期刊
TOXICOLOGY LETTERS
卷 237, 期 2, 页码 121-132出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2015.06.005
关键词
Metallothionein; Autophagy; Hypertensive heart disease; L-NAME
类别
资金
- International Cooperation Fund of Shaanxi [2015KW-06]
- National Natural Science Foundation of China [81470500]
Hypertension is an independent risk factor for heart disease and is responsible for the increased cardiac morbidity and mortality. Oxidative stress plays a key role in hypertensive heart diseases although the precise mechanism remains unclear. This study was designed to examine the effect of cardiac-specific overexpression of metallothionein, a cysteine-rich antioxidant, on myocardial contractile and intracellular Ca2+ anomalies in N-G-nitro-L-arginine methyl ester (L-NAME)-induced experimental hypertension and the mechanism involved with a focus on autophagy. Our results revealed that L-NAME treatment (14 days) led to hypertension and myocardial anomalies evidenced by interstitial fibrosis, cardiomyocyte hypertrophy, increased LV end systolic and diastolic diameters (LVESD and LVEDD) along with suppressed fractional shortening. L-NAME compromised cardiomyocyte contractile and intracellular Ca2+ properties manifested as depressed peak shortening, maximal velocity of shortening/relengthening, electrically-stimulated rise in intracellular Ca2+, elevated baseline and peak intracellular Ca2+. These L-NAME-induced histological and mechanical changes were attenuated or reconciled by metallothionein. Protein levels of autophagy markers LC3B and p62 were decreased and increased, respectively. Autophagy signaling molecules AMPK, TSC2 and ULK1 were inactivated while those of mTOR and p70s6K were activated by L-NAME, the effects of which were ablated by metallothionein. Autophagy induction mimicked whereas autophagy inhibition nullified the beneficial effect of metallothionein against L-NAME. These findings suggested that metallothionein protects against L-NAME- induced myocardial anomalies possibly through restoration of autophagy. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据