ELA-11 protects the heart against oxidative stress injury induced apoptosis through ERK/MAPK and PI3K/AKT signaling pathways

Abstract

Increasing evidence revealed that apoptosis and oxidative stress injury were associated with the pathophysiology of doxorubicin (DOX)-induced myocardial injury. ELABELA (ELA) is a newly identified peptide with 32 amino acids, can reduce hypertension with exogenous infusion. However, the effect of 11-residue furn-cleaved fragment (ELA-11) is still unclear. We first administrated ELA-11 in DOX-injured mice and measured the cardiac function and investigated the effect of ELA-11 in vivo. We found that ELA-11 alleviated heart injury induced by DOX and inhibited cardiac tissues from apoptosis. In vitro, ELA-11 regulated the sensitivity towards apoptosis induced by oxidative stress with DOX treatment through PI3K/AKT and ERK/MAPK signaling pathway. Similarly, ELA-11 inhibited oxidative stress-induced apoptosis in cobalt chloride (CoCl2)-injured cardiomyocytes. Moreover, ELA-11 protected cardiomyocyte by interacting with Apelin receptor (APJ) by using 4-oxo-6-((pyrimidin-2-ylthio) methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221). Hence, our results indicated a protective role of ELA-11 in oxidative stress-induced apoptosis in DOX-induced myocardial injury.

ELABELA-APJ-Akt/YAP Signaling Axis: A Novel Mechanism of Aerobic Exercise in Cardioprotection of Myocardial Infarction Rats

“…They exhibited inotropic activities both in vitro and in animal disease models (25). Wang et al (42) found that ELA-11 alleviated heart injury induced by DOX and inhibited cardiac tissues from apoptosis. In vitro , ELA-11 regulated the sensitivity toward apoptosis induced by oxidative stress with DOX treatment through PI3K/AKT and ERK/MAPK signaling pathway.…”

APJ as Promising Therapeutic Target of Peptide Analogues in Myocardial Infarction- and Hypertension-Induced Heart Failure

“…As for the involved pathways, several articles reported that APJ ligands exert cardioprotection against I/R mainly triggering PI3K-Akt-NO and MEK 1/2-ERK1/2 signalling pathways [ 85 , 88 , 89 , 90 , 91 , 92 , 93 ].…”

“…Only a few studies investigated the cardioprotective role of ELA [ 85 , 92 , 97 , 100 ], though its effectiveness against I/R injury was confirmed in other organs, such as kidney, brain, and lung [ 110 , 111 , 112 , 113 ].…”