Involvement of MsrB1 in the regulation of redox balance and inhibition of peroxynitrite-induced apoptosis in human lens epithelial cells.

Abstract

Methionine sulfoxide reductases (Msrs) in lens cells are important for the maintenance of lens cell viability and resistance to oxidative stress damage. Peroxynitrite (ONOO(-)), as a strong oxidizing and nitrating agent, occurred in diabetic retinopathy patients and diabetic model animal. In an attempt to shed light on the roles of MsrB1, known as selenoprotein R, in protecting human lens epithelial (HLE) cells against peroxynitrite damage, and contribution of loss of its normal activity to cataract, the influences of MsrB1 gene silencing on peroxynitrite-induced apoptosis in HLE cells were studied. The results showed that both exogenous peroxynitrite and MsrB1 gene silencing by short interfering RNA (siRNA) independently resulted in oxidative stress, endoplasmic reticulum (ER) stress, activation of caspase-3 as well as an increase of apoptosis in HLE cells; moreover, when MsrB1-gene-silenced cells were exposed to 300 μM peroxynitrite, these indexes were further aggravated at the same conditions and DNA strand breaks occurred. The results demonstrate that in HLE cells MsrB1 may play important roles in regulating redox balance and mitigating ER stress as induced by oxidative stress under physiological conditions; MsrB1 may also protect HLE cells against peroxynitrite-induced apoptosis by inhibiting the activation of caspase-3 and oxidative damage of DNA under pathological conditions. Our results imply that loss of its normal activity is likely to contribute to cataract.

• Authors: Yi Jia, Yi Li, Shaoqing Du, Kaixun Huang
• Journal: Experimental eye research (Exp Eye Res) Vol. 100 Pg. 7-16 (Jul 2012) ISSN: 1096-0007 [Electronic] England
• PMID: 22713178 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Endoplasmic Reticulum Chaperone BiP
• Heat-Shock Proteins
• Microfilament Proteins
• RNA, Messenger
• RNA, Small Interfering
• Reactive Oxygen Species
• Transcription Factors
• Peroxynitrous Acid
• Malondialdehyde
• MSRB2 protein, human
• Methionine Sulfoxide Reductases
• Caspase 3

Topics

• Apoptosis (drug effects)
• Blotting, Western
• Caspase 3 (metabolism)
• Cell Survival (physiology)
• Cells, Cultured
• Endoplasmic Reticulum (metabolism)
• Endoplasmic Reticulum Chaperone BiP
• Epithelial Cells (enzymology, pathology)
• Flow Cytometry
• Gene Silencing (physiology)
• Heat-Shock Proteins (metabolism)
• Humans
• Lens, Crystalline (enzymology, pathology)
• Malondialdehyde (metabolism)
• Methionine Sulfoxide Reductases (physiology)
• Microfilament Proteins
• Oxidation-Reduction
• Oxidative Stress
• Peroxynitrous Acid (toxicity)
• RNA, Messenger (metabolism)
• RNA, Small Interfering (genetics)
• Reactive Oxygen Species (metabolism)
• Real-Time Polymerase Chain Reaction
• Spectrometry, Fluorescence
• Transcription Factors (physiology)