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.

Apelin Is a Prototype of Novel Drugs for the Treatment of Acute Myocardial Infarction and Adverse Myocardial Remodeling

“…Apelins can protect the heart against adverse remodeling in animals with myocardial infarction and pressure overload. Worth studying is a decrease in the protective effect of apelins or the disappearance of their effect as their concentration is increased [ 43 , 46 , 51 , 57 ]. It is unclear whether this is a result of their interaction with other receptors (non-apelin receptors) or a result of the presence of peptide impurities.…”

“…The molecular mechanism of this effect is unclear because cardiac fibroblasts do not express the apelin receptor [ 24 ]. Apelin-13 stimulated the proliferation of H9c2 cardiomyoblasts [ 57 ]. The maximum effect was observed at a concentration of 200 nmol/L.…”

“…The maximum effect was observed at a concentration of 200 nmol/L. The effect disappeared at a concentration of 800 nmol/L [ 57 ]. These data are credible because the apelin receptors are expressed on cardiomyocytes [ 24 ].…”

Apelin, APJ, and ELABELA: Role in Placental Function, Pregnancy, and Foetal Development—An Overview

“…Of particular importance was the fact that activation of signalling pathway cascades was connected with different biological effects of this adipokine. Specifically, apelin stimulated proliferation by phosphoinositide 3-kinase (PI3K) phosphorylation in porcine ovarian follicles [ 17 ] while a similar effect was observed for apelin-13 in cultured rat cardiomyoblasts (H9c2) via activation of AKT and ERK1/2 [ 55 ]. Moreover, apelin protected mouse neurons from cell death by reducing reactive oxygen species (ROS) production and activation of actin kinase [ 56 ], while changes in AMPK phosphorylation by apelin-13 blocked the process of mouse neuronal apoptosis after stroke.…”