Skin resistance to oxidative stress induced by resveratrol: From Nrf2 activation to GSH biosynthesis

Sœur, Jérémie; Eilstein, Joan; Léreaux, Guillaume; Jones, Christophe; Marrot, Laurent

doi:10.1016/j.freeradbiomed.2014.10.510

Cited by 90 publications

(64 citation statements)

References 55 publications

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“…The here elaborated pro-oxidative features of RSV and the redox-environment shifting concept can fully explain such recent claims 43 . Of note, whereas RSV might remain stable under low pH conditions in the stomach (see Figure 1 and 2 in Reference 31 ), physiologically well-known neutralization in the duodenum -by high concentrations of bicarbonate derived from the pancreas -might induce so far largely unexplored pro-oxidative features of RSV in the intestine.…”

Section: Resultsmentioning

confidence: 60%

Hormetic Shifting of Redox Environment by Pro-Oxidative Resveratrol Protects Cells Against Stress

Plauth

Geikowski

Cichon

et al. 2016

Preprint

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ABSTRACT:Resveratrol has gained tremendous interest owing to multiple reported healthbeneficial effects. However, the underlying key mechanism of action of resveratrol remained largely controversial. Here, we demonstrate that under physiologically relevant conditions major biological effects of resveratrol can be attributed to the generation of oxidation products such as reactive oxygen species (ROS). At low hormetic concentrations (< 50 µM), treatment with resveratrol increased cell viability in a set of representative cell models, whereas application of quenchers of ROS completely truncated these beneficial effects. Notably, application of resveratrol led to mild, Nrf2-specific cellular gene expression reprogramming. For example, in 2 primary human epidermal keratinocytes this resulted in a 1.3-fold increase of endogenous metabolites such as glutathione (GSH) and subsequently in a quantitative reduction of the cellular redox environment by 2.61 mV mmol GSH per g protein.After external application of oxidative stress by using 0.8% (v/v) ethanol, endogenous generation of ROS was consequently reduced by 24% in resveratrol pre-treated cells.In contrast to the common perception that resveratrol acts mainly as a chemical antioxidant or as a target protein-specific ligand, we propose that effects from resveratrol treatment are essentially based on oxidative triggering of cells. In relevant physiological microenvironments this effect can lead to hormetic shifting of cellular defence towards a more reductive state to improve resilience to oxidative stress in a manner that can be exactly defined by the redox-environment of the cell.

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Section: Resultsmentioning

confidence: 60%

Hormetic Shifting of Redox Environment by Pro-Oxidative Resveratrol Protects Cells Against Stress

Plauth

Geikowski

Cichon

et al. 2016

Preprint

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“…The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) functions as a master regulator of the antioxidant response by regulating the expression of cytoprotective genes, including genes involved in the antioxidant GSH pathway (14–16). Notably, a Hcy-activated Nrf2-antioxidant reaction has been demonstrated in mouse macrophage and human hepatoma cell lines (6,9,10).…”

Section: Introductionmentioning

confidence: 99%

Nrf2 mediates the protective effects of homocysteine by increasing the levels of GSH content in HepG2 cells

Zhang

Dong

Chen

et al. 2017

Molecular Medicine Reports

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Homocysteine (Hcy) and glutathione (GSH) are crucial reduction-oxidation mediators. The underlying mechanisms governing the effects of Hcy on GSH generation in the progression of alcoholic liver disease has so far received little attention. The present study hypothesized that the antioxidant transcriptional factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) may participate in Hcy-mediated regulation of GSH production in HepG2 human liver cancer cells. MTT assay was used to study the cytotoxicity of homocysteine, western blot analysis and immunofluorescence staining were used to determine the effect of Hcy on Nrf2 expression. Our data demonstrated that HepG2 cells exposed to exogenous levels of Hcy (0–100 µM) exhibited elevated GSH levels in a concentration-dependent manner. Furthermore, 4-hydroxynonenal (4-HNE)-induced cell injury was attenuated by Hcy; however, this protective effect was blocked by the GSH-production inhibitor buthionine sulfoximine. Hcy treatment was able to induce Nrf2 protein expression in HepG2 cells. Treatment with the Nrf2 activator tert-butylhydroquinone (0–100 µM) increased GSH expression in a concentration-dependent manner; however, Nrf2-siRNA abolished the Hcy-induced increase in GSH expression and cellular protection in 4-HNE-stressed HepG2 cells. In conclusion, the antioxidant transcriptional factor Nrf2 was demonstrated to mediate the Hcy-induced increase in GSH expression levels and cellular protection in HepG2 cells.

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“…It has been reported that resveratrol induced Hsp25 and Hsp70 proteins in G93A-SOD1 mutant mice cells and can prevent motor neuron losses [48]. Resveratrol dose-dependently increased glutathione expression through the Nrf2 pathway in normal human keratocytes [49]. In the human neuroblastoma cell line SH-SY5Y, resveratrol dose-dependently increased HO-1 expression and HO-1-dependent autophagic flux and prevented rotatone-induced apoptosis [50].…”

Section: Gene Expression and Regulation In Mammalian Cells -Transcripmentioning

confidence: 99%

Stress Response of Dietary Phytochemicals in a Hormetic Manner for Health and Longevity

Gezer¹

2018

Gene Expression and Regulation in Mammalian Cells - Transcription Toward the Establishment of Novel Therapeutics

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The stress responses observed in mammalian cells can be classified as heat shock response, unfolded protein response, autophagic response, deoxyribonucleic acid damage response, antioxidant response, and sirtuin response at the intracellular and molecular levels. Factors that strengthen the hemodynamic structure causing low-level molecular damage and activating one or several stress response pathways are called hormetins. Hormetins can be categorized as physical, physiological, biological, and nutritional hormetins. Nutritional hormetins provide an interesting, comprehensive research topic because of their effects on health and lifespan. Dietary phytochemicals, with their low-level stress-inducing effects, are potential nutritional hormetins. Resveratrol, curcumin, epicatechin, isothiocyanates, ferulic acid, and certain vitamin-minerals can induce a heat shock response, unfolded protein response, autophagic response, deoxyribonucleic acid damage response, antioxidant response, and sirtuin response causing the stimulation of kinases and transcription factors. Studies have shown that these phytochemicals are related to nuclear factor-erythroid 2, sirtuins, nuclear factor-kappa B, and heat shock response pathways. In this chapter, the stress response of dietary phytochemicals will be systematically examined in a hormetic manner for delay of age-related diseases, healthy aging, and longevity based on current data.

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Skin resistance to oxidative stress induced by resveratrol: From Nrf2 activation to GSH biosynthesis

Cited by 90 publications

References 55 publications

Hormetic Shifting of Redox Environment by Pro-Oxidative Resveratrol Protects Cells Against Stress

Hormetic Shifting of Redox Environment by Pro-Oxidative Resveratrol Protects Cells Against Stress

Nrf2 mediates the protective effects of homocysteine by increasing the levels of GSH content in HepG2 cells

Stress Response of Dietary Phytochemicals in a Hormetic Manner for Health and Longevity

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