title: Pim-2 protects H9c2 cardiomyocytes from hypoxia/reoxygenation-induced apoptosis via downregulation of Bim expression.
abstract: We know that silencing Bim, a pro-apoptosis protein, significantly attenuates glucose and oxygen-deprived induced apoptosis in cardiomyocytes. However, the mechanisms underlying the regulation of the Bim activation in the heart have remained unknown. Pim-2 is one of three Pim serine/threonine kinase family members thought to be involved in cell survival and proliferation. H9c2 cardiomyocytes were subjected to a hypoxia/reoxygenation (H/R) condition in vitro, mimicking ischemic/reperfusion injury in vivo. H/R augmented the expression of Bim, Cyt C, and Pim-2 and induced H9c2 cell apoptosis. Overexpression of Pim-2 attenuated apoptosis which induced by H/R in H9c2 cells, via downregulation of Bim and Cyt C expression. Silencing of Pim-2 promoted H/R-induced apoptosis via upregulation of Bim and Cyt C expression. Co-IP revealed the interaction between Pim-2 and Bim protein, with Bim Ser65phosphorylated by Pim-2. Furthermore, blocking proteasome activity by MG132 prevented Bim degradation, and Bim S65A mutation could reverse the anti-apoptotic role of Pim-2 which induced by H/R. These data demonstrated that Pim-2 is a novel Bim-interacting protein, which negatively regulates Bim degradation and protects H9c2 cardiomyocytes from H/R-induced apoptosis.
authors: Department of Cardiovascular, Second affiliated Hospital of Nanchang University, Institute of Cardiovascular disease in Nanchang University, Nan Chang, Jiang Xi, 330006, China.
authors: Yan
authors: Y
authors: Xu
authors: Department of Cardiovascular, Second affiliated Hospital of Nanchang University, Institute of Cardiovascular disease in Nanchang University, Nan Chang, Jiang Xi, 330006, China.
authors: Yawei
authors: Y
authors: Xing
authors: Department of Cardiovascular, Second affiliated Hospital of Nanchang University, Institute of Cardiovascular disease in Nanchang University, Nan Chang, Jiang Xi, 330006, China.
authors: Yanjie
authors: Y
authors: Xu
authors: Department of Cardiovascular, Second affiliated Hospital of Nanchang University, Institute of Cardiovascular disease in Nanchang University, Nan Chang, Jiang Xi, 330006, China.
authors: Chahua
authors: C
authors: Huang
authors: Department of Cardiovascular, Second affiliated Hospital of Nanchang University, Institute of Cardiovascular disease in Nanchang University, Nan Chang, Jiang Xi, 330006, China.
authors: Huihui
authors: H
authors: Bao
authors: Department of Cardiovascular, Second affiliated Hospital of Nanchang University, Institute of Cardiovascular disease in Nanchang University, Nan Chang, Jiang Xi, 330006, China; Medical Molecular Laboratory, the Second Affiliated Hospital of Nanchang University, Nanchang, 330006, PR China.
authors: Kui
authors: K
authors: Hong
authors: Department of Cardiovascular, Second affiliated Hospital of Nanchang University, Institute of Cardiovascular disease in Nanchang University, Nan Chang, Jiang Xi, 330006, China. Electronic address: xiaoshumenfan1@126.com.
authors: Xiaoshu
authors: X
authors: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000072224:Bcl-2-Like Protein 11 / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D015687:Cell Hypoxia / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D047468:Immunoprecipitation; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D010100:Oxygen / Q000633:toxicity*; D017354:Point Mutation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D051381:Rats
chemical_list: D000072224:Bcl-2-Like Protein 11; C000606778:Bcl2l11 protein, rat; C000614153:Pim2 protein, rat; D017346:Protein Serine-Threonine Kinases; D010100:Oxygen
keywords: Apoptosis; Bim; Cardiomyocytes; Pim-2