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Resveratrol prevention of oxidative stress damage to lens epithelial cell cultures is mediated by forkhead box O activity.

Abstract：

PURPOSE:To evaluate the potential role that FoxO transcription factors play in modulating resveratrol's protective effects against oxidative stress in lens epithelial cells. METHODS:Primary human or porcine lens epithelial cells (LECs) were treated with resveratrol (RES) 25 μM and incubated under either physiologic (5%) or chronic hyperoxic (40%) oxygen conditions. Acute oxidative stress was applied using 600 μM H(2)O(2). Changes in expression of FoxO1A, FoxO3A, and FoxO4 were analyzed. The production of intracellular reactive oxygen species (iROS), SA-β-galactosidase (SA-β-gal) activity, and autofluorescence (AF) was assessed by flow cytometry. SiRNAs of FoxO1A, FoxO3A, and FoxO4 were used to study the roles that these transcription factors play in resveratrol's protective effects against cell death induced by oxidative stress. RESULTS:RES incubation under 40% oxygen increased the expression of FoxO1A, FoxO3A, and FoxO4. RES also increases mitochondrial membrane potential under 5% and/or 40% O(2) conditions and significantly decreased iROS, SA-β-gal, and AF normally induced by hyperoxic conditions. While RES had a mild pro-apoptotic effect in nonstressed cells, it significantly prevented apoptosis induced by H(2)O(2) stress. SiRNA inhibition of FoxO1A, FoxO3A, and FoxO4 not only led to loss of the anti-apoptotic effects of RES in stressed cells but actually exhibited a mild pro-apoptotic effect. CONCLUSIONS:RES exerts a protective effect against oxidative damage in LEC cultures. The levels of expression of FoxO1A, FoxO3A, and FoxO4 appear to play a central role in determining the pro- or anti-apoptotic effects of RES. This has implications for future studies on oxidative stress-related lenticular disorders such as cataract formation.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Li G,Luna C,Navarro ID,Epstein DL,Huang W,Gonzalez P,Challa P

doi

10.1167/iovs.10-6652

subject

Has Abstract

pub_date

2011-06-21 00:00:00

pages

4395-401

issue

eissn

0146-0404

issn

1552-5783

pii

iovs.10-6652

journal_volume

pub_type

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Resveratrol prevention of oxidative stress damage to lens epithelial cell cultures is mediated by forkhead box O activity.