RT Journal Article
SR Electronic
T1 Hormetic Shifting of Redox Environment by Pro-Oxidative Resveratrol Protects Cells Against Stress
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 045567
DO 10.1101/045567
A1 Annabell Plauth
A1 Anne Geikowski
A1 Susanne Cichon
A1 Silvia J. Wowro
A1 Linda Liedgens
A1 Morten Rousseau
A1 Christopher Weidner
A1 Luise Fuhr
A1 Magdalena Kliem
A1 Gail Jenkins
A1 Silvina Lotito
A1 Linda J. Wainwright
A1 Sascha Sauer
YR 2016
UL http://biorxiv.org/content/early/2016/03/24/045567.abstract
AB Resveratrol has gained tremendous interest owing to multiple reported health-beneficial 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 redox-environment of the cell.