JMJD5 attenuates oxygen–glucose deprivation and reperfusion‐induced injury in cardiomyocytes through regulation of HIF‐1α‐BNIP3

Abstract

Abstract Proteins in Jumonji family function as histone demethylases and participate in cardiac development. Jumonji domain containing 5 (JMJD5) is responsible for the embryonic development through removing methyl moieties from H3K36me2 histone, and has pro‐proliferative effect on heart and eye development. However, the protective role of JMJD5 against oxygen–glucose deprivation and reperfusion (OGD/R)‐induced injury in cardiomyocytes has not been fully understood. Firstly, myocardial ischemia/reperfusion (I/R) rat model was established by ligation of left coronary artery. OGD/R was performed in non‐transfected H9C2 or H9C2 transfected with pcDNA‐JMJD5 plasmid to induce cell cytotoxicity. Data from qRT‐PCR and western blot showed that JMJD5 was reduced in the heart tissues of myocardial I/R rat model and OGD/R‐induced H9C2. Secondly, JMJD5 over‐expression attenuated OGD/R‐induced decrease in cell viability and increase in lactate dehydrogenase secretion and cell apoptosis in H9C2. Mitophagy was promoted by pcDNA‐mediated over‐expression of JMJD5 with enhanced protein expression of LC3‐I, LC3‐II, Atg5, and Beclin 1. Thirdly, knockdown of JMJD5 aggravated OGD/R‐induced decrease in hypoxia‐inducible factor‐1α (HIF‐1α), whereas JMJD5 over‐expression enhanced BNIP3 (Bcl‐2/adenovirus E1B 19‐kDa interacting protein) through upregulation of HIF‐1α. Lastly, BNIP3 silencing promoted cell apoptosis, suppressed mitophagy, and attenuated the protective effects of JMJD5 over‐expression against OGD/R‐induced injury in H9C2. In conclusion, JMJD5 exerted protective effects against OGD/R‐induced injury in cardiomyocytes through upregulation of HIF‐1α‐BNIP3.

Keywords

• apoptosis
• BNIP3
• JMJD5
• mitophagy
• OGD/R