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学科主题: 基础医学
题名:
Mitofusin-2 is a major determinant of oxidative stress-mediated heart muscle cell apoptosis
作者: Shen, Tao; Zheng, Ming; Cao, Chunmei; Chen, Chunlei; Tang, Jian; Zhang, Wanrui; Cheng, Heping; Chen, Kuang-Hueih; Xiao, Rui-Ping
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2007-08-10
DOI: 10.1074/jbc.M702657200
卷: 282, 期:32, 页:23354-23361
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: FAILING HUMAN HEART ; MITOCHONDRIAL FUSION ; CARDIOMYOCYTE APOPTOSIS ; MAMMALIAN HOMOLOGS ; SIGNALING PATHWAY ; CARDIAC MYOCYTES ; DEATH ; FAILURE ; BAX ; MFN2
英文摘要:

An inexorable loss of terminally differentiated heart muscle cells is a crucial causal factor for heart failure. Here, we have provided several lines of evidence to demonstrate that mitofusin-2 (Mfn-2; also called hyperplasia suppressor gene), a member of the mitofusin family, is a major determinant of oxidative stress-mediated cardiomyocyte apoptosis. First, oxidative stress with H2O2 led to concurrent increases in Mfn-2 expression and apoptosis in cultured neonatal rat cardiomyocytes. Second, overexpression of Mfn-2 to a level similar to that induced by H2O2 was sufficient to trigger myocyte apoptosis, which is associated with profound inhibition of Akt activation without altering ERK1/2 signaling. Third, Mfn-2 silencing inhibited oxidative stress-induced apoptosis in H9C2 cells, a cardiac muscle cell line. Furthermore, Mfn-2-induced myocyte apoptosis was abrogated by inhibition of caspase-9 (but not caspase-8) and by overexpression of Bcl-x(L) or enhanced activation of phosphatidylinositol 3-kinase-Akt, suggesting that inhibition of Akt signaling and activation of the mitochondrial death pathway are essentially involved in Mfn-2-induced heart muscle cell apoptosis. These results indicate that increased cardiac Mfn-2 expression is both necessary and sufficient for oxidative stress-induced heart muscle cell apoptosis, suggesting that Mfn-2 deregulation may be a crucial pathogenic element and a potential therapeutic target for heart failure.

语种: 英语
WOS记录号: WOS:000248577500036
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56996
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China
2.NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA
3.Peking Univ, Inst Cardiovasc Sci, Beijing 100083, Peoples R China

Recommended Citation:
Shen, Tao,Zheng, Ming,Cao, Chunmei,et al. Mitofusin-2 is a major determinant of oxidative stress-mediated heart muscle cell apoptosis[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2007,282(32):23354-23361.
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