress levels and life span. The expression levels of stress- and life span-relevant gerontogenes, viz. daf-16, skn-1, and sir. 2.1, and oxidative enzymes, such as glutathione S-transferase 4 (GST-4) and superoxide dismutase 3 (SOD-3), were also found to be highly enhanced to attenuate the intracellular reactive oxygen species (ROS) damage and to delay the aging process. Our study promotes the use of FA to mitigate abiotic stresses and other aging-related ailments. PMID:26546011

  8. Growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of Candida glabrata are affected by different glucose concentrations.

    PubMed

    Ng, Tzu Shan; Desa, Mohd Nasir Mohd; Sandai, Doblin; Chong, Pei Pei; Than, Leslie Thian Lung

    2016-06-01

    Glucose is an important fuel source to support many living organisms. Its importance in the physiological fitness and pathogenicity of Candida glabrata, an emerging human fungal pathogen has not been extensively studied. The present study aimed to investigate the effects of glucose on the growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of C. glabrata. In addition, its effect on the expression of a putative high affinity glucose sensor gene, SNF3 was also investigated. Glucose concentrations were found to exert effects on the physiological responses of C. glabrata. The growth rate of the species correlated positively to the amount of glucose. In addition, low glucose environments were found to induce C. glabrata to form biofilm and resist amphotericin B. Conversely, high glucose environments promoted oxidative stress resistance of C. glabrata. The expression of CgSNF3 was found to be significantly up-regulated in low glucose environments. The expression of SNF3 gene in clinical isolates was found to be higher compared to ATCC laboratory strains in low glucose concentrations, which may explain the better survivability of clinical isolates in the low glucose environment. These observations demonstrated the impact of glucose in directing the physiology and virulence fitness of C. glabrata through the possible modulation by SNF3 as a glucose sensor, which in turn aids the species to adapt, survive and thrive in hostile host environment. PMID:26358577

  9. Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance

    PubMed Central

    Tsang, Chi Kwan; Liu, Yuan; Thomas, Janice; Zhang, Yanjie; Zheng, X. F. Steven

    2015-01-01

    Summary Superoxide dismutase 1 (Sod1) has been known for nearly half a century for catalysis of superoxide to hydrogen peroxide. Here we report a new Sod1 function in oxidative signaling: in response to elevated endogenous and exogenous reactive oxygen species (ROS), Sod1 rapidly relocates into the nucleus, which is important for maintaining genomic stability. Interestingly, H2O2 is sufficient to promote Sod1 nuclear localization, indicating that it is responding to general ROS rather than Sod1 substrate superoxide. ROS signaling is mediated by Mec1/ATM and its effector Dun1/Cds1 kinase, through Dun1 interaction with Sod1 and regulation of Sod1 by phosphorylation at S60, 99. In the nucleus, Sod1 binds to the promoters and regulates the expression of oxidative resistance and repair genes. Altogether, our study unravels an unorthodox function of Sod1 as a transcription factor and elucidates the regulatory mechanism for its localization. PMID:24647101

  10. Tualang honey improves human corneal epithelial progenitor cell migration and cellular resistance to oxidative stress in vitro.

    PubMed

    Tan, Jun Jie; Azmi, Siti Maisura; Yong, Yoke Keong; Cheah, Hong Leong; Lim, Vuanghao; Sandai, Doblin; Shaharuddin, Bakiah

    2014-01-01

    Stem cells with enhanced resistance to oxidative stress after in vitro expansion have been shown to have improved engraftment and regenerative capacities. Such cells can be generated by preconditioning them with exposure to an antioxidant. In this study we evaluated the effects of Tualang honey (TH), an antioxidant-containing honey, on human corneal epithelial progenitor (HCEP) cells in culture. Cytotoxicity, gene expression, migration, and cellular resistance to oxidative stress were evaluated. Immunofluorescence staining revealed that HCEP cells were holoclonal and expressed epithelial stem cell marker p63 without corneal cytokeratin 3. Cell viability remained unchanged after cells were cultured with 0.004, 0.04, and 0.4% TH in the medium, but it was significantly reduced when the concentration was increased to 3.33%. Cell migration, tested using scratch migration assay, was significantly enhanced when cells were cultured with TH at 0.04% and 0.4%. We also found that TH has hydrogen peroxide (H2O2) scavenging ability, although a trace level of H2O2 was detected in the honey in its native form. Preconditioning HCEP cells with 0.4% TH for 48 h showed better survival following H2O2-induced oxidative stress at 50 µM than untreated group, with a significantly lower number of dead cells (15.3 ± 0.4%) were observed compared to the untreated population (20.5 ± 0.9%, p<0.01). Both TH and ascorbic acid improved HCEP viability following induction of 100 µM H2O2, but the benefit was greater with TH treatment than with ascorbic acid. However, no significant advantage was demonstrated using 5-hydroxymethyl-2-furancarboxaldehyde, a compound that was found abundant in TH using GC/MS analysis. This suggests that the cellular anti-oxidative capacity in HCEP cells was augmented by native TH and was attributed to its antioxidant properties. In conclusion, TH possesses antioxidant properties and can improve cell migration and cellular resistance to oxidative stress in HCEP cells

  11. Tualang Honey Improves Human Corneal Epithelial Progenitor Cell Migration and Cellular Resistance to Oxidative Stress In Vitro

    PubMed Central

    Tan, Jun Jie; Azmi, Siti Maisura; Yong, Yoke Keong; Cheah, Hong Leong; Lim, Vuanghao; Sandai, Doblin; Shaharuddin, Bakiah

    2014-01-01

    Stem cells with enhanced resistance to oxidative stress after in vitro expansion have been shown to have improved engraftment and regenerative capacities. Such cells can be generated by preconditioning them with exposure to an antioxidant. In this study we evaluated the effects of Tualang honey (TH), an antioxidant-containing honey, on human corneal epithelial progenitor (HCEP) cells in culture. Cytotoxicity, gene expression, migration, and cellular resistance to oxidative stress were evaluated. Immunofluorescence staining revealed that HCEP cells were holoclonal and expressed epithelial stem cell marker p63 without corneal cytokeratin 3. Cell viability remained unchanged after cells were cultured with 0.004, 0.04, and 0.4% TH in the medium, but it was significantly reduced when the concentration was increased to 3.33%. Cell migration, tested using scratch migration assay, was significantly enhanced when cells were cultured with TH at 0.04% and 0.4%. We also found that TH has hydrogen peroxide (H2O2) scavenging ability, although a trace level of H2O2 was detected in the honey in its native form. Preconditioning HCEP cells with 0.4% TH for 48 h showed better survival following H2O2-induced oxidative stress at 50 µM than untreated group, with a significantly lower number of dead cells (15.3±0.4%) were observed compared to the untreated population (20.5±0.9%, p<0.01). Both TH and ascorbic acid improved HCEP viability following induction of 100 µM H2O2, but the benefit was greater with TH treatment than with ascorbic acid. However, no significant advantage was demonstrated using 5-hydroxymethyl-2-furancarboxaldehyde, a compound that was found abundant in TH using GC/MS analysis. This suggests that the cellular anti-oxidative capacity in HCEP cells was augmented by native TH and was attributed to its antioxidant properties. In conclusion, TH possesses antioxidant properties and can improve cell migration and cellular resistance to oxidative stress in HCEP cells in

  12. Withaferin A protects against palmitic acid-induced endothelial insulin resistance and dysfunction through suppression of oxidative stress and inflammation

    PubMed Central

    Batumalaie, Kalaivani; Amin, Muhammad Arif; Murugan, Dharmani Devi; Sattar, Munavvar Zubaid Abdul; Abdullah, Nor Azizan

    2016-01-01

    Activation of inflammatory pathways via reactive oxygen species (ROS) by free fatty acids (FFA) in obesity gives rise to insulin resistance and endothelial dysfunction. Withaferin A (WA), possesses both antioxidant and anti-inflammatory properties and therefore would be a good strategy to suppress palmitic acid (PA)-induced oxidative stress and inflammation and hence, insulin resistance and dysfunction in the endothelium. Effect of WA on PA-induced insulin resistance in human umbilical vein endothelial cells (HUVECs) was determined by evaluating insulin signaling mechanisms whilst effect of this drug on PA-induced endothelial dysfunction was determined in acetylcholine-mediated relaxation in isolated rat aortic preparations. WA significantly inhibited ROS production and inflammation induced by PA. Furthermore, WA significantly decreased TNF-α and IL-6 production in endothelial cells by specifically suppressing IKKβ/NF-κβ phosphorylation. WA inhibited inflammation-stimulated IRS-1 serine phosphorylation and improved the impaired insulin PI3-K signaling, and restored the decreased nitric oxide (NO) production triggered by PA. WA also decreased endothelin-1 and plasminogen activator inhibitor type-1 levels, and restored the impaired endothelium-mediated vasodilation in isolated aortic preparations. These findings suggest that WA inhibited both ROS production and inflammation to restore impaired insulin resistance in cultured endothelial cells and improve endothelial dysfunction in rat aortic rings. PMID:27250532

  13. Withaferin A protects against palmitic acid-induced endothelial insulin resistance and dysfunction through suppression of oxidative stress and inflammation.

    PubMed

    Batumalaie, Kalaivani; Amin, Muhammad Arif; Murugan, Dharmani Devi; Sattar, Munavvar Zubaid Abdul; Abdullah, Nor Azizan

    2016-01-01

    Activation of inflammatory pathways via reactive oxygen species (ROS) by free fatty acids (FFA) in obesity gives rise to insulin resistance and endothelial dysfunction. Withaferin A (WA), possesses both antioxidant and anti-inflammatory properties and therefore would be a good strategy to suppress palmitic acid (PA)-induced oxidative stress and inflammation and hence, insulin resistance and dysfunction in the endothelium. Effect of WA on PA-induced insulin resistance in human umbilical vein endothelial cells (HUVECs) was determined by evaluating insulin signaling mechanisms whilst effect of this drug on PA-induced endothelial dysfunction was determined in acetylcholine-mediated relaxation in isolated rat aortic preparations. WA significantly inhibited ROS production and inflammation induced by PA. Furthermore, WA significantly decreased TNF-α and IL-6 production in endothelial cells by specifically suppressing IKKβ/NF-κβ phosphorylation. WA inhibited inflammation-stimulated IRS-1 serine phosphorylation and improved the impaired insulin PI3-K signaling, and restored the decreased nitric oxide (NO) production triggered by PA. WA also decreased endothelin-1 and plasminogen activator inhibitor type-1 levels, and restored the impaired endothelium-mediated vasodilation in isolated aortic preparations. These findings suggest that WA inhibited both ROS production and inflammation to restore impaired insulin resistance in cultured endothelial cells and improve endothelial dysfunction in rat aortic rings. PMID:27250532

  14. Corynebacterium glutamicum methionine sulfoxide reductase A uses both mycoredoxin and thioredoxin for regeneration and oxidative stress resistance.

    PubMed

    Si, Meiru; Zhang, Lei; Chaudhry, Muhammad Tausif; Ding, Wei; Xu, Yixiang; Chen, Can; Akbar, Ali; Shen, Xihui; Liu, Shuang-Jiang

    2015-04-01

    Oxidation of methionine leads to the formation of the S and R diastereomers of methionine sulfoxide (MetO), which can be reversed by the actions of two structurally unrelated classes of methionine sulfoxide reductase (Msr), MsrA and MsrB, respectively. Although MsrAs have long been demonstrated in numerous bacteria, their physiological and biochemical functions remain largely unknown in Actinomycetes. Here, we report that a Corynebacterium glutamicum methionine sulfoxide reductase A (CgMsrA) that belongs to the 3-Cys family of MsrAs plays important roles in oxidative stress resistance. Deletion of the msrA gene in C. glutamicum resulted in decrease of cell viability, increase of ROS production, and increase of protein carbonylation levels under various stress conditions. The physiological roles of CgMsrA in resistance to oxidative stresses were corroborated by its induced expression under various stresses, regulated directly by the stress-responsive extracytoplasmic-function (ECF) sigma factor SigH. Activity assays performed with various regeneration pathways showed that CgMsrA can reduce MetO via both the thioredoxin/thioredoxin reductase (Trx/TrxR) and mycoredoxin 1/mycothione reductase/mycothiol (Mrx1/Mtr/MSH) pathways. Site-directed mutagenesis confirmed that Cys56 is the peroxidatic cysteine that is oxidized to sulfenic acid, while Cys204 and Cys213 are the resolving Cys residues that form an intramolecular disulfide bond. Mrx1 reduces the sulfenic acid intermediate via the formation of an S-mycothiolated MsrA intermediate (MsrA-SSM) which is then recycled by mycoredoxin and the second molecule of mycothiol, similarly to the glutathione/glutaredoxin/glutathione reductase (GSH/Grx/GR) system. However, Trx reduces the Cys204-Cys213 disulfide bond in CgMsrA produced during MetO reduction via the formation of a transient intermolecular disulfide bond between Trx and CgMsrA. While both the Trx/TrxR and Mrx1/Mtr/MSH pathways are operative in reducing CgMsrA under

  15. Copper-resistant bacteria reduces oxidative stress and uptake of copper in lentil plants: potential for bacterial bioremediation.

    PubMed

    Islam, Faisal; Yasmeen, Tahira; Ali, Qasim; Mubin, Muhammad; Ali, Shafaqat; Arif, Muhammad Saleem; Hussain, Sabir; Riaz, Muhammad; Abbas, Farhat

    2016-01-01

    For effective microbe-assisted bioremediation, metal-resistant plant growth-promoting bacteria (PGPB) must facilitate plant growth by restricting excess metal uptake in plants, leading to prevent its bio-amplification in the ecosystem. The aims of our study were to isolate and characterize copper (Cu)-resistant PGPB from waste water receiving contaminated soil. In addition, we investigated the phytotoxic effect of copper on the lentil plants inoculated with copper-resistant bacteria Providencia vermicola, grown in copper-contaminated soil. Copper-resistant P. vermicola showed multiple plant growth promoting characteristics, when used as a seed inoculant. It protected the lentil plants from copper toxicity with a considerable increase in root and shoot length, plant dry weight and leaf area. A notable increase in different gas exchange characteristics such as A, E, C i , g s , and A/E, as well as increase in N and P accumulation were also recorded in inoculated plants as compared to un-inoculated copper stressed plants. In addition, leaf chlorophyll content, root nodulation, number of pods, 1,000 seed weight were also higher in inoculated plants as compared with non-inoculated ones. Anti-oxidative defense mechanism improved significantly via elevated expression of reactive oxygen species -scavenging enzymes including ascorbate peroxidase, superoxide dismutase, catalase, and guaiacol peroxidase with alternate decrease in malondialdehyde and H2O2 contents, reduced electrolyte leakage, proline, and total phenolic contents suggesting that inoculation of P. vermicola triggered heavy metals stress-related defense pathways under copper stress. Overall, the results demonstrated that the P. vermicola seed inoculation confer heavy metal stress tolerance in lentil plant which can be used as a potent biotechnological tool to cope with the problems of copper pollution in crop plants for better yield. PMID:26387695

  16. Increased resistance to oxidative stress in transgenic plants that overexpress chloroplastic Cu/Zn superoxide dismutase.

    PubMed Central

    Gupta, A S; Heinen, J L; Holaday, A S; Burke, J J; Allen, R D

    1993-01-01

    Transgenic tobacco plants that express a chimeric gene that encodes chloroplast-localized Cu/Zn superoxide dismutase (SOD) from pea have been developed. To investigate whether increased expression of chloroplast-targeted SOD could alter the resistance of photosynthesis to environmental stress, these plants were subjected to chilling temperatures and moderate (500 mumol of quanta per m2 per s) or high (1500 mumol of quanta per m2 per s) light intensity. During exposure to moderate stress, transgenic SOD plants retained rates of photosynthesis approximately 20% higher than untransformed tobacco plants, implicating active oxygen species in the reduction of photosynthesis during chilling. Unlike untransformed plants, transgenic SOD plants were capable of maintaining nearly 90% of their photosynthetic capacity (determined by their photosynthetic rates at 25 degrees C) following exposure to chilling at high light intensity for 4 hr. These plants also showed reduced levels of light-mediated cellular damage from the superoxide-generating herbicide methyl viologen. These results demonstrate that SOD is a critical component of the active-oxygen-scavenging system of plant chloroplasts and indicate that modification of SOD expression in transgenic plants can improve plant stress tolerance. Images PMID:8434026

  17. Increased ANG II sensitivity following recovery from acute kidney injury: role of oxidant stress in skeletal muscle resistance arteries

    PubMed Central

    Phillips, Shane A.; Pechman, Kimberly R.; Leonard, Ellen C.; Friedrich, Jessica L.; Bian, Jing-Tan; Beal, Alisa G.

    2010-01-01

    Ischemia-reperfusion (I/R)-induced acute kidney injury (AKI) results in prolonged impairment of peripheral (i.e., nonrenal) vascular function since skeletal muscle resistance arteries derived from rats 5 wk post-I/R injury, show enhanced responses to ANG II stimulation but not other constrictors. Because vascular superoxide increases ANG II sensitivity, we hypothesized that peripheral responsiveness following recovery from AKI was attributable to vascular oxidant stress. Gracilis arteries (GA) isolated from post-I/R rats (∼5 wk recovery) showed significantly greater superoxide levels relative to sham-operated controls, as detected by dihydroeithidium, which was further augmented by acute ANG II stimulation in vitro. Hydrogen peroxide measured by dichlorofluorescein was not affected by ANG II. GA derived from postischemic animals manifested significantly greater constrictor responses in vitro to ANG II than GA from sham-operated controls. The addition of the superoxide scavenging reagent Tempol (10−5 M) normalized the response to values similar to sham-operated controls. Apocynin (10−6 M) and endothelial denudation nearly abrogated all ANG II-stimulated constrictor activity in GA from post-AKI rats, suggesting an important role for an endothelial-derived source of peripheral oxidative stress. Apocynin treatment in vivo abrogated GA oxidant stress and attenuated ANG II-induced pressor responses post-AKI. Interestingly, gene expression studies in GA vessels indicated a paradoxical reduction in NADPH oxidase subunit and AT1-receptor genes and no effect on several antioxidant genes. Taken together, this study demonstrates that AKI alters peripheral vascular responses by increasing oxidant stress, likely in the endothelium, via an undefined mechanism. PMID:20335375

  18. Skin resistance to oxidative stress induced by resveratrol: from Nrf2 activation to GSH biosynthesis.

    PubMed

    Soeur, J; Eilstein, J; Léreaux, G; Jones, C; Marrot, L

    2015-01-01

    Skin is particularly exposed to oxidative stress, either from environmental insults such as sunlight or pollution or as a consequence of specific impairments in antioxidant status resulting from pathologies or aging. Traditionally, antioxidant products are exogenously provided to neutralize pro-oxidant species. However, another approach based on stimulation of endogenous antioxidant defense pathways is more original. Resveratrol (RSV) was reported to display such a behavior in various tissues, but data about the mechanisms of action in skin are scarce. We show here that, in primary culture of normal human keratinocytes (NHKs) or in full-thickness reconstructed human skin, RSV activated the Nrf2 pathway at nontoxic doses, from 20 µM up to 100µM. Among the Nrf2 downstream genes, glutamylcysteinyl ligase and glutathione peroxidase-2 were induced at the mRNA and protein levels. In parallel, a significant increase in glutathione content, assessed by LC/MS analysis, was observed in both models. Nrf2 gene silencing experiments performed in NHKs confirmed that Nrf2 was involved in RSV-induced modulation of cellular antioxidant status, in part by increasing cellular glutathione content. Finally, improvement of endogenous defenses induced in RSV-pretreated reconstructed skin ensured protection against the toxic oxidative effects of cumene hydroperoxide (CHP). In fact after RSV pretreatment, in response to CHP stress, glutathione content did not decrease as in unprotected samples. Cellular alterations at the dermal-epidermal junction were clearly prevented. Together, these complementary experiments demonstrated the beneficial effects of RSV on skin, beyond its direct antioxidant properties, by upregulation of a cutaneous endogenous antioxidant pathway. PMID:25451641

  19. Escherichia coli O157:H7 Glutamate- and Arginine-dependent Acid Resistance Systems Protect Against Oxidative Stress During Extreme Acid Challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Microorganisms may simultaneously encounter multiple stresses in their environment. To investigate the protection that several known Escherichia coli O157:H7 acid resistance systems might provide against both oxidative and acid stress, the addition of diamide, a membrane-permeable thiol-specific ox...

  20. Constitutive production of nitric oxide leads to enhanced drought stress resistance and extensive transcriptional reprogramming in Arabidopsis

    PubMed Central

    Shi, Haitao; Ye, Tiantian; Zhu, Jian-Kang; Chan, Zhulong

    2014-01-01

    Nitric oxide (NO) is involved in plant responses to many environmental stresses. Transgenic Arabidopsis lines that constitutively express rat neuronal NO synthase (nNOS) were described recently. In this study, it is reported that the nNOS transgenic Arabidopsis plants displayed high levels of osmolytes and increased antioxidant enzyme activities. Transcriptomic analysis identified 601 or 510 genes that were differentially expressed as a consequence of drought stress or nNOS transformation, respectively. Pathway and gene ontology (GO) term enrichment analyses revealed that genes involved in photosynthesis, redox, stress, and phytohormone and secondary metabolism were greatly affected by the nNOS transgene. Several CBF genes and members of zinc finger gene families, which are known to regulate transcription in the stress response, were changed by the nNOS transgene. Genes regulated by both the nNOS transgene and abscisic acid (ABA) treatments were compared and identified, including those for two ABA receptors (AtPYL4 and AtPYL5). Moreover, overexpression of AtPYL4 and AtPYL5 enhanced drought resistance, antioxidant enzyme activity, and osmolyte levels. These observations increase our understanding of the role of NO in drought stress response in Arabidopsis. PMID:24868034

  1. Enriching the drinking water of rats with extracts of Salvia officinalis and Thymus vulgaris increases their resistance to oxidative stress.

    PubMed

    Horváthová, Eva; Srančíková, Annamária; Regendová-Sedláčková, Eva; Melušová, Martina; Meluš, Vladimír; Netriová, Jana; Krajčovičová, Zdenka; Slameňová, Darina; Pastorek, Michal; Kozics, Katarína

    2016-01-01

    Nature is an attractive source of therapeutic compounds. In comparison to the artificial drugs, natural compounds cause less adverse side effects and are suitable for current molecularly oriented approaches to drug development and their mutual combining. Medicinal plants represent one of the most available remedy against various diseases. Proper examples are Salvia officinalis L. and Thymus vulgaris L. which are known aromatic medicinal plants. They are very popular and frequently used in many countries. The molecular mechanism of their biological activity has not yet been fully understood. The aim of this study was to ascertain if liver cells of experimental animals drinking extracts of sage or thyme will manifest increased resistance against oxidative stress. Adult Sprague-Dawley rats were divided into seven groups. They drank sage or thyme extracts for 2 weeks. At the end of the drinking period, blood samples were collected for determination of liver biochemical parameters and hepatocytes were isolated to analyze (i) oxidatively generated DNA damage (conventional and modified comet assay), (ii) activities of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx)] and (iii) content of glutathione. Intake of sage and thyme had no effect either on the basal level of DNA damage or on the activity of SOD in rat hepatocytes and did not change the biochemical parameters of blood plasma. Simultaneously, the activity of GPx was significantly increased and the level of DNA damage induced by oxidants was decreased. Moreover, sage extract was able to start up the antioxidant protection expressed by increased content of glutathione. Our results indicate that the consumption of S.officinalis and T.vulgaris extracts positively affects resistency of rat liver cells against oxidative stress and may have hepatoprotective potential. PMID:26297740

  2. Twofold cost of reproduction: an increase in parental effort leads to higher malarial parasitaemia and to a decrease in resistance to oxidative stress

    PubMed Central

    Christe, Philippe; Glaizot, Olivier; Strepparava, Nicole; Devevey, Godefroy; Fumagalli, Luca

    2012-01-01

    Parental effort is usually associated with high metabolism that could lead to an increase in the production of reactive oxidative species giving rise to oxidative stress. Since many antioxidants involved in the resistance to oxidative stress can also enhance immune function, an increase in parental effort may diminish the level of antioxidants otherwise involved in parasite resistance. In the present study, we performed brood size manipulation in a population of great tits (Parus major) to create different levels of parental effort. We measured resistance to oxidative stress and used a newly developed quantitative PCR assay to quantify malarial parasitaemia. We found that males with an enlarged brood had significantly higher level of malarial parasites and lower red blood cell resistance to free radicals than males rearing control and reduced broods. Brood size manipulation did not affect female parasitaemia, although females with an enlarged brood had lower red blood cell resistance than females with control and reduced broods. However, for both sexes, there was no relationship between the level of parasitaemia and resistance to oxidative stress, suggesting a twofold cost of reproduction. Our results thus suggest the presence of two proximate and independent mechanisms for the well-documented trade-off between current reproductive effort and parental survival. PMID:21920974

  3. IscR plays a role in oxidative stress resistance and pathogenicity of a plant pathogen, Xanthomonas campestris.

    PubMed

    Fuangthong, Mayuree; Jittawuttipoka, Thichakorn; Wisitkamol, Ratiphorn; Romsang, Adisak; Duang-nkern, Jintana; Vattanaviboon, Paiboon; Mongkolsuk, Skorn

    2015-01-01

    Iron-sulfur ([Fe-S]) cluster is an essential cofactor of proteins involved in various physiological processes including cellular defense against oxidative stress. In Xanthomonas campestris pv. campestris (Xcc), IscR plays a negative role in regulation of the transcription of [Fe-S] assembly genes, iscR-sufBCDS. The expression level of sufBCDS was up-regulated in an Xcc iscR mutant. In addition, the iscR promoter activity in an Xcc iscR mutant was also higher than the wild-type strain, indicating an autoregulatory circuit. Purified IscR was shown to bind at the iscR promoter region and three putative IscR binding sites were identified. The expression of iscR-suf operon was highly induced by oxidant treatments and iron limited conditions. The iscR mutant showed increased sensitivity toward hydrogen peroxide phenotype but, surprisingly, had hyper-resistant phenotype toward plumbagin compared to the wild-type strain. Most importantly, the iscR mutant was impaired in its ability to cause lesion on leaves of a compatible host plant, Chinese radish (Raphanus sativus). These results demonstrate that a transcription regulator gene, iscR, negatively regulates genes involved in [Fe-S] biosynthesis and plays a role in oxidative stress response and pathogenesis of Xcc. PMID:25200360

  4. Cafeteria diet induces obesity and insulin resistance associated with oxidative stress but not with inflammation: improvement by dietary supplementation with a melon superoxide dismutase.

    PubMed

    Carillon, Julie; Romain, Cindy; Bardy, Guillaume; Fouret, Gilles; Feillet-Coudray, Christine; Gaillet, Sylvie; Lacan, Dominique; Cristol, Jean-Paul; Rouanet, Jean-Max

    2013-12-01

    Oxidative stress is involved in obesity. However, dietary antioxidants could prevent oxidative stress-induced damage. We have previously shown the preventive effects of a melon superoxide dismutase (SODB) on oxidative stress. However, the mechanism of action of SODB is still unknown. Here, we evaluated the effects of a 1-month curative supplementation with SODB on the liver of obese hamsters. Golden Syrian hamsters received either a standard diet or a cafeteria diet composed of high-fat, high-sugar, and high-salt supermarket products, for 15 weeks. This diet resulted in insulin resistance and in increased oxidative stress in the liver. However, inflammatory markers (IL-6, TNF-α, and NF-κB) were not enhanced and no liver steatosis was detected, although these are usually described in obesity-induced insulin resistance models. After the 1-month supplementation with SODB, body weight and insulin resistance induced by the cafeteria diet were reduced and hepatic oxidative stress was corrected. This could be due to the increased expression of the liver antioxidant defense proteins (manganese and copper/zinc superoxide dismutase, catalase, and glutathione peroxidase). Even though no inflammation was detected in the obese hamsters, inflammatory markers were decreased after SODB supplementation, probably through the reduction of oxidative stress. These findings suggest for the first time that SODB could exert its antioxidant properties by inducing the endogenous antioxidant defense. The mechanisms underlying this induction need to be further investigated. PMID:23792771

  5. Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes

    PubMed Central

    Kahleova, H; Matoulek, M; Malinska, H; Oliyarnik, O; Kazdova, L; Neskudla, T; Skoch, A; Hajek, M; Hill, M; Kahle, M; Pelikanova, T

    2011-01-01

    Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [–6.2 kg (95% CI –6.6 to –5.3) vs. –3.2 kg (95% CI –3.7 to –2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5–39) vs. 20% (95% CI 14–25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0

  6. Ameliorative effect of vanadyl(IV)-ascorbate complex on high-fat high-sucrose diet-induced hyperglycemia, insulin resistance, and oxidative stress in mice.

    PubMed

    Liu, Yanjun; Xu, Jie; Guo, Yongli; Xue, Yong; Wang, Jingfeng; Xue, Changhu

    2015-10-01

    There is mounting evidence demonstrating causative links between hyperglycemia, oxidative stress, and insulin resistance, the core pathophysiological features of type 2 diabetes mellitus. Using a combinational approach, we synthesized a vanadium-antioxidant (i.e., l-ascorbic acid) complex and examined its effect on insulin resistance and oxidative stress. This study was designed to examine whether vanadyl(IV)-ascorbate complex (VOAsc) would reduce oxidative stress, hyperglycemia, and insulin resistance in high-fat high-sucrose diet (HFSD)-induced type 2 diabetes in mice. Male C57BL/6J mice were fed a HFSD for 12 weeks to induce insulin resistance, rendering them diabetic. Diabetic mice were treated with rosiglitazone, sodium l-ascorbate, or VOAsc. At the end of treatment, fasting blood glucose, fasting serum insulin, homeostasis model assessment-insulin resistance index, and serum adipocytokine levels were measured. Serum levels of nitric oxide (NO) parameters were also determined. The liver was isolated and used for determination of malondialdehyde, reduced glutathione, and catalase levels, and superoxide dismutase and glutathione peroxidase activities. VOAsc groups exhibited significant reductions in serum adipocytokine and NO levels, and oxidative stress parameters compared to the corresponding values in the untreated diabetic mice. The results indicated that VOAsc is non-toxic. In conclusion, we identified VOAsc as a potentially effective adjunct therapy for the management of type 2 diabetes. PMID:26302923

  7. Deficiency of multidrug resistance 2 contributes to cell transformation through oxidative stress

    PubMed Central

    Tebbi, Ali; Levillayer, Florence; Jouvion, Grégory; Fiette, Laurence; Soubigou, Guillaume; Varet, Hugo; Boudjadja, Nesrine; Cairo, Stefano; Hashimoto, Kosuke; Suzuki, Ana Maria; Carninci, Piero; Carissimo, Annamaria; di Bernardo, Diego; Wei, Yu

    2016-01-01

    Multidrug resistance 2 (Mdr2), also called adenosine triphosphate-binding cassette B4 (ABCB4), is the transporter of phosphatidylcholine (PC) at the canalicular membrane of mouse hepatocytes, which plays an essential role for bile formation. Mutations in human homologue MDR3 are associated with several liver diseases. Knockout of Mdr2 results in hepatic inflammation, liver fibrosis and hepatocellular carcinoma (HCC). Whereas the pathogenesis in Mdr2 −/− mice has been largely attributed to the toxicity of bile acids due to the absence of PC in the bile, the question of whether Mdr2 deficiency per se perturbs biological functions in the cell has been poorly addressed. As Mdr2 is expressed in many cell types, we used mouse embryonic fibroblasts (MEF) derived from Mdr2 −/− embryos to show that deficiency of Mdr2 increases reactive oxygen species accumulation, lipid peroxidation and DNA damage. We found that Mdr2 −/− MEFs undergo spontaneous transformation and that Mdr2 −/− mice are more susceptible to chemical carcinogen-induced intestinal tumorigenesis. Microarray analysis in Mdr2−/− MEFs and cap analysis of gene expression in Mdr2 −/− HCCs revealed extensively deregulated genes involved in oxidation reduction, fatty acid metabolism and lipid biosynthesis. Our findings imply a close link between Mdr2 −/−-associated tumorigenesis and perturbation of these biological processes and suggest potential extrahepatic functions of Mdr2/MDR3. PMID:26542370

  8. Development and characterization of a hydrogen peroxide-resistant cholangiocyte cell line: A novel model of oxidative stress-related cholangiocarcinoma genesis

    SciTech Connect

    Thanan, Raynoo; Techasen, Anchalee; Hou, Bo; Jamnongkan, Wassana; Armartmuntree, Napat; Yongvanit, Puangrat; Murata, Mariko

    2015-08-14

    Oxidative stress is a cause of inflammation–related diseases, including cancers. Cholangiocarcinoma is a liver cancer with bile duct epithelial cell phenotypes. Our previous studies in animal and human models indicated that oxidative stress is a major cause of cholangiocarcinoma development. Hydrogen peroxide (H{sub 2}O{sub 2}) can generate hydroxyl radicals, which damage lipids, proteins, and nucleic acids, leading to cell death. However, some cells can survive by adapting to oxidative stress conditions, and selective clonal expansion of these resistant cells would be involved in oxidative stress-related carcinogenesis. The present study aimed to establish H{sub 2}O{sub 2}-resistant cell line from an immortal cholangiocyte cell line (MMNK1) by chronic treatment with low-concentration H{sub 2}O{sub 2} (25 μM). After 72 days of induction, H{sub 2}O{sub 2}-resistant cell lines (ox-MMNK1-L) were obtained. The ox-MMNK1-L cell line showed H{sub 2}O{sub 2}-resistant properties, increasing the expression of the anti-oxidant genes catalase (CAT), superoxide dismutase-1 (SOD1), superoxide dismutase-2 (SOD2), and superoxide dismutase-3 (SOD3) and the enzyme activities of CAT and intracellular SODs. Furthermore, the resistant cells showed increased expression levels of an epigenetics-related gene, DNA methyltransferase-1 (DNMT1), when compared to the parental cells. Interestingly, the ox-MMNK1-L cell line had a significantly higher cell proliferation rate than the MMNK1 normal cell line. Moreover, ox-MMNK1-L cells showed pseudopodia formation and the loss of cell-to-cell adhesion (multi-layers) under additional oxidative stress (100 μM H{sub 2}O{sub 2}). These findings suggest that H{sub 2}O{sub 2}-resistant cells can be used as a model of oxidative stress-related cholangiocarcinoma genesis through molecular changes such as alteration of gene expression and epigenetic changes. - Highlights: • An H{sub 2}O{sub 2}-resistant ox-MMNK1-L cells was established from

  9. A natural formulation (imoviral™) increases macrophage resistance to LPS-induced oxidative and inflammatory stress in vitro.

    PubMed

    Menghini, L; Leporini, L; Pintore, G; Ferrante, C; Recinella, L; Orlando, G; Vacca, M; Brunetti, L

    2014-01-01

    Imoviral™ is a natural product formulation containing a mixture of uncaria, shiitake and ribes extracts. All ingredients are recognized as antioxidant, anti-inflammatory agent and immunomodulant. In order to evaluate the rational basis of extract mixture as immunomodulatory agent, we tested the effect of Imoviral™ formulation on macrophage response to lipopolysaccharide (LPS)-induced stress. The effect was evaluated as variation of reactive oxygen species (ROS) and prostaglandin E2 (PGE2) production and as cytokine gene expression. The extract did not affect cell viability up to 250 μg/ml. Treatment with extract (10-150 μg/ml) reduced ROS and PGE2 production as well as IL-8 and TNF-α gene expression. A pre-treatment with extract blunted LPS-induced production of ROS and PGE2, markers of oxidative and inflammatory stress, as well as the gene expression of all cytokines tested, indicators, in vitro, of immune response activation. In conclusion, we demonstrated that Imoviral™ formulation could be a useful tool to modulate the immune function, reducing the oxidative and inflammatory markers related to bacterial attack. Experimental data suggest that Imoviral™ extract mixture could also represent a preventive pharmacological strategy to enhance cell resistance to bacterial infections. PMID:25620186

  10. Differential resistance of mammalian sperm chromatin to oxidative stress as assessed by a two-tailed comet assay.

    PubMed

    Enciso, María; Johnston, Stephen D; Gosálvez, Jaime

    2011-01-01

    Protamines of eutherian species are cysteine-rich molecules that become cross-linked by disulfide bonds during epididymal transit, whereas the protamines of most marsupial species lack cysteine residuals. The present study made use of the differences in protamine structure between eutherian and metatherian mammal spermatozoa to examine the comparative resistance of sperm DNA to oxidative damage in three eutherian species (Mus musculus, Homo sapiens, Sus domesticus) and three metatherian species (Vombatus ursinus, Phascolarctos cinereus, Macropus giganteus). Sperm DNA fragmentation of samples exposed to increasing concentrations of hydrogen peroxide was assessed by means of the two-tailed comet assay. The sperm DNA of the marsupial species studied were significantly more sensitive to oxidative stress than the spermatozoa of eutherian species. Such susceptibility is consistent with the lack of disulfide cross-linking in marsupial sperm chromatin and suggests that the oxidation of thiols to disulfides for chromatin condensation during epididymal transit in eutherian mammals is likely to be important in order to provide stability and protect these cells from the genotoxic effects of adverse environments. PMID:21635811

  11. Proteomic Identification of Oxidized Proteins in Entamoeba histolytica by Resin-Assisted Capture: Insights into the Role of Arginase in Resistance to Oxidative Stress.

    PubMed

    Shahi, Preeti; Trebicz-Geffen, Meirav; Nagaraja, Shruti; Alterzon-Baumel, Sharon; Hertz, Rivka; Methling, Karen; Lalk, Michael; Ankri, Serge

    2016-01-01

    Entamoeba histolytica is an obligate protozoan parasite of humans, and amebiasis, an infectious disease which targets the intestine and/or liver, is the second most common cause of human death due to a protozoan after malaria. Although amebiasis is usually asymptomatic, E. histolytica has potent pathogenic potential. During host infection, the parasite is exposed to reactive oxygen species that are produced and released by cells of the innate immune system at the site of infection. The ability of the parasite to survive oxidative stress (OS) is essential for a successful invasion of the host. Although the effects of OS on the regulation of gene expression in E. histolytica and the characterization of some proteins whose function in the parasite's defense against OS have been previously studied, our knowledge of oxidized proteins in E. histolytica is lacking. In order to fill this knowledge gap, we performed a large-scale identification and quantification of the oxidized proteins in oxidatively stressed E. histolytica trophozoites using resin-assisted capture coupled to mass spectrometry. We detected 154 oxidized proteins (OXs) and the functions of some of these proteins were associated with antioxidant activity, maintaining the parasite's cytoskeleton, translation, catalysis, and transport. We also found that oxidation of the Gal/GalNAc impairs its function and contributes to the inhibition of E. histolytica adherence to host cells. We also provide evidence that arginase, an enzyme which converts L-arginine into L-ornithine and urea, is involved in the protection of the parasite against OS. Collectively, these results emphasize the importance of OS as a critical regulator of E. histolytica's functions and indicate a new role for arginase in E. histolytica's resistance to OS. PMID:26735309

  12. Proteomic Identification of Oxidized Proteins in Entamoeba histolytica by Resin-Assisted Capture: Insights into the Role of Arginase in Resistance to Oxidative Stress

    PubMed Central

    Shahi, Preeti; Trebicz-Geffen, Meirav; Nagaraja, Shruti; Alterzon-Baumel, Sharon; Hertz, Rivka; Methling, Karen; Lalk, Michael; Ankri, Serge

    2016-01-01

    Entamoeba histolytica is an obligate protozoan parasite of humans, and amebiasis, an infectious disease which targets the intestine and/or liver, is the second most common cause of human death due to a protozoan after malaria. Although amebiasis is usually asymptomatic, E. histolytica has potent pathogenic potential. During host infection, the parasite is exposed to reactive oxygen species that are produced and released by cells of the innate immune system at the site of infection. The ability of the parasite to survive oxidative stress (OS) is essential for a successful invasion of the host. Although the effects of OS on the regulation of gene expression in E. histolytica and the characterization of some proteins whose function in the parasite's defense against OS have been previously studied, our knowledge of oxidized proteins in E. histolytica is lacking. In order to fill this knowledge gap, we performed a large-scale identification and quantification of the oxidized proteins in oxidatively stressed E. histolytica trophozoites using resin-assisted capture coupled to mass spectrometry. We detected 154 oxidized proteins (OXs) and the functions of some of these proteins were associated with antioxidant activity, maintaining the parasite's cytoskeleton, translation, catalysis, and transport. We also found that oxidation of the Gal/GalNAc impairs its function and contributes to the inhibition of E. histolytica adherence to host cells. We also provide evidence that arginase, an enzyme which converts L-arginine into L-ornithine and urea, is involved in the protection of the parasite against OS. Collectively, these results emphasize the importance of OS as a critical regulator of E. histolytica's functions and indicate a new role for arginase in E. histolytica's resistance to OS. PMID:26735309

  13. Escherichia coli O157:H7 Glutamate- and Arginine-dependent Acid Resistance Systems Protect Against Oxidative Stress During Extreme Acid Challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To investigate the protection that several known Escherichia coli O157:H7 acid resistance systems provide against oxidative stress, the addition of diamide or hydrogen peroxide were used concomitant with acid challenge at pH 2.5 to determine bacterial survival. Diamide and hydrogen peroxide both de...

  14. Differential transcription of cytochrome P450s and glutathione S transferases in DDT-susceptible and resistant Drosophila melanogaster strains in response to DDT and oxidative stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Metabolic DDT resistance in Drosophila melanogaster has previously been associated with constitutive over-transcription of cytochrome P450s. Increased P450 activity has also been associated with increased oxidative stress. In contrast, over-transcription of glutathione S transferases (GSTs) has been...

  15. Green tea extract decreases oxidative stress and improves insulin sensitivity in an animal model of insulin resistance, the fructose- fed rat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Metabolic syndrome is characterized by insulin resistance, dyslipidemia, and increased oxidative stress. Tea polyphenols, as both insulin potentiating factors and antioxidants, might act in preventing the metabolic syndrome. We aimed to determine the effects of green tea extract consumption on oxida...

  16. Stress corrosion resistant fasteners

    NASA Technical Reports Server (NTRS)

    Roach, T. A.

    1985-01-01

    A family of high performance aerospace fasteners made from corrosion resistant alloys for use in applications where corrosion and stress-corrosion cracking are of major concern are discussed. The materials discussed are mainly A-286, Inconel 718, MP35N and MP159. Most of the fasteners utilize cold worked and aged materials to achieve the desired properties. The fasteners are unique in that they provide a combination of high strength and immunity to stress corrosion cracking not previously attainable. A discussion of fastener stress corrosion failures is presented including a review of the history and a description of the mechanism. Case histories are presented to illustrate the problems which can arise when material selection is made without proper regard for the environmental conditions. Mechanical properties and chemical compositions are included for the fasteners discussed. Several aspects of the application of high performance corrosion resistant fasteners are discussed including galvanic compatibility and torque-tension relationships.

  17. Stable over-expression of the 2-oxoglutarate carrier enhances neuronal cell resistance to oxidative stress via Bcl-2-dependent mitochondrial GSH transport

    PubMed Central

    Wilkins, Heather M.; Brock, Samantha; Gray, Josie J.; Linseman, Daniel A.

    2015-01-01

    Mitochondrial glutathione (GSH) is a key endogenous antioxidant and its maintenance is critical for cell survival. Here, we generated stable NSC34 motor neuron-like cell lines over-expressing the mitochondrial GSH transporter, the 2-oxoglutarate carrier (OGC), to further elucidate the importance of mitochondrial GSH transport in determining neuronal resistance to oxidative stress. Two stable OGC cell lines displayed specific increases in mitochondrial GSH content and resistance to oxidative and nitrosative stressors, but not staurosporine. Inhibition of transport through OGC reduced levels of mitochondrial GSH and resensitized the stable cell lines to oxidative stress. The stable OGC cell lines displayed significant up-regulation of the anti-apoptotic protein, B cell lymphoma 2 (Bcl-2). This result was reproduced in parental NSC34 cells by chronic treatment with GSH monoethylester, which specifically increased mitochondrial GSH levels. Knockdown of Bcl-2 expression decreased mitochondrial GSH and resensitized the stable OGC cells to oxidative stress. Finally, endogenous OGC was co-immunoprecipitated with Bcl-2 from rat brain lysates in a GSH-dependent manner. These data are the first to show that increased mitochondrial GSH transport is sufficient to enhance neuronal resistance to oxidative stress. Moreover, sustained and specific enhancement of mitochondrial GSH leads to increased Bcl-2 expression, a required mechanism for the maintenance of increased mitochondrial GSH levels. PMID:24606213

  18. Natural thioallyl compounds increase oxidative stress resistance and lifespan in Caenorhabditis elegans by modulating SKN-1/Nrf.

    PubMed

    Ogawa, Takahiro; Kodera, Yukihiro; Hirata, Dai; Blackwell, T Keith; Mizunuma, Masaki

    2016-01-01

    Identification of biologically active natural compounds that promote health and longevity, and understanding how they act, will provide insights into aging and metabolism, and strategies for developing agents that prevent chronic disease. The garlic-derived thioallyl compounds S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC) have been shown to have multiple biological activities. Here we show that SAC and SAMC increase lifespan and stress resistance in Caenorhabditis elegans and reduce accumulation of reactive oxygen species (ROS). These compounds do not appear to activate DAF-16 (FOXO orthologue) or mimic dietary restriction (DR) effects, but selectively induce SKN-1 (Nrf1/2/3 orthologue) targets involved in oxidative stress defense. Interestingly, their treatments do not facilitate SKN-1 nuclear accumulation, but slightly increased intracellular SKN-1 levels. Our data also indicate that thioallyl structure and the number of sulfur atoms are important for SKN-1 target induction. Our results indicate that SAC and SAMC may serve as potential agents that slow aging. PMID:26899496

  19. Natural thioallyl compounds increase oxidative stress resistance and lifespan in Caenorhabditis elegans by modulating SKN-1/Nrf

    PubMed Central

    Ogawa, Takahiro; Kodera, Yukihiro; Hirata, Dai; Blackwell, T. Keith; Mizunuma, Masaki

    2016-01-01

    Identification of biologically active natural compounds that promote health and longevity, and understanding how they act, will provide insights into aging and metabolism, and strategies for developing agents that prevent chronic disease. The garlic-derived thioallyl compounds S-allylcysteine (SAC) and S-allylmercaptocysteine (SAMC) have been shown to have multiple biological activities. Here we show that SAC and SAMC increase lifespan and stress resistance in Caenorhabditis elegans and reduce accumulation of reactive oxygen species (ROS). These compounds do not appear to activate DAF-16 (FOXO orthologue) or mimic dietary restriction (DR) effects, but selectively induce SKN-1 (Nrf1/2/3 orthologue) targets involved in oxidative stress defense. Interestingly, their treatments do not facilitate SKN-1 nuclear accumulation, but slightly increased intracellular SKN-1 levels. Our data also indicate that thioallyl structure and the number of sulfur atoms are important for SKN-1 target induction. Our results indicate that SAC and SAMC may serve as potential agents that slow aging. PMID:26899496

  20. Process for the deposition of high temperature stress and oxidation resistant coatings on silicon-based substrates

    DOEpatents

    Sarin, Vinod K.

    1991-01-01

    A process for depositing a high temperature stress and oxidation resistant coating on a silicon nitride- or silicon carbide-based substrate body. A gas mixture is passed over the substrate at about 900.degree.-1500.degree. C. and about 1 torr to about ambient pressure. The gas mixture includes one or more halide vapors with other suitable reactant gases. The partial pressure ratios, flow rates, and process times are sufficient to deposit a continuous, fully dense, adherent coating. The halide and other reactant gases are gradually varied during deposition so that the coating is a graded coating of at least two layers. Each layer is a graded layer changing in composition from the material over which it is deposited to the material of the layer and further to the material, if any, deposited thereon, so that no clearly defined compositional interfaces exist. The gases and their partial pressures are varied according to a predetermined time schedule and the halide and other reactant gases are selected so that the layers include (a) an adherent, continuous intermediate layer about 0.5-20 microns thick of an aluminum nitride or an aluminum oxynitride material, over and chemically bonded to the substrate body, and (b) an adherent, continuous first outer layer about 0.5-900 microns thick including an oxide of aluminum or zirconium over and chemically bonded to the intermediate layer.

  1. Process for the deposition of high temperature stress and oxidation resistant coatings on silicon-based substrates

    DOEpatents

    Sarin, V.K.

    1991-07-30

    A process is disclosed for depositing a high temperature stress and oxidation resistant coating on a silicon nitride- or silicon carbide-based substrate body. A gas mixture is passed over the substrate at about 900--1500 C and about 1 torr to about ambient pressure. The gas mixture includes one or more halide vapors with other suitable reactant gases. The partial pressure ratios, flow rates, and process times are sufficient to deposit a continuous, fully dense, adherent coating. The halide and other reactant gases are gradually varied during deposition so that the coating is a graded coating of at least two layers. Each layer is a graded layer changing in composition from the material over which it is deposited to the material of the layer and further to the material, if any, deposited thereon, so that no clearly defined compositional interfaces exist. The gases and their partial pressures are varied according to a predetermined time schedule and the halide and other reactant gases are selected so that the layers include (a) an adherent, continuous intermediate layer about 0.5-20 microns thick of an aluminum nitride or an aluminum oxynitride material, over and chemically bonded to the substrate body, and (b) an adherent, continuous first outer layer about 0.5-900 microns thick including an oxide of aluminum or zirconium over and chemically bonded to the intermediate layer.

  2. Effect of taurine supplementation on hyperhomocysteinemia and markers of oxidative stress in high fructose diet induced insulin resistance

    PubMed Central

    2010-01-01

    Background High intake of dietary fructose is accused of being responsible for the development of the insulin resistance (IR) syndrome. Concern has arisen because of the realization that fructose, at elevated concentrations, can promote metabolic changes that are potentially deleterious. Among these changes is IR which manifests as a decreased biological response to normal levels of plasma insulin. Methods Oral glucose tolerance tests (OGTT) were carried out, homeostasis model assessment of insulin resistance (HOMA) was calculated, homocysteine (Hcy), lipid concentrations and markers of oxidative stress were measured in male Wistar rats weighing 170-190 g. The rats were divided into four groups, kept on either control diet or high fructose diet (HFD), and simultaneously supplemented with 300 mg/kg/day taurine via intra-peritoneal (i.p.) route for 35 days. Results Fructose-fed rats showed significantly impaired glucose tolerance, impaired insulin sensitivity, hypertriglyceridemia, hypercholesterolemia, hyperhomocysteinemia (HHcy), lower total antioxidant capacity (TAC), lower paraoxonase (PON) activity, and higher nitric oxide metabolites (NOx) concentration, when compared to rats fed on control diet. Supplementing the fructose-fed rats with taurine has ameliorated the rise in HOMA by 56%, triglycerides (TGs) by 22.5%, total cholesterol (T-Chol) by 11%, and low density lipoprotein cholesterol (LDL-C) by 21.4%. Taurine also abolished any significant difference of TAC, PON activity and NOx concentration among treated and control groups. TAC positively correlated with PON in both rats fed on the HFD and those received taurine in addition to the HFD. Fructose-fed rats showed 34.7% increase in Hcy level. Taurine administration failed to prevent the observed HHcy in the current dosage and duration. Conclusion Our results indicate that HFD could induce IR which could further result in metabolic syndrome (MS), and that taurine has a protective role against the metabolic

  3. Stable over-expression of the 2-oxoglutarate carrier enhances neuronal cell resistance to oxidative stress via Bcl-2-dependent mitochondrial GSH transport.

    PubMed

    Wilkins, Heather M; Brock, Samantha; Gray, Josie J; Linseman, Daniel A

    2014-07-01

    Mitochondrial glutathione (GSH) is a key endogenous antioxidant and its maintenance is critical for cell survival. Here, we generated stable NSC34 motor neuron-like cell lines over-expressing the mitochondrial GSH transporter, the 2-oxoglutarate carrier (OGC), to further elucidate the importance of mitochondrial GSH transport in determining neuronal resistance to oxidative stress. Two stable OGC cell lines displayed specific increases in mitochondrial GSH content and resistance to oxidative and nitrosative stressors, but not staurosporine. Inhibition of transport through OGC reduced levels of mitochondrial GSH and resensitized the stable cell lines to oxidative stress. The stable OGC cell lines displayed significant up-regulation of the anti-apoptotic protein, B cell lymphoma 2 (Bcl-2). This result was reproduced in parental NSC34 cells by chronic treatment with GSH monoethylester, which specifically increased mitochondrial GSH levels. Knockdown of Bcl-2 expression decreased mitochondrial GSH and resensitized the stable OGC cells to oxidative stress. Finally, endogenous OGC was co-immunoprecipitated with Bcl-2 from rat brain lysates in a GSH-dependent manner. These data are the first to show that increased mitochondrial GSH transport is sufficient to enhance neuronal resistance to oxidative stress. Moreover, sustained and specific enhancement of mitochondrial GSH leads to increased Bcl-2 expression, a required mechanism for the maintenance of increased mitochondrial GSH levels. Stable over-expression of the 2-oxoglutarate carrier (OGC) in a motor neuronal cell line induced a specific increase in mitochondrial GSH and markedly enhanced resistance to oxidative stress. Over-expression of OGC also induced Bcl-2 expression which was owing to the specific increase in mitochondrial GSH. Intriguingly, enhanced expression of Bcl-2 was required to sustain OGC-dependent GSH transport into the mitochondria. Thus, OGC and Bcl-2 work in a concerted manner to maintain the

  4. Human IGF1 regulates midgut oxidative stress and epithelial homeostasis to balance lifespan and Plasmodium falciparum resistance in Anopheles stephensi.

    PubMed

    Drexler, Anna L; Pietri, Jose E; Pakpour, Nazzy; Hauck, Eric; Wang, Bo; Glennon, Elizabeth K K; Georgis, Martha; Riehle, Michael A; Luckhart, Shirley

    2014-06-01

    Insulin and insulin-like growth factor signaling (IIS) regulates cell death, repair, autophagy, and renewal in response to stress, damage, and pathogen challenge. Therefore, IIS is fundamental to lifespan and disease resistance. Previously, we showed that insulin-like growth factor 1 (IGF1) within a physiologically relevant range (0.013-0.13 µM) in human blood reduced development of the human parasite Plasmodium falciparum in the Indian malaria mosquito Anopheles stephensi. Low IGF1 (0.013 µM) induced FOXO and p70S6K activation in the midgut and extended mosquito lifespan, whereas high IGF1 (0.13 µM) did not. In this study the physiological effects of low and high IGF1 were examined in detail to infer mechanisms for their dichotomous effects on mosquito resistance and lifespan. Following ingestion, low IGF1 induced phosphorylation of midgut c-Jun-N-terminal kinase (JNK), a critical regulator of epithelial homeostasis, but high IGF1 did not. Low and high IGF1 induced midgut mitochondrial reactive oxygen species (ROS) synthesis and nitric oxide (NO) synthase gene expression, responses which were necessary and sufficient to mediate IGF1 inhibition of P. falciparum development. However, increased ROS and apoptosis-associated caspase-3 activity returned to baseline levels following low IGF1 treatment, but were sustained with high IGF1 treatment and accompanied by aberrant expression of biomarkers for mitophagy, stem cell division and proliferation. Low IGF1-induced ROS are likely moderated by JNK-induced epithelial cytoprotection as well as p70S6K-mediated growth and inhibition of apoptosis over the lifetime of A. stephensi to facilitate midgut homeostasis and enhanced survivorship. Hence, mitochondrial integrity and homeostasis in the midgut, a key signaling center for IIS, can be targeted to coordinately optimize mosquito fitness and anti-pathogen resistance for improved control strategies for malaria and other vector-borne diseases. PMID:24968248

  5. Human IGF1 Regulates Midgut Oxidative Stress and Epithelial Homeostasis to Balance Lifespan and Plasmodium falciparum resistance in Anopheles stephensi

    PubMed Central

    Drexler, Anna L.; Pietri, Jose E.; Pakpour, Nazzy; Hauck, Eric; Wang, Bo; Glennon, Elizabeth K. K.; Georgis, Martha; Riehle, Michael A.; Luckhart, Shirley

    2014-01-01

    Insulin and insulin-like growth factor signaling (IIS) regulates cell death, repair, autophagy, and renewal in response to stress, damage, and pathogen challenge. Therefore, IIS is fundamental to lifespan and disease resistance. Previously, we showed that insulin-like growth factor 1 (IGF1) within a physiologically relevant range (0.013–0.13 µM) in human blood reduced development of the human parasite Plasmodium falciparum in the Indian malaria mosquito Anopheles stephensi. Low IGF1 (0.013 µM) induced FOXO and p70S6K activation in the midgut and extended mosquito lifespan, whereas high IGF1 (0.13 µM) did not. In this study the physiological effects of low and high IGF1 were examined in detail to infer mechanisms for their dichotomous effects on mosquito resistance and lifespan. Following ingestion, low IGF1 induced phosphorylation of midgut c-Jun-N-terminal kinase (JNK), a critical regulator of epithelial homeostasis, but high IGF1 did not. Low and high IGF1 induced midgut mitochondrial reactive oxygen species (ROS) synthesis and nitric oxide (NO) synthase gene expression, responses which were necessary and sufficient to mediate IGF1 inhibition of P. falciparum development. However, increased ROS and apoptosis-associated caspase-3 activity returned to baseline levels following low IGF1 treatment, but were sustained with high IGF1 treatment and accompanied by aberrant expression of biomarkers for mitophagy, stem cell division and proliferation. Low IGF1-induced ROS are likely moderated by JNK-induced epithelial cytoprotection as well as p70S6K-mediated growth and inhibition of apoptosis over the lifetime of A. stephensi to facilitate midgut homeostasis and enhanced survivorship. Hence, mitochondrial integrity and homeostasis in the midgut, a key signaling center for IIS, can be targeted to coordinately optimize mosquito fitness and anti-pathogen resistance for improved control strategies for malaria and other vector-borne diseases. PMID:24968248

  6. Exploring the role of trehalose metabolism in resistance to oxidative and desiccation stress in Fusarium verticillioides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fusarium verticillioides is a pathogenic filamentous fungus that primarily affects maize. We are exploring stress response mechanisms in F. verticillioides, particularly the role of trehalose, a disaccharide known to be involved in the ability of several organisms to withstand desiccation or drought...

  7. Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating

    PubMed Central

    Balvan, Jan; Gumulec, Jaromir; Raudenska, Martina; Krizova, Aneta; Stepka, Petr; Babula, Petr; Kizek, Rene; Adam, Vojtech; Masarik, Michal

    2015-01-01

    Resistant cancer phenotype is a key obstacle in the successful therapy of prostate cancer. The primary aim of our study was to explore resistance mechanisms in the advanced type of prostate cancer cells (PC-3) and to clarify the role of autophagy in these processes. We performed time-lapse experiment (48 hours) with ROS generating plumbagin by using multimodal holographic microscope. Furthermore, we also performed the flow-cytometric analysis and the qRT-PCR gene expression analysis at 12 selected time points. TEM and confocal microscopy were used to verify the results. We found out that autophagy (namely mitophagy) is an important resistance mechanism. The major ROS producing mitochondria were coated by an autophagic membrane derived from endoplasmic reticulum and degraded. According to our results, increasing ROS resistance may be also accompanied by increased average cell size and polyploidization, which seems to be key resistance mechanism when connected with an escape from senescence. Many different types of cell-cell interactions were recorded including entosis, vesicular transfer, eating of dead or dying cells, and engulfment and cannibalism of living cells. Entosis was disclosed as a possible mechanism of polyploidization and enabled the long-term survival of cancer cells. Significantly reduced cell motility was found after the plumbagin treatment. We also found an extensive induction of pluripotency genes expression (NANOG, SOX2, and POU5F1) at the time-point of 20 hours. We suppose, that overexpression of pluripotency genes in the portion of prostate tumour cell population exposed to ROS leads to higher developmental plasticity and capability to faster respond to changes in the extracellular environment that could ultimately lead to an alteration of cell fate. PMID:26671576

  8. Oxidative Stress Resistance in Metastatic Prostate Cancer: Renewal by Self-Eating.

    PubMed

    Balvan, Jan; Gumulec, Jaromir; Raudenska, Martina; Krizova, Aneta; Stepka, Petr; Babula, Petr; Kizek, Rene; Adam, Vojtech; Masarik, Michal

    2015-01-01

    Resistant cancer phenotype is a key obstacle in the successful therapy of prostate cancer. The primary aim of our study was to explore resistance mechanisms in the advanced type of prostate cancer cells (PC-3) and to clarify the role of autophagy in these processes. We performed time-lapse experiment (48 hours) with ROS generating plumbagin by using multimodal holographic microscope. Furthermore, we also performed the flow-cytometric analysis and the qRT-PCR gene expression analysis at 12 selected time points. TEM and confocal microscopy were used to verify the results. We found out that autophagy (namely mitophagy) is an important resistance mechanism. The major ROS producing mitochondria were coated by an autophagic membrane derived from endoplasmic reticulum and degraded. According to our results, increasing ROS resistance may be also accompanied by increased average cell size and polyploidization, which seems to be key resistance mechanism when connected with an escape from senescence. Many different types of cell-cell interactions were recorded including entosis, vesicular transfer, eating of dead or dying cells, and engulfment and cannibalism of living cells. Entosis was disclosed as a possible mechanism of polyploidization and enabled the long-term survival of cancer cells. Significantly reduced cell motility was found after the plumbagin treatment. We also found an extensive induction of pluripotency genes expression (NANOG, SOX2, and POU5F1) at the time-point of 20 hours. We suppose, that overexpression of pluripotency genes in the portion of prostate tumour cell population exposed to ROS leads to higher developmental plasticity and capability to faster respond to changes in the extracellular environment that could ultimately lead to an alteration of cell fate. PMID:26671576

  9. Curcumin prevents inflammatory response, oxidative stress and insulin resistance in high fructose fed male Wistar rats: Potential role of serine kinases.

    PubMed

    Maithilikarpagaselvi, Nachimuthu; Sridhar, Magadi Gopalakrishna; Swaminathan, Rathinam Palamalai; Zachariah, Bobby

    2016-01-25

    Emerging evidence suggests that high fructose consumption may be a potentially important factor responsible for the rising incidence of insulin resistance and diabetes worldwide. The present study investigated the preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high fructose fed male Wistar rats at the molecular level. Fructose feeding for 10 weeks caused oxidative stress, inflammation and insulin resistance. Curcumin treatment attenuated the insulin resistance by decreasing IRS-1 serine phosphorylation and increasing IRS-1 tyrosine phosphorylation in the skeletal muscle of high fructose fed rats. It also attenuated hyperinsulinemia, glucose intolerance and HOMA-IR level. Curcumin administration lowered tumor necrosis factor alpha (TNF-α), C reactive protein (CRP) levels and downregulated the protein expression of cyclo-oxygenase 2 (COX-2), protein kinase theta (PKCθ). In addition, inhibitor κB alpha (IκBα) degradation was prevented by curcumin supplementation. Treatment with curcumin inhibited the rise of malondialdehyde (MDA), total oxidant status (TOS) and suppressed the protein expression of extracellular kinase ½ (ERK ½), p38 in the skeletal muscle of fructose fed rats. Further, it enhanced Glutathione Peroxidase (GPx) activity in the muscle of fructose fed rats. At the molecular level, curcumin inhibited the activation of stress sensitive kinases and inflammatory cascades. Our findings conclude that curcumin attenuated glucose intolerance and insulin resistance through its antioxidant and anti-inflammatory effects. Thus, we suggest the use of curcumin as a therapeutic adjuvant in the management of diabetes, obesity and their associated complications. PMID:26713546

  10. Contribution of the stereospecific methionine sulphoxide reductases MsrA and MsrB to oxidative and nitrosative stress resistance in the food-borne pathogen Campylobacter jejuni.

    PubMed

    Atack, John M; Kelly, David J

    2008-08-01

    The microaerophilic food-borne pathogen Campylobacter jejuni is exposed to highly variable oxygen concentrations during its life cycle and employs a variety of protection mechanisms to resist oxidative stress. However, not all of the enzymes that mediate such protection have yet been identified. Two genes in strain NCTC 11168, Cj0637c and Cj1112c, are predicted to encode unrelated methionine sulphoxide reductases, which may repair oxidized methionine residues in proteins and thus contribute to oxidative stress defence. Cj0637 and Cj1112 were overexpressed, purified and shown by a coupled thioredoxin-thioredoxin reductase-NADPH assay to catalyse the stereospecific reduction of the S and R diastereoisomers, respectively, of the model compound methyl p-tolyl sulphoxide. Cj0637 is thus identified as MsrA and Cj1112 as MsrB. The contribution of these enzymes to oxidative and nitrosative stress resistance in C. jejuni was assessed by phenotypic analysis of a set of isogenic msrA, msrB and msrA/B insertion mutants. As RT-PCR data suggested a polar effect on Cj1111c in the msrB mutant, an msrB/msrB(+) merodiploid complementation strain was also constructed. The msrA/B strain was severely growth inhibited under standard microaerobic conditions, whereas the msrA and msrB strains grew normally. Agar plate disc diffusion assays showed that all mutants displayed increased sensitivity to hydrogen peroxide, organic peroxide, superoxide, and nitrosative and disulphide stress, but quantitative cell viability assays showed that the msrA/B double mutant was markedly more sensitive to both oxidative and nitrosative stress. All of the stress-sensitivity phenotypes observed for the msrB mutant were restored to wild-type in the msrB/msrB(+) merodiploid. It is concluded that MsrA and MsrB make a significant contribution to the protection of C. jejuni against oxidative and nitrosative stress. PMID:18667555

  11. Oxidation Resistant Graphite Studies

    SciTech Connect

    W. Windes; R. Smith

    2014-07-01

    The Very High Temperature Reactor (VHTR) Graphite Research and Development Program is investigating doped nuclear graphite grades exhibiting oxidation resistance. During a oxygen ingress accident the oxidation rates of the high temperature graphite core region would be extremely high resulting in significant structural damage to the core. Reducing the oxidation rate of the graphite core material would reduce the structural effects and keep the core integrity intact during any air-ingress accident. Oxidation testing of graphite doped with oxidation resistant material is being conducted to determine the extent of oxidation rate reduction. Nuclear grade graphite doped with varying levels of Boron-Carbide (B4C) was oxidized in air at nominal 740°C at 10/90% (air/He) and 100% air. The oxidation rates of the boronated and unboronated graphite grade were compared. With increasing boron-carbide content (up to 6 vol%) the oxidation rate was observed to have a 20 fold reduction from unboronated graphite. Visual inspection and uniformity of oxidation across the surface of the specimens were conducted. Future work to determine the remaining mechanical strength as well as graphite grades with SiC doped material are discussed.

  12. Staphylococcal response to oxidative stress

    PubMed Central

    Gaupp, Rosmarie; Ledala, Nagender; Somerville, Greg A.

    2012-01-01

    Staphylococci are a versatile genus of bacteria that are capable of causing acute and chronic infections in diverse host species. The success of staphylococci as pathogens is due in part to their ability to mitigate endogenous and exogenous oxidative and nitrosative stress. Endogenous oxidative stress is a consequence of life in an aerobic environment; whereas, exogenous oxidative and nitrosative stress are often due to the bacteria's interaction with host immune systems. To overcome the deleterious effects of oxidative and nitrosative stress, staphylococci have evolved protection, detoxification, and repair mechanisms that are controlled by a network of regulators. In this review, we summarize the cellular targets of oxidative stress, the mechanisms by which staphylococci sense oxidative stress and damage, oxidative stress protection and repair mechanisms, and regulation of the oxidative stress response. When possible, special attention is given to how the oxidative stress defense mechanisms help staphylococci control oxidative stress in the host. PMID:22919625

  13. The catalytic subunit of DNA-dependent protein kinase is required for cellular resistance to oxidative stress independent of DNA double strand break repair

    PubMed Central

    Li, Mengxia; Lin, Yu-Fen; Palchik, Guillermo; Matsunaga, Shinji; Wang, Dong; Chen, Benjamin P.C.

    2014-01-01

    DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Ataxia telangiectasia mutated (ATM) are the two major kinases involved in DNA double-strand break (DSB) repair, and are required for cellular resistance to ionizing radiation. While ATM is the key upstream kinase for DSB signaling, DNA-PKcs is primarily involved in DSB repair through the non-homologous end-joining (NHEJ) mechanism. In addition to DSB repair, ATM has been shown to be involved in oxidative stress response and could be activated directly in vitro upon hydrogen peroxide (H2O2) treatment. However, the role of DNA-PKcs in cellular response to oxidative stress is not clear. We hypothesize that DNA-PKcs may participate in the regulation of ATM activation in response to oxidative stress, and that this regulatory role is independent of its role in DNA double strand break repair. Our findings reveal that H2O2 induces hyperactivation of ATM signaling in DNA-PKcs deficient, but not Ligase 4 deficient cells, suggesting an NHEJ-independent role for DNA-PKcs. Furthermore, DNA-PKcs deficiency leads to the elevation of reactive oxygen species (ROS) production, and to a decrease in cellular survival against H2O2. For the first time, our results reveal that DNA-PKcs plays a non-canonical role in the cellular response to oxidative stress, which is independent from its role in NHEJ. In addition, DNA-PKcs is a critical regulator of the oxidative stress response and contributes to the maintenance of redox homeostasis. Our findings reveal that DNA-PKcs is required for cellular resistance to oxidative stress and suppression of ROS build-up independently to its function in DSB repair. PMID:25224041

  14. Oxidative stress contributes to the tamoxifen-induced killing of breast cancer cells: implications for tamoxifen therapy and resistance

    PubMed Central

    Bekele, Raie T.; Venkatraman, Ganesh; Liu, Rong-Zong; Tang, Xiaoyun; Mi, Si; Benesch, Matthew G. K.; Mackey, John R.; Godbout, Roseline; Curtis, Jonathan M.; McMullen, Todd P. W.; Brindley, David N.

    2016-01-01

    Tamoxifen is the accepted therapy for patients with estrogen receptor-α (ERα)-positive breast cancer. However, clinical resistance to tamoxifen, as demonstrated by recurrence or progression on therapy, is frequent and precedes death from metastases. To improve breast cancer treatment it is vital to understand the mechanisms that result in tamoxifen resistance. This study shows that concentrations of tamoxifen and its metabolites, which accumulate in tumors of patients, killed both ERα-positive and ERα-negative breast cancer cells. This depended on oxidative damage and anti-oxidants rescued the cancer cells from tamoxifen-induced apoptosis. Breast cancer cells responded to tamoxifen-induced oxidation by increasing Nrf2 expression and subsequent activation of the anti-oxidant response element (ARE). This increased the transcription of anti-oxidant genes and multidrug resistance transporters. As a result, breast cancer cells are able to destroy or export toxic oxidation products leading to increased survival from tamoxifen-induced oxidative damage. These responses in cancer cells also occur in breast tumors of tamoxifen-treated mice. Additionally, high levels of expression of Nrf2, ABCC1, ABCC3 plus NAD(P)H dehydrogenase quinone-1 in breast tumors of patients at the time of diagnosis were prognostic of poor survival after tamoxifen therapy. Therefore, overcoming tamoxifen-induced activation of the ARE could increase the efficacy of tamoxifen in treating breast cancer. PMID:26883574

  15. Oxidation resistance of silicon ceramics

    NASA Technical Reports Server (NTRS)

    Yasutoshi, H.; Hirota, K.

    1984-01-01

    Oxidation resistance, and examples of oxidation of SiC, Si3N4 and sialon are reviewed. A description is given of the oxidation mechanism, including the oxidation product, oxidation reaction and the bubble size. The oxidation reactions are represented graphically. An assessment is made of the oxidation process, and an oxidation example of silicon ceramics is given.

  16. The effect of hyperthermia on liver histology, oxidative stress and disease resistance of the Wuchang bream, Megalobrama amblycephala.

    PubMed

    Liu, Bo; Xu, Pao; Brown, Paul B; Xie, Jun; Ge, Xianping; Miao, Linghong; Zhou, Qunlan; Ren, Mingchun; Pan, Liangkun

    2016-05-01

    This study aimed to investigate the effects of hyperthermia on serum hormones, hepatic oxidization indices, hepatic heat shock protein (HSP60, 70, and 90) mRNA expression levels and liver cell ultrastructure in Megalobrama amblycephala before and after high temperature stress. Fish were exposed to the optimal temperature (25 ± 1 °C) or high temperature (32 ± 1 °C) and then challenged with Aeromonas hydrophila. The results showed that hyperthermic stress significantly increased serum adrenocorticotropic hormone (ACTH) at 0.5 and 2 d, serum cortisol (COR) at 0.5, 14, and 21 d and serum 3,5,3'-triiodothyronine (T3) at 1, 14, and 21 d after stress. Additionally, hyperthermia led to oxidative stress, as evidenced by a significant decrease in the hepatic anti-superoxide anion free radical concentration (ASAFER) at 1, 2, 7, and 21 d and in hepatic superoxide dismutase (SOD) activity at 1, 2, 14 and 21 d after stress; however, hepatic malondialdehyde content (MDA) increased at 1, 2, and 7 d after stress. Moreover, the expression of HSP60 at 1 d, HSP70 at 1 and 2 d, and HSP90 at 0.25, 0.5, 1 and 2 d after stress was higher in the stress group compared with the control group. The histological results clearly showed that hyperthermia resulted in fat and glycogen accumulation and structural alterations of the hepatocytes, mitochondria, and nuclei. The cumulative mortality increased in the high temperature stress group at 1 d after acute stress and at 2 and 7 d after chronic stress compared with the control group. Overall, 1 d or 2 d after hyperthermia stress damaged the hepatic ultrastructure and impaired mitochondrial bioenergetics. Dysfunction of the mitochondria subsequently mediated oxidative stress and improved HSP expression modulated the cellular anti-stress response, which in turn led to reduced efficacy of the immune system and increased mortality from Aeromonas hydrophila infection in Megalobrama amblycephala. PMID:27016402

  17. PerR Controls Oxidative Stress Resistance and Iron Storage Proteins and Is Required for Virulence in Staphylococcus aureus

    PubMed Central

    Horsburgh, Malcolm J.; Clements, Mark O.; Crossley, Howard; Ingham, Eileen; Foster, Simon J.

    2001-01-01

    The Staphylococcus aureus genome encodes three ferric uptake regulator (Fur) homologues: Fur, PerR, and Zur. To determine the exact role of PerR, we inactivated the gene by allelic replacement using a kanamycin cassette, creating strain MJH001 (perR). PerR was found to control transcription of the genes encoding the oxidative stress resistance proteins catalase (KatA), alkyl hydroperoxide reductase (AhpCF), bacterioferritin comigratory protein (Bcp), and thioredoxin reductase (TrxB). Furthermore, PerR regulates transcription of the genes encoding the iron storage proteins ferritin (Ftn) and the ferritin-like Dps homologue, MrgA. Transcription of perR was autoregulated, and PerR repressed transcription of the iron homeostasis regulator Fur, which is a positive regulator of catalase expression. PerR functions as a manganese-dependent, transcriptional repressor of the identified regulon. Elevated iron concentrations produced induction of the PerR regulon. PerR may act as a peroxide sensor, since addition of external hydrogen peroxide to 8325-4 (wild type) resulted in increased transcription of most of the PerR regulon, except for fur and perR itself. The PerR-regulated katA gene encodes the sole catalase of S. aureus, which is an important starvation survival determinant but is surprisingly not required for pathogenicity in a murine skin abscess model of infection. In contrast, PerR is not necessary for starvation survival but is required for full virulence (P < 0.005) in this model of infection. PerR of S. aureus may act as a redox sentinel protein during infection, analogous to the in vitro activities of OxyR and PerR of Escherichia coli and Bacillus subtilis, respectively. However, it differs in its response to the metal balance within the cell and has the added capability of regulating iron uptake and storage. PMID:11349039

  18. Oxidative stress in autism.

    PubMed

    Chauhan, Abha; Chauhan, Ved

    2006-08-01

    Autism is a severe developmental disorder with poorly understood etiology. Oxidative stress in autism has been studied at the membrane level and also by measuring products of lipid peroxidation, detoxifying agents (such as glutathione), and antioxidants involved in the defense system against reactive oxygen species (ROS). Lipid peroxidation markers are elevated in autism, indicating that oxidative stress is increased in this disease. Levels of major antioxidant serum proteins, namely transferrin (iron-binding protein) and ceruloplasmin (copper-binding protein), are decreased in children with autism. There is a positive correlation between reduced levels of these proteins and loss of previously acquired language skills in children with autism. The alterations in ceruloplasmin and transferrin levels may lead to abnormal iron and copper metabolism in autism. The membrane phospholipids, the prime target of ROS, are also altered in autism. The levels of phosphatidylethanolamine (PE) are decreased, and phosphatidylserine (PS) levels are increased in the erythrocyte membrane of children with autism as compared to their unaffected siblings. Several studies have suggested alterations in the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase in autism. Additionally, altered glutathione levels and homocysteine/methionine metabolism, increased inflammation, excitotoxicity, as well as mitochondrial and immune dysfunction have been suggested in autism. Furthermore, environmental and genetic factors may increase vulnerability to oxidative stress in autism. Taken together, these studies suggest increased oxidative stress in autism that may contribute to the development of this disease. A mechanism linking oxidative stress with membrane lipid abnormalities, inflammation, aberrant immune response, impaired energy metabolism and excitotoxicity, leading to clinical symptoms and pathogenesis of autism is proposed. PMID:16766163

  19. Effect of S-Methyl-L-Cysteine on Oxidative Stress, Inflammation and Insulin Resistance in Male Wistar Rats Fed with High Fructose Diet

    PubMed Central

    Thomas, Sithara; Senthilkumar, Gandhipuram Periyasamy; Sivaraman, Kuppuswamy; Bobby, Zachariah; Paneerselvam, Sankar; Harichandrakumar, Kotten Thazhath

    2015-01-01

    Background S-methyl cysteine (SMC) is a hydrophilic cysteine-containing compound naturally found in garlic and onion. The purpose of the present study was to investigate the protective effect of SMC on oxidative stress, inflammation and insulin resistance in an experiment of metabolic syndrome. Methods Male Wistar rats were divided into five groups (6 rats in each group), namely; control, control+S-methyl cysteine (SMC), high fructose diet (HFD), HFD+SMC and HFD+metformin. The 60% fructose used for 8 weeks and SMC in the dose of 100 mg/kg bw/day/rat was used in the study. The fasting glucose, insulin, insulin resistance, and tumor necrosis factor alpha and erythrocyte enzymatic antioxidants were measured. Results Increased levels of plasma glucose, insulin, malondialdehyde, tumor necrosis factor-alpha, and insulin resistance and decreased levels of glutathione, glutathione peroxidase, and catalase were found in rats on a high fructose diet. Oral administration of SMC (100 mg/kg bw/day/rat) for 60 days resulted in significant attenuation of plasma glucose, insulin, tumor necrosis factor–alpha, insulin resistance and improved antioxidant enzyme activities. Conclusion Oral treatment of SMC is effective in improving insulin resistance while attenuating metabolic syndrome, inflammation, and oxidative stress in male rats fed with fructose rich diet. PMID:25650289

  20. Amelioration of oxidative stress and insulin resistance by soy isoflavones (from Glycine max) in ovariectomized Wistar rats fed with high fat diet: the molecular mechanisms.

    PubMed

    Sankar, P; Zachariah, Bobby; Vickneshwaran, V; Jacob, Sajini Elizabeth; Sridhar, M G

    2015-03-01

    Estrogen deficiency after menopause accelerates the redox imbalance and insulin signaling, leading to oxidative stress (OS) and insulin resistance (IR). The molecular mechanisms by which the loss of ovarian hormone leads to OS and IR remain unclear. In the present study we found that rats when subjected to ovariectomy (OVX) resulted in reduction of whole blood antioxidants and elevation of oxidant markers. The expression of anti-oxidant enzymes, superoxide dismutase (SOD1) and glutathione peroxidase (GPX1) was suppressed whereas the pro-oxidative enzyme NADPH oxidase (NOX4) and mitogen activated protein (MAP) kinases ERK 1/2 and p38 were increased at different tissues. Treatment with soy (SIF, 150 mg/kg BW for 12 weeks) extract markedly reversed these metabolic changes and improved OS. Ovariectomized rats also displayed glucose intolerance (GI) and IR as evident from the impaired glucose tolerance test, and reduced expression of adipose and hepatic insulin receptor beta (IRβ) and adipose tissue GLUT4. Treatment with SIF reversed the ovariectomy induced GI and IR. On the other hand, all these metabolic changes were further augmented when ovariectomy was followed by a high fat diet, and these changes were also reversed by SIF. Taken together, these findings emphasized the antioxidant property and anti-diabetic effects of soy isoflavones suggesting the use of this natural phytoestrogen as a strategy for relieving oxidative stress and insulin resistance in postmenopausal women. PMID:25660477

  1. Hypoxia, Oxidative Stress and Fat.

    PubMed

    Netzer, Nikolaus; Gatterer, Hannes; Faulhaber, Martin; Burtscher, Martin; Pramsohler, Stephan; Pesta, Dominik

    2015-01-01

    Metabolic disturbances in white adipose tissue in obese individuals contribute to the pathogenesis of insulin resistance and the development of type 2 diabetes mellitus. Impaired insulin action in adipocytes is associated with elevated lipolysis and increased free fatty acids leading to ectopic fat deposition in liver and skeletal muscle. Chronic adipose tissue hypoxia has been suggested to be part of pathomechanisms causing dysfunction of adipocytes. Hypoxia can provoke oxidative stress in human and animal adipocytes and reduce the production of beneficial adipokines, such as adiponectin. However, time-dose responses to hypoxia relativize the effects of hypoxic stress. Long-term exposure of fat cells to hypoxia can lead to the production of beneficial substances such as leptin. Knowledge of time-dose responses of hypoxia on white adipose tissue and the time course of generation of oxidative stress in adipocytes is still scarce. This paper reviews the potential links between adipose tissue hypoxia, oxidative stress, mitochondrial dysfunction, and low-grade inflammation caused by adipocyte hypertrophy, macrophage infiltration and production of inflammatory mediators. PMID:26061760

  2. Oxidative Stress and Psychological Disorders

    PubMed Central

    Salim, Samina

    2014-01-01

    Oxidative stress is an imbalance between cellular production of reactive oxygen species and the counteracting antioxidant mechanisms. The brain with its high oxygen consumption and a lipid-rich environment is considered highly susceptible to oxidative stress or redox imbalances. Therefore, the fact that oxidative stress is implicated in several mental disorders including depression, anxiety disorders, schizophrenia and bipolar disorder, is not surprising. Although several elegant studies have established a link between oxidative stress and psychiatric disorders, the causal relationship between oxidative stress and psychiatric diseases is not fully determined. Another critical aspect that needs much attention and effort is our understanding of the association between cellular oxidative stress and emotional stress. This review examines some of the recent discoveries that link oxidative status with anxiety, depression, schizophrenia and bipolar disorder. A discussion of published results and questions that currently exist in the field regarding a causal relationship between oxidative and emotional stress is also provided. PMID:24669208

  3. Pyrroloquinoline quinone enhances the resistance to oxidative stress and extends lifespan upon DAF-16 and SKN-1 activities in C. elegans.

    PubMed

    Wu, J Z; Huang, J H; Khanabdali, R; Kalionis, B; Xia, S J; Cai, W J

    2016-07-01

    Pyrroloquinoline quinone (PQQ) is linked to fundamental biological processes such as mitochondrial biogenesis and lipid metabolism. PQQ may also function as an essential micronutrient during animal development. Recent studies have shown the therapeutic potential of PQQ for several age-related diseases due to its antioxidant capacity. However, whether PQQ can promote longevity is unknown. Here, we investigate the effects of PQQ on oxidative stress resistance as well as lifespan modulation in Caenorhabditis elegans. We find that PQQ enhances resistance to oxidative stress and extends the lifespan of C. elegans at optimal doses. The underlying molecular mechanism involves the increased activities of the primary lifespan extension transcriptional factors DAF-16/FOXO, the conserved oxidative stress-responsive transcription factor SKN-1/Nrf2, and upregulation of daf-16, skn-1 downstream targets including sod-3, hsp16.2, gst-1 and gst-10. Our findings uncover a novel role of PQQ in longevity, supporting PQQ as a possible dietary supplement for overall health improvement. PMID:27090484

  4. Cutaneous oxidative stress.

    PubMed

    Polefka, Thomas G; Meyer, Thomas A; Agin, Patricia P; Bianchini, Robert J

    2012-03-01

    The earliest known microfossil records suggest that microorganisms existed on the earth approximately 3.8 billion years ago. Not only did sunlight drive this evolutionary process, but it also allowed photosynthetic organisms to elaborate oxygen and fundamentally change the earth's atmosphere and subsequent evolution. Paradoxically, however, an atmosphere of 20% oxygen offers aerobic organisms both benefits and some key challenges, particularly, to the external integument. This mini-review summarizes almost 40 years of research and provides a "60 000-foot" perspective on cutaneous oxidative stress. Topics reviewed include the following: What are free radicals and reactive oxygen species? Where do they come from? What is their chemistry? What are their roles and/or impact on the skin? What antioxidant defenses are available to mitigate oxidative stress. PMID:22360336

  5. A wheat lipid transfer protein 3 could enhance the basal thermotolerance and oxidative stress resistance of Arabidopsis.

    PubMed

    Wang, Fei; Zang, Xin-shan; Kabir, Muhammad Rezaul; Liu, Ke-lu; Liu, Zhen-shan; Ni, Zhong-fu; Yao, Ying-yin; Hu, Zhao-rong; Sun, Qi-xin; Peng, Hui-ru

    2014-10-15

    Wheat (Triticum aestivum L.) is one of the major grain crops, and heat stress adversely affects wheat production in many regions of the world. Previously, we found a heat-responsive gene named Lipid Transfer Protein 3 (TaLTP3) in wheat. TaLTP3 was deduced to be regulated by cold, ABA, MeJA, Auxin and oxidative stress according to cis-acting motifs in its promoter sequences. In this study, we show that TaLTP3 is responsive to prolonged water deficit, salt or ABA treatment in wheat seedlings. Also, TaLTP3 accumulation was observed after the plant suffered from heat stress both at the seedling and the grain-filling stages. TaLTP3 protein was localized in the cell membrane and cytoplasm of tobacco epidermal cells. Overexpression of TaLTP3 in yeast imparted tolerance to heat stress compared to cells expressing the vector alone. Most importantly, transgenic Arabidopsis plants engineered to overexpress TaLTP3 showed higher thermotolerance than control plants at the seedling stage. Further investigation indicated that transgenic lines decreased H₂O₂ accumulation and membrane injury under heat stress. Taken together, our results demonstrate that TaLTP3 confers heat stress tolerance possibly through reactive oxygen species (ROS) scavenging. PMID:25106859

  6. Oxidative Stress in Malaria

    PubMed Central

    Percário, Sandro; Moreira, Danilo R.; Gomes, Bruno A. Q.; Ferreira, Michelli E. S.; Gonçalves, Ana Carolina M.; Laurindo, Paula S. O. C.; Vilhena, Thyago C.; Dolabela, Maria F.; Green, Michael D.

    2012-01-01

    Malaria is a significant public health problem in more than 100 countries and causes an estimated 200 million new infections every year. Despite the significant effort to eradicate this dangerous disease, lack of complete knowledge of its physiopathology compromises the success in this enterprise. In this paper we review oxidative stress mechanisms involved in the disease and discuss the potential benefits of antioxidant supplementation as an adjuvant antimalarial strategy. PMID:23208374

  7. Oxidative Stress in Myopia

    PubMed Central

    Francisco, Bosch-Morell; Salvador, Mérida; Amparo, Navea

    2015-01-01

    Myopia affected approximately 1.6 billion people worldwide in 2000, and it is expected to increase to 2.5 billion by 2020. Although optical problems can be corrected by optics or surgical procedures, normal myopia and high myopia are still an unsolved medical problem. They frequently predispose people who have them to suffer from other eye pathologies: retinal detachment, glaucoma, macular hemorrhage, cataracts, and so on being one of the main causes of visual deterioration and blindness. Genetic and environmental factors have been associated with myopia. Nevertheless, lack of knowledge in the underlying physiopathological molecular mechanisms has not permitted an adequate diagnosis, prevention, or treatment to be found. Nowadays several pieces of evidence indicate that oxidative stress may help explain the altered regulatory pathways in myopia and the appearance of associated eye diseases. On the one hand, oxidative damage associated with hypoxia myopic can alter the neuromodulation that nitric oxide and dopamine have in eye growth. On the other hand, radical superoxide or peroxynitrite production damage retina, vitreous, lens, and so on contributing to the appearance of retinopathies, retinal detachment, cataracts and so on. The objective of this review is to suggest that oxidative stress is one of the key pieces that can help solve this complex eye problem. PMID:25922643

  8. EmrA1 Membrane Fusion Protein of Francisella tularensis LVS is required for Resistance to Oxidative Stress, Intramacrophage Survival and Virulence in Mice

    PubMed Central

    Ma, Zhuo; Banik, Sukalyani; Rane, Harshita; Mora, Vanessa T.; Rabadi, Seham M.; Doyle, Christopher R.; Thanassi, David G.; Bakshi, Chandra Shekhar; Malik, Meenakshi

    2014-01-01

    Francisella tularensis is a Category A Biodefense agent that causes a fatal human disease known as tularemia. The pathogenicity of F. tularensis depends on its ability to persist inside host immune cells primarily by resisting an attack from host-generated reactive oxygen and nitrogen species (ROS/RNS). Based on the ability of F. tularensis to resist high ROS/RNS levels, we have hypothesized that additional unknown factors act in conjunction with known antioxidant defenses to render ROS resistance. By screening a transposon insertion library of F. tularensis LVS in the presence of hydrogen peroxide, we have identified an oxidant sensitive mutant in putative EmrA1 (FTL_0687) secretion protein. The results demonstrate that the emrA1 mutant is highly sensitive to oxidants and several antimicrobial agents, and exhibits diminished intramacrophage growth that can be restored to wild type F. tularensis LVS levels either by transcomplementation, inhibition of ROS generation, or infection in NADPH oxidase deficient (gp91Phox−/−) macrophages. The emrA1 mutant is attenuated for virulence, which is restored by infection in gp91Phox−/− mice. Further, EmrA1 contributes to oxidative stress resistance by affecting secretion of Francisella antioxidant enzymes SodB and KatG. This study exposes unique links between transporter activity and the antioxidant defense mechanisms of F. tularensis. PMID:24397487

  9. A eukaryotic-type signalling system of Pseudomonas aeruginosa contributes to oxidative stress resistance, intracellular survival and virulence

    PubMed Central

    2011-01-01

    Background The genome of Pseudomonas aeruginosa contains at least three genes encoding eukaryotic-type Ser/Thr protein kinases, one of which, ppkA, has been implicated in P. aeruginosa virulence. Together with the adjacent pppA phosphatase gene, they belong to the type VI secretion system (H1-T6SS) locus, which is important for bacterial pathogenesis. To determine the biological function of this protein pair, we prepared a pppA-ppkA double mutant and characterised its phenotype and transcriptomic profiles. Results Phenotypic studies revealed that the mutant grew slower than the wild-type strain in minimal media and exhibited reduced secretion of pyoverdine. In addition, the mutant had altered sensitivity to oxidative and hyperosmotic stress conditions. Consequently, mutant cells had an impaired ability to survive in murine macrophages and an attenuated virulence in the plant model of infection. Whole-genome transcriptome analysis revealed that pppA-ppkA deletion affects the expression of oxidative stress-responsive genes, stationary phase σ-factor RpoS-regulated genes, and quorum-sensing regulons. The transcriptome of the pppA-ppkA mutant was also analysed under conditions of oxidative stress and showed an impaired response to the stress, manifested by a weaker induction of stress adaptation genes as well as the genes of the SOS regulon. In addition, expression of either RpoS-regulated genes or quorum-sensing-dependent genes was also affected. Complementation analysis confirmed that the transcription levels of the differentially expressed genes were specifically restored when the pppA and ppkA genes were expressed ectopically. Conclusions Our results suggest that in addition to its crucial role in controlling the activity of P. aeruginosa H1-T6SS at the post-translational level, the PppA-PpkA pair also affects the transcription of stress-responsive genes. Based on these data, it is likely that the reduced virulence of the mutant strain results from an impaired

  10. Yeast thioredoxin peroxidase expression enhances the resistance of Escherichia coli to oxidative stress induced by singlet oxygen.

    PubMed

    Kim, Sun Yee; Kim, Eun Ju; Park, Jeen-Woo

    2002-01-01

    Singlet oxygen ((1)O(2)) is a highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules. A soluble protein from Saccharomyces cerevisiae specifically provides protection against a thiol-containing metal-catalyzed oxidation system (thiol/Fe(3+)/O(2)) but not against an oxidation system without thiol. This 25 kDa protein acts as a peroxidase but requires the NADPH-dependent thioredoxin system or a thiol-containing intermediate, and was named thioredoxin peroxidase (TPx). The role of TPx in the cellular defense against oxidative stress induced by singlet oxygen was investigated in Escherichia coli containing an expression vector with a yeast genomic DNA fragment that encodes TPx and mutant in which the catalytically essential amino acid cysteine (Cys-47) has been replaced with alanine by a site-directed mutagenesis. Upon exposure to methylene blue and visible light, which generates singlet oxygen, there was a distinct difference between the two strains in regard to growth kinetics, viability, the accumulation of oxidized proteins and lipids, and modulation of activities of superoxide dismutase and catalase. The results suggest that TPx may play an important protective role in a singlet oxygen-mediated cellular damage. PMID:12189053

  11. The bcp gene in the bcp-recA-vimA-vimE-vimF operon is important in oxidative stress resistance in Porphyromonas gingivalis W83.

    PubMed

    Johnson, N A; McKenzie, R M E; Fletcher, H M

    2011-02-01

    The ability of Porphyromonas gingivalis to overcome oxidative stress in the inflammatory environment of the periodontal pocket is critical for its survival. We have previously demonstrated that the recA locus, which carries the bacterioferritin co-migratory protein (bcp) gene and has a unique genetic architecture, plays a role in virulence regulation and oxidative stress resistance in P. gingivalis. To further characterize the bcp gene, which was confirmed to be part of the bcp-recA-vimA-vimE-vimF operon, we created a P. gingivalis bcp-defective isogenic mutant (FLL302) by allelic exchange. Compared with the wild-type, FLL302 had a similar growth rate, black pigmentation, β-hemolysis and UV sensitivity. Although there was no change in the distribution of gingipain activity, there was a 30% reduction in both Arg-X and Lys-X activities in the mutant strain compared with the wild-type. When exposed to 0.25 mm hydrogen peroxide, P. gingivalis FLL302 was more sensitive than the wild-type. In addition, the cloned P. gingivalis bcp gene increased resistance to 0.25 mm hydrogen peroxide in a bcp-defective Escherichia coli mutant. The mutant also demonstrated decreased aerotolerance when compared with the wild-type. Porphyromonas gingivalis FLL302 and the wild-type strain had similar virulence profiles in a mouse model of virulence. These observations suggest that the bcp gene may play a role in oxidative stress resistance but has a decreased functional significance in the pathogenic potential of P. gingivalis. PMID:21214873

  12. The Involvement of Glutamate Metabolism in the Resistance to Thermal, Nutritional, and Oxidative Stress in Trypanosoma cruzi

    PubMed Central

    Magdaleno, Anahí; Suárez Mantilla, Brian; Rocha, Sandra C.; Pral, Elizabeth M. F.; Silber, Ariel M.

    2011-01-01

    The inhibition of some glutamate metabolic pathways could lead to diminished parasite survival. In this study, the effects of L-methionine sulfoximine (MS), DL-methionine sulfone (MSO), and DL-methionine sulfoxide (MSE), three glutamate analogs, on several biological processes were evaluated. We found that these analogs inhibited the growth of epimastigotes cells and showed a synergistic effect with stress conditions such as temperature, nutritional starvation, and oxidative stress. The specific activity for the reductive amination of α-ketoglutaric acid, catalyzed by the NADP+-linked glutamate dehydrogenase, showed an increase in the NADP+ levels, when MS, MSE, and MSO were added. It suggests an eventual conversion of the compounds tested by the T. cruzi cells. The fact that trypomastigote bursting was not significantly inhibited when infected cells were treated with these compounds, remarks the existence of relevant metabolic differences among the different life-cycle stages. It must be considered when proposing a new therapeutic drug. PMID:21629861

  13. Influence of Insulin Resistance and TNF-α on the Inflammatory Process, Oxidative Stress, and Disease Activity in Patients with Rheumatoid Arthritis

    PubMed Central

    Delongui, Francieli; Alfieri, Daniela Frizon; Lozovoy, Marcell Alysson Batisti; Amin, Ricardo Braga; Dichi, Isaias; Simão, Andréa Name Colado

    2016-01-01

    The aim of this study was to evaluate the involvement of TNF-α and insulin resistance (IR) in the inflammatory process, oxidative stress, and disease activity in patients with rheumatoid arthritis (RA). This cross-sectional study included 270 subjects (control group, n = 97) and RA patients (n = 173). RA patients were divided into four groups: the first group without IR and not using antitumor necrosis factor-α (TNF−) (G1, IR− TNF−); the second group without IR and using anti-TNF-α (G2, IR− TNF+); the third group with IR and not using anti-TNF-α (G3, IR+ TNF−); and the fourth group with IR and using anti-TNF-α (G4, IR+ TNF+). G3 and G4 had higher (p < 0.05) advanced oxidation protein products (AOPPs) and oxidative stress index (OSI) compared to G1. G4 group presented higher (p < 0.05) AOPPs and OSI than G2. TRAP was significantly lower in G3 compared to G1. Plasma TNF-α levels were significantly higher in G4 and G2 compared to G1 (p < 0.0001) and G3 (p < 0.0001 and p < 0.01, resp.). The presence of insulin resistance was robustly associated with both oxidative stress and TNF-α levels. More studies are warranted to verify if IR can be involved in therapeutic failure with TNF-α inhibitors. This trial is registered with Brazilian Clinical Trials Registry Register number RBR-2jvj92. PMID:27340510

  14. Plant-Adapted Escherichia coli Show Increased Lettuce Colonizing Ability, Resistance to Oxidative Stress and Chemotactic Response

    PubMed Central

    Dublan, Maria de los Angeles; Ortiz-Marquez, Juan Cesar Federico; Lett, Lina; Curatti, Leonardo

    2014-01-01

    Background Escherichia coli is a widespread gut commensal and often a versatile pathogen of public health concern. E. coli are also frequently found in different environments and/or alternative secondary hosts, such as plant tissues. The lifestyle of E. coli in plants is poorly understood and has potential implications for food safety. Methods/Principal Findings This work shows that a human commensal strain of E. coli K12 readily colonizes lettuce seedlings and produces large microcolony-like cell aggregates in leaves, especially in young leaves, in proximity to the vascular tissue. Our observations strongly suggest that those cell aggregates arise from multiplication of single bacterial cells that reach those spots. We showed that E. coli isolated from colonized leaves progressively colonize lettuce seedlings to higher titers, suggesting a fast adaptation process. E. coli cells isolated from leaves presented a dramatic rise in tolerance to oxidative stress and became more chemotactic responsive towards lettuce leaf extracts. Mutant strains impaired in their chemotactic response were less efficient lettuce colonizers than the chemotactic isogenic strain. However, acclimation to oxidative stress and/or minimal medium alone failed to prime E. coli cells for enhanced lettuce colonization efficiency. Conclusion/Significance These findings help to understand the physiological adaptation during the alternative lifestyle of E. coli in/on plant tissues. PMID:25313845

  15. Oxidative stress by inorganic nanoparticles.

    PubMed

    Tee, Jie Kai; Ong, Choon Nam; Bay, Boon Huat; Ho, Han Kiat; Leong, David Tai

    2016-05-01

    Metallic and metallic oxide nanoparticles (NPs) have been increasingly used for various bio-applications owing to their unique physiochemical properties in terms of conductivity, optical sensitivity, and reactivity. With the extensive usage of NPs, increased human exposure may cause oxidative stress and lead to undesirable health consequences. To date, various endogenous and exogenous sources of oxidants contributing to oxidative stress have been widely reported. Oxidative stress is generally defined as an imbalance between the production of oxidants and the activity of antioxidants, but it is often misrepresented as a single type of cellular stress. At the biological level, NPs can initiate oxidative stress directly or indirectly through various mechanisms, leading to profound effects ranging from the molecular to the disease level. Such effects of oxidative stress have been implicated owing to their small size and high biopersistence. On the other hand, cellular antioxidants help to counteract oxidative stress and protect the cells from further damage. While oxidative stress is commonly known to exert negative biological effects, measured and intentional use of NPs to induce oxidative stress may provide desirable effects to either stimulate cell growth or promote cell death. Hence, NP-induced oxidative stress can be viewed from a wide paradigm. Because oxidative stress is comprised of a wide array of factors, it is also important to use appropriate assays and methods to detect different pro-oxidant and antioxidant species at molecular and disease levels. WIREs Nanomed Nanobiotechnol 2016, 8:414-438. doi: 10.1002/wnan.1374 For further resources related to this article, please visit the WIREs website. PMID:26359790

  16. PGC1α Expression Defines a Subset of Human Melanoma Tumors with Increased Mitochondrial Capacity and Resistance to Oxidative Stress

    PubMed Central

    Vazquez, Francisca; Lim, Ji-Hong; Chim, Helen; Bhalla, Kavita; Girnun, Geoff; Pierce, Kerry; Clish, Clary B.; Granter, Scott R.; Widlund, Hans R.; Spiegelman, Bruce M.; Puigserver, Pere

    2013-01-01

    SUMMARY Cancer cells reprogram their metabolism using different strategies to meet energy and anabolic demands to maintain growth and survival. Understanding the molecular and genetic determinants of these metabolic programs is critical to successfully exploit them for therapy. Here, we report that the oncogenic melanocyte lineage-specification transcription factor MITF drives PGC1α (PPARGC1A) overexpression in a subset of human melanomas and derived cell lines. Functionally, PGC1α positive melanoma cells exhibit increased mitochondrial energy metabolism and ROS detoxification capacities that enables survival under oxidative stress conditions. Conversely, PGC1α negative melanoma cells are more glycolytic and sensitive to ROS-inducing drugs. These results demonstrate that differences in PGC1α levels in melanoma tumors have a profound impact in their metabolism, biology and drug sensitivity. PMID:23416000

  17. Evaluation of Oxidative Stress in Women with Polycystic Ovarian Syndrome as Represented by Serum Ischemia Modified Albumin and Its Correlation with Testosterone and Insulin Resistance.

    PubMed

    Beyazit, Fatma; Yilmaz, Nafiye; Balci, Osman; Adam, Magdi; Yaman, Selen Taflan

    2016-01-01

    Objective Ischemia-mediated oxidative stress and inflammation have been reported to be important contributors to the pathogenesis of polycystic ovary syndrome (PCOS). Ischemia-modified albumin (IMA) is a novel marker generated under ischemic and oxidative conditions and may reflect disease activity in distinct disease states. Therefore, we investigated whether the serum IMA levels are affected in infertile PCOS patients. Methods Forty-six patients with infertile PCOS, 30 patients with unexplained infertility, and 31 age- and body mass index (BMI)-matched controls were included in this cross-sectional study. Biochemical parameters, serum IMA levels, and their correlations with serum testosterone and insulin resistance were determined for each subject. Results In patients with infertile PCOS, the serum IMA levels were significantly elevated (p=0.003) compared with unexplained infertility patients and controls. A correlation analysis suggested that the IMA levels only correlated with the serum free testosterone levels in PCOS patients (r=0.43, p=0.028). Conclusion Elevations in the serum IMA levels in infertile PCOS patients may suggest a possible additional role of oxidative stress mechanisms in disease pathophysiology. Moreover, correlation between serum IMA and testosterone levels may influence the quality of oocytes via alterations in the balance of critical follicular fluid factors in the follicular microenvironment. PMID:27580534

  18. BRCA1 and Oxidative Stress

    PubMed Central

    Yi, Yong Weon; Kang, Hyo Jin; Bae, Insoo

    2014-01-01

    The breast cancer susceptibility gene 1 (BRCA1) has been well established as a tumor suppressor and functions primarily by maintaining genome integrity. Genome stability is compromised when cells are exposed to oxidative stress. Increasing evidence suggests that BRCA1 regulates oxidative stress and this may be another mechanism in preventing carcinogenesis in normal cells. Oxidative stress caused by reactive oxygen species (ROS) is implicated in carcinogenesis and is used strategically to treat human cancer. Thus, it is essential to understand the function of BRCA1 in oxidative stress regulation. In this review, we briefly summarize BRCA1’s many binding partners and mechanisms, and discuss data supporting the function of BRCA1 in oxidative stress regulation. Finally, we consider its significance in prevention and/or treatment of BRCA1-related cancers. PMID:24704793

  19. An Evaluation of Acylated Ghrelin and Obestatin Levels in Childhood Obesity and Their Association with Insulin Resistance, Metabolic Syndrome, and Oxidative Stress

    PubMed Central

    Razzaghy-Azar, Maryam; Nourbakhsh, Mitra; Pourmoteabed, Abdolreza; Nourbakhsh, Mona; Ilbeigi, Davod; Khosravi, Mohsen

    2016-01-01

    Background: Ghrelin is a 28-amino acid peptide with an orexigenic property, which is predominantly produced by the stomach. Acylated ghrelin is the active form of this hormone. Obestatin is a 23-amino acid peptide which is produced by post-translational modification of a protein precursor that also produces ghrelin. Obestatin has the opposite effect of ghrelin on food intake. The aim of this study was to evaluate acylated ghrelin and obestatin levels and their ratio in obese and normal-weight children and adolescents, and their association with metabolic syndrome (MetS) parameters. Methods: Serum acyl-ghrelin, obestatin, leptin, insulin, fasting plasma glucose (FPG), lipid profile, and malondialdehyde (MDA) were evaluated in 73 children and adolescents (42 obese and 31 control). Insulin resistance was calculated by a homeostasis model assessment of insulin resistance (HOMA-IR). MetS was determined according to IDF criteria. Results: Acyl-ghrelin levels were significantly lower in obese subjects compared to the control group and lower in obese children with MetS compared to obese subjects without MetS. Obestatin was significantly higher in obese subjects compared to that of the control, but it did not differ significantly among those with or without MetS. Acyl-ghrelin to obestatin ratio was significantly lower in obese subjects compared to that in normal subjects. Acyl-ghrelin showed significant negative and obestatin showed significant positive correlations with body mass index (BMI), BMI Z-score, leptin, insulin, and HOMA-IR. Acyl-ghrelin had a significant negative correlation with MDA as an index of oxidative stress. Conclusion: Ghrelin is decreased and obestatin is elevated in obesity. Both of these hormones are associated with insulin resistance, and ghrelin is associated with oxidative stress. The balance between ghrelin and obestatin seems to be disturbed in obesity. PMID:27348010

  20. Oxidative stress in Alzheimer disease

    PubMed Central

    Durany, Nuria

    2009-01-01

    Alzheimer disease (AD) is a progressive dementia affecting a large proportion of the aging population. The histopathological changes in AD include neuronal cell death, formation of amyloid plaques and neurofibrillary tangles. There is also evidence that brain tissue in patients with AD is exposed to oxidative stress (e.g., protein oxidation, lipid oxidation, DNA oxidation and glycoxidation) during the course of the disease. Advanced glycation endproducts (AGEs) are present in amyloid plaques in AD, and its extracellular accumulation may be caused by an accelerated oxidation of glycated proteins. AGEs participate in neuronal death causing direct (chemical) and indirect (cellular) free radical production and consequently increase oxidative stress. The development of drugs for the treatment of AD that breaks the vicious cycles of oxidative stress and neurodegeneration offer new opportunities. These approaches include AGE-inhibitors, antioxidants and anti-inflammatory substances, which prevent free radical production. PMID:19372765

  1. Oxidation resistant alloys, method for producing oxidation resistant alloys

    DOEpatents

    Dunning, John S.; Alman, David E.

    2002-11-05

    A method for producing oxidation-resistant austenitic alloys for use at temperatures below 800.degree. C. comprising of: providing an alloy comprising, by weight %: 14-18% chromium, 15-18% nickel, 1-3% manganese, 1-2% molybdenum, 2-4% silicon, 0% aluminum and the balance being iron; heating the alloy to 800.degree. C. for between 175-250 hours prior to use in order to form a continuous silicon oxide film and another oxide film. The method provides a means of producing stainless steels with superior oxidation resistance at temperatures above 700.degree. C. at a low cost

  2. Oxidation resistant alloys, method for producing oxidation resistant alloys

    DOEpatents

    Dunning, John S.; Alman, David E.

    2002-11-05

    A method for producing oxidation-resistant austenitic alloys for use at temperatures below 800 C. comprising of: providing an alloy comprising, by weight %: 14-18% chromium, 15-18% nickel, 1-3% manganese, 1-2% molybdenum, 2-4% silicon, 0% aluminum and the balance being iron; heating the alloy to 800 C. for between 175-250 hours prior to use in order to form a continuous silicon oxide film and another oxide film. The method provides a means of producing stainless steels with superior oxidation resistance at temperatures above 700 C. at a low cost

  3. MnSOD marks cord blood late outgrowth endothelial cells and accompanies robust resistance to oxidative stress

    SciTech Connect

    Cai Hao; Gehrig, Peter; Scott, Thomas M.; Zimmermann, Roland; Schlapbach, Ralph; Zisch, Andreas H. . E-mail: andreas.zisch@usz.ch

    2006-11-17

    Cord blood is source of colony-forming progenitors to vascular endothelial cells for potential use in cell therapies. These cells-called blood late outgrowth endothelial cells (OECs)-have undergone endothelial differentiation, but appear to still possess functional properties different from mature endothelial cells. A large-scale comparative proteomics screen of cord blood OECs versus human vein endothelial cells (HUVECs) using two-dimensional gel electrophoresis and mass spectrometry identified specific expression of manganese superoxide dismutase (MnSOD), a key antioxidant enzyme expressed in the mitochondria, in OECs but not in HUVECs. Immunoblotting verified significant MnSOD levels in all OEC isolates tested and maintained throughout passaging. Endothelial function and cell survival/proliferation assays in the presence of high cytotoxic doses of the superoxide generator compound LY83583 showed OECs profoundly better protected against oxidative stress than HUVECs. Such cytoprotective levels of MnSOD cells could give therapeutic cell transplants a survival advantage in necrotic or ischemic conditions.

  4. Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked: considerable variation in oxidative stress resistance exists among and within species and ...

  5. Overexpression of peptide-methionine sulfoxide reductase in Saccharomyces cerevisiae and human T cells provides them with high resistance to oxidative stress

    PubMed Central

    Moskovitz, Jackob; Flescher, Eliezer; Berlett, Barbara S.; Azare, Janeen; Poston, J. Michael; Stadtman, Earl R.

    1998-01-01

    The yeast peptide-methionine sulfoxide reductase (MsrA) was overexpressed in a Saccharomyces cerevisiae null mutant of msrA by using a high-copy plasmid harboring the msrA gene and its promoter. The resulting strain had about 25-fold higher MsrA activity than its parent strain. When exposed to either hydrogen peroxide, paraquat, or 2,2′-azobis-(2-amidinopropane) dihydrochloride treatment, the MsrA overexpressed strain grew better, had lower free and protein-bound methionine sulfoxide and had a better survival rate under these conditions than did the msrA mutant and its parent strain. Substitution of methionine with methionine sulfoxide in a medium lacking hydrogen peroxide had little effect on the growth pattern, which suggests that the oxidation of free methionine in the growth medium was not the main cause of growth inhibition of the msrA mutant. Ultraviolet A radiation did not result in obvious differences in survival rates among the three strains. An enhanced resistance to hydrogen peroxide treatment was shown in human T lymphocyte cells (Molt-4) that were stably transfected with the bovine msrA and exposed to hydrogen peroxide. The survival rate of the transfected strain was much better than its parent strain when grown in the presence of hydrogen peroxide. These results support the proposition that the msrA gene is involved in the resistance of yeast and mammalian cells to oxidative stress. PMID:9826655

  6. Oxidant stress in the vasculature.

    PubMed

    Maytin, M; Leopold, J; Loscalzo, J

    1999-09-01

    Vascular disease and vasomotor responses are largely influenced by oxidant stress. Superoxide is generated via the cellular oxidase systems, xanthine oxidase, and NADH/NADPH oxidases. Once formed, superoxides participate in a number of reactions, yielding various free radicals such as hydrogen peroxide, peroxynitrite, oxidized low-density lipoprotein, or hypochlorous acid. Numerous cellular antioxidant systems exist to defend against oxidant stress; glutathione and the enzymes superoxide dismutase and glutathione peroxidase are critical for maintaining the redox balance of the cell. However, the redox state is disrupted by certain vascular diseases. It appears that oxidant stress both promotes and is induced by diseases such as hypertension, atherosclerosis, and restenosis as well as by certain risk factors for coronary artery disease including hyperlipidemia, diabetes, and cigarette smoking. Once oxidant stress is invoked, characteristic pathophysiologic features ensue, namely adverse vessel reactivity, vascular smooth muscle cell proliferation, macrophage adhesion, platelet activation, and lipid peroxidation. PMID:11122705

  7. Expression of the Laccase Gene from a White Rot Fungus in Pichia pastoris Can Enhance the Resistance of This Yeast to H2O2-Mediated Oxidative Stress by Stimulating the Glutathione-Based Antioxidative System

    PubMed Central

    Fan, Fangfang; Zhuo, Rui; Ma, Fuying; Gong, Yangmin; Wan, Xia; Jiang, Mulan

    2012-01-01

    Laccase is a copper-containing polyphenol oxidase that has great potential in industrial and biotechnological applications. Previous research has suggested that fungal laccase may be involved in the defense against oxidative stress, but there is little direct evidence supporting this hypothesis, and the mechanism by which laccase protects cells from oxidative stress also remains unclear. Here, we report that the expression of the laccase gene from white rot fungus in Pichia pastoris can significantly enhance the resistance of yeast to H2O2-mediated oxidative stress. The expression of laccase in yeast was found to confer a strong ability to scavenge intracellular H2O2 and to protect cells from lipid oxidative damage. The mechanism by which laccase gene expression increases resistance to oxidative stress was then investigated further. We found that laccase gene expression in Pichia pastoris could increase the level of glutathione-based antioxidative activity, including the intracellular glutathione levels and the enzymatic activity of glutathione peroxidase, glutathione reductase, and γ-glutamylcysteine synthetase. The transcription of the laccase gene in Pichia pastoris was found to be enhanced by the oxidative stress caused by exogenous H2O2. The stimulation of laccase gene expression in response to exogenous H2O2 stress further contributed to the transcriptional induction of the genes involved in the glutathione-dependent antioxidative system, including PpYAP1, PpGPX1, PpPMP20, PpGLR1, and PpGSH1. Taken together, these results suggest that the expression of the laccase gene in Pichia pastoris can enhance the resistance of yeast to H2O2-mediated oxidative stress by stimulating the glutathione-based antioxidative system to protect the cell from oxidative damage. PMID:22706050

  8. Organic Nitrates and Nitrate Resistance in Diabetes: The Role of Vascular Dysfunction and Oxidative Stress with Emphasis on Antioxidant Properties of Pentaerithrityl Tetranitrate

    PubMed Central

    Oelze, Matthias; Schuhmacher, Swenja; Daiber, Andreas

    2010-01-01

    Organic nitrates represent a class of drugs which are clinically used for treatment of ischemic symptoms of angina as well as for congestive heart failure based on the idea to overcome the impaired NO bioavailability by “NO” replacement therapy. The present paper is focused on parallels between diabetes mellitus and nitrate tolerance, and aims to discuss the mechanisms underlying nitrate resistance in the setting of diabetes. Since oxidative stress was identified as an important factor in the development of tolerance to organic nitrates, but also represents a hallmark of diabetic complications, this may represent a common principle for both disorders where therapeutic intervention should start. This paper examines the evidence supporting the hypothesis that pentaerithrityl tetranitrate may represent a nitrate for treatment of ischemia in diabetic patients. This evidence is based on the considerations of parallels between diabetes mellitus and nitrate tolerance as well as on preliminary data from experimental diabetes studies. PMID:21234399

  9. Staphylococcus aureus adapts to oxidative stress by producing H2O2-resistant small-colony variants via the SOS response.

    PubMed

    Painter, Kimberley L; Strange, Elizabeth; Parkhill, Julian; Bamford, Kathleen B; Armstrong-James, Darius; Edwards, Andrew M

    2015-05-01

    The development of chronic and recurrent Staphylococcus aureus infections is associated with the emergence of slow-growing mutants known as small-colony variants (SCVs), which are highly tolerant of antibiotics and can survive inside host cells. However, the host and bacterial factors which underpin SCV emergence during infection are poorly understood. Here, we demonstrate that exposure of S. aureus to sublethal concentrations of H2O2 leads to a specific, dose-dependent increase in the population frequency of gentamicin-resistant SCVs. Time course analyses revealed that H2O2 exposure caused bacteriostasis in wild-type cells during which time SCVs appeared spontaneously within the S. aureus population. This occurred via a mutagenic DNA repair pathway that included DNA double-strand break repair proteins RexAB, recombinase A, and polymerase V. In addition to triggering SCV emergence by increasing the mutation rate, H2O2 also selected for the SCV phenotype, leading to increased phenotypic stability and further enhancing the size of the SCV subpopulation by reducing the rate of SCV reversion to the wild type. Subsequent analyses revealed that SCVs were significantly more resistant to the toxic effects of H2O2 than wild-type bacteria. With the exception of heme auxotrophs, gentamicin-resistant SCVs displayed greater catalase activity than wild-type bacteria, which contributed to their resistance to H2O2. Taken together, these data reveal a mechanism by which S. aureus adapts to oxidative stress via the production of a subpopulation of H2O2-resistant SCVs with enhanced catalase production. PMID:25690100

  10. Staphylococcus aureus Adapts to Oxidative Stress by Producing H2O2-Resistant Small-Colony Variants via the SOS Response

    PubMed Central

    Painter, Kimberley L.; Strange, Elizabeth; Bamford, Kathleen B.; Armstrong-James, Darius

    2015-01-01

    The development of chronic and recurrent Staphylococcus aureus infections is associated with the emergence of slow-growing mutants known as small-colony variants (SCVs), which are highly tolerant of antibiotics and can survive inside host cells. However, the host and bacterial factors which underpin SCV emergence during infection are poorly understood. Here, we demonstrate that exposure of S. aureus to sublethal concentrations of H2O2 leads to a specific, dose-dependent increase in the population frequency of gentamicin-resistant SCVs. Time course analyses revealed that H2O2 exposure caused bacteriostasis in wild-type cells during which time SCVs appeared spontaneously within the S. aureus population. This occurred via a mutagenic DNA repair pathway that included DNA double-strand break repair proteins RexAB, recombinase A, and polymerase V. In addition to triggering SCV emergence by increasing the mutation rate, H2O2 also selected for the SCV phenotype, leading to increased phenotypic stability and further enhancing the size of the SCV subpopulation by reducing the rate of SCV reversion to the wild type. Subsequent analyses revealed that SCVs were significantly more resistant to the toxic effects of H2O2 than wild-type bacteria. With the exception of heme auxotrophs, gentamicin-resistant SCVs displayed greater catalase activity than wild-type bacteria, which contributed to their resistance to H2O2. Taken together, these data reveal a mechanism by which S. aureus adapts to oxidative stress via the production of a subpopulation of H2O2-resistant SCVs with enhanced catalase production. PMID:25690100

  11. Induction of intrinsic and extrinsic apoptosis through oxidative stress in drug-resistant cancer by a newly synthesized Schiff base copper chelate.

    PubMed

    Banerjee, Kaushik; Basu, Soumya; Das, Satyajit; Sinha, Abhinaba; Biswas, Manas Kumar; Choudhuri, Soumitra Kumar

    2016-04-01

    Multidrug resistance (MDR) in cancer represents a variety of strategies employed by tumor cells to evade the beneficial cytotoxic effects of structurally different anticancer drugs and thus confers impediments to the successful treatment of cancers. Efflux of drugs by MDR protein-1, functional P-glycoprotein and elevated level of reduced glutathione confer resistance to cell death or apoptosis and thus provide a possible therapeutic target for overcoming MDR in cancer. Previously, we reported that a Schiff base ligand, potassium-N-(2-hydroxy 3-methoxy-benzaldehyde)-alaninate (PHMBA) overcomes MDR in both in vivo and in vitro by targeting intrinsic apoptotic/necrotic pathway through induction of reactive oxygen species (ROS). The present study describes the synthesis and spectroscopic characterization of a copper chelate of Schiff base, viz., copper (II)-N-(2-hydroxy-3-methoxy-benzaldehyde)-alaninate (CuPHMBA) and the underlying mechanism of cell death induced by CuPHMBA in vitro. CuPHMBA kills both the drug-resistant and sensitive cell types irrespective of their drug resistance phenotype. The cell death induced by CuPHMBA follows apoptotic pathway and moreover, the cell death is associated with intrinsic mitochondrial and extrinsic receptor-mediated pathways. Oxidative stress plays a pivotal role in the process as proved by the fact that antioxidant enzyme; polyethylene glycol conjugated-catalase completely blocked CuPHMBA-induced ROS generation and abrogated cell death. To summarize, the present work provides a compelling rationale for the future clinical use of CuPHMBA, a redox active copper chelate in the treatment of cancer patients, irrespective of their drug-resistance status. PMID:26733073

  12. Gene expression changes linked to antimicrobial resistance, oxidative stress, iron depletion and retained motility are observed when Burkholderia cenocepacia grows in cystic fibrosis sputum

    PubMed Central

    Drevinek, Pavel; Holden, Matthew TG; Ge, Zhaoping; Jones, Andrew M; Ketchell, Ian; Gill, Ryan T; Mahenthiralingam, Eshwar

    2008-01-01

    Background Bacteria from the Burkholderia cepacia complex (Bcc) are the only group of cystic fibrosis (CF) respiratory pathogens that may cause death by an invasive infection known as cepacia syndrome. Their large genome (> 7000 genes) and multiple pathways encoding the same putative functions make virulence factor identification difficult in these bacteria. Methods A novel microarray was designed to the genome of Burkholderia cenocepacia J2315 and transcriptomics used to identify genes that were differentially regulated when the pathogen was grown in a CF sputum-based infection model. Sputum samples from CF individuals infected with the same B. cenocepacia strain as genome isolate were used, hence, other than a dilution into a minimal growth medium (used as the control condition), no further treatment of the sputum was carried out. Results A total of 723 coding sequences were significantly altered, with 287 upregulated and 436 downregulated; the microarray-observed expression was validated by quantitative PCR on five selected genes. B. cenocepacia genes with putative functions in antimicrobial resistance, iron uptake, protection against reactive oxygen and nitrogen species, secretion and motility were among the most altered in sputum. Novel upregulated genes included: a transmembrane ferric reductase (BCAL0270) implicated in iron metabolism, a novel protease (BCAL0849) that may play a role in host tissue destruction, an organic hydroperoxide resistance gene (BCAM2753), an oxidoreductase (BCAL1107) and a nitrite/sulfite reductase (BCAM1676) that may play roles in resistance to the host defenses. The assumptions of growth under iron-depletion and oxidative stress formulated from the microarray data were tested and confirmed by independent growth of B. cenocepacia under each respective environmental condition. Conclusion Overall, our first full transcriptomic analysis of B. cenocepacia demonstrated the pathogen alters expression of over 10% of the 7176 genes within

  13. Brucella melitensis MucR, an Orthologue of Sinorhizobium meliloti MucR, Is Involved in Resistance to Oxidative, Detergent, and Saline Stresses and Cell Envelope Modifications

    PubMed Central

    Mirabella, A.; Terwagne, M.; Zygmunt, M. S.; Cloeckaert, A.; De Bolle, X.

    2013-01-01

    Brucella spp. and Sinorhizobium meliloti are alphaproteobacteria that share not only an intracellular lifestyle in their respective hosts, but also a crucial requirement for cell envelope components and their timely regulation for a successful infectious cycle. Here, we report the characterization of Brucella melitensis mucR, which encodes a zinc finger transcriptional regulator that has previously been shown to be involved in cellular and mouse infections at early time points. MucR modulates the surface properties of the bacteria and their resistance to environmental stresses (i.e., oxidative stress, cationic peptide, and detergents). We show that B. melitensis mucR is a functional orthologue of S. meliloti mucR, because it was able to restore the production of succinoglycan in an S. meliloti mucR mutant, as detected by calcofluor staining. Similar to S. meliloti MucR, B. melitensis MucR also represses its own transcription and flagellar gene expression via the flagellar master regulator ftcR. More surprisingly, we demonstrate that MucR regulates a lipid A core modification in B. melitensis. These changes could account for the attenuated virulence of a mucR mutant. These data reinforce the idea that there is a common conserved circuitry between plant symbionts and animal pathogens that regulates the relationship they have with their hosts. PMID:23161025

  14. [Heme metabolism and oxidative stress].

    PubMed

    Kaliman, P A; Barannik, T B

    2001-01-01

    The role of heme metabolism in oxidative stress development and defense reactions formation in mammals under different stress factors are discussed in the article. Heme metabolism is considered as the totality of synthesis, degradation, transport and exchange processes of exogenous heme and heme liberated from erythrocyte hemoglobin under erythrocyte aging and hemolysis. The literature data presented display normal heme metabolism including mammals heme-binding proteins and intracellular free heme pool and heme metabolism alterations under oxidative stress development. The main attention is focused to the prooxidant action of heme, the interaction of heme transport and lipid exchange, and to the heme metabolism key enzymes (delta-aminolevulinate synthase and heme oxygenase), serum heme-binding protein hemopexin and intracellular heme-binding proteins participating in metabolism adaptation under the action of factors, which cause oxidative stress. PMID:11599427

  15. Helicobacter pylori in sedentary men is linked to higher heart rate, sympathetic activity, and insulin resistance but not inflammation or oxidative stress

    PubMed Central

    Cherkas, Andriy; Eckl, Peter; Guéraud, Françoise; Abrahamovych, Orest; Serhiyenko, Victoria; Yatskevych, Ostap; Pliatsko, Mykhailo; Golota, Sergii

    2016-01-01

    Aim To compare anthropometric parameters, body composition, hormonal and inflammatory profiles, oxidative stress indices, and heart rate variability (HRV) in Heliobacter pylori (H.pylori) positive and negative healthy sedentary participants. Methods Among 30 recruited apparently healthy male participants (age between 20 and 40) enrolled in this cross-sectional study, 18 were H.pylori negative and 12 were positive (stool antigen test). Participants underwent routine physical examination and body composition determination. The following biochemical parameters were determined in blood: fasting whole blood glucose, glycated hemoglobin, insulin, C-peptide, cortisol, aldosterone, testosterone, thyroid stimulating hormone, C-reactive protein, interleukins 6 and 10, tumor necrosis factor-α, and the urinary level of 1,4-dihydroxynonane mercapturic acid. For HRV evaluation, electrocardiogram in supine position and in orthostatic test was performed. Results H.pylori contamination was not significantly associated with any changes in anthropometric parameters, body composition, blood pressure, fasting glucose, or glycated hemoglobin levels. No significant difference was found for inflammatory markers as well as 1,4-dihydroxynonane mercapturic acid. H.pylori-positive participants, however, had significantly higher heart rate (P = 0.009), sympathetic/parasympathetic balance in orthostatic test (P = 0.029), fasting insulin level (P = 0.037), and HOMA-index (P = 0.047). Conclusions H.pylori contamination is linked to a significantly higher heart rate, sympathetic activation, and increased insulin resistance, while inflammatory and oxidative stress markers remain unaffected in healthy sedentary male subjects. PMID:27106356

  16. Spatio-temporal changes in glutathione and thioredoxin redox couples during ionizing radiation-induced oxidative stress regulate tumor radio-resistance.

    PubMed

    Patwardhan, R S; Sharma, D; Checker, R; Thoh, M; Sandur, S K

    2015-10-01

    Ionizing radiation (IR)-induced oxidative stress in tumor cells is effectively managed by constitutive and inducible antioxidant defense systems. This study was initiated to understand the relative contribution of different redox regulatory systems in determining the tumor radio-resistance. In this study, human T-cell lymphoma (Jurkat) cells were exposed to IR (4 Gy) and monitored for the spatio-temporal changes in cellular redox regulatory parameters. We monitored the changes in the levels of reactive oxygen species (ROS) (total, mitochondrial, primary, and secondary), thiols (total, surface, and intracellular), GSH/GSSG ratio, antioxidant enzyme activity viz. thioredoxin (Trx), Trx reductase (TrxR), glutathione peroxidase, and glutathione reductase with respect to time. We have also measured protein glutathionylation. We observed that tumor cells mount a biphasic response after IR exposure which can be divided into early (0-6 h) and late (16-48 h) responses in terms of changes in cellular redox parameters. During early response, constitutively active GSH and Trx systems respond to restore cellular redox balance to pre-exposure levels and help in activation of redox-sensitive transcription factor Nrf-2. During late response, increase in the levels of antioxidants GSH and Trx rescue cells against IR-mediated damage. We observed that disruption of either glutathione or thioredoxin metabolism led to partial impairment of ability of cells to survive against IR-induced damage. But simultaneous disruption of both the pathways significantly increased radio sensitivity of Jurkat cells. This highlighted the importance of these two antioxidant pathways in regulating redox homeostasis under conditions of IR-induced oxidative stress. PMID:26021764

  17. Moderate Exercise Prevents Functional Remodeling of the Anterior Pituitary Gland in Diet-Induced Insulin Resistance in Rats: Role of Oxidative Stress and Autophagy.

    PubMed

    Mercau, María E; Repetto, Esteban M; Perez, Matías N; Martinez Calejman, Camila; Sanchez Puch, Silvia; Finkielstein, Carla V; Cymeryng, Cora B

    2016-03-01

    A sustained elevation of glucocorticoid production, associated with the establishment of insulin resistance (IR) could add to the deleterious effects of the IR state. The aim of this study is to analyze the consequences of long-term feeding with a sucrose-rich diet (SRD) on Pomc/ACTH production, define the underlying cellular processes, and determine the effects of moderate exercise (ME) on these parameters. Animals fed a standard chow with or without 30% sucrose in the drinking water were subjected to ME. Circulating hormone levels were determined, and pituitary tissues were processed and analyzed by immunobloting and quantitative real-time PCR. Parameters of oxidative stress (OxS), endoplasmic reticulum stress, and autophagy were also determined. Rats fed SRD developed a decrease in pituitary Pomc/ACTH expression levels, increased expression of antioxidant enzymes, and induction of endoplasmic reticulum stress and autophagy. ME prevented pituitary dysfunction as well as induction of antioxidant enzymes and autophagy. Reporter assays were performed in AtT-20 corticotroph cells incubated in the presence of palmitic acid. Pomc transcription was inhibited by palmitic acid-dependent induction of OxS and autophagy, as judged by the effect of activators and inhibitors of both processes. Long-term feeding with SRD triggers the generation of OxS and autophagy in the pituitary gland, which could lead to a decline in Pomc/ACTH/glucocorticoid production. These effects could be attributed to an increase in fatty acids availability to the pituitary gland. ME was able to prevent these alterations, suggesting additional beneficial effects of ME as a therapeutic strategy in the management of IR. PMID:26672805

  18. Direct renin inhibitor ameliorates insulin resistance by improving insulin signaling and oxidative stress in the skeletal muscle from post-infarct heart failure in mice.

    PubMed

    Fukushima, Arata; Kinugawa, Shintaro; Takada, Shingo; Matsumoto, Junichi; Furihata, Takaaki; Mizushima, Wataru; Tsuda, Masaya; Yokota, Takashi; Matsushima, Shouji; Okita, Koichi; Tsutsui, Hiroyuki

    2016-05-15

    Insulin resistance can occur as a consequence of heart failure (HF). Activation of the renin-angiotensin system (RAS) may play a crucial role in this phenomenon. We thus investigated the effect of a direct renin inhibitor, aliskiren, on insulin resistance in HF after myocardial infarction (MI). MI and sham operation were performed in male C57BL/6J mice. The mice were divided into 4 groups and treated with sham-operation (Sham, n=10), sham-operation and aliskiren (Sham+Aliskiren; 10mg/kg/day, n=10), MI (n=11), or MI and aliskiren (MI+Aliskiren, n=11). After 4 weeks, MI mice showed left ventricular dilation and dysfunction, which were not affected by aliskiren. The percent decrease of blood glucose after insulin load was significantly smaller in MI than in Sham (14±5% vs. 36±2%), and was ameliorated in MI+Aliskiren (34±5%) mice. Insulin-stimulated serine-phosphorylation of Akt and glucose transporter 4 translocation were decreased in the skeletal muscle of MI compared to Sham by 57% and 69%, and both changes were ameliorated in the MI+Aliskiren group (91% and 94%). Aliskiren administration in MI mice significantly inhibited plasma renin activity and angiotensin II (Ang II) levels. Moreover, (pro)renin receptor expression and local Ang II production were upregulated in skeletal muscle from MI and were attenuated in MI+Aliskiren mice, in tandem with a decrease in superoxide production and NAD(P)H oxidase activities. In conclusion, aliskiren ameliorated insulin resistance in HF by improving insulin signaling in the skeletal muscle, at least partly by inhibiting systemic and (pro)renin receptor-mediated local RAS activation, and subsequent NAD(P)H oxidase-induced oxidative stress. PMID:26988296

  19. The origin and future of oxidative stress pathology: From the recognition of carcinogenesis as an iron addiction with ferroptosis-resistance to non-thermal plasma therapy.

    PubMed

    Toyokuni, Shinya

    2016-05-01

    Helmut Sies established the concept of oxidative stress in 1985. However, it took some time to introduce this concept into pathology, where investigators count on formalin-fixed paraffin-embedded tissue sections. I sought out antigens for this purpose based on an oxidative stress-induced rat renal carcinogenesis model, which revealed that 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins are ideal. These two monoclonal antibodies successfully revealed the involvement of oxidative stress in numerous human diseases, including carcinogenesis and atherosclerosis. Shigeru Okada established the aforementioned ferric nitrilotriacetate (Fe-NTA)-induced rat renal carcinogenesis model, which thus far has answered many questions regarding the presence of target genes in oxidative stress-induced carcinogenesis and the sites that are susceptible to oxidative stress in the genome. Particularly, the similarity of genomic alterations between Fe-NTA-induced renal cancer and human cancers suggests that excess iron plays a role also in human carcinogenesis. Furthermore, excess iron is a major pathology in asbestos-induced mesothelioma, including chrysotile. Despite an analogy to asbestos, multi-wall carbon nanotubes were distinct in that diameter is another responsible factor for mesothelial carcinogenesis. Recently, non-thermal plasma emerged as a candidate for medical intervention for wounds and cancers via manipulating oxidative stress. Counteracting excess iron is a promising preventive strategy for major diseases. PMID:26931176

  20. Oxidative Stress Markers in Sputum

    PubMed Central

    Antus, Balazs

    2016-01-01

    Although oxidative stress is thought to play a pivotal role in the pathogenesis of inflammatory airway diseases, its assessment in clinical practice remains elusive. In recent years, it has been conceptualized that oxidative stress markers in sputum should be employed to monitor oxidative processes in patients with asthma, chronic obstructive pulmonary disease (COPD), or cystic fibrosis (CF). In this review, the use of sputum-based oxidative markers was explored and potential clinical applications were considered. Among lipid peroxidation-derived products, 8-isoprostane and malondialdehyde have been the most frequently investigated, while nitrosothiols and nitrotyrosine may serve as markers of nitrosative stress. Several studies have showed higher levels of these products in patients with asthma, COPD, or CF compared to healthy subjects. Marker concentrations could be further increased during exacerbations and decreased along with recovery of these diseases. Measurement of oxidized guanine species and antioxidant enzymes in the sputum could be other approaches for assessing oxidative stress in pulmonary patients. Collectively, even though there are promising findings in this field, further clinical studies using more established detection techniques are needed to clearly show the benefit of these measurements in the follow-up of patients with inflammatory airway diseases. PMID:26885248

  1. Phagocytes and oxidative stress.

    PubMed

    Babior, B M

    2000-07-01

    Neutrophils and other phagocytes manufacture O(2)(-) (superoxide) by the one-electron reduction of oxygen at the expense of NADPH. Most of the O(2)(-) reacts with itself to form H(2)O(2) (hydrogen peroxide). From these agents a large number of highly reactive microbicidal oxidants are formed, including HOCl (hypochlorous acid), which is produced by the myeloperoxidase-catalyzed oxidation of Cl(-) by H(2)O(2); OH(*) (hydroxyl radical), produced by the reduction of H(2)O(2) by Fe(++) or Cu(+); ONOO(-) (peroxynitrite), formed by the reaction between O(2)(-) and NO(*); and many others. These reactive oxidants are manufactured for the purpose of killing invading microorganisms, but they also inflict damage on nearby tissues, and are thought to be of pathogenic significance in a large number of diseases. Included among these are emphysema, acute respiratory distress syndrome, atherosclerosis, reperfusion injury, malignancy and rheumatoid arthritis. PMID:10936476

  2. Oxidative Stress in Atopic Dermatitis

    PubMed Central

    Ji, Hongxiu; Li, Xiao-Kang

    2016-01-01

    Atopic dermatitis (AD) is a chronic pruritic skin disorder affecting many people especially young children. It is a disease caused by the combination of genetic predisposition, immune dysregulation, and skin barrier defect. In recent years, emerging evidence suggests oxidative stress may play an important role in many skin diseases and skin aging, possibly including AD. In this review, we give an update on scientific progress linking oxidative stress to AD and discuss future treatment strategies for better disease control and improved quality of life for AD patients. PMID:27006746

  3. Ethanol and oxidative stress.

    PubMed

    Sun, A Y; Ingelman-Sundberg, M; Neve, E; Matsumoto, H; Nishitani, Y; Minowa, Y; Fukui, Y; Bailey, S M; Patel, V B; Cunningham, C C; Zima, T; Fialova, L; Mikulikova, L; Popov, P; Malbohan, I; Janebova, M; Nespor, K; Sun, G Y

    2001-05-01

    This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Albert Y. Sun. The presentations were (1) Ethanol-inducible cytochrome P-4502E1 in alcoholic liver disease, by Magnus Ingelman-Sundberg and Etienne Neve; (2) Regulation of NF-kappaB by ethanol, by H. Matsumoto, Y. Nishitani, Y. Minowa, and Y. Fukui; (3) Chronic ethanol consumption increases concentration of oxidized proteins in rat liver, by Shannon M. Bailey, Vinood B. Patel, and Carol C. Cunningham; (4) Antiphospholipids antibodies and oxidized modified low-density lipoprotein in chronic alcoholic patients, by Tomas Zima, Lenka Fialova, Ludmila Mikulikova, Ptr Popov, Ivan Malbohan, Marta Janebova, and Karel Nespor; and (5) Amelioration of ethanol-induced damage by polyphenols, by Albert Y. Sun and Grace Y. Sun. PMID:11391077

  4. Hemoglobin oxidative stress

    NASA Astrophysics Data System (ADS)

    Croci, S.; Ortalli, I.; Pedrazzi, G.; Passeri, G.; Piccolo, P.

    2000-07-01

    Venous blood obtained from healthy donors and from patients suffering from breast cancer have been treated with acetylphenylhydrazine (APH) for different time. Mössbauer spectra of the packed red cells have been recorded and compared. The largest difference occurs after 50 min of treatment with APH where the patient samples show a broad spectral pattern indicating an advanced hemoglobin oxidation. These results may have some relevance in early cancer diagnosis.

  5. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways.

    PubMed

    Dues, Dylan J; Andrews, Emily K; Schaar, Claire E; Bergsma, Alexis L; Senchuk, Megan M; Van Raamsdonk, Jeremy M

    2016-04-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

  6. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    PubMed Central

    Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

  7. AbuO, a TolC-Like Outer Membrane Protein of Acinetobacter baumannii, Is Involved in Antimicrobial and Oxidative Stress Resistance

    PubMed Central

    Srinivasan, Vijaya Bharathi; Vaidyanathan, Vasanth

    2014-01-01

    Although Acinetobacter baumannii is well accepted as a nosocomial pathogen, only a few of the outer membrane proteins (OMPs) have been functionally characterized. In this study, we demonstrate the biological functions of AbuO, a homolog of TolC from Escherichia coli. Inactivation of abuO led to increased sensitivity to high osmolarity and oxidative stress challenge. The ΔabuO mutant displayed increased susceptibility to antibiotics, such as amikacin, carbenicillin, ceftriaxone, meropenem, streptomycin, and tigecycline, and hospital-based disinfectants, such as benzalkonium chloride and chlorhexidine. The reverse transcription (RT)-PCR analysis indicated increased expression of efflux pumps (resistance nodulation cell division [RND] efflux pump acrD, 8-fold; SMR-type emrE homolog, 12-fold; and major facilitator superfamily [MFS]-type ampG homolog, 2.7-fold) and two-component response regulators (baeR, 4.67-fold; ompR, 10.43-fold) in the ΔabuO mutant together with downregulation of rstA (4.22-fold) and the pilin chaperone (9-fold). The isogenic mutant displayed lower virulence in a nematode model (P < 0.01). Experimental evidence for the binding of MerR-type transcriptional regulator SoxR to radiolabeled abuO promoter suggests regulation of abuO by SoxR in A. baumannii. PMID:25512405

  8. AbuO, a TolC-like outer membrane protein of Acinetobacter baumannii, is involved in antimicrobial and oxidative stress resistance.

    PubMed

    Srinivasan, Vijaya Bharathi; Vaidyanathan, Vasanth; Rajamohan, Govindan

    2015-02-01

    Although Acinetobacter baumannii is well accepted as a nosocomial pathogen, only a few of the outer membrane proteins (OMPs) have been functionally characterized. In this study, we demonstrate the biological functions of AbuO, a homolog of TolC from Escherichia coli. Inactivation of abuO led to increased sensitivity to high osmolarity and oxidative stress challenge. The ΔabuO mutant displayed increased susceptibility to antibiotics, such as amikacin, carbenicillin, ceftriaxone, meropenem, streptomycin, and tigecycline, and hospital-based disinfectants, such as benzalkonium chloride and chlorhexidine. The reverse transcription (RT)-PCR analysis indicated increased expression of efflux pumps (resistance nodulation cell division [RND] efflux pump acrD, 8-fold; SMR-type emrE homolog, 12-fold; and major facilitator superfamily [MFS]-type ampG homolog, 2.7-fold) and two-component response regulators (baeR, 4.67-fold; ompR, 10.43-fold) in the ΔabuO mutant together with downregulation of rstA (4.22-fold) and the pilin chaperone (9-fold). The isogenic mutant displayed lower virulence in a nematode model (P<0.01). Experimental evidence for the binding of MerR-type transcriptional regulator SoxR to radiolabeled abuO promoter suggests regulation of abuO by SoxR in A. baumannii. PMID:25512405

  9. High temperature oxidation resistant cermet compositions

    NASA Technical Reports Server (NTRS)

    Phillips, W. M. (Inventor)

    1976-01-01

    Cermet compositions are designed to provide high temperature resistant refractory coatings on stainless steel or molybdenum substrates. A ceramic mixture of chromium oxide and aluminum oxide form a coating of chromium oxide as an oxidation barrier around the metal particles, to provide oxidation resistance for the metal particles.

  10. Cadmium-induced oxidative stress tolerance in cadmium resistant Aspergillus foetidus: its possible role in cadmium bioremediation.

    PubMed

    Chakraborty, Shatarupa; Mukherjee, Abhishek; Khuda-Bukhsh, Anisur Rahman; Das, Tapan Kumar

    2014-08-01

    Toxic effects of cadmium (Cd) were examined on a cadmium-resistant strain of Aspergillus foetidus isolated from wastewater. The Cd removal potential was analyzed. The results indicated that the strain could tolerate up to 25 mM and 63 mM Cd in liquid and solid Czapek-Dox media, respectively. It efficiently removed Cd from liquid growth media and industrial wastewater by mycelial biosorption. The strain produced oxalic acid for the purpose of Cd bioleaching as confirmed by the presence of cadmium oxalate crystals on the mycelial surface. Intracellular proline contents and the antioxidative enzyme activities increased up to a certain level to detoxify the overproduced free radicals. These data indicate that the strain has inherent mechanisms to grow in Cd contaminated environment, tolerate high Cd doses and high Cd uptake potential which are pre-requisite for acting as a suitable candidate for Cd bioremediation. PMID:24836877

  11. Oxidative Stress and Neurodegenerative Disorders

    PubMed Central

    Li, Jie; O, Wuliji; Li, Wei; Jiang, Zhi-Gang; Ghanbari, Hossein A.

    2013-01-01

    Living cells continually generate reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS) is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS, oxidative stress and its toxic mechanisms underlying a number of neurodegenerative diseases, and the possible involvement of ROS in chemotherapy-induced toxicity to the CNS and PNS. We ultimately assess the value for antioxidants as neuroprotective drugs and provide our comments on the unmet needs. PMID:24351827

  12. Space flight and oxidative stress.

    PubMed

    Stein, T P

    2002-10-01

    Space flight is associated with an increase in oxidative stress after return to 1g. The effect is more pronounced after long-duration space flight. The effects lasts for several weeks after landing. In humans there is increased lipid peroxidation in erythrocyte membranes, reduction in some blood antioxidants, and increased urinary excretion of 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine. Isoprostane 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine are markers for oxidative damage to lipids and DNA, respectively. The changes have been attributed to a combination of the energy deficiency that occurs during flight and substrate competition for amino acids occurring between repleting muscle and other tissues during the recovery phase. The observations in humans have been complemented by rodent studies. Most rodent studies showed increased production of lipid peroxidation products postflight and decreased antioxidant enzyme activity postflight. The rodent observations were attributed to the stress associated with reentry into Earth's gravity. Decreasing the imbalance between the production of endogenous oxidant defenses and oxidant production by increasing the supply of dietary antioxidants may lessen the severity of the postflight increase in oxidative stress. PMID:12361781

  13. Space flight and oxidative stress

    NASA Technical Reports Server (NTRS)

    Stein, T. P.

    2002-01-01

    Space flight is associated with an increase in oxidative stress after return to 1g. The effect is more pronounced after long-duration space flight. The effects lasts for several weeks after landing. In humans there is increased lipid peroxidation in erythrocyte membranes, reduction in some blood antioxidants, and increased urinary excretion of 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine. Isoprostane 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine are markers for oxidative damage to lipids and DNA, respectively. The changes have been attributed to a combination of the energy deficiency that occurs during flight and substrate competition for amino acids occurring between repleting muscle and other tissues during the recovery phase. The observations in humans have been complemented by rodent studies. Most rodent studies showed increased production of lipid peroxidation products postflight and decreased antioxidant enzyme activity postflight. The rodent observations were attributed to the stress associated with reentry into Earth's gravity. Decreasing the imbalance between the production of endogenous oxidant defenses and oxidant production by increasing the supply of dietary antioxidants may lessen the severity of the postflight increase in oxidative stress.

  14. Oxidative stress and alopecia areata

    PubMed Central

    Prie, BE; Voiculescu, VM; Ionescu-Bozdog, OB; Petrutescu, B; Iosif, L; Gaman, LE; Clatici, VG; Stoian, I; Giurcaneanu, C

    2015-01-01

    Alopecia areata (AA) is an inflammatory and autoimmune disease presenting with non-scarring hair loss. The aethiopathogenesis of alopecia areata is unclear and many factors including autoimmunity, genetic predisposition, emotional and environmental stress are thought to play important roles in its development. Antioxidant/ oxidant balance perturbation is a common feature in autoimmune, emotional and environmental stress. Therefore, our paper discusses the implications of oxidative stress in alopecia areata. Abbreviations: AA = alopecia areata, ROS = reactive oxygen species, H2O2 = hydrogen peroxide, TBARS = thiobarbituric acid rective substances, MDA = malondialdehyde, TBARS = thiobarbituric acid-reactive substances, SOD = superoxide dismutase, CAT = catalase, GSH-Px = glutathione peroxidase, PON1 = paraoxonase 1, HO-1 = hemoxigenase 1, TrxR = thioredoxin reductase, GSH = glutathione PMID:26361510

  15. Marine carotenoids and oxidative stress.

    PubMed

    Riccioni, Graziano

    2012-01-01

    Oxidative stress induced by reactive oxygen species plays an important role in the etiology of many diseases. Dietary phytochemical products, such as bioactive food components and marine carotenoids (asthaxantin, lutein, β-carotene, fucoxanthin), have shown an antioxidant effect in reducing oxidative markers stress. Scientific evidence supports the beneficial role of phytochemicals in the prevention of some chronic diseases. Many carotenoids with high antioxidant properties have shown a reduction in disease risk both in epidemiological studies and supplementation human trials. However, controlled clinical trials and dietary intervention studies using well-defined subjects population have not provided clear evidence of these substances in the prevention of diseases. The most important aspects of this special issue will cover the synthesis, biological activities, and clinical applications of marine carotenoids, with particular attention to recent evidence regarding anti-oxidant and anti-inflammatory properties in the prevention of cardiovascular disease. PMID:22363224

  16. Marine Carotenoids and Oxidative Stress

    PubMed Central

    Riccioni, Graziano

    2012-01-01

    Oxidative stress induced by reactive oxygen species plays an important role in the etiology of many diseases. Dietary phytochemical products, such as bioactive food components and marine carotenoids (asthaxantin, lutein, β-carotene, fucoxanthin), have shown an antioxidant effect in reducing oxidative markers stress. Scientific evidence supports the beneficial role of phytochemicals in the prevention of some chronic diseases. Many carotenoids with high antioxidant properties have shown a reduction in disease risk both in epidemiological studies and supplementation human trials. However, controlled clinical trials and dietary intervention studies using well-defined subjects population have not provided clear evidence of these substances in the prevention of diseases. The most important aspects of this special issue will cover the synthesis, biological activities, and clinical applications of marine carotenoids, with particular attention to recent evidence regarding anti-oxidant and anti-inflammatory properties in the prevention of cardiovascular disease. PMID:22363224

  17. Involvement of Prx3, a Drosophila ortholog of the thiol-dependent peroxidase PRDX3, in age-dependent oxidative stress resistance.

    PubMed

    Kayashima, Yasunari; Yamakawa-Kobayashi, Kimiko

    2012-01-01

    Peroxiredoxins (Prxs) are a family of multifunctional antioxidant thioredoxin-dependent peroxidases. We used Drosophila melanogaster to examine the function of Prx3, the Drosophila homolog of human PRDX3. The oxidative stress response in adult Drosophila is age-dependent. RNAiinduced Prx3 knockdown in adult flies did not change their phenotype in normal conditions, but they had a shorter survival than the Prx3(+) controls in the presence of H2O2. The expression levels of the Prx3 were reduced by aging. These results suggest that Prx3 plays an important role in the oxidative stress response and is involved in the age-dependent competence of the oxidative stress response. PMID:23124252

  18. OxyR-regulated catalase activity is critical for oxidative stress resistance, nodulation and nitrogen fixation in Azorhizobium caulinodans.

    PubMed

    Zhao, Yue; Nickels, Logan M; Wang, Hui; Ling, Jun; Zhong, Zengtao; Zhu, Jun

    2016-07-01

    The legume-rhizobial interaction results in the formation of symbiotic nodules in which rhizobia fix nitrogen. During the process of symbiosis, reactive oxygen species (ROS) are generated. Thus, the response of rhizobia to ROS is important for successful nodulation and nitrogen fixation. In this study, we investigated how Azorhizobium caulinodans, a rhizobium that forms both root and stem nodules on its host plant, regulates ROS resistance. We found that in-frame deletions of a gene encoding the putative catalase-peroxidase katG or a gene encoding a LysR-family regulatory protein, oxyR, exhibited increased sensitivity to H2O2 We then showed that OxyR positively regulated katG expression in an H2O2-independent fashion. Furthermore, we found that deletion of katG or oxyR led to significant reduction in the number of stem nodules and decrease of nitrogen fixation capacities in symbiosis. Our results revealed that KatG and OxyR are not only critical for antioxidant defense in vitro, but also important for nodule formation and nitrogen fixation during interaction with plant hosts. PMID:27190162

  19. Protein Quality Control Under Oxidative Stress Conditions

    PubMed Central

    Dahl, Jan-Ulrik; Gray, Michael J.; Jakob, Ursula

    2015-01-01

    Accumulation of reactive oxygen and chlorine species (RO/CS) is generally regarded to be a toxic and highly undesirable event, which serves as contributing factor in aging and many age-related diseases. However, it is also put to excellent use during host defense, when high levels of RO/CS are produced to kill invading microorganisms and regulate bacterial colonization. Biochemical and cell biological studies of how bacteria and other microorganisms deal with RO/CS have now provided important new insights into the physiological consequences of oxidative stress, the major targets that need protection, and the cellular strategies employed by organisms to mitigate the damage. This review examines the redox-regulated mechanisms by which cells maintain a functional proteome during oxidative stress. We will discuss the well-characterized redox-regulated chaperone Hsp33, and review recent discoveries demonstrating that oxidative stress-specific activation of chaperone function is a much more widespread phenomenon than previously anticipated. New members of this group include the cytosolic ATPase Get3 in yeast, the E. coli protein RidA, and the mammalian protein α2-macroglobin. We will conclude our review with recent evidence showing that inorganic polyphosphate (polyP), whose accumulation significantly increases bacterial oxidative stress resistance, works by a protein-like chaperone mechanism. Understanding the relationship between oxidative and proteotoxic stresses will improve our understanding of both host-microbe interactions and of how mammalian cells combat the damaging side effects of uncontrolled RO/CS production, a hallmark of inflammation. PMID:25698115

  20. Protein quality control under oxidative stress conditions.

    PubMed

    Dahl, Jan-Ulrik; Gray, Michael J; Jakob, Ursula

    2015-04-10

    Accumulation of reactive oxygen and chlorine species (RO/CS) is generally regarded to be a toxic and highly undesirable event, which serves as contributing factor in aging and many age-related diseases. However, it is also put to excellent use during host defense, when high levels of RO/CS are produced to kill invading microorganisms and regulate bacterial colonization. Biochemical and cell biological studies of how bacteria and other microorganisms deal with RO/CS have now provided important new insights into the physiological consequences of oxidative stress, the major targets that need protection, and the cellular strategies employed by organisms to mitigate the damage. This review examines the redox-regulated mechanisms by which cells maintain a functional proteome during oxidative stress. We will discuss the well-characterized redox-regulated chaperone Hsp33, and we will review recent discoveries demonstrating that oxidative stress-specific activation of chaperone function is a much more widespread phenomenon than previously anticipated. New members of this group include the cytosolic ATPase Get3 in yeast, the Escherichia coli protein RidA, and the mammalian protein α2-macroglobulin. We will conclude our review with recent evidence showing that inorganic polyphosphate (polyP), whose accumulation significantly increases bacterial oxidative stress resistance, works by a protein-like chaperone mechanism. Understanding the relationship between oxidative and proteotoxic stresses will improve our understanding of both host-microbe interactions and how mammalian cells combat the damaging side effects of uncontrolled RO/CS production, a hallmark of inflammation. PMID:25698115

  1. The Crystal Structure of Peroxiredoxin Asp f3 Provides Mechanistic Insight into Oxidative Stress Resistance and Virulence of Aspergillus fumigatus.

    PubMed

    Hillmann, Falk; Bagramyan, Karine; Straßburger, Maria; Heinekamp, Thorsten; Hong, Teresa B; Bzymek, Krzysztof P; Williams, John C; Brakhage, Axel A; Kalkum, Markus

    2016-01-01

    Invasive aspergillosis and other fungal infections occur in immunocompromised individuals, including patients who received blood-building stem cell transplants, patients with chronic granulomatous disease (CGD), and others. Production of reactive oxygen species (ROS) by immune cells, which incidentally is defective in CGD patients, is considered to be a fundamental process in inflammation and antifungal immune response. Here we show that the peroxiredoxin Asp f3 of Aspergillus fumigatus inactivates ROS. We report the crystal structure and the catalytic mechanism of Asp f3, a two-cysteine type peroxiredoxin. The latter exhibits a thioredoxin fold and a homodimeric structure with two intermolecular disulfide bonds in its oxidized state. Replacement of the Asp f3 cysteines with serine residues retained its dimeric structure, but diminished Asp f3's peroxidase activity, and extended the alpha-helix with the former peroxidatic cysteine residue C61 by six residues. The asp f3 deletion mutant was sensitive to ROS, and this phenotype was rescued by ectopic expression of Asp f3. Furthermore, we showed that deletion of asp f3 rendered A. fumigatus avirulent in a mouse model of pulmonary aspergillosis. The conserved expression of Asp f3 homologs in medically relevant molds and yeasts prompts future evaluation of Asp f3 as a potential therapeutic target. PMID:27624005

  2. [Statins and oxidative stress].

    PubMed

    Filip-Ciubotaru, Florina; Foia, Liliana; Manciuc, Carmen

    2009-01-01

    Statins, as inhibitors of the first regulatory enzyme in cholesterol biosynthesis --HMG-CoA reductase--have a special impact in medical practice. Given their therapeutic efficacy, statins are believed to be the strongest class of agents in the treatment of cardiovascular disorders. Moreover, besides decreasing total cholesterol and C-LDL levels, numerous fundamental and clinical researches suggest that statins also have an antiinflammatory effect. Inflammation is closely related to the production of oxygen-derived reactive species (ROS). The antioxidant effects of statins associated with their ability to block the formation and/or action of ROS may add up their therapeutic efficacy. Within this context, the present paper presents data in literature related to the effect of statins on the expression and activity of NAD(P)H oxidase, activity of the enzymes involved in the antioxidative defence (SOD, GPx, catalase, paraoxonase), and their ability to act as free radical scavengers and oxidized-LDL inhibitors. By their antioxidant properties statins may decrease the atherogenic potential of lipoproteins. PMID:21495335

  3. Oxidative stress and adrenocortical insufficiency

    PubMed Central

    Prasad, R; Kowalczyk, J C; Meimaridou, E; Storr, H L; Metherell, L A

    2014-01-01

    Maintenance of redox balance is essential for normal cellular functions. Any perturbation in this balance due to increased reactive oxygen species (ROS) leads to oxidative stress and may lead to cell dysfunction/damage/death. Mitochondria are responsible for the majority of cellular ROS production secondary to electron leakage as a consequence of respiration. Furthermore, electron leakage by the cytochrome P450 enzymes may render steroidogenic tissues acutely vulnerable to redox imbalance. The adrenal cortex, in particular, is well supplied with both enzymatic (glutathione peroxidases and peroxiredoxins) and non-enzymatic (vitamins A, C and E) antioxidants to cope with this increased production of ROS due to steroidogenesis. Nonetheless oxidative stress is implicated in several potentially lethal adrenal disorders including X-linked adrenoleukodystrophy, triple A syndrome and most recently familial glucocorticoid deficiency. The finding of mutations in antioxidant defence genes in the latter two conditions highlights how disturbances in redox homeostasis may have an effect on adrenal steroidogenesis. PMID:24623797

  4. Oxidative stress in prostate cancer.

    PubMed

    Khandrika, Lakshmipathi; Kumar, Binod; Koul, Sweaty; Maroni, Paul; Koul, Hari K

    2009-09-18

    As prostate cancer and aberrant changes in reactive oxygen species (ROS) become more common with aging, ROS signaling may play an important role in the development and progression of this malignancy. Increased ROS, otherwise known as oxidative stress, is a result of either increased ROS generation or a loss of antioxidant defense mechanisms. Oxidative stress is associated with several pathological conditions including inflammation and infection. ROS are products of normal cellular metabolism and play vital roles in stimulation of signaling pathways in response to changing intra- and extracellular environmental conditions. Chronic increases in ROS over time are known to induce somatic mutations and neoplastic transformation. In this review we summarize the causes for increased ROS generation and its potential role in etiology and progression of prostate cancer. PMID:19185987

  5. Oxidative Stress and Major Depression

    PubMed Central

    Verma, Akhilesh Kumar; Srivastava, Mona; Srivastava, Ragini

    2014-01-01

    Background: Major causative factor for major depression is inflammation, autoimmune tissue damage and prolonged psychological stress, which leads to oxidative stress. The aim of this study was to know the association of free radicals and antioxidant status in subjects suffering from major depression. Materials and Methods: Sixty patients diagnosed as a case of unipolar depression as per DSM IV, fulfilling the inclusion and exclusion criteria were compared with 40 healthy age and sex matched controls. The sera of both the groups were collected taking aseptic precautions and were evaluated for the markers of oxidative stress and for the antioxidants. The age group of the sample and the controls was between 18-60 y, both males and females were equally represented in the groups. Results: A significantly high level of malondialdehyde (MDA) was found in the patients with major depression (1.95 ± 1.04 mmol/L) as compared to healthy controls (0.366 ± 0.175 mmol/L) (p < 0.0001). The serum level of nitrite was found to be lower in cases (23.18 ± 12.08 μmol/L) in comparison to controls (26.18 ± 8.68 μmol/L) (p = 0.1789). Similarly the serum level of ascorbic acid and superoxide dismutase (SOD) were significantly below as compared to healthy controls (all p < 0.0001). Ceruloplasmin levels were also depressed in cases (p = 0.3943). Conclusion: The study concluded that in the absence of known oxidative injury causative agents, the lowered levels of antioxidants and higher levels of MDA implicate the high degree of oxidative stress in unipolar depression. PMID:25653939

  6. Polarized Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cell Monolayers Have Higher Resistance to Oxidative Stress-Induced Cell Death Than Nonpolarized Cultures

    PubMed Central

    Hsiung, Jamie; Zhu, Danhong

    2015-01-01

    Oxidative stress-mediated injury to the retinal pigment epithelium (RPE) is a major factor involved in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. Human embryonic stem cell (hESC)-derived RPE cells are currently being evaluated for their potential for cell therapy in AMD patients through subretinal injection of cells in suspension and subretinal placement as a polarized monolayer. To gain an understanding of how transplanted RPE cells will respond to the highly oxidatively stressed environment of an AMD patient eye, we compared the survival of polarized and nonpolarized RPE cultures following oxidative stress treatment. Polarized, nonpolarized/confluent, nonpolarized/subconfluent hESC-RPE cells were treated with H2O2. Terminal deoxynucleotidyl transferase dUTP nick end labeling stains revealed the highest amount of cell death in subconfluent hESC-RPE cells and little cell death in polarized hESC-RPE cells with H2O2 treatment. There were higher levels of proapoptotic factors (phosphorylated p38, phosphorylated c-Jun NH2-terminal kinase, Bax, and cleaved caspase 3 fragments) in treated nonpolarized RPE—particularly subconfluent cells—relative to polarized cells. On the other hand, polarized RPE cells had constitutively higher levels of cell survival and antiapoptotic signaling factors such as p-Akt and Bcl-2, as well as antioxidants superoxide dismutase 1 and catalase relative to nonpolarized cells, that possibly contributed to polarized cells’ higher tolerance to oxidative stress compared with nonpolarized RPE cells. Subconfluent cells were particularly sensitive to oxidative stress-induced apoptosis. These results suggest that implantation of polarized hESC-RPE monolayers for treating AMD patients with geographic atrophy should have better survival than injections of hESC-RPE cells in suspension. PMID:25411476

  7. Liver-specific knockdown of IGF-1 decreases vascular oxidative stress resistance by impairing the Nrf2-dependent antioxidant response: a novel model of vascular aging.

    PubMed

    Bailey-Downs, Lora C; Mitschelen, Matthew; Sosnowska, Danuta; Toth, Peter; Pinto, John T; Ballabh, Praveen; Valcarcel-Ares, M Noa; Farley, Julie; Koller, Akos; Henthorn, Jim C; Bass, Caroline; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2012-04-01

    Recent studies demonstrate that age-related dysfunction of NF-E2-related factor-2 (Nrf2)-driven pathways impairs cellular redox homeostasis, exacerbating age-related cellular oxidative stress and increasing sensitivity of aged vessels to oxidative stress-induced cellular damage. Circulating levels of insulin-like growth factor (IGF)-1 decline during aging, which significantly increases the risk for cardiovascular diseases in humans. To test the hypothesis that adult-onset IGF-1 deficiency impairs Nrf2-driven pathways in the vasculature, we utilized a novel mouse model with a liver-specific adeno-associated viral knockdown of the Igf1 gene using Cre-lox technology (Igf1(f/f) + MUP-iCre-AAV8), which exhibits a significant decrease in circulating IGF-1 levels (~50%). In the aortas of IGF-1-deficient mice, there was a trend for decreased expression of Nrf2 and the Nrf2 target genes GCLC, NQO1 and HMOX1. In cultured aorta segments of IGF-1-deficient mice treated with oxidative stressors (high glucose, oxidized low-density lipoprotein, and H(2)O(2)), induction of Nrf2-driven genes was significantly attenuated as compared with control vessels, which was associated with an exacerbation of endothelial dysfunction, increased oxidative stress, and apoptosis, mimicking the aging phenotype. In conclusion, endocrine IGF-1 deficiency is associated with dysregulation of Nrf2-dependent antioxidant responses in the vasculature, which likely promotes an adverse vascular phenotype under pathophysiological conditions associated with oxidative stress (eg, diabetes mellitus, hypertension) and results in accelerated vascular impairments in aging. PMID:22021391

  8. Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

    NASA Technical Reports Server (NTRS)

    Bhattacharya, Sharmila; Hosamani, Ravikumar

    2015-01-01

    Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

  9. Transcriptional Up-Regulation of APE1/Ref-1 in Hepatic Tumor: Role in Hepatocytes Resistance to Oxidative Stress and Apoptosis

    PubMed Central

    Di Maso, Vittorio; Mediavilla, María Gabriela; Vascotto, Carlo; Lupo, Francesco; Baccarani, Umberto; Avellini, Claudio; Tell, Gianluca; Tiribelli, Claudio; Crocè, Lory Saveria

    2015-01-01

    Objective Human Hepatocellular Carcinoma (HCC) is the fifth most frequent neoplasm worldwide and the most serious complication of long-standing chronic liver diseases (CLD). Its development is associated with chronic inflammation and sustained oxidative stress. Deregulation of apurinic apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1), a master regulator of cellular response to oxidative stress, has been associated with poor prognosis in several cancers including HCC. Design In the present study we investigated the APE1/Ref-1 mRNA levels in cirrhotic and HCC tissues obtained during HCC resection. The possible protective role of APE1/Ref-1 against oxidative stress and apoptosis was evaluated in vitro in immortalized human hepatocytes (IHH) over-expressing APE1/Ref-1. Results APE1/Ref-1 was up-regulated in HCC, regulation occurring at the transcriptional level. APE1/Ref-1 mRNA content increased with the progression of liver disease with the transcriptional up-regulation present in cirrhosis significantly increased in HCC. The up-regulation was higher in the less differentiated cancers. In vitro, over-expression of APE1/Ref-1 in normal hepatocytes conferred cell protection against oxidative stress and it was associated with BAX inhibition and escape from apoptosis. Conclusion APE1/Ref-1 is up-regulated in HCC and this over-expression correlates with cancer aggressiveness. The up-regulation occurs at the transcriptional level and it is present in the earliest phases of hepatocarcinogenesis. The APE-1/Ref-1 over-expression is associated with hepatocyte survival and inhibits BAX activation and apoptosis. These data suggest a possible role of APE1/Ref-1 over-expression both in hepatocyte survival and HCC development calling attention to this molecule as a promising marker for HCC diagnosis and treatment. PMID:26624999

  10. Screening for stress-resistance mutations in the mouse

    PubMed Central

    Chick, Wallace S.; Ludwig, Michael; Zhao, Xiaoyun; Kitzenberg, David; Williams, Kristina; Johnson, Thomas E.

    2014-01-01

    Longevity is correlated with stress resistance in many animal models. However, previous efforts through the boosting of the antioxidant defense system did not extend life span, suggesting that longevity related stress resistance is mediated by other uncharacterized pathways. We have developed a high-throughput platform for screening and rapid identification of novel genetic mutants in the mouse that are stress resistant. Selection for resistance to stressors occurs in mutagenized mouse embryonic stem (ES) cells, which are carefully treated so as to maintain pluripotency for mouse production. Initial characterization of these mutant ES cells revealed mutations in Pigl, Tiam1, and Rffl, among others. These genes are implicated in glycosylphosphatidylinositol biosynthesis, NADPH oxidase function, and inflammation. These mutants: (1) are resistant to two different oxidative stressors, paraquat and the omission of 2-mercaptoethanol, (2) have reduced levels of endogenous reactive oxygen species (ROS), (3) are capable of generating live mice, and (4) transmit the stress resistance phenotype to the mice. This strategy offers an efficient way to select for new mutants expressing a stress resistance phenotype, to rapidly identify the causative genes, and to develop mice for in vivo studies. PMID:25250048

  11. Oxidative Stress in Neurodegenerative Diseases.

    PubMed

    Niedzielska, Ewa; Smaga, Irena; Gawlik, Maciej; Moniczewski, Andrzej; Stankowicz, Piotr; Pera, Joanna; Filip, Małgorzata

    2016-08-01

    The pathophysiologies of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD), are far from being fully explained. Oxidative stress (OS) has been proposed as one factor that plays a potential role in the pathogenesis of neurodegenerative disorders. Clinical and preclinical studies indicate that neurodegenerative diseases are characterized by higher levels of OS biomarkers and by lower levels of antioxidant defense biomarkers in the brain and peripheral tissues. In this article, we review the current knowledge regarding the involvement of OS in neurodegenerative diseases, based on clinical trials and animal studies. In addition, we analyze the effects of the drug-induced modulation of oxidative balance, and we explore pharmacotherapeutic strategies for OS reduction. PMID:26198567

  12. Oxidative Stress in Cardiovascular Disease

    PubMed Central

    Csányi, Gábor; Miller, Francis J.

    2014-01-01

    In the special issue “Oxidative Stress in Cardiovascular Disease” authors were invited to submit papers that investigate key questions in the field of cardiovascular free radical biology. The original research articles included in this issue provide important information regarding novel aspects of reactive oxygen species (ROS)-mediated signaling, which have important implications in physiological and pathophysiological cardiovascular processes. The issue also included a number of review articles that highlight areas of intense research in the fields of free radical biology and cardiovascular medicine. PMID:24722571

  13. Oxidative stress in cardiovascular disease.

    PubMed

    Csányi, Gábor; Miller, Francis J

    2014-01-01

    In the special issue "Oxidative Stress in Cardiovascular Disease" authors were invited to submit papers that investigate key questions in the field of cardiovascular free radical biology. The original research articles included in this issue provide important information regarding novel aspects of reactive oxygen species (ROS)-mediated signaling, which have important implications in physiological and pathophysiological cardiovascular processes. The issue also included a number of review articles that highlight areas of intense research in the fields of free radical biology and cardiovascular medicine. PMID:24722571

  14. Oxidative stress in inherited mitochondrial diseases.

    PubMed

    Hayashi, Genki; Cortopassi, Gino

    2015-11-01

    Mitochondria are a source of reactive oxygen species (ROS). Mitochondrial diseases are the result of inherited defects in mitochondrially expressed genes. One potential pathomechanism for mitochondrial disease is oxidative stress. Oxidative stress can occur as the result of increased ROS production or decreased ROS protection. The role of oxidative stress in the five most common inherited mitochondrial diseases, Friedreich ataxia, LHON, MELAS, MERRF, and Leigh syndrome (LS), is discussed. Published reports of oxidative stress involvement in the pathomechanisms of these five mitochondrial diseases are reviewed. The strongest evidence for an oxidative stress pathomechanism among the five diseases was for Friedreich ataxia. In addition, a meta-analysis was carried out to provide an unbiased evaluation of the role of oxidative stress in the five diseases, by searching for "oxidative stress" citation count frequency for each disease. Of the five most common mitochondrial diseases, the strongest support for oxidative stress is for Friedreich ataxia (6.42%), followed by LHON (2.45%), MELAS (2.18%), MERRF (1.71%), and LS (1.03%). The increased frequency of oxidative stress citations was significant relative to the mean of the total pool of five diseases (p<0.01) and the mean of the four non-Friedreich diseases (p<0.0001). Thus there is support for oxidative stress in all five most common mitochondrial diseases, but the strongest, significant support is for Friedreich ataxia. PMID:26073122

  15. Oxidative stress in oral diseases.

    PubMed

    Kesarwala, A H; Krishna, M C; Mitchell, J B

    2016-01-01

    Oxidative species, including reactive oxygen species (ROS), are components of normal cellular metabolism and are required for intracellular processes as varied as proliferation, signal transduction, and apoptosis. In the situation of chronic oxidative stress, however, ROS contribute to various pathophysiologies and are involved in multiple stages of carcinogenesis. In head and neck cancers specifically, many common risk factors contribute to carcinogenesis via ROS-based mechanisms, including tobacco, areca quid, alcohol, and viruses. Given their widespread influence on the process of carcinogenesis, ROS and their related pathways are attractive targets for intervention. The effects of radiation therapy, a central component of treatment for nearly all head and neck cancers, can also be altered via interfering with oxidative pathways. These pathways are also relevant to the development of many benign oral diseases. In this review, we outline how ROS contribute to pathophysiology with a focus toward head and neck cancers and benign oral diseases, describing potential targets and pathways for intervention that exploit the role of oxidative species in these pathologic processes. PMID:25417961

  16. Analysis of Oxidative Stress in Zebrafish Embryos

    PubMed Central

    Mugoni, Vera; Camporeale, Annalisa; Santoro, Massimo M.

    2014-01-01

    High levels of reactive oxygen species (ROS) may cause a change of cellular redox state towards oxidative stress condition. This situation causes oxidation of molecules (lipid, DNA, protein) and leads to cell death. Oxidative stress also impacts the progression of several pathological conditions such as diabetes, retinopathies, neurodegeneration, and cancer. Thus, it is important to define tools to investigate oxidative stress conditions not only at the level of single cells but also in the context of whole organisms. Here, we consider the zebrafish embryo as a useful in vivo system to perform such studies and present a protocol to measure in vivo oxidative stress. Taking advantage of fluorescent ROS probes and zebrafish transgenic fluorescent lines, we develop two different methods to measure oxidative stress in vivo: i) a “whole embryo ROS-detection method” for qualitative measurement of oxidative stress and ii) a “single-cell ROS detection method” for quantitative measurements of oxidative stress. Herein, we demonstrate the efficacy of these procedures by increasing oxidative stress in tissues by oxidant agents and physiological or genetic methods. This protocol is amenable for forward genetic screens and it will help address cause-effect relationships of ROS in animal models of oxidative stress-related pathologies such as neurological disorders and cancer. PMID:25046434

  17. The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel

    PubMed Central

    2010-01-01

    Background Drinking water contaminated with inorganic arsenic is associated with increased risk for different types of cancer. Paradoxically, arsenic trioxide can also be used to induce remission in patients with acute promyelocytic leukemia (APL) with a success rate of approximately 80%. A comprehensive study examining the mechanisms and potential signaling pathways contributing to the anti-tumor properties of arsenic trioxide has not been carried out. Methods Here we applied a systems biology approach to identify gene biomarkers that underlie tumor cell responses to arsenic-induced cytotoxicity. The baseline gene expression levels of 14,500 well characterized human genes were associated with the GI50 data of the NCI-60 tumor cell line panel from the developmental therapeutics program (DTP) database. Selected biomarkers were tested in vitro for the ability to influence tumor susceptibility to arsenic trioxide. Results A significant association was found between the baseline expression levels of 209 human genes and the sensitivity of the tumor cell line panel upon exposure to arsenic trioxide. These genes were overlayed onto protein-protein network maps to identify transcriptional networks that modulate tumor cell responses to arsenic trioxide. The analysis revealed a significant enrichment for the oxidative stress response pathway mediated by nuclear factor erythroid 2-related factor 2 (NRF2) with high expression in arsenic resistant tumor cell lines. The role of the NRF2 pathway in protecting cells against arsenic-induced cell killing was validated in tumor cells using shRNA-mediated knock-down. Conclusions In this study, we show that the expression level of genes in the NRF2 pathway serve as potential gene biomarkers of tumor cell responses to arsenic trioxide. Importantly, we demonstrate that tumor cells that are deficient for NRF2 display increased sensitivity to arsenic trioxide. The results of our study will be useful in understanding the mechanism of

  18. Siderophore Biosynthesis but Not Reductive Iron Assimilation Is Essential for the Dimorphic Fungus Nomuraea rileyi Conidiation, Dimorphism Transition, Resistance to Oxidative Stress, Pigmented Microsclerotium Formation, and Virulence.

    PubMed

    Li, Yan; Wang, Zhongkang; Liu, Xuee; Song, Zhangyong; Li, Ren; Shao, Changwen; Yin, Youping

    2016-01-01

    reduced capacity for iron acquisition leads to the loss of virulence in Spodoptera litura while the ΔNrFtrA mutants behaved as WT during infection. Together, these results prove siderophore-assisted iron mobilization is the major pathway of cellular iron uptake and essential for conidiation, dimorphism transition, oxidative stress resistance, pigmented microsclerotium formation and full virulence. PMID:27379061

  19. Siderophore Biosynthesis but Not Reductive Iron Assimilation Is Essential for the Dimorphic Fungus Nomuraea rileyi Conidiation, Dimorphism Transition, Resistance to Oxidative Stress, Pigmented Microsclerotium Formation, and Virulence

    PubMed Central

    Li, Yan; Wang, Zhongkang; Liu, Xuee; Song, Zhangyong; Li, Ren; Shao, Changwen; Yin, Youping

    2016-01-01

    capacity for iron acquisition leads to the loss of virulence in Spodoptera litura while the ΔNrFtrA mutants behaved as WT during infection. Together, these results prove siderophore-assisted iron mobilization is the major pathway of cellular iron uptake and essential for conidiation, dimorphism transition, oxidative stress resistance, pigmented microsclerotium formation and full virulence. PMID:27379061

  20. IMPROVED TOLERANCE TO ENVIRONMENTALLY INDUCED OXIDATIVE STRESSES IN TRANSGENIC TOMATO OVEREXPRESSING ASCORBATE PEROXIDASE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We studied the effect on oxidative stress resistance of overexpressing, in transgenic tomato (Lycopersicon esculentum) plants, a cytosolic ascorbate peroxidase (APX) gene derived from pea (Pisum sativum). Transformants were selected using Kanamycin resistance and confirmed by PCR, Southern and Nort...

  1. Testosterone and oxidative stress: the oxidation handicap hypothesis

    PubMed Central

    Alonso-Alvarez, Carlos; Bertrand, Sophie; Faivre, Bruno; Chastel, Olivier; Sorci, Gabriele

    2006-01-01

    Secondary sexual traits (SST) are usually thought to have evolved as honest signals of individual quality during mate choice. Honesty of SST is guaranteed by the cost of producing/maintaining them. In males, the expression of many SST is testosterone-dependent. The immunocompetence handicap hypothesis has been proposed as a possible mechanism ensuring honesty of SST on the basis that testosterone, in addition to its effect on sexual signals, also has an immunosuppressive effect. The immunocompetence handicap hypothesis has received mixed support. However, the cost of testosterone-based signalling is not limited to immunosuppression and might involve other physiological functions such as the antioxidant machinery. Here, we tested the hypothesis that testosterone depresses resistance to oxidative stress in a species with a testosterone-dependent sexual signal, the zebra finch. Male zebra finches received subcutaneous implants filled with flutamide (an anti-androgen) or testosterone, or kept empty (control). In agreement with the prediction, we found that red blood cell resistance to a free radical attack was the highest in males implanted with flutamide and the lowest in males implanted with testosterone. We also found that cell-mediated immune response was depressed in testosterone-treated birds, supporting the immunocompetence handicap hypothesis. The recent finding that red blood cell resistance to free radicals is negatively associated with mortality in this species suggests that benefits of sexual signalling might trade against the costs derived from oxidation. PMID:17251089

  2. Testosterone and oxidative stress: the oxidation handicap hypothesis.

    PubMed

    Alonso-Alvarez, Carlos; Bertrand, Sophie; Faivre, Bruno; Chastel, Olivier; Sorci, Gabriele

    2007-03-22

    Secondary sexual traits (SST) are usually thought to have evolved as honest signals of individual quality during mate choice. Honesty of SST is guaranteed by the cost of producing/maintaining them. In males, the expression of many SST is testosterone-dependent. The immunocompetence handicap hypothesis has been proposed as a possible mechanism ensuring honesty of SST on the basis that testosterone, in addition to its effect on sexual signals, also has an immunosuppressive effect. The immunocompetence handicap hypothesis has received mixed support. However, the cost of testosterone-based signalling is not limited to immunosuppression and might involve other physiological functions such as the antioxidant machinery. Here, we tested the hypothesis that testosterone depresses resistance to oxidative stress in a species with a testosterone-dependent sexual signal, the zebra finch. Male zebra finches received subcutaneous implants filled with flutamide (an anti-androgen) or testosterone, or kept empty (control). In agreement with the prediction, we found that red blood cell resistance to a free radical attack was the highest in males implanted with flutamide and the lowest in males implanted with testosterone. We also found that cell-mediated immune response was depressed in testosterone-treated birds, supporting the immunocompetence handicap hypothesis. The recent finding that red blood cell resistance to free radicals is negatively associated with mortality in this species suggests that benefits of sexual signalling might trade against the costs derived from oxidation. PMID:17251089

  3. Etiologies of sperm oxidative stress

    PubMed Central

    Sabeti, Parvin; Pourmasumi, Soheila; Rahiminia, Tahereh; Akyash, Fatemeh; Talebi, Ali Reza

    2016-01-01

    Sperm is particularly susceptible to reactive oxygen species (ROS) during critical phases of spermiogenesis. However, the level of seminal ROS is restricted by seminal antioxidants which have beneficial effects on sperm parameters and developmental potentials. Mitochondria and sperm plasma membrane are two major sites of ROS generation in sperm cells. Besides, leukocytes including polymer phonuclear (PMN) leukocytes and macrophages produce broad category of molecules including oxygen free radicals, non-radical species and reactive nitrogen species. Physiological role of ROS increase the intracellular cAMP which then activate protein kinase in male reproductive system. This indicates that spermatozoa need small amounts of ROS to acquire the ability of nuclear maturation regulation and condensation to fertilize the oocyte. There is a long list of intrinsic and extrinsic factors which can induce oxidative stress to interact with lipids, proteins and DNA molecules. As a result, we have lipid peroxidation, DNA fragmentation, axonemal damage, denaturation of the enzymes, over generation of superoxide in the mitochondria, lower antioxidant activity and finally abnormal spermatogenesis. If oxidative stress is considered as one of the main cause of DNA damage in the germ cells, then there should be good reason for antioxidant therapy in these conditions. PMID:27351024

  4. Etiologies of sperm oxidative stress.

    PubMed

    Sabeti, Parvin; Pourmasumi, Soheila; Rahiminia, Tahereh; Akyash, Fatemeh; Talebi, Ali Reza

    2016-04-01

    Sperm is particularly susceptible to reactive oxygen species (ROS) during critical phases of spermiogenesis. However, the level of seminal ROS is restricted by seminal antioxidants which have beneficial effects on sperm parameters and developmental potentials. Mitochondria and sperm plasma membrane are two major sites of ROS generation in sperm cells. Besides, leukocytes including polymer phonuclear (PMN) leukocytes and macrophages produce broad category of molecules including oxygen free radicals, non-radical species and reactive nitrogen species. Physiological role of ROS increase the intracellular cAMP which then activate protein kinase in male reproductive system. This indicates that spermatozoa need small amounts of ROS to acquire the ability of nuclear maturation regulation and condensation to fertilize the oocyte. There is a long list of intrinsic and extrinsic factors which can induce oxidative stress to interact with lipids, proteins and DNA molecules. As a result, we have lipid peroxidation, DNA fragmentation, axonemal damage, denaturation of the enzymes, over generation of superoxide in the mitochondria, lower antioxidant activity and finally abnormal spermatogenesis. If oxidative stress is considered as one of the main cause of DNA damage in the germ cells, then there should be good reason for antioxidant therapy in these conditions. PMID:27351024

  5. Peroxisomal metabolism and oxidative stress.

    PubMed

    Nordgren, Marcus; Fransen, Marc

    2014-03-01

    Peroxisomes are ubiquitous and multifunctional organelles that are primarily known for their role in cellular lipid metabolism. As many peroxisomal enzymes catalyze redox reactions as part of their normal function, these organelles are also increasingly recognized as potential regulators of oxidative stress-related signaling pathways. This in turn suggests that peroxisome dysfunction is not only associated with rare inborn errors of peroxisomal metabolism, but also with more common age-related diseases such as neurodegeneration, type 2 diabetes, and cancer. This review intends to provide a comprehensive picture of the complex role of mammalian peroxisomes in cellular redox metabolism. We highlight how peroxisomal metabolism may contribute to the bioavailability of important mediators of oxidative stress, with particular emphasis on reactive oxygen species. In addition, we review the biological properties of peroxisome-derived signaling messengers and discuss how these molecules may mediate various biological responses. Furthermore, we explore the emerging concepts that peroxisomes and mitochondria share an intricate redox-sensitive relationship and cooperate in cell fate decisions. This is particularly relevant to the observed demise of peroxisome function which accompanies cellular senescence, organismal aging, and age-related diseases. PMID:23933092

  6. Inflammation, Oxidative Stress, and Obesity

    PubMed Central

    Fernández-Sánchez, Alba; Madrigal-Santillán, Eduardo; Bautista, Mirandeli; Esquivel-Soto, Jaime; Morales-González, Ángel; Esquivel-Chirino, Cesar; Durante-Montiel, Irene; Sánchez-Rivera, Graciela; Valadez-Vega, Carmen; Morales-González, José A.

    2011-01-01

    Obesity is a chronic disease of multifactorial origin and can be defined as an increase in the accumulation of body fat. Adipose tissue is not only a triglyceride storage organ, but studies have shown the role of white adipose tissue as a producer of certain bioactive substances called adipokines. Among adipokines, we find some inflammatory functions, such as Interleukin-6 (IL-6); other adipokines entail the functions of regulating food intake, therefore exerting a direct effect on weight control. This is the case of leptin, which acts on the limbic system by stimulating dopamine uptake, creating a feeling of fullness. However, these adipokines induce the production of reactive oxygen species (ROS), generating a process known as oxidative stress (OS). Because adipose tissue is the organ that secretes adipokines and these in turn generate ROS, adipose tissue is considered an independent factor for the generation of systemic OS. There are several mechanisms by which obesity produces OS. The first of these is the mitochondrial and peroxisomal oxidation of fatty acids, which can produce ROS in oxidation reactions, while another mechanism is over-consumption of oxygen, which generates free radicals in the mitochondrial respiratory chain that is found coupled with oxidative phosphorylation in mitochondria. Lipid-rich diets are also capable of generating ROS because they can alter oxygen metabolism. Upon the increase of adipose tissue, the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), was found to be significantly diminished. Finally, high ROS production and the decrease in antioxidant capacity leads to various abnormalities, among which we find endothelial dysfunction, which is characterized by a reduction in the bioavailability of vasodilators, particularly nitric oxide (NO), and an increase in endothelium-derived contractile factors, favoring atherosclerotic disease. PMID:21686173

  7. Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies.

    PubMed

    Rani, Vibha; Deep, Gagan; Singh, Rakesh K; Palle, Komaraiah; Yadav, Umesh C S

    2016-03-01

    Increased body weight and metabolic disorder including insulin resistance, type 2 diabetes and cardiovascular complications together constitute metabolic syndrome. The pathogenesis of metabolic syndrome involves multitude of factors. A number of studies however indicate, with some conformity, that oxidative stress along with chronic inflammatory condition pave the way for the development of metabolic diseases. Oxidative stress, a state of lost balance between the oxidative and anti-oxidative systems of the cells and tissues, results in the over production of oxidative free radicals and reactive oxygen species (ROS). Excessive ROS generated could attack the cellular proteins, lipids and nucleic acids leading to cellular dysfunction including loss of energy metabolism, altered cell signalling and cell cycle control, genetic mutations, altered cellular transport mechanisms and overall decreased biological activity, immune activation and inflammation. In addition, nutritional stress such as that caused by high fat high carbohydrate diet also promotes oxidative stress as evident by increased lipid peroxidation products, protein carbonylation, and decreased antioxidant system and reduced glutathione (GSH) levels. These changes lead to initiation of pathogenic milieu and development of several chronic diseases. Studies suggest that in obese person oxidative stress and chronic inflammation are the important underlying factors that lead to development of pathologies such as carcinogenesis, obesity, diabetes, and cardiovascular diseases through altered cellular and nuclear mechanisms, including impaired DNA damage repair and cell cycle regulation. Here we discuss the aspects of metabolic disorders-induced oxidative stress in major pathological conditions and strategies for their prevention and therapy. PMID:26851532

  8. Dietary sardine protein lowers insulin resistance, leptin and TNF-α and beneficially affects adipose tissue oxidative stress in rats with fructose-induced metabolic syndrome.

    PubMed

    Madani, Zohra; Louchami, Karim; Sener, Abdullah; Malaisse, Willy J; Ait Yahia, Dalila

    2012-02-01

    The present study aims at exploring the effects of sardine protein on insulin resistance, plasma lipid profile, as well as oxidative and inflammatory status in rats with fructose-induced metabolic syndrome. Rats were fed sardine protein (S) or casein (C) diets supplemented or not with high-fructose (HF) for 2 months. Rats fed the HF diets had greater body weight and adiposity and lower food intake as compared to control rats. Increased plasma glucose, insulin, HbA1C, triacylglycerols, free fatty acids and impaired glucose tolerance and insulin resistance was observed in HF-fed rats. Moreover, a decline in adipose tissues antioxidant status and a rise in lipid peroxidation and plasma TNF-α and fibrinogen were noted. Rats fed sardine protein diets exhibited lower food intake and fat mass than those fed casein diets. Sardine protein diets diminished plasma insulin and insulin resistance. Plasma triacylglycerol and free fatty acids were also lower, while those of α-tocopherol, taurine and calcium were enhanced as compared to casein diets. Moreover, S-HF diet significantly decreased plasma glucose and HbA1C. Sardine protein consumption lowered hydroperoxide levels in perirenal and brown adipose tissues. The S-HF diet, as compared to C-HF diet decreased epididymal hydroperoxides. Feeding sardine protein diets decreased brown adipose tissue carbonyls and increased glutathione peroxidase activity. Perirenal and epididymal superoxide dismutase and catalase activities and brown catalase activity were significantly greater in S-HF group than in C-HF group. Sardine protein diets also prevented hyperleptinemia and reduced inflammatory status in comparison with rats fed casein diets. Taken together, these results support the beneficial effect of sardine protein in fructose-induced metabolic syndrome on such variables as hyperglycemia, insulin resistance, hyperlipidemia and oxidative and inflammatory status, suggesting the possible use of sardine protein as a protective

  9. Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress.

    PubMed

    Singh, Surendra; Brocker, Chad; Koppaka, Vindhya; Chen, Ying; Jackson, Brian C; Matsumoto, Akiko; Thompson, David C; Vasiliou, Vasilis

    2013-03-01

    Reactive oxygen species (ROS) are continuously generated within living systems and the inability to manage ROS load leads to elevated oxidative stress and cell damage. Oxidative stress is coupled to the oxidative degradation of lipid membranes, also known as lipid peroxidation. This process generates over 200 types of aldehydes, many of which are highly reactive and toxic. Aldehyde dehydrogenases (ALDHs) metabolize endogenous and exogenous aldehydes and thereby mitigate oxidative/electrophilic stress in prokaryotic and eukaryotic organisms. ALDHs are found throughout the evolutionary gamut, from single-celled organisms to complex multicellular species. Not surprisingly, many ALDHs in evolutionarily distant, and seemingly unrelated, species perform similar functions, including protection against a variety of environmental stressors such as dehydration and ultraviolet radiation. The ability to act as an "aldehyde scavenger" during lipid peroxidation is another ostensibly universal ALDH function found across species. Upregulation of ALDHs is a stress response in bacteria (environmental and chemical stress), plants (dehydration, salinity, and oxidative stress), yeast (ethanol exposure and oxidative stress), Caenorhabditis elegans (lipid peroxidation), and mammals (oxidative stress and lipid peroxidation). Recent studies have also identified ALDH activity as an important feature of cancer stem cells. In these cells, ALDH expression helps abrogate oxidative stress and imparts resistance against chemotherapeutic agents such as oxazaphosphorine, taxane, and platinum drugs. The ALDH superfamily represents a fundamentally important class of enzymes that contributes significantly to the management of electrophilic/oxidative stress within living systems. Mutations in various ALDHs are associated with a variety of pathological conditions in humans, highlighting the fundamental importance of these enzymes in physiological and pathological processes. PMID:23195683

  10. Oxidative Stress in Cystinosis Patients

    PubMed Central

    Vaisbich, Maria Helena; Pache de Faria Guimaraes, Luciana; Shimizu, Maria Heloisa Mazzola; Seguro, Antonio Carlos

    2011-01-01

    Background/Aims Nephropathic cystinosis (NC) is a severe systemic disease and cysteamine improves its prognosis. Lysosomal cystine accumulation is the hallmark of cystinosis and is regarded as the primary defect due to mutations in the CTNS gene. However, there is great evidence that cystine accumulation itself is not responsible for all abnormalities observed in NC. Studies have demonstrated altered ATP metabolism, increased apoptosis, and cell oxidation. An increased number of autophagosomes and autophagic vacuoles have been observed in cystinotic fibroblasts and renal epithelial cells, suggesting that altered autophagy plays a role in NC, leading to increased production of reactive oxygen species. Therefore, cystinosis patients can be more susceptible to oxidative stress (OS) and it can contribute to the progression of the renal disease. Our goal was to evaluate a marker of OS (serum TBARS) in NC children, and to compare the results with those observed in healthy controls and correlated with renal function parameters. Methods The study included patients aged under 18 years, with good adherence to the treatment and out of renal replacement therapy. The following parameters were evaluated: serum creatinine, BUN, creatinine clearance estimated by stature and serum TBARS levels. Results We selected 20 patients aged 8.0 ±3.6 years and observed serum TBARS levels of 4.03 ±1.02 nmol/ml. Serum TBARS levels in the 43 healthy controls, aged 7.4 ±1.1 years, were 1.60 ±0.04 nmol/ml. There was a significant difference between the plasma TBARS levels among the 2 groups (p < 0.0001). We detected no significant correlation between plasma TBARS levels and renal function. Conclusion An increased level of serum TBARS in patients with NC was observed and this abnormality was not correlated with the renal function status degree. This is the first report that shows increased oxidative stress in serum of NC patients. PMID:22470381

  11. Diverse Oxidative Stress Resistance Mechanisms in Sulfate-reducing Bacteria as Revealed by Global Analysis of the Impact of H2O2 Exposure on Desulfovibrio vulgaris Hildenborough

    NASA Astrophysics Data System (ADS)

    Zhou, A.; Mukhopadhyay, A.; He, Z.; Hemme, C. L.; Keasling, J. D.; Arkin, A. P.; Hazen, T. C.; Wall, J. D.; Zhou, J.

    2008-12-01

    Desulfovibrio vulgaris Hildenborough (DvH) plays important roles in the bioremediation of toxic metals. It has been shown aero-tolerant. In order to understand the molecular mechanism of DvH oxidative stress response, mid-log DvH cells were subjected to 1 mM of H2O2 and the transcriptomic changes were examined at 30, 60, 120, 240 and 480 min. The microarray data demonstrated that the gene expression was extensively affected with 29% of genes in the genome significantly up- or down-regulated after 120-min H2O2 treatment. In response to elevated cellular H2O2, expression of thiol-peroxidase genes ahpC and bcp were increased in addition to the significant induction of many thioredoxin reductase and thioredoxin genes, which represent the thiol switch in the oxidative stress response. Increased gene expression PerR regulon genes including PerR itself provided evidence for the regulatory role of PerR in oxidative stress response. The role of Fur was suggested by the significant up-regulation of Fur regulon genes. In terms of the H2O2 scavenging enzymes, different from the stress response to air where both rbr and rbr2 were induced, only rbr2 was up-regulated in response to H2O2; together with up-regulated rdl, they might be the additional players for the detoxification of H2O2. Superoxide scavenging enzyme katA was significantly down-regulated, which is in contrast to its role in facultative microbes such as E.coli and B. subtilis. The links between the up- regulated genes involved in H2O2 scavenging, protein fate, DNA metabolism and lipid metabolism and the down-regulated genes involved in sulfate reduction, energy production and translation were demonstrated by the gene co-expression network. The proteomics data provided further evidence in translation level and complemented the transcriptomics data. Taken together, the cellular response of D. vulgaris Hildenborough to H2O2 was the up-regulation of detoxification, protein and DNA repair systems and the down

  12. Resistance of functional Lactobacillus plantarum strains against food stress conditions.

    PubMed

    Ferrando, Verónica; Quiberoni, Andrea; Reinhemer, Jorge; Suárez, Viviana

    2015-06-01

    The survival of three Lactobacillus plantarum strains (Lp 790, Lp 813 and Lp 998) with functional properties was studied taking into account their resistance to thermal, osmotic and oxidative stress factors. Stress treatments applied were: 52 °C-15 min (Phosphate Buffer pH 7, thermal shock), H2O2 0.1% (p/v) - 30 min (oxidative shock) and NaCl aqueous solution at 17, 25 and 30% (p/v) (room temperature - 1 h, osmotic shock). The osmotic stress was also evaluated on cell growth in MRS broth added of 2, 4, 6, 8 and 10% (p/v) of NaCl, during 20 h at 30 °C. The cell thermal adaptation was performed in MRS broth, selecting 45 °C for 30 min as final conditions for all strains. Two strains (Lp 813 and Lp 998) showed, in general, similar behaviour against the three stress factors, being clearly more resistant than Lp 790. An evident difference in growth kinetics in presence of NaCl was observed between Lp 998 and Lp 813, Lp998 showing a higher optical density (OD570nm) than Lp 813 at the end of the assay. Selected thermal adaptation improved by 2 log orders the thermal resistance of both strains, but cell growth in presence of NaCl was enhanced only in Lp 813. Oxidative resistance was not affected with this thermal pre-treatment. These results demonstrate the relevance of cell technological resistance when selecting presumptive "probiotic" cultures, since different stress factors might considerably affect viability or/and performance of the strains. The incidence of stress conditions on functional properties of the strains used in this work are currently under research in our group. PMID:25790993

  13. Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver

    PubMed Central

    Satapati, Santhosh; Kucejova, Blanka; Duarte, Joao A.G.; Fletcher, Justin A.; Reynolds, Lacy; Sunny, Nishanth E.; He, Tianteng; Nair, L. Arya; Livingston, Kenneth; Fu, Xiaorong; Merritt, Matthew E.; Sherry, A. Dean; Malloy, Craig R.; Shelton, John M.; Lambert, Jennifer; Parks, Elizabeth J.; Corbin, Ian; Magnuson, Mark A.; Browning, Jeffrey D.; Burgess, Shawn C.

    2015-01-01

    Mitochondria are critical for respiration in all tissues; however, in liver, these organelles also accommodate high-capacity anaplerotic/cataplerotic pathways that are essential to gluconeogenesis and other biosynthetic activities. During nonalcoholic fatty liver disease (NAFLD), mitochondria also produce ROS that damage hepatocytes, trigger inflammation, and contribute to insulin resistance. Here, we provide several lines of evidence indicating that induction of biosynthesis through hepatic anaplerotic/cataplerotic pathways is energetically backed by elevated oxidative metabolism and hence contributes to oxidative stress and inflammation during NAFLD. First, in murine livers, elevation of fatty acid delivery not only induced oxidative metabolism, but also amplified anaplerosis/cataplerosis and caused a proportional rise in oxidative stress and inflammation. Second, loss of anaplerosis/cataplerosis via genetic knockdown of phosphoenolpyruvate carboxykinase 1 (Pck1) prevented fatty acid–induced rise in oxidative flux, oxidative stress, and inflammation. Flux appeared to be regulated by redox state, energy charge, and metabolite concentration, which may also amplify antioxidant pathways. Third, preventing elevated oxidative metabolism with metformin also normalized hepatic anaplerosis/cataplerosis and reduced markers of inflammation. Finally, independent histological grades in human NAFLD biopsies were proportional to oxidative flux. Thus, hepatic oxidative stress and inflammation are associated with elevated oxidative metabolism during an obesogenic diet, and this link may be provoked by increased work through anabolic pathways. PMID:26571396

  14. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    PubMed Central

    Duan, Xiaochun; Wen, Zunjia; Shen, Haitao; Shen, Meifen

    2016-01-01

    Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches. PMID:27190572

  15. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy.

    PubMed

    Duan, Xiaochun; Wen, Zunjia; Shen, Haitao; Shen, Meifen; Chen, Gang

    2016-01-01

    Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches. PMID:27190572

  16. Ablation of the mitochondrial complex IV assembly protein Surf1 leads to increased expression of the UPR(MT) and increased resistance to oxidative stress in primary cultures of fibroblasts.

    PubMed

    Pharaoh, Gavin; Pulliam, Daniel; Hill, Shauna; Sataranatarajan, Kavithalakshmi; Van Remmen, Holly

    2016-08-01

    Mice deficient in the electron transport chain (ETC) complex IV assembly protein SURF1 have reduced assembly and activity of cytochrome c oxidase that is associated with an upregulation of components of the mitochondrial unfolded protein response (UPR(MT)) and increased mitochondrial number. We hypothesized that the upregulation of proteins associated with the UPR(MT) in response to reduced cytochrome c oxidase activity in Surf1(-/-) mice might contribute to increased stress resistance. To test this hypothesis we asked whether primary cultures of fibroblasts from Surf1(-/-) mice exhibit enhanced resistance to stressors compared to wild-type fibroblasts. Here we show that primary dermal fibroblasts isolated from Surf1(-/-) mice have increased expression of UPR(MT) components ClpP and Hsp60, and increased expression of Lon protease. Fibroblasts from Surf1(-/-) mice are significantly more resistant to cell death caused by oxidative stress induced by paraquat or tert-Butyl hydroperoxide compared to cells from wild-type mice. In contrast, Surf1(-/-) fibroblasts show no difference in sensitivity to hydrogen peroxide stress. The enhanced cell survival in response to paraquat or tert-Butyl hydroperoxide in Surf1(-/-) fibroblasts compared to wild-type fibroblasts is associated with induced expression of Lon, ClpP, and Hsp60, increased maximal respiration, and increased reserve capacity as measured using the Seahorse Extracellular Flux Analyzer. Overall these data support a protective role for the activation of the UPR(MT) in cell survival. PMID:27208630

  17. Stress dependent oxidation of sputtered niobium and effects on superconductivity

    NASA Astrophysics Data System (ADS)

    David Henry, M.; Wolfley, Steve; Monson, Todd; Clark, Blythe G.; Shaner, Eric; Jarecki, Robert

    2014-02-01

    We report on the suppression of room temperature oxidation of DC sputtered niobium films and the effects upon the superconductive transition temperature, Tc. Niobium was sputter-deposited on silicon dioxide coated 150 mm wafers and permitted to oxidize at room temperature and pressure for up to two years. Resistivity and stress measurements indicate that tensile films greater than 400 MPa resist bulk oxidation with measurements using transmission electron microscope, electron dispersive X-ray spectroscopy, x-ray photoelectric spectroscopy, and secondary ion mass spectrometry confirming this result. Although a surface oxide, Nb2O5, consumed the top 6-10 nm, we measure less than 1 at. % oxygen and nitrogen in the bulk of the films after the oxidation period. Tc measurements using a SQUID magnetometer indicate that the tensile films maintained a Tc approaching the dirty superconductive limit of 8.4 K after two years of oxidation while maintaining room temperature sheet resistance. This work demonstrates that control over niobium film stress during deposition can prevent bulk oxidation by limiting the vertical grain boundaries ability to oxidize, prolonging the superconductive properties of sputtered niobium when exposed to atmosphere.

  18. Stress dependent oxidation of sputtered niobium and effects on superconductivity

    SciTech Connect

    David Henry, M. Wolfley, Steve; Monson, Todd; Clark, Blythe G.; Shaner, Eric; Jarecki, Robert

    2014-02-28

    We report on the suppression of room temperature oxidation of DC sputtered niobium films and the effects upon the superconductive transition temperature, T{sub c}. Niobium was sputter-deposited on silicon dioxide coated 150 mm wafers and permitted to oxidize at room temperature and pressure for up to two years. Resistivity and stress measurements indicate that tensile films greater than 400 MPa resist bulk oxidation with measurements using transmission electron microscope, electron dispersive X-ray spectroscopy, x-ray photoelectric spectroscopy, and secondary ion mass spectrometry confirming this result. Although a surface oxide, Nb{sub 2}O{sub 5}, consumed the top 6–10 nm, we measure less than 1 at. % oxygen and nitrogen in the bulk of the films after the oxidation period. T{sub c} measurements using a SQUID magnetometer indicate that the tensile films maintained a T{sub c} approaching the dirty superconductive limit of 8.4 K after two years of oxidation while maintaining room temperature sheet resistance. This work demonstrates that control over niobium film stress during deposition can prevent bulk oxidation by limiting the vertical grain boundaries ability to oxidize, prolonging the superconductive properties of sputtered niobium when exposed to atmosphere.

  19. Induction of Oxidative Stress in Kidney

    PubMed Central

    Ozbek, Emin

    2012-01-01

    Oxidative stress has a critical role in the pathophysiology of several kidney diseases, and many complications of these diseases are mediated by oxidative stress, oxidative stress-related mediators, and inflammation. Several systemic diseases such as hypertension, diabetes mellitus, and hypercholesterolemia; infection; antibiotics, chemotherapeutics, and radiocontrast agents; and environmental toxins, occupational chemicals, radiation, smoking, as well as alcohol consumption induce oxidative stress in kidney. We searched the literature using PubMed, MEDLINE, and Google scholar with “oxidative stress, reactive oxygen species, oxygen free radicals, kidney, renal injury, nephropathy, nephrotoxicity, and induction”. The literature search included only articles written in English language. Letters or case reports were excluded. Scientific relevance, for clinical studies target populations, and study design, for basic science studies full coverage of main topics, are eligibility criteria for articles used in this paper. PMID:22577546

  20. Primary and secondary oxidative stress in Bacillus.

    PubMed

    Mols, Maarten; Abee, Tjakko

    2011-06-01

    Coping with oxidative stress originating from oxidizing compounds or reactive oxygen species (ROS), associated with the exposure to agents that cause environmental stresses, is one of the prerequisites for an aerobic lifestyle of Bacillus spp. such as B. subtilis, B. cereus and B. anthracis. This minireview highlights novel insights in the primary oxidative stress response caused by oxidizing compounds including hydrogen peroxide and the secondary oxidative stress responses apparent upon exposure to a range of agents and conditions leading to environmental stresses such as antibiotics, heat and acid. Insights in the pathways and damaging radicals involved have been compiled based among others on transcriptome studies, network analyses and fluorescence techniques for detection of ROS at single cell level. Exploitation of the current knowledge for the control of spoilage and pathogenic bacteria is discussed. PMID:21352461

  1. Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage.

    PubMed

    Li-Byarlay, Hongmei; Huang, Ming Hua; Simone-Finstrom, Michael; Strand, Micheline K; Tarpy, David R; Rueppell, Olav

    2016-10-01

    Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked; considerable variation in oxidative stress resistance exists among and within species and typically covaries with life expectancy. However, it is unclear whether stress-resistant, long-lived individuals avoid, repair, or tolerate molecular damage to survive longer than others. The honey bee (Apis mellifera L.) is an emerging model system that is well-suited to address this question. Furthermore, this species is the most economically important pollinator, whose health may be compromised by pesticide exposure, including oxidative stressors. Here, we develop a protocol for inducing oxidative stress in honey bee males (drones) via Paraquat injection. After injection, individuals from different colony sources were kept in common social conditions to monitor their survival compared to saline-injected controls. Oxidative stress was measured in susceptible and resistant individuals. Paraquat drastically reduced survival but individuals varied in their resistance to treatment within and among colony sources. Longer-lived individuals exhibited higher levels of lipid peroxidation than individuals dying early. In contrast, the level of protein carbonylation was not significantly different between the two groups. This first study of oxidative stress in male honey bees suggests that survival of an acute oxidative stressor is due to tolerance, not prevention or repair, of oxidative damage to lipids. It also demonstrates colony differences in oxidative stress resistance that might be useful for breeding stress-resistant honey bees. PMID:27422326

  2. Bridges between mitochondrial oxidative stress, ER stress and mTOR signaling in pancreatic β cells.

    PubMed

    Wang, Jing; Yang, Xin; Zhang, Jingjing

    2016-08-01

    Pancreatic β cell dysfunction, i.e., failure to provide insulin in concentrations sufficient to control blood sugar, is central to the etiology of all types of diabetes. Current evidence implicates mitochondrial oxidative stress and endoplasmic reticulum (ER) stress in pancreatic β cell loss and impaired insulin secretion. Oxidative and ER stress are interconnected so that misfolded proteins induce reactive oxygen species (ROS) production; likewise, oxidative stress disturbs the ER redox state thereby disrupting correct disulfide bond formation and proper protein folding. mTOR signaling regulates many metabolic processes including protein synthesis, cell growth, survival and proliferation. Oxidative stress inhibits mTORC1, which is considered an important suppressor of mitochondrial oxidative stress in β cells, and ultimately, controls cell survival. The interplay between ER stress and mTORC1 is complicated, since the unfolded protein response (UPR) activation can occur upstream or downstream of mTORC1. Persistent activation of mTORC1 initiates protein synthesis and UPR activation, while in the later phase induces ER stress. Chronic activation of ER stress inhibits Akt/mTORC1 pathway, while under particular settings, acute activation of UPR activates Akt-mTOR signaling. Thus, modulating mitochondrial oxidative stress and ER stress via mTOR signaling may be an approach that will effectively suppress obesity- or glucolipotoxicity-induced metabolic disorders such as insulin resistance and type 2 diabetes mellitus (T2DM). In this review, we focus on the regulations between mTOR signaling and mitochondrial oxidative or ER stress in pancreatic β cells. PMID:27185188

  3. Role of oxidative stress and nitric oxide in atherothrombosis

    PubMed Central

    Lubos, Edith; Handy, Diane E.; Loscalzo, Joseph

    2008-01-01

    During the last decade basic and clinical research has highlighted the central role of reactive oxygen species (ROS) in cardiovascular disease. Enhanced production or attenuated degradation of ROS leads to oxidative stress, a process that affects endothelial and vascular function, and contributes to vascular disease. Nitric oxide (NO), a product of the normal endothelium, is a principal determinant of normal endothelial and vascular function. In states of inflammation, NO production by the vasculature increases considerably and, in conjunction with other ROS, contributes to oxidative stress. This review examines the role of oxidative stress and NO in mechanisms of endothelial and vascular dysfunction with an emphasis on atherothrombosis. PMID:18508590

  4. Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

    SciTech Connect

    Lefevre, Sophie; Sliwa, Dominika; Rustin, Pierre; Camadro, Jean-Michel; Santos, Renata

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. Black-Right-Pointing-Pointer Oxidative stress induces complete mitochondrial fragmentation in {Delta}yfh1 cells. Black-Right-Pointing-Pointer Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. Black-Right-Pointing-Pointer Inhibition of mitochondrial fission in {Delta}yfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron-sulfur cluster assembly. Yeast cells lacking frataxin ({Delta}yfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in {Delta}yfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

  5. Up-regulation of Survivin during Immortalization of Human Myofibroblasts Is Linked to Repression of Tumor Suppressor p16INK4a Protein and Confers Resistance to Oxidative Stress*

    PubMed Central

    Kan, Chin-Yi; Petti, Carlotta; Bracken, Lauryn; Maritz, Michelle; Xu, Ning; O'Brien, Rosemary; Yang, Chen; Liu, Tao; Yuan, Jun; Lock, Richard B.; MacKenzie, Karen L.

    2013-01-01

    Survivin is an essential component of the chromosomal passenger complex and a member of the inhibitor of apoptosis family. It is expressed at high levels in a large variety of malignancies, where it has been implicated in drug resistance. It was also shown previously that survivin is up-regulated during telomerase-mediated immortalization, which occurs at a relatively early stage during carcinogenesis. This study shows that up-regulation of survivin during immortalization of human myofibroblasts is an indirect consequence of the repression of p16INK4a. Survivin and p16INK4a were functionally linked by assays that showed that either the up-regulation of survivin or repression of p16INK4a rendered telomerase-transduced MRC-5 myofibroblasts resistant to oxidative stress. Conversely, siRNA-mediated down-regulation of survivin activated caspases and enhanced the sensitivity of immortal MRC-5 cells to oxidative stress. The E2F1 transcription factor, which is negatively regulated by the pRB/p16INK4a tumor suppressor pathway, was implicated in the up-regulation of survivin. Using the ChIP assay, it was shown that E2F1 directly interacted with the survivin gene (BIRC5) promoter in cells that spontaneously silenced p16INK4a during telomerase-mediated immortalization. E2F1 binding to the BIRC5 was also enhanced in telomerase-transduced cells subjected to shRNA-mediated repression of p16INK4a. Together, these data show that repression of p16INK4a contributes to the up-regulation of survivin and thereby provides a survival advantage to cells exposed to oxidative stress during immortalization. The up-regulation of survivin during immortalization likely contributes to the vulnerability of immortal cells to transformation by oncogenes that alter intracellular redox state. PMID:23449974

  6. Clinical Relevance of Biomarkers of Oxidative Stress

    PubMed Central

    Frijhoff, Jeroen; Winyard, Paul G.; Zarkovic, Neven; Davies, Sean S.; Stocker, Roland; Cheng, David; Knight, Annie R.; Taylor, Emma Louise; Oettrich, Jeannette; Ruskovska, Tatjana; Gasparovic, Ana Cipak; Cuadrado, Antonio; Weber, Daniela; Poulsen, Henrik Enghusen; Grune, Tilman; Schmidt, Harald H.H.W.

    2015-01-01

    Abstract Significance: Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. Recent Advances: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. Critical Issues: The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. Future Directions: Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker. Antioxid. Redox Signal. 23, 1144–1170. PMID:26415143

  7. Aflatoxin Biosynthesis Is a Novel Source of Reactive Oxygen Species—A Potential Redox Signal to Initiate Resistance to Oxidative Stress?

    PubMed Central

    Roze, Ludmila V.; Laivenieks, Maris; Hong, Sung-Yong; Wee, Josephine; Wong, Shu-Shyan; Vanos, Benjamin; Awad, Deena; Ehrlich, Kenneth C.; Linz, John E.

    2015-01-01

    Aflatoxin biosynthesis in the filamentous fungus Aspergillus parasiticus involves a minimum of 21 enzymes, encoded by genes located in a 70 kb gene cluster. For aflatoxin biosynthesis to be completed, the required enzymes must be transported to specialized early and late endosomes called aflatoxisomes. Of particular significance, seven aflatoxin biosynthetic enzymes are P450/monooxygenases which catalyze reactions that can produce reactive oxygen species (ROS) as byproducts. Thus, oxidative reactions in the aflatoxin biosynthetic pathway could potentially be an additional source of intracellular ROS. The present work explores the hypothesis that the aflatoxin biosynthetic pathway generates ROS (designated as “secondary” ROS) in endosomes and that secondary ROS possess a signaling function. We used specific dyes that stain ROS in live cells and demonstrated that intracellular ROS levels correlate with the levels of aflatoxin synthesized. Moreover, feeding protoplasts with precursors of aflatoxin resulted in the increase in ROS generation. These data support the hypothesis. Our findings also suggest that secondary ROS may fulfill, at least in part, an important mechanistic role in increased tolerance to oxidative stress in germinating spores (seven-hour germlings) and in regulation of fungal development. PMID:25928133

  8. Oxidative Stress, Lens Gap Junctions, and Cataracts

    PubMed Central

    Beyer, Eric C.

    2009-01-01

    Abstract The eye lens is constantly subjected to oxidative stress from radiation and other sources. The lens has several mechanisms to protect its components from oxidative stress and to maintain its redox state, including enzymatic pathways and high concentrations of ascorbate and reduced glutathione. With aging, accumulation of oxidized lens components and decreased efficiency of repair mechanisms can contribute to the development of lens opacities or cataracts. Maintenance of transparency and homeostasis of the avascular lens depend on an extensive network of gap junctions. Communication through gap junction channels allows intercellular passage of molecules (up to 1 kDa) including antioxidants. Lens gap junctions and their constituent proteins, connexins (Cx43, Cx46, and Cx50), are also subject to the effects of oxidative stress. These observations suggest that oxidative stress-induced damage to connexins (and consequent altered intercellular communication) may contribute to cataract formation. Antioxid. Redox Signal. 11, 339–353. PMID:18831679

  9. Oxidative Stress Related Diseases in Newborns

    PubMed Central

    Aykac, Kubra

    2016-01-01

    We review oxidative stress-related newborn disease and the mechanism of oxidative damage. In addition, we outline diagnostic and therapeutic strategies and future directions. Many reports have defined oxidative stress as an imbalance between an enhanced reactive oxygen/nitrogen species and the lack of protective ability of antioxidants. From that point of view, free radical-induced damage caused by oxidative stress seems to be a probable contributing factor to the pathogenesis of many newborn diseases, such as respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and retinopathy of prematurity. We share the hope that the new understanding of the concept of oxidative stress and its relation to newborn diseases that has been made possible by new diagnostic techniques will throw light on the treatment of those diseases. PMID:27403229

  10. Oxidative Stress Related Diseases in Newborns.

    PubMed

    Ozsurekci, Yasemin; Aykac, Kubra

    2016-01-01

    We review oxidative stress-related newborn disease and the mechanism of oxidative damage. In addition, we outline diagnostic and therapeutic strategies and future directions. Many reports have defined oxidative stress as an imbalance between an enhanced reactive oxygen/nitrogen species and the lack of protective ability of antioxidants. From that point of view, free radical-induced damage caused by oxidative stress seems to be a probable contributing factor to the pathogenesis of many newborn diseases, such as respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and retinopathy of prematurity. We share the hope that the new understanding of the concept of oxidative stress and its relation to newborn diseases that has been made possible by new diagnostic techniques will throw light on the treatment of those diseases. PMID:27403229