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Metallothionein prevents intermittent hypoxia-induced cardiac endoplasmic reticulum stress and cell death likely via activation of Akt signaling pathway in mice 期刊论文

编号：

a8e7c673-36a0-48f2-8168-cca490a9611f
作者：

Zhou, Shansha#^[1,2]Yin, Xia(尹霞)^[1,2]Zheng, Yang(郑杨)*^[1]Miao, Xiao^[2,3];Feng, Wenke^[4];Cai, Jun^[2];Cai, Lu(蔡露)*^[2,4]
语种：

英文
期刊：

TOXICOLOGY LETTERS ISSN：0378-4274 2014 年 227 卷 2 期 (113 - 123) ; JUN 5
收录：
关键词：

Obstructive sleep apnea Intermittent hypoxia Metallothionein Cardiomyopathy ER stress
摘要：

Endoplasmic reticulum (ER) stress, an adaptive response normally, causes apoptotic cell death under pathological conditions. Cardiac ER stress and associated cell death involve in the inflammatory responses that often cause cardiac remodeling and dysfunction. Here we examined whether chronic intermittent hypoxia (IH) induces cardiac ER stress and associated cell death along with inflammatory response and if so, whether these effects can be affected by transgenic overexpression or deletion of metallothionein gene (MT-TG or MT-KO). IH exposures for 3 days to 4 weeks significantly increased cardiac ER stress and apoptosis, shown by the increased expression of GRP78, ATF6 and CHOP, the activation of caspase-12 and capase-3, and the decreased Bc12/Bax expression ratio, predominantly in the 3rd week of IH exposures. These effects were significantly exacerbated in MT-KO mice, but completely prevented in MT-TG mice. In vitro mechanistic study with H9c2 cardiac and primary neonatal cardiomyocytes showed that MT protection from ER stress-induced apoptosis was mediated by up-regulating Akt phosphorylation since inhibition of Akt phosphorylation abolished MT"s protection MT from ER stress and apoptosis. These findings suggest that chronic IH is able to induce cardiac ER stress, cell death and inflammation can be prevented by MT, probably via up-regulation of Akt function. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
推荐引用方式
GB/T 7714：

Zhou Shansha,Yin Xia,Zheng Yang, et al. Metallothionein prevents intermittent hypoxia-induced cardiac endoplasmic reticulum stress and cell death likely via activation of Akt signaling pathway in mice [J].TOXICOLOGY LETTERS,2014,227(2):113-123.
APA：

Zhou Shansha,Yin Xia,Zheng Yang,Miao Xiao,&Cai Lu.(2014).Metallothionein prevents intermittent hypoxia-induced cardiac endoplasmic reticulum stress and cell death likely via activation of Akt signaling pathway in mice .TOXICOLOGY LETTERS,227(2):113-123.
MLA：

Zhou Shansha, et al. "Metallothionein prevents intermittent hypoxia-induced cardiac endoplasmic reticulum stress and cell death likely via activation of Akt signaling pathway in mice" .TOXICOLOGY LETTERS 227,2(2014):113-123.
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