title: Glucagon-like peptide-1 protects cardiomyocytes from advanced oxidation protein product-induced apoptosis via the PI3K/Akt/Bad signaling pathway.
abstract: Cardiomyocyte apoptosis is a major event in the pathogenesis of diabetic cardiomyopathy. Currently, no single effective treatment for diabetic cardiomyopathy exists. The present study investigated whether advanced oxidative protein products (AOPPs) have a detrimental role in the survival of cardiomyocytes and if glucagon-like peptide-1 (GLP-1) exerts a cardioprotective effect under these circumstances. The present study also aimed to determine the underlying mechanisms. H9c2 cells were exposed to increasing concentrations of AOPPs in the presence or absence of GLP-1, and the viability and apoptotic rate were detected using a cell counting kit-8 assay and flow cytometry, respectively. In addition, a phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) inhibitor, LY294002, was employed to illustrate the mechanism of the antiapoptotic effect of GLP-1. The expression levels of the apoptotic-associated proteins, Akt, B-cell lymphoma (Bcl)-2, Bcl-2-associated death promoter (Bad), Bcl-2-associated X protein (Bax) and caspase-3 were measured by western blotting. It was revealed that GLP-1 significantly attenuated AOPP-induced cell toxicity and apoptosis. AOPPs inactivated the phosphorylation of Akt, reduced the phosphorylation of Bad, decreased the expression of Bcl-2, increased the expression of Bax and the activation of caspase-3 in H9c2 cells. GLP-1 reversed the above changes induced by AOPPs and the protective effects of GLP-1 were abolished by the PI3K inhibitor, LY294002. In conclusion, the present data suggested that GLP-1 protected cardiomyocytes against AOPP-induced apoptosis, predominantly via the PI3K/Akt/Bad pathway. These results provided a conceivable mechanism for the development of diabetic cardiomyopathy and rendered a novel application of GLP-1 exerting favorable cardiac effects for the treatment of diabetic cardiomyopathy.
authors.affiliation: Department of Endocrinology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Zhouyi
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.affiliation: Department of Endocrinology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D062107:Advanced Oxidation Protein Products / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002867:Chromones / Q000008:administration & dosage; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051058:Oncogene Protein v-akt / Q000096:biosynthesis; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D051025:bcl-Associated Death Protein / Q000096:biosynthesis
chemical_list: D062107:Advanced Oxidation Protein Products; D002867:Chromones; D052216:Glucagon-Like Peptide 1; D009025:Morpholines; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051025:bcl-Associated Death Protein; C494819:BAD protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one