title: Mechanism underlying the inhibitory effect of Apelin-13 on glucose deprivation-induced autophagy in rat cardiomyocytes.
abstract: The aim of the present study was to investigate the effect of Apelin-13 on cardiomyocyte autophagy and to determine the underlying mechanism of this effect. To establish an autophagic model system, the cardiomyocytes of Sprague Dawley rats (postnatal day 3) were cultured and divided into five groups: normal control (Co), glucose deprivation (GD), GD+Apelin-13, GD+Apelin-13 treated with the Akt-specific inhibitor triciribine (GD+Apelin-13+Triciribine) and triciribine alone (Triciribine). The intracellular autophagosomes were then observed using transmission electron microscopy (TEM) and the expression levels of cellular autophagy-related protein microtubule-associated protein 1 light chain 3 (LC3), phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) protein were measured using western blotting. Compared with the Co group, the ratio of LC3-II/LC3-I increased significantly in all treatment groups, with the exception of the Triciribine group (P<0.05). Compared with the GD group, the ratio of LC3-II/LC3-I was significantly decreased, and the PI3K and mTOR expression was significantly enhanced in the GD+Apelin-13 and GD+Apelin-13+Triciribine groups (P<0.05). Compared with the GD+Apelin-13 group, the ratio of LC3-II/LC3-I increased significantly (P<0.05) and the PI3K expression remained unchanged in the GD+Apelin-13+Triciribine group (P>0.05), but mTOR expression was significantly reduced (P<0.05). GD led to increased numbers of autophagosomes and augmented the LC3-II/LC3-I ratio (P<0.05). Apelin-13 pretreatment attenuated GD-induced cardiomyocte injury, decreased the autophagosome number and the ratio of LC3-II/LC3-I (P<0.05), enhanced PI3K activity (P<0.05) and upregulated the phosphorylation levels of the Akt and mTOR proteins (P<0.05). The Akt-specific inhibitor triciribine weakened the protective role of Apelin-13 (P<0.05). To a certain extent, Apelin-13 inhibited GD-induced cardiomyocyte autophagy, which may be related in part to the activation of the PI3K/Akt/mTOR signaling pathway.
authors: Department of Cardiology, The Third Affilated Hospital of Liaoning Medical University, Jinzhou 121001,  P.R. China.
authors: Hui
authors: H
authors: Jiao
authors: Zhi
authors: Z
authors: Zhang
authors: Qinghua
authors: Q
authors: Ma
authors: Wei
authors: W
authors: Fu
authors: Zidong
authors: Z
authors: Liu
keywords: Apelin-13; PI3K/Akt/mTOR pathway; autophagy; cardiomyocytes; glucose deprivation; light chain 3
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