LAUSR

This study aimed to explore the role of dual specificity phosphatase 12 (DUSP12) in regulating myocardial ischemia–reperfusion (I/R) injury and the underlying mechanism. The expression of DUSP12 in myocardial tissues and heat‐shock protein beta‐8 (HSPB8) and mitophagy‐related proteins in myocardial tissues and H9c2 cells were detected by western blot analysis. The serum creatine kinase isoenzymes (CK‐MB) and lactate dehydrogenase (LDH), levels of reactive oxygen species and malondialdehyde, superoxide dismutase activity in myocardial tissues and H9c2 cells, and caspase‐3 activity in H9c2 cells were analyzed by corresponding assay kits. The infarct area in the rat's heart was observed by triphenyl tetrazolium chloride staining. The apoptosis of myocardial cells in myocardial tissues and H9c2 cells was detected by terminal‐deoxynucleotidyl transferase dUTP‐biotin nick‐end labeling assay. The interaction between DUSP12 and HSPB8 was clarified by the coimmunoprecipitation assay. The transfection efficacy of si‐HSPB8#1 and si‐HSPB8#2 in H9c2 cells was confirmed by real‐time quantitative‐polymerase chain reaction and western blot analysis. As a result, DUSP12 expression was downregulated in I/R rats, which was promoted by lentivirus‐expressing DUSP12. DUSP12 overexpression reduced the serum creatine kinase isoenzymes (CK‐MB) and LDH, decreased the infarct area in the rat's heart, and suppressed the apoptosis and oxidative stress in myocardial tissues. DUSP12 overexpression also upregulated the expression of HSPB8 to promote mitophagy. The coimmunoprecipitation assay indicated that DUSP12 could be combined with HSPB8. In addition, DUSP12 overexpression could inhibit hypoxia/reoxygenation‐elicited apoptosis as well as oxidative stress in H9c2 cells by upregulating HSPB8 expression to promote mitophagy, which was countervailed by HSPB8 deficiency. In conclusion, DUSP12 overexpression decreased the apoptosis and oxidative stress in myocardial I/R injury through HSPB8‐induced mitophagy.