Apelin-13 promotes cell proliferation in the H9c2 cardiomyoblast cell line by triggering extracellular signal-regulated kinase 1/2 and protein kinase B phosphorylation

Abstract

Apelin-13 (APL-13), a peptide hormone that serves as a ligand for G-protein coupled receptors, has been demonstrated to be highly expressed in left ventricular hypertrophy rat models. It has been implicated in cardio-protection under pathological states. The present study aimed to assess the physiological proliferation effect of APL-13 in cultured H9c2 cardiomyoblast cells, and to elucidate the underlying mechanisms. Cell proliferation was determined by MTT assay. The extracellular signal-regulated kinase (ERK) 1/2 and protein kinase B (Akt) signaling pathway was identified, and protein expression levels were detected using western blot analysis. The results demonstrated that APL-13 markedly increased cell proliferation. Western blotting results suggested that APL-13 significantly enhanced the expression of phosphoinositide ERK1/2 and Akt activation in a dose-dependent manner. U0126 (10 μM; ERK1/2 inhibitor) and/or 10 μM LY294002 (Akt inhibitor) were used to help to determine the APL-signaling mechanism. As a result, LY294002 and U0126 partially blocked the APL-13 induced H9c2 proliferation. In conclusion, these data suggested that APL-13 has a proliferative effect on myocardium cells via the Akt and ERK1/2 signaling pathways, and provide potential novel pharmaceutical targets for cardiovascular disease.