TY  - JOUR
A1  - Plauth, Annabell
A1  - Geikowski, Anne
A1  - Cichon, Susanne
A1  - Wowro, Sylvia J.
A1  - Liedgens, Linda
A1  - Rousseau, Morten
A1  - Weidner, Christopher
A1  - Fuhr, Luise
A1  - Kliem, Magdalena
A1  - Jenkins, Gail
A1  - Lotito, Silvina
A1  - Wainwright, Linda J.
A1  - Sauer, Sascha
T1  - Hormetic shifting of redox environment by pro-oxidative resveratrol protects cells against stress
JF  - Free Radical Biology and Medicine
N2  - Resveratrol has gained tremendous interest owing to multiple reported health-beneficial effects. However, the underlying key mechanism of action of this natural product remained largely controversial. Here, we demonstrate that under physiologically relevant conditions major biological effects of resveratrol can be attributed to its generation of oxidation products such as reactive oxygen species (ROS). At low nontoxic concentrations (in general < 50 mu M), treatment with resveratrol increased viability in a set of representative cell models, whereas application of quenchers of ROS completely truncated these beneficial effects. Notably, resveratrol treatment led to mild, Nrf2-specific gene expression reprogramming. For example, in primary epidermal keratinocytes derived from human skin this coordinated process resulted in a 1.3-fold increase of endogenously generated glutathione (GSH) and subsequently in a quantitative reduction of the cellular redox environment by 2.61 mV mmol GSH per g protein. After induction of oxidative stress by using 0.78% (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 the cellular response to resveratrol treatment is essentially based on oxidative triggering. In physiological microenvironments this molecular training can lead to hormetic shifting of cellular defense towards a more reductive state to improve physiological resilience to oxidative stress.
KW  - Trans-reservatrol
KW  - Hydrogen-peroxide
KW  - In-vitro
KW  - Hormesis
KW  - Ethanol
KW  - Oxygen
KW  - Nrf2
KW  - Glutathione
KW  - Metabolism
KW  - Polyphenols
KW  - ROS
KW  - Oxidative stress
KW  - Redox environment
KW  - Skin
KW  - Epidermis
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187186
VL  - 99
ER  -