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Hormetic shifting of redox environment by pro-oxidative resveratrol protects cells against stress

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Item Type:Preprint
Title:Hormetic shifting of redox environment by pro-oxidative resveratrol protects cells against stress
Creators Name:Plauth, A. and Geikowski, A. and Cichon, S. and Wowro, S.J. and Liedgens, L. and Rousseau, M. and Weidner, C. and Fuhr, L. and Kliem, M. and Jenkins, G. and Lotito, S. and Wainwright, L.J. and Sauer, S.
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 primary human epidermal keratinocytes this resulted in a 1.3-fold increase of endogenous metabolites such as gluthathione (GSH) and subsequently in a quantitative reduction of the cellular redox environment by 2.61 mV mmol GSH (g protein)-1. In particular in resveratrol pre-treated cells, after external application of oxidative stress by using 0.8 % ethanol, endogenous ROS generation was consequently reduced by 24 %. 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 redoxenvironment of the cell.
Publisher:Cold Spring Harbor Laboratory Press
Article Number:045567
Date:24 March 2016
Official Publication:https://doi.org/10.1101/045567
Related to:
http://edoc.mdc-berlin.de/15932/Final version

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