Effects of GCN2/eIF2α on myocardial ischemia/hypoxia reperfusion and myocardial cells injury.

Myocardial ischemia/hypoxia-reperfusion injury is a common and severe cardiovascular disorder. General control non-derepressible 2 (GCN2) plays an important role in the role of cardiomyocyte glucose metabolism. Therefore, our study focused on the expression of GCN2/eIF2α in myocardial ischemia/hypoxia-reperfusion injury and its mechanism of myocardial cell injury. In the volunteers and patients with myocardial ischemia and hypoxia- reperfusion, the expression of GCN2 and eIF2α on serum were detected by RT-qPCR. The GCN2, eIF2α interference and GCN2 overexpression plasmids were constructed and transfected into cells. Then, the level of TNF-α, IL-1β, IL-6, IFN-γ were detected by ELISA and the level of ROS, MDA, LDH and SOD were measured by the corresponding kits, respectively. Besides, the expression of GCN2/eIF2 signaling pathway (p-eIF2α, ATF4, CHOP, UCP2 and eIF2α) and apoptosis-related proteins (Bax, Bcl-2 and cleaved caspase3) was detected by western blot. Flow cytometry was performed to value cell apoptosis. The expression of GCN2 is increased in oxygen-glucose deprivation/reoxygenation (OGD/R) model cells and GCN2 interference reduces the inflammation and oxidative stress in H9C2 cells after OGD/R. GCN2 interference reduced the level of apoptosis in OGD/R model cells and inhibited the expression of GCN2/eIF2α signaling pathway. We found that eIF2α interference could offset the effects of GCN2 overexpression on oxidative stress and apoptosis in H9C2 cells, and verified that GCN2 is produced by eIF2α phosphorylation. Together, GCN2/eIF2α signaling pathway plays an important role in myocardial ischemia/hypoxia-reperfusion injury, which could provide a new idea for the treatment of myocardial infarction on clinical. AJTR