Attenuation by metallothionein of early cardiac cell death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy

doi:10.1016/j.jacc.2006.07.022

科研成果详情

题名	Attenuation by metallothionein of early cardiac cell death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy
作者	Cai, Lu ; Wang, Yuehui ; Zhou, Guihua ; Chen, Teresa ; Song, Ye ; Li, Xiaokun ; Kang, Y. James
发表期刊	JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	TRANSGENIC MOUSE HEART ; APOPTOSIS ; OVEREXPRESSION ; HYPERGLYCEMIA ; RATS ; INHIBITION ; ACTIVATION ; DAMAGE ; MICE
摘要	OBJECTIVES We aimed to test whether attenuation of early-phase cardiac cell death can prevent diabetic cardiomyopathy. BACKGROUND Our previous study showed that cardiac apoptosis as a major early cellular response to diabetes is induced by hyperglycemia-derived oxidative stress that activates a mitochondrial cytochrome c-mediated caspase-3 activation pathway. Metallothionein (MT) as a potent antioxidant prevents the development of diabetic cardiomyopathy. METHODS Diabetes was induced by a single dose of streptozotocin (STZ) (150 mg/kg) in cardiac-specific, metallothionein-overexpressing transgenic (MT-TG) mice and wild-type (WT) controls. On days 7, 14, and 21 after STZ treatment, cardiac apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and caspase-3 activation. Cardiomyopathy was evaluated by cardiac ultrastructure and fibrosis in the diabetic mice 6 months after STZ treatment. RESULTS A significant reduction in diabetes-induced increases in TUNEL-positive cells, caspase-3 activation, and cytochrome c release from mitochondria was observed in the MT-TG mice as compared to WT mice. Cardiac protein nitration (3-nitrotyrosine [3-NT]) and lipid peroxidation were significantly increased, and there was an increase in mitochondrial oxidized glutathione and a decrease in mitochondrial reduced glutathione in the WT, but not in the MT-TG, diabetic mice. Double staining for cardiomyocytes with alpha sarcomeric actin and caspase-3 or 3-NT confirmed the cardiomyocyte-specific effects. A significant prevention of diabetic cardiomyopathy and enhanced animal survival were observed in the MT-TG diabetic mice as compared to WT diabetic mice. CONCLUSIONS These results suggest that attenuation of early-phase cardiac cell death by MT results in a significant prevention of the development of diabetic cardiomyopathy. This process is mediated by MT suppression of mitochondrial oxidative stress.
资助项目	NHLBI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [HL59225, HL63760] Funding Source: Medline; NATIONAL HEART, LUNG, AND BLOOD INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01HL063760, R01HL059225] Funding Source: NIH RePORTER
出版者	ELSEVIER SCIENCE INC
出版地	NEW YORK
ISSN	0735-1097
EISSN	1558-3597
卷号	48 期号:8 页码:1688-1697
DOI	10.1016/j.jacc.2006.07.022
WOS类目	Cardiac & Cardiovascular Systems
WOS研究方向	Cardiovascular System & Cardiology
WOS记录号	WOS:000241414600026
收录类别	SCIE ; SCOPUS
发表日期	2006-10-17
URL	查看原文
Scopus记录号	2-s2.0-33749513188
自科自定义期刊分类	T2(B)类
引用统计	被引频次：293[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/4339
专题	药学院（分析测试中心）
通讯作者	Cai, Lu
作者单位	1.Univ Louisville, Dept Med, Louisville, KY 40292 USA; 2.Univ Louisville, Dept Pharmacol, Louisville, KY 40292 USA; 3.Univ Louisville, Dept Toxicol, Louisville, KY 40292 USA; 4.Wenzhou Med Coll, Sch Pharmaceut Sci, Wenzhou, Peoples R China
推荐引用方式 GB/T 7714	Cai, Lu,Wang, Yuehui,Zhou, Guihua,et al. Attenuation by metallothionein of early cardiac cell death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy[J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY,2006,48(8):1688-1697.
APA	Cai, Lu., Wang, Yuehui., Zhou, Guihua., Chen, Teresa., Song, Ye., ... & Kang, Y. James. (2006). Attenuation by metallothionein of early cardiac cell death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 48(8), 1688-1697.
MLA	Cai, Lu,et al."Attenuation by metallothionein of early cardiac cell death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy".JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 48.8(2006):1688-1697.