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Celastrol protects human retinal pigment epithelial cells against hydrogen peroxide mediated oxidative stress, autophagy, and apoptosis through sirtuin 3 signal pathway
Author(s) -
Du Zhaojiang,
Zhang Wen,
Wang Shengyu,
Zhang Jing,
He Jingang,
Wang Yuan,
Dong Yuhong,
Huo Min
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28326
Subject(s) - celastrol , sirt3 , oxidative stress , apoptosis , autophagy , chemistry , microbiology and biotechnology , sirtuin , retinal pigment epithelium , small interfering rna , retinal , biology , biochemistry , transfection , acetylation , gene
Age‐related macular degeneration (AMD), one of the most common causes of visual impairment, often occurrs in the elderly in developed countries. Oxidative stress, autophagy, and apoptosis of retinal pigment epithelial (RPE) cells play roles in the pathogenesis of AMD. In the current study, the protective effect of celastrol against hydrogen peroxide (H 2 O 2 )‐induced oxidative stress and apoptosis was investigated using a human RPE cell line (ARPE‐19). H 2 O 2 inhibited ARPE‐19 cells' survival and autophagy and induced their oxidative stress and apoptosis. Compared with the H 2 O 2 group, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay showed that celastrol increased ARPE‐19 cells' survival in a dose‐ and time‐dependent manner. Further, studies have suggested that celastrol has antioxidative stress and antiapoptosis effects in H 2 O 2 ‐treated ARPE‐19 cells. Also, cell autophagy is activated by celastrol in H 2 O 2 ‐treated ARPE‐19 cells. Reverse transcription polymerase chain reaction and Western blot showed that celastrol elevated the messenger RNA (mRNA) and protein expression of sirtuin 3 (SIRT3) in H 2 O 2 ‐induced ARPE‐19 cells. Inhibition of the level of SIRT3 by SIRT3 small interfering RNA (siRNA) reversed the effects of celastrol on oxidative stress, autophagy, and apoptosis in H 2 O 2 ‐induced ARPE‐19 cells. In conclusion, these observations suggest that celastrol activates the SIRT3 pathway in RPE cells and protects against H 2 O 2 ‐induced oxidative stress and apoptosis.