Role of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 in myocardial cells in diabetes.
Role of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 in myocardial cells in diabetes.
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Bcl-2/腺病毒 E1B 19 kDa 相互作用蛋白 3 在糖尿病心肌细胞中的作用。
DOI：
10.3892/etm.2015.2439
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发表时间：
2015
影响因子：
2.7
通讯作者：
Min Luo
中科院分区：
文献类型：
--
作者：
Wenzhong Zhou;Jian Yang;Di;Feng;Guo Li;Yanyun Gu;Min Luo
心血管并发症是与2型糖尿病相关的发病率和死亡率的主要原因。在大血管并发症中，糖尿病心肌病（DCM）通常被认为是认识和管理不足。Bcl-2/腺病毒E1 B 19 kDa相互作用蛋白3（BNIP 3）在心脏缺氧和酸中毒诱导的线粒体凋亡途径的启动中起关键作用。目前还不清楚BNIP 3是否对心脏细胞存活或适应高血糖也很重要。基于先前发现BNIP 3在糖尿病大鼠心脏中显著诱导，本研究将BNIP 3转染原代大鼠心肌细胞和H9 c2细胞系。过表达BNIP 3可降低线粒体膜电位，诱导细胞凋亡。当BNIP 3被敲低时，对细胞凋亡的影响被逆转。转录组分析表明，调节线粒体代谢的基因，如肉毒碱棕榈酰转移酶1b，细胞色素c氧化酶亚基VIIIb和肌酸激酶（脑），以及那些调节心脏纤维化的基因，如基质金属肽酶9，可能是BNIP 3在大鼠心肌细胞中的靶点。总之，高血糖诱导的BNIP 3表达可能会损害心脏细胞的存活和功能。在糖尿病状态下，BNIP 3可能参与线粒体功能、脂代谢和纤维化的调节。因此，BNIP 3可以作为针对糖尿病大血管并发症，特别是DCM的潜在药物靶标。
Cardiovascular complications are the major causes of morbidity and mortality associated with Type 2 Diabetes. Among the macrovascular complications, diabetic cardiomyopathy (DCM) is generally considered to be inadequately recognized and managed. Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3), is known to play a key role in the initiation of the mitochondrial pathway of apoptosis induced by hypoxia and acidosis in the heart. It is unknown whether BNIP3 is also important for cardiac cell survival or adaption in response to hyperglycemia. Based on the previous finding that BNIP3 was significantly induced in the diabetic rat heart, BNIP3 was transfected in primary rat cardiomyocytes and the H9c2 cell line in the present study. Overexpressed BNIP3 decreased the mitochondrial membrane potential and induced cell apoptosis. When BNIP3 was knocked down, the effect on cell apoptosis was reversed. Transcriptome analysis showed that the genes regulating mitochondrial metabolism, such as carnitine palmitoyltransferase 1b, cytochrome c oxidase subunit VIIIb and creatine kinase (brain), and those regulating cardiac fibrosis, such as matrix metallopeptidase 9, could be the targets of BNIP3 in rat cardiomyocytes. In conclusion, hyperglycemia-induced BNIP3 expression may compromise cardiac cell survival and function. Under the diabetic condition, BNIP3 could be involved in the regulation of mitochondrial function, lipid metabolism and fibrosis. BNIP3 could therefore serve as a potential drug target against diabetic macrovascular complications and, in particular, DCM.
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DOI：
10.1016/j.bbamcr.2011.01.014
发表时间：
2011-07
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Duncan JG
通讯作者：
Duncan JG
影响因子：
16.2
作者：
Bertoni, AG;Tsai, A;Brancati, FL
通讯作者：
Brancati, FL
影响因子：
10.8
作者：
Yu, Tianzheng;Sheu, Shey-Shing;Yoon, Yisang
通讯作者：
Yoon, Yisang
影响因子：
15.9
作者：
Diwan, Abhinav;Krenz, Maike;Dorn, Gerald W., II
通讯作者：
Dorn, Gerald W., II
影响因子：
11.2
作者：
Papandreou, I;Krishna, C;Denko, NC
通讯作者：
Denko, NC