title: Role of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 in myocardial cells in diabetes.
abstract: 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, cytochromecoxidase 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.
authors.affiliation: Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Wenzhong
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: D I
authors.initials: DI
authors.lastname: Zhang
authors.affiliation: Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Fengyin
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai 200025, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
keywords: Bcl-2/adenovirus E1B 19 kDa-interacting protein 3; diabetes; diabetic cardiomyopathy