Selenoprotein R Protects Human Lens Epithelial Cells against D-Galactose-Induced Apoptosis by Regulating Oxidative Stress and Endoplasmic Reticulum Stress.

Jie Dai,Kaixun Huang,Jun Zhou,Hongmei Liu

doi:10.3390/ijms17020231

Jie Dai, Kaixun Huang + Show 2 more

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https://doi.org/10.3390/ijms17020231

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Abstract

Selenium is an essential micronutrient for humans. Much of selenium’s beneficial influence on health is attributed to its presence within 25 selenoproteins. Selenoprotein R (SelR), known as methionine sulfoxide reductase B1 (MsrB1), is a selenium-dependent enzyme that, like other Msrs, is required for lens cell viability. In order to investigate the roles of SelR in protecting human lens epithelial (hLE) cells against damage, the influences of SelR gene knockdown on d-galactose-induced apoptosis in hLE cells were studied. The results showed that both d-galactose and SelR gene knockdown by siRNA independently induced oxidative stress. When SelR-gene-silenced hLE cells were exposed to d-galactose, glucose-regulated protein 78 (GRP78) protein level was further increased, mitochondrial membrane potential was significantly decreased and accompanied by a release of mitochondrial cytochrome c. At the same time, the apoptosis cells percentage and the caspase-3 activity were visibly elevated in hLE cells. These results suggested that SelR might protect hLE cell mitochondria and mitigating apoptosis in hLE cells against oxidative stress and endoplasmic reticulum (ER) stress induced by d-galactose, implying that selenium as a micronutrient may play important roles in hLE cells.

Highlights

Selenium is an essential micronutrient for humans
These results imply that Selenoprotein R (SelR) plays important roles in protecting human lens epithelial (hLE) cells against apoptosis cells treated by SelR SiRNA were exposed to D-galactose, glucose-regulated protein 78 (GRP78) protein level was further increased; there was a similar increase for the percentage of apoptosis cells
Our results show that when the cells were only treated with SelR knockdown by short interfering RNAs (siRNA), mitochondrial dysfunction occurred; when SelR-gene-silenced cells were exposed to D-galactose (150 mM) for 36 h, mitochondrial dysfunction was further exacerbated, and the decrease of ∆ψm was accompanied (Figure 6) by an increased ratio of cytosolic-to-mitochondrial cytochrome c concentrations (Figure 7), with an increased activity of caspase-3 (Figure 8), indicating a role of SelR in protection mitochondria against D-galactose-induced mitochondrial damage in hLE cells

Summary

Introduction

Selenium is an essential micronutrient for humans. Much of selenium’s beneficial influence on health is attributed to its presence within 25 selenoproteins [1,2,3,4,5]. Previous studies showed that supplementation of selenium could slow the development of naphthalene cataract, possibly by attenuating the oxidative stress in the lens [6]. The mechanism of selenium in preventing or slowing cataract onset and progression remains virtually unclear. Oxidative stress is believed to play a major role in cataract formation. The research results [7,8] showed that the content of methionine sulfoxide (MetO) in membrane-bound protein of the lens increases with age, and in cataracts as much as 60% of the total membrane-bound protein methionine is found as MetO, suggesting a possible linkage between methionine oxidation and age-related cataracts. Among Msrs, MsrB1 is the only selenoprotein, named as Selenoprotein R (SelR). SelR is widely distributed throughout different tissues [10] and localized in the cell nucleus and cytosol [11,12]

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