title: Supplementation of procyanidins B2 attenuates photooxidation-induced apoptosis in ARPE-19 cells.
abstract: During the aging process, dimers of dietary vitamin A accumulated in retinal pigment epithelium (RPE) cells. Vitamin A dimer-mediated photooxidation resulted in RPE apoptosis, which is associated with age-related degenerative disease of retina, leading to blindness. It has been reported that proanthocyanidin-rich grape seed extract reduces oxidative stress in the eye. In this study, we investigated the underlying mechanism of photooxidation-induced apoptosis inhibition by procyanidins B2 (PB2), one of the main components of grape seed proanthocyanidin. To mimic vitamin A dimer-mediated photooxidation, ARPE-19 cells that accumulated vitamin A dimer, A2E, were used as a model system. Exposure of A2E loaded ARPE-19 cells to blue light induced ER stress and resulted in significant apoptosis. Pretreatment of blue light-exposed A2E containing ARPE-19 cells with PB2 inhibited apoptosis, increased the ratio of Bcl-2/Bax in the mitochondria, attenuated ROS and cytochrome c release, and decreased caspase cleavage. Additionally, PB2 inhibited the phosphorylation of ER stress markers elF2α and IRE1α and reduced CHOP expression. Moreover, PB2 inhibition of apoptosis is dependent on the UPR chaperone GRP78, indicating PB2 inhibits vitamin A dimer-mediated apoptosis in RPE cells by activating the UPR.
authors.affiliation: a College of Agriculture and Biology , Shanghai Jiaotong University , Shanghai , China.
authors.forename: Weinan
authors.initials: W
authors.lastname: Li
authors.affiliation: a College of Agriculture and Biology , Shanghai Jiaotong University , Shanghai , China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: a College of Agriculture and Biology , Shanghai Jiaotong University , Shanghai , China.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.affiliation: a College of Agriculture and Biology , Shanghai Jiaotong University , Shanghai , China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yao
authors.affiliation: a College of Agriculture and Biology , Shanghai Jiaotong University , Shanghai , China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D044946:Biflavonoids / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D002460:Cell Line; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D056604:Grape Seed Extract / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D044945:Proanthocyanidins / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014801:Vitamin A / Q000009:adverse effects*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D044946:Biflavonoids; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D014801:Vitamin A; D051742:Transcription Factor CHOP; C101003:ELF2 protein, human; C479580:procyanidin B2; D002392:Catechin; D045304:Cytochromes c; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases
keywords: Apoptosis; oxidative stress; photooxidation; procyanidins B2; retinal pigment epithelium