Pro-Glu-Trp(PEW),a whey protein-derived peptide,has been previously shown in vitro to have antihyperuricemic potential.The current study further evaluated the roles and the underlying mechanism of PEW in the managemen...Pro-Glu-Trp(PEW),a whey protein-derived peptide,has been previously shown in vitro to have antihyperuricemic potential.The current study further evaluated the roles and the underlying mechanism of PEW in the management of hyperuricemia(HUA)in rat induced by potassium oxonate(PO)and hypoxanthine.Results revealed that PEW significantly reduced the levels of uric acid(UA),creatinine(Cr),and blood urea nitrogen(BUN)in serum,and effectively suppressed the activities of xanthine oxidase(XOD)associated with UA synthesis and modulated the expression of organic ion transporters related to UA excretion.Moreover,PEW alleviated UAinduced renal inflammation by regulating oxidative stress,suppressing the level of pro-inflammatory cytokines,and inhibiting the activation of NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome and Toll-like receptor 4/myeloid differentiation factor 88/NF-kappaB(TLR4/MyD88/NF-κB)signaling pathway.Taken together,these relults indicated that PEW improved HUA and renal inflammation by inhibiting UA synthesis,promoting renal UA excretion and suppressing NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling pathways.展开更多
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 i...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.展开更多
文摘Pro-Glu-Trp(PEW),a whey protein-derived peptide,has been previously shown in vitro to have antihyperuricemic potential.The current study further evaluated the roles and the underlying mechanism of PEW in the management of hyperuricemia(HUA)in rat induced by potassium oxonate(PO)and hypoxanthine.Results revealed that PEW significantly reduced the levels of uric acid(UA),creatinine(Cr),and blood urea nitrogen(BUN)in serum,and effectively suppressed the activities of xanthine oxidase(XOD)associated with UA synthesis and modulated the expression of organic ion transporters related to UA excretion.Moreover,PEW alleviated UAinduced renal inflammation by regulating oxidative stress,suppressing the level of pro-inflammatory cytokines,and inhibiting the activation of NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome and Toll-like receptor 4/myeloid differentiation factor 88/NF-kappaB(TLR4/MyD88/NF-κB)signaling pathway.Taken together,these relults indicated that PEW improved HUA and renal inflammation by inhibiting UA synthesis,promoting renal UA excretion and suppressing NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling pathways.
文摘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.
