Photooxidative damage in retinal pigment epithelial cells via GRP78 and the protective role of grape skin polyphenols

被引：46
作者：
Zhao, Zhao [1 ]
Sun, Tao [1 ]
Jiang, Yun [1 ]
Wu, Lijiang [1 ]
Cai, Xiangzhong [1 ]
Sun, Xiaodong [2 ,3 ]
Sun, Xiangjun [1 ]
机构：
[1] Shanghai Jiao Tong Univ, Coll Agr & Biol, Shanghai 200030, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Ophthalmol, Shanghai 200030, Peoples R China
[3] Shanghai Jiao Tong Univ, Eye Res Inst, Shanghai 200030, Peoples R China
来源：
FOOD AND CHEMICAL TOXICOLOGY | 2014年 / 74卷
基金：
中国国家自然科学基金;
关键词：
Grape skin polyphenols; RPE; Apoptosis; Photooxidation; ER stress; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; OXIDATIVE STRESS; INDUCED APOPTOSIS; ER STRESS; IN-VITRO; MITOCHONDRIAL DYSFUNCTION; LIPOFUSCIN FLUOROPHORE; RPE CELLS; A2E;
D O I：
10.1016/j.fct.2014.10.001
中图分类号：
TS2 [食品工业];
学科分类号：
0832 ;
摘要：
Blue light induced oxidative damage and ER stress are related to the pathogenesis of age-related macular degeneration (AMD). However, the mechanism of blue light-induced damage remained obscure. The objective of this work is to assess the photooxidative damage to retinal pigment epithelial cells (RPE) and oxidation-induced changes in expression of ER stress associated apoptotic proteins, and investigate the mechanism underlying the protective effects of grape skin extracts. To mimic lipofuscin-mediated photooxidation in vivo, ARPE-19 cells that accumulated A2E, one of lipofuscin fluorophores, were used as a model system to investigate the mechanism of photooxidative damage and the protective effects of grape skin polyphenols. Exposure of A2E containing ARPE-19 cells to blue light resulted in significant apoptosis and increases in levels of GRP78, CHOP, p-JNK, Bax, cleaved caspase-9, and cleaved caspase-3, indicating that photooxidative damage to RPE cells is mediated by the ER-stress-induced intrinsic apoptotic pathway. Cells in which GRP78 had been knocked down with shRNA were more vulnerable to photooxidative damage. Pre-treatment of blue-light-exposed A2E containing ARPE-19 cells, with grape skin extracts, inhibited apoptosis, in a dose dependent manner. Knockdown GRP78 blocked the protective effect of grape skin extracts. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码：216 / 224
页数：9
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