Metallothionein-2A protect Cardiomyocytes from Ischemia/Reperfusion through inhibiting p38

Abstract

The resumption of coronary artery blood supply is often accompanied by myocardial ischemia/reperfusion (I/R) injury after the occurrence of myocardial infarction, shock, cardiac surgery and other events. Metallothionein-2A (MT2A) has the functions of scavenging free radicals, anti-oxidative stress, anti-apoptosis, anti-autophagy, promoting vascular growth. The activation of p38 MAPK pathway can induce cardiomyocyte apoptosis in H9c2 cardiomyocytes during I/R, thereby aggravating the myocardial I/R injury. However, it is not clear that the effect of MT2A on p38 in cardiomyocytes under I/R. A simulated I/R model was used. Our objective was to investigate the protective effect of MT2A on I/R-caused mortality in H9c2 cardiomyocytes through its influence on p38, as well as the relationships among these processes. The results indicate that both endogenously overexpressed MT2A and exogenously added MT2A can inhibit the active expression of p38 during I/R. Based on these results, I/R induces apoptosis and p-p38 in cardiomyocytes. MT2A can inhibit the active expression of p38. MT2A protects cardiomyocytes from I/R injury, and that p38 is one of the molecules of MT2A against I/R injury in cardiomyocytes.

The role of Zn2+ in shaping intracellular Ca2+ dynamics in the heart

“…MT-induced inhibition of the NF-κB pathway has been linked to prevention of age-associated cardiomyopathy ( Cong et al, 2016 ). A recent study suggests that MT2A protects cardiomyocytes from I/R through p38 inhibition ( Zhao et al, 2021 Preprint ). It has also been shown that MT inhibits doxorubicin-induced mitochondrial cytochrome c release and caspase-3 activation in cardiomyocytes ( Wang et al, 2001 ).…”