Piceatannol Protect Rpe Cells Against Photooxidative Damage

Vitamin A dimer-mediated photooxidation induced retinal pigment epithelium(RPE)damage,which is associated with age-related degenerative disease of retina,leading to blindness.At present,dietary supplement of natural antioxidants is an important method to prevent and delay the oxidative damage of RPE cells.It has been reported that polyphenols in grape reduces oxidative stress in the eye.Piceatannol is one of these polyphenols with a nutural stilbene structure.It has been reported that piceatannol provides potent biological activities and health benefits.Based on these reports,we hypothesized that piceatannol may protect RPE cells against photooxidate damage.To investigate this hypothesis,ARPE-19 cells that accumulate vitamin A dimer,A2 E,were used as a model system to mimic vitamin A dimer-mediated photooxidation.And here we address the molecular mechanism by which piceatannol protect RPE cells against photooxidate damage.The main results as followings:1.Piceatannol protect RPE cells from photooxidate damage.Exposure of A2 E loaded ARPE-19 cells to blue light resulted in apoptosis,which was significantly inhibited by pre-treatment with piceatannol(p<0.01).2.Photooxidation enhanced ROS production(p <0.01).Pre-treatment of blue light-exposed A2 E containing ARPE-19 cells with Piceatannol attenuated ROS(p<0.05).3.Pre-treatment with piceatannol increased nuclear transportation of Nrf2,upregulated the expression of HO-1 and NQO-1(p<0.05).Additionally,the protective effect of piceatannol against photooxidation-induced apoptosis was blocked in cells in which Nrf2 had been knocked down;and the up-regulation of HO-1 and NQO-1 expression was attenuated.4.Pre-treatment with piceatannol enhanced p-Akt expression(p<0.05).Moreover,PI3K/Akt was identified as the upstream targets of HO-1 and NQO-1 expression using PI3K/Akt inhibitor,which revealed that PI3K/AKT pathway played a critical role in Nrf2 pathway activation induced by piceatannol.5.Piceatannol can attenuate endoplasmic reticulum stress(ER stress)in photooxidative damaged RPE cells as evidenced by the reduced expression level of ER stress apoptosis makers including CHOP,ATF6 and p-IRE1?(p < 0.05).In addition,the ER stress inhibiting effect of piceatannol was blocked in cells in which Nrf2 had been knocked down.Together,Piceatannol protected RPE cells from Vitamin A dimermediated photooxidative damage by up-regulating HO-1and NQO-1 expression and inhibiting ER stress via the activation of Nrf2 nuclear,and the PI3K/Akt pathway is involved in this process.