title: Photooxidative damage in retinal pigment epithelial cells via GRP78  and the protective role of grape skin polyphenols.
abstract: 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.
authors.affiliation: College of Agriculture and Biology, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Yun
authors.initials: Y
authors.lastname: Jiang
authors.forename: Lijiang
authors.initials: L
authors.lastname: Wu
authors.forename: Xiangzhong
authors.initials: X
authors.lastname: Cai
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D000091342:Endoplasmic Reticulum Chaperone BiP; D005456:Fluorescent Dyes; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008027:Light; D008928:Mitochondria / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects*; D012168:Retinal Pigments / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D027843:Vitis / Q000737:chemistry*
chemical_list: C112040:A2-E (N-retinylidene-N-retinylethanolamine); D000091342:Endoplasmic Reticulum Chaperone BiP; D005456:Fluorescent Dyes; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D010936:Plant Extracts; D059808:Polyphenols; D020011:Protective Agents; D012168:Retinal Pigments; D012176:Retinoids