Inhibition of Starvation-Triggered Endoplasmic Reticulum Stress, Autophagy, and Apoptosis in ARPE-19 Cells by Taurine through Modulating the Expression of Calpain-1 and Calpain-2

牛磺酸通过调节钙蛋白酶-1和钙蛋白酶-2的表达抑制ARPE-19细胞中饥饿引发的内质网应激、自噬和凋亡

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作者:Yuanyuan Zhang, Shu Ren, Yuci Liu, Kun Gao, Zheng Liu, Zhou Zhang

Abstract

Age-related macular degeneration (AMD) is a complex disease with multiple initiators and pathways that converge on death for retinal pigment epithelial (RPE) cells. In this study, effects of taurine on calpains, autophagy, endoplasmic reticulum (ER) stress, and apoptosis in ARPE-19 cells (a human RPE cell line) were investigated. We first confirmed that autophagy, ER stress and apoptosis in ARPE-19 cells were induced by Earle's balanced salt solution (EBSS) through starvation to induce RPE metabolic stress. Secondly, inhibition of ER stress by 4-phenyl butyric acid (4-PBA) alleviated autophagy and apoptosis, and suppression of autophagy by 3-methyl adenine (3-MA) reduced the cell apoptosis, but the ER stress was minimally affected. Thirdly, the apoptosis, ER stress and autophagy were inhibited by gene silencing of calpain-2 and overexpression of calpain-1, respectively. Finally, taurine suppressed both the changes of the important upstream regulators (calpain-1 and calpain-2) and the activation of ER stress, autophagy and apoptosis, and taurine had protective effects on the survival of ARPE-19 cells. Collectively, this data indicate that taurine inhibits starvation-triggered endoplasmic reticulum stress, autophagy, and apoptosis in ARPE-19 cells by modulating the expression of calpain-1 and calpain-2.

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