PEDF and PEDF-derived peptide 44mer protect cardiomyocytes against hypoxia-induced apoptosis and necroptosis via anti-oxidative effect

Pigment epithelium-derived factor (PEDF) has many biological activities. But it's not known whether PEDF and its functional peptides could protect against hypoxia-induced cell death and the mechanisms are still unclear. We used cultured H9c2 cells and primary cardiomyocytes to show that apoptosis and necroptosis were significantly increased after hypoxia. Both PEDF and its fuctional peptides 44mer reduced apoptosis and necroptosis rates and inhibited the expression of cleaved caspase 3 and receptor-interacting protein 3 (RIP3). Furthermore, PEDF and 44mer could up-regulate super oxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels, promote clearing of reactive oxygen species (ROS) and malondialdehyde (MDA). While, 34mer, another functional peptides had no effect on cell apoptosis and necroptosis. Hereby this is the first evidence that PEDF and its functional peptide 44mer protect cultured H9c2 cells and primary cardiomyocytes against apoptosis and necroptosis under hypoxic condition via the anti-oxidative mechanism.