title: Apelin-13 promotes cardiomyocyte hypertrophy via PI3K-Akt-ERK1/2-p70S6K and PI3K-induced autophagy.
abstract: Apelin is highly expressed in rat left ventricular hypertrophy Sprague Dawley rat models, and it plays a crucial role in the cardiovascular system. The aim this study was to clarify whether apelin-13 promotes hypertrophy in H9c2 rat cardiomyocytes and to investigate its underlying mechanism. The cardiomyocyte hypertrophy was observed by measuring the diameter, volume, and protein content of H9c2 cells. The activation of autophagy was evaluated by observing the morphology of autophagosomes by transmission electron microscopy, observing the subcellular localization of LC3 by light microscopy, and detecting the membrane-associated form of LC3 by western blot analysis. The phosphatidylinositol 3-kinase (PI3K) signaling pathway was identified and the proteins expression was detected using western blot analysis. The results revealed that apelin-13 increased the diameter, volume, and protein content of H9c2 cells and promoted the phosphorylation of PI3K, Akt, ERK1/2, and p70S6K. Apelin-13 activated the PI3K-Akt-ERK1/2-p70S6K pathway. PI3K inhibitor LY294002, Akt inhibitor 1701-1, ERK1/2 inhibitor PD98059 attenuated the increase of the cell diameter, volume, protein content induced by apelin-13. Apelin-13 increased the autophagosomes and up-regulated the expressions of beclin 1 and LC3-II/I both transiently and stably. The autophagy inhibitor 3MA ameliorated the increase of cell diameter, volume, and protein content that were induced by apelin-13. These results suggested that apelin-13 promotes H9c2 rat cardiomyocyte hypertrophy via PI3K-Akt-ERK1/2-p70S6K and PI3K-induced autophagy.
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xie
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China Department of Pharmacy, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Feng
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China.
authors.forename: Lu
authors.initials: L
authors.lastname: He
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China.
authors.forename: Deguan
authors.initials: D
authors.lastname: Lv
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China.
authors.forename: Xuping
authors.initials: X
authors.lastname: Qin
authors.affiliation: Departments of Microbiology and Immunology, University of South China, Hengyang 421001, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China lxchen6@126.com Wjliu829@yahoo.com.cn.
authors.forename: Lanfang
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China lxchen6@126.com Wjliu829@yahoo.com.cn.
authors.forename: Linxi
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000073861:Apelin; D001343:Autophagy; D006332:Cardiomegaly / Q000378:metabolism*; D002460:Cell Line; D002867:Chromones / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009025:Morpholines / Q000737:chemistry; D032383:Myocytes, Cardiac / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*
chemical_list: D000073861:Apelin; C498579:Apln protein, rat; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D036341:Intercellular Signaling Peptides and Proteins; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: APJ; PI3K; apelin; autophagy; cardiomyocyte hypertrophy