Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.
Int J Mol Sci. 2017 Oct 14;18(10):2146. doi: 10.3390/ijms18102146.
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.
年龄相关性黄斑变性（AMD）是一种复杂的疾病，有多种启动子和途径，最终导致视网膜色素上皮（RPE）细胞死亡。在这项研究中，我们研究了牛磺酸对钙蛋白酶、自噬、内质网（ER）应激和 ARPE-19 细胞（一种人 RPE 细胞系）凋亡的影响。首先，我们通过饥饿诱导 RPE 代谢应激，用 Earle 的平衡盐溶液（EBSS）证实了 ARPE-19 细胞中的自噬、ER 应激和凋亡。其次，用 4-苯丁酸（4-PBA）抑制 ER 应激可减轻自噬和凋亡，用 3-甲基腺嘌呤（3-MA）抑制自噬可减少细胞凋亡，但对 ER 应激的影响很小。第三，钙蛋白酶-2 的基因沉默抑制了细胞凋亡、ER 应激和自噬，而钙蛋白酶-1 的过表达则分别抑制了自噬、ER 应激和细胞凋亡。最后，牛磺酸抑制了重要上游调节剂（钙蛋白酶-1 和钙蛋白酶-2）的变化以及 ER 应激、自噬和凋亡的激活，牛磺酸对 ARPE-19 细胞的存活具有保护作用。综上所述，这些数据表明，牛磺酸通过调节钙蛋白酶-1 和钙蛋白酶-2 的表达抑制了 ARPE-19 细胞因饥饿引起的内质网应激、自噬和凋亡。
