hCINAP serves a critical role in hypoxia-induced cardiomyocyte apoptosis via modulating lactate production and mitochondrial-mediated apoptosis signaling

Acute myocardial infarction (AMI) is a major cause of heart failure and is associated with insufficient myocardial oxygen supply. However, the molecular mechanisms underlying hypoxia-induced cardiomyocyte apoptosis are not completely understood. In the present study, the role of human coilin interacting nuclear ATPase protein (hCINAP) in cardiomyocytes was investigated. AC16 cells were divided into the following four groups: i) Small interfering (si)RNA-control (Ctrl); (ii) siRNA-hCINAP; (iii) empty vector; and (iv) hCINAP-Flag. Protein expression was assessed using western blotting. MTT and apoptosis assays were conducted to detect cell viability and apoptosis, respectively. CCK8 assays and apoptosis assays were used to detect cell viability and apoptosis, respectively. hCINAP promoter activity was examined by luciferase reporter assay. hCINAP expression was induced in a hypoxia-inducible factor-1 alpha-dependent manner under hypoxic conditions. Compared with the siRNA-Ctrl group, hCINAP knockdown inhibited apoptosis, whereas compared with the vector group, hCINAP overexpression increased apoptosis under hypoxic conditions. Mechanistically, compared with the siRNA-Ctrl group, hCINAP knockdown decreased hypoxia-induced lactate accumulation via regulating lactate dehydrogenase A activity. Moreover, the results indicated that hCINAP was associated with mitochondrial-mediated apoptosis via Caspase signaling. Collectively, the present study suggested that hCINAP was an important regulator in hypoxia-induced apoptosis and may serve as a promising therapeutic target for AMI.