Role of redox potential and reactive oxygen species in stress signaling

Adler, Victor; Yin, Zhimin; Tew, Kenneth D.; Ronai, Ze’ev

doi:10.1038/sj.onc.1203128

Cited by 629 publications

(409 citation statements)

References 101 publications

(63 reference statements)

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“…Several lines of evidence suggest a role for ROS in the production of cytokines, growth factors, and hormones and the activation of nuclear transcription, although the mechanisms are still unclear (31). Probably, ROS exerts a direct effect on kinases or redoxsensitive proteins by inducing conformational changes that are required for protein activation and these early signals can then elicit transcriptional activity (32). In all biological systems H 2 O 2 is a physiological product and is well documented as influencing mast cell behavior, although the findings are often contradictory about the beneficial or detrimental effects of H 2 O 2 on mast cell effector responses (33,34).…”

Section: Discussionmentioning

confidence: 99%

Selective Activation of Fyn/PI3K and p38 MAPK Regulates IL-4 Production in BMMC under Nontoxic Stress Condition

Frossi

Rivera

Hirsch

et al. 2007

The Journal of Immunology

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Mast cells have the ability to react to multiple stimuli, implicating these cells in many immune responses. Specific signals from the microenvironment in which mast cells reside can activate different molecular events that govern distinct mast cells responses. We previously demonstrated that hydrogen peroxide (H2O2) promotes IL-4 and IL-6 mRNA production and potentates FcεRI-induced cytokine release in rat basophilic leukemia RBL-2H3 cells. To further evaluate the effect of an oxidative microenvironment (which is physiologically present in an inflammatory site) on mast cell function and the molecular events responsible for mast cell cytokine production in this environment, we analyzed the effect of H2O2 treatment on IL-4 production in bone marrow-derived, cultured mast cells. Our findings show that nanomolar concentrations of H2O2 induce cytokine secretion and enhance IL-4 production upon FcεRI triggering. Oxidative stimulation activates a distinct signal transduction pathway that induces Fyn/PI3K/Akt activation and the selective phosphorylation of p38 MAP kinase. Moreover, H2O2 induces AP-1 and NFAT complexes that recognize the IL-4 promoter. The absence of Fyn and PI3K or the inhibition of p38 MAPK activity demonstrated that they are essential for H2O2-driven IL-4 production. These findings show that mast cells can respond to an oxidative microenvironment by initiating specific signals capable of eliciting a selective response. The findings also demonstrate the dominance of the Fyn/p38 MAPK pathway in driving IL-4 production.

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Section: Discussionmentioning

confidence: 99%

Selective Activation of Fyn/PI3K and p38 MAPK Regulates IL-4 Production in BMMC under Nontoxic Stress Condition

Frossi

Rivera

Hirsch

et al. 2007

The Journal of Immunology

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“…Recent studies suggest that different signals may rely on different MAPKKK and/or MAPK (Tournier et al, 2001). For oxidant-induced activation of these pathways, changes in the cellular redox state may be a key factor (Adler et al, 1999a). For example, under normal conditions the redox regulatory protein thioredoxin (Trx) has been shown to bind to and inhibit the activity of apoptosis signal-regulating kinase 1 (ASK1), a MAPKKK involved in both JNK and p38 kinase activation (Saitoh et al, 1998).…”

Section: Sapk Pathwaysmentioning

confidence: 99%

Cellular response to oxidative stress: Signaling for suicide and survival*

Martindale

Holbrook

2002

Journal Cellular Physiology

2,059

1,567

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Reactive oxygen species (ROS), whether produced endogenously as a consequence of normal cell functions or derived from external sources, pose a constant threat to cells living in an aerobic environment as they can result in severe damage to DNA, protein, and lipids. The importance of oxidative damage to the pathogenesis of many diseases as well as to degenerative processes of aging has becoming increasingly apparent over the past few years. Cells contain a number of antioxidant defenses to minimize fluctuations in ROS, but ROS generation often exceeds the cell's antioxidant capacity, resulting in a condition termed oxidative stress. Host survival depends upon the ability of cells and tissues to adapt to or resist the stress, and repair or remove damaged molecules or cells. Numerous stress response mechanisms have evolved for these purposes, and they are rapidly activated in response to oxidative insults. Some of the pathways are preferentially linked to enhanced survival, while others are more frequently associated with cell death. Still others have been implicated in both extremes depending on the particular circumstances. In this review, we discuss the various signaling pathways known to be activated in response to oxidative stress in mammalian cells, the mechanisms leading to their activation, and their roles in influencing cell survival. These pathways constitute important avenues for therapeutic interventions aimed at limiting oxidative damage or attenuating its sequelae. Published 2002 Wiley‐Liss, Inc.

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“…Likewise, ROS production also leads to the activation of signaling cascades such as ERKs, which in turn induce NFκB immune response provoking changes in histone acetylation/deacetylation that finally result in altered transcription initiation (Adler et al, 1999). An increase in proinflammatory cytokines that contributes to the chronicity comes as a consequence of these ROS mediated mechanisms.…”

Section: Inflammation Oxidative Stress and Hypoxiamentioning

confidence: 99%

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

Milagro

Mansego

Miguel

et al. 2013

Molecular Aspects of Medicine

245

160

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Nutritional factors play a life-long role in human health. Indeed, there is growing evidence that one of the mechanisms by which nutrients and bioactive compounds affect metabolic traits is epigenetics. Complex interactions among food components and histone modifications, DNA methylation, non-coding RNA expression and chromatin remodeling factors lead to a dynamic regulation of gene expression that controls the cellular phenotype. Although perinatal period is the time of highest phenotypic plasticity, contributing largely to developmental programming, also during adulthood there is evidence about a nutritional influence on epigenetic regulation. Similarly to type 2 diabetes, hypertension, atherosclerosis and other metabolic disorders, obesity predisposition and weight loss outcomes have been repeatedly associated to changes in epigenetic patterns. Different non-nutritional risk factors that usually accompany obesity seem also to be involved in these epigenetic modifications, especially hyperglycemia, inflammation, hypoxia and oxidative stress. There are currently three major objectives in epigenetic research in relation to obesity: to search for epigenetic biomarkers to predict future health problems or detect the individuals at most risk, to understand the obesity-related environmental factors that could modulate gene expression by affecting epigenetic mechanisms, and to study novel therapeutic strategies based on nutritional or pharmacological agents that can modify epigenetic marks. At this level, the major tasks are: development of robust epigenetic biomarkers of weight regulation, description of those epigenetic marks more susceptible to be modified by dietary exposures, identification of the active ingredients (and the doses) that alter the epigenome, assessment of the real importance of other obesity-related factors on epigenetic regulation, determination of the period of life in which best results are obtained, and understanding of the importance of the inheritance of these epigenetic marks.

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Role of redox potential and reactive oxygen species in stress signaling

Cited by 629 publications

References 101 publications

Selective Activation of Fyn/PI3K and p38 MAPK Regulates IL-4 Production in BMMC under Nontoxic Stress Condition

Selective Activation of Fyn/PI3K and p38 MAPK Regulates IL-4 Production in BMMC under Nontoxic Stress Condition

Cellular response to oxidative stress: Signaling for suicide and survival*

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

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