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: BNIP3; JMJD5; OGD/R; apoptosis; mitophagy.
© 2021 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.