Heme Oxygenase-1 Prevents Cardiac Dysfunction in Streptozotocin-Diabetic Mice by Reducing Inflammation, Oxidative Stress, Apoptosis and Enhancing Autophagy

被引：120

作者：

Zhao, Yanli ^{[1
,2
]}

Zhang, Lina ^{[1
,6
]}

Qiao, Yu ^{[1
]}

Zhou, Xiaoling ^{[1
]}

Wu, Guodong ^{[1
]}

Wang, Lujing ^{[1
]}

Peng, Yahui ^{[1
]}

Dong, Xingli ^{[1
]}

Huang, Hui ^{[1
]}

Si, Lining ^{[5
]}

Zhang, Xueying ^{[1
]}

Zhang, Lei ^{[1
]}

Li, Jihong ^{[1
]}

Wang, Wei ^{[1
]}

Zhou, Lingyun ^{[1
]}

Gao, Xu ^{[1
,3
,4
]}

机构：

[1] Harbin Med Univ, Dept Biochem, Harbin, Heilongjiang, Peoples R China

[2] Qinghai Univ, Coll Med, Dept Biochem, Xining, Qinghai, Peoples R China

[3] Harbin Med Univ, Minist Educ, Key Lab Cardiovasc Med Res, Harbin, Heilongjiang, Peoples R China

[4] Harbin Med Univ, State Prov Key Labs Biomed Pharmaceut China, Harbin, Heilongjiang, Peoples R China

[5] Qinghai Univ, Sch Med, Affiliated Hosp, Dept Critical Care Med, Xining, Qinghai, Peoples R China

[6] Daqing Oilfield Gen Hosp, Dept Clin Lab, Daqing, Heilongjiang, Peoples R China

来源：

PLOS ONE | 2013年 / 8卷 / 09期

关键词：

SIGNALING PATHWAY; NADPH OXIDASE; CELL-DEATH; PROTECTIVE ROLE; GROWTH-FACTOR; CARDIOMYOPATHY; HEART; MECHANISMS; EXPRESSION; KINASE;

D O I：

10.1371/journal.pone.0075927

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Heme oxygenase-1 (HO-1) has been implicated in cardiac dysfunction, oxidative stress, inflammation, apoptosis and autophagy associated with heart failure, and atherosclerosis, in addition to its recognized role in metabolic syndrome and diabetes. Numerous studies have presented contradictory findings about the role of HO-1 in diabetic cardiomyopathy (DCM). In this study, we explored the role of HO-1 in myocardial dysfunction, myofibril structure, oxidative stress, inflammation, apoptosis and autophagy using a streptozotocin (STZ)-induced diabetes model in mice systemically overexpressing HO-1 (Tg-HO-1) or mutant HO-1 (Tg-mutHO-1). The diabetic mouse model was induced by multiple peritoneal injections of STZ. Two months after injection, left ventricular (LV) function was measured by echocardiography. In addition, molecular biomarkers related to oxidative stress, inflammation, apoptosis and autophagy were evaluated using classical molecular biological/biochemical techniques. Mice with DCM exhibited severe LV dysfunction, myofibril structure disarray, aberrant cardiac oxidative stress, inflammation, apoptosis, autophagy and increased levels of HO-1. In addition, we determined that systemic overexpression of HO-1 ameliorated left ventricular dysfunction, myofibril structure disarray, oxidative stress, inflammation, apoptosis and autophagy in DCM mice. Furthermore, serine/threonine-specific protein kinase (Akt) and AMP-activated protein kinase (AMPK) phosphorylation is normally inhibited in DCM, but overexpression of the HO-1 gene restored the phosphorylation of these kinases to normal levels. In contrast, the functions of HO-1 in DCM were significantly reversed by overexpression of mutant HO-1. This study underlines the unique roles of HO-1, including the inhibition of oxidative stress, inflammation and apoptosis and the enhancement of autophagy, in the pathogenesis of DCM.

引用

页数：12

共 73 条

[1] Overexpression of human heme oxygenase-1 attenuates endothelial cell sloughing in experimental diabetes [J].