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.
Highlights
Age-related macular degeneration (AMD) is a progressive retinal degenerative disease affecting more than 150 million people in the world [1,2]
We have demonstrated that the inhibition of starvation-triggered endoplasmic reticulum (ER) stress, autophagy, and apoptosis in ARPE-19 cells by taurine is caused by the modulation of the expression of calpain-1 and calpain-2 levels
Our findings suggest remarkably protective effects of taurine on Earle’s balanced salt solution (EBSS)-induced ARPE-19 cells apoptosis by attenuating ER stress and autophagy via mechanisms involving the inhibition of calpain-2 and the activation of calpain-1 (Figures 6 and 7)
Summary
Age-related macular degeneration (AMD) is a progressive retinal degenerative disease affecting more than 150 million people in the world [1,2]. Disruption of retinal pigment epithelium (RPE) is one of the major pathological changes in AMD. Cells with nutrient deficiencies have been found to be hypersensitive to various cell death stimuli, such as autophagy [6], loss of calcium homeostasis [7], and ER stress [8,9]. Autophagy is the major intracellular degradation system that regulates the degradation of long-lived proteins, organelles, and other cellular contents [10]. This process occurs at basal levels in all cells but it is rapidly upregulated in response to nutrient deprivation, endoplasmic reticulum (ER) stress, pathogen infection, and/or hypoxia [11]. Autophagy activation leads to the reduction of accumulation of misfolded and aggregated proteins in several neurodegenerative disorders
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