Adropin reduces hypoxia/reoxygenation‑induced myocardial injury via the reperfusion injury salvage kinase pathway

Abstract

Adropin is a secreted polypeptide that has been demonstrated to serve an important role in protecting the vascular endothelium. Pharmacological activation of pro-survival kinases, such as PI3K-Akt and ERK1/2, are involved in the reperfusion injury salvage kinase (RISK) pathway. In the present study, the effects of adropin in cardiomyocyte injury induced by simulated ischemia/reperfusion (SI/R) were assessed. Additionally, the current study also assessed the mechanisms that govern SI/R in a H9c2 cardiomyoblast cell model. Cell viability was measured using an MTT assay. Cell injury was assessed using creatine kinase MB measurements. Apoptosis was assessed using flow cytometry and caspase-3 activity. The inflammatory response was measured using tumor necrosis factor α and interleukin-10 expression. Oxidative stress was assessed using malondialdehyde and superoxide dismutase. The expression levels of Akt, ERK1/2, glycogen synthase kinase 3β (GSK3β), Bcl-2 and Bax were determined using western blot analysis. The results of the current study revealed that moderate-dose adropin increased cell viability, reduced early apoptosis and caspase-3 activity, promoted Bcl-2 expression, inhibited Bax and increased the Bcl-2/Bax ratio. Adropin significantly increased the phosphorylation of Akt, ERK1/2 and GSK3β, whereas inhibitors of PI3K and ERK1/2, respectively, LY294002 and PD98059, abolished the cardioprotective role of adropin. Furthermore, no significant difference was observed in phosphorylated-STAT3/total-STAT3 expression between the adropin and SI/R groups and Janus kinase 2 inhibitor AG490 did not significantly inhibit the protective role of adropin. These results indicate that adropin exerts a protective effect against SI/R injury through the RISK pathway instead of the survivor activating factor enhancement pathway.

Adropin as A Fat-Burning Hormone with Multiple Functions—Review of a Decade of Research

“…Yang et al showed that exogenous adropin causes attenuation of endothelial cell permeability during ischemia, an effect mediated via the ROCK-MLC2 signaling pathway [49]. In a recent study, Wu et al found that adropin protects against cardiomyocyte injury by ischemia/reperfusion [50]. Furthermore, adropin promotes glucose oxidation in mice a fed high-fat diet [51].…”

Adropin expression correlates with age-related neuropathologies in the human brain and improves neuroinflammation and cognitive function in aging mice

“…3). Adropin regulates angiogenesis and endothelial function 24,39,40,50 . Clinical studies have identi ed correlations with aging-related endothelial dysfunction 67 .…”

“…Adropin regulates peripheral carbohydrate and lipid metabolism 17,20,21,23,25,26,[30][31][32][33][34][35][36][37] and vascular function 24,[38][39][40] . Expression of the ENHO transcript is however several orders of magnitude higher in the brain relative to non-neural tissues 17,34,[41][42][43][44] .…”

Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction

“…The biological effects of adropin are mainly mediated through the activation of the orphan G proteincoupled receptor 19 26 . Adropin has a protective effect on the endothelial function and cardiomyocyte survival via the RISK pathway 12,14 . Since antiapoptosis by the activation of pro-survival cascades is an important strategy in optimized cell therapy 3,19,28 , in this study, adropin was used to produce dual protective effects.…”