摘要
Mitochondria-dependent myoblast apoptosis induced by oxidative stress and decrease in successful protein synthesis play a crucial role in loss of muscle mass and functionality further to result in sarcopenia.Here,we investigated the relationship between milk fat globule-EGF factor VIII(MFG-E8)and mitochondrial-dependent apoptosis pathway.MFG-E8 exert cytoprotection through increasing L6 cells survival/apoptotic ratio,increasing mitochondrial membrane potential and regulating S and G2/M phases.By observing cell ultrastructure,MFG-E8 improved mitochondrial homeostasis mainly through decreasing cytochrome-c release,expression of caspase-9 and caspase-3,mitochondrial vacuolation and mitophagy thereby inhibiting cell apoptosis.From molecular perspective,MFG-E8 repaired mitochondria fragmentation by increasing mitochondrial DNA replication and regulated expression of key mitochondrial-apoptotic factors(upregulation:B-cell lymphoma-2 like 1(bcl2l1),bcl2l2,cyclooxygenase-1 and mitochondrial uncoupling protein-2;Downregulation:p21 and p53)further to improve mitochondrial function and inhibit apoptosis.Moreover,MFG-E8 inhibited mitochondrialdependent apoptosis via Akt/bcl-2/bax/caspase-3 signaling cascades.Taken together,our research provided a promising approach for deep exploration of MFG-E8 on cytoprotection against mitochondrial injury and mitochondrial-mediated apoptosis and application of anti-apoptosis in alleviating sarcopenia.
