Protective effect of stress-associated endoplasmic reticulum protein 1 on glucose and oxygen deprivation-induced injury in cardiomyocytes

Abstract

Objective To study the protective effect of stress-associated endoplasmic reticulum protein 1(SERP1)on glucose and oxygen deprivation-induced injury in cardiomyocytes. Methods Gene expression was analyzed in the public database Gene Expression Omnibus(GEO)and screened for any difference in gene expression in myocardial tissues between the control group and the ischemia-reperfusion group(IR group). Rat H9C2 cardiomyocytes were cultured and a myocardial cell injury model was established by oxygen glucose deprivation(OGD). The effect of SERP1 expression on cell viability, apoptosis and the endoplasmic reticulum stress pathway in cardiomyocytes were examined. Results Western blot results showed that the expression of SERP1 in myocardial tissues decreased in the IR group, compared with the control group(t=6.83, P=0.006). Oxygen and glucose deprivation induced decreased levels of SERP1 mRNA and protein expression in H9C2 cardiomyocytes in a time-dependent manner(F=8.50 and 15.70, P=0.007 and 0.001). In addition, oxygen and glucose deprivation led to decreased cell viability and increased apoptosis, while exogenous addition of SERP1 had protective effects in H9C2 cardiomyocytes by promoting cell viability and reduced cell apoptosis.The lncRNA microarray and real-time PCR results showed that SERP1 could inhibit the expression of lncRNA CDKN2B-AS1 and further increase the phosphorylation of JAK2 and STAT3, leading to decreased expression of endoplasmic reticulum stress markers GRP78 and CHOP(all P<0.05). Conclusions SERP1 can inhibit cardiomyocyte injury induced by glucose deprivation, and the underlying molecular mechanism may be related to the inhibition of CDKN2B-AS1 expression, promotion of the JAK2/STAT3 signaling pathway, and suppression of endoplasmic reticulum stress. Key words: Myocardial ischemia; Myocardial infarction; Reperfusion injury; Stress