Mechanism of Liraglutide Improving Oxidative Stress,Mitochondrial Dysfunction and Autophagy Damage in SH-SY5Y Cells
Objective:To investigate the mechanism of liraglutide(Lira)intervention on oxidative stress,mitochondrial function and autophagy damage in human neuroblastoma(SH-SY5Y)cells.Methods:SH-SY5Y cells were divided into control group,high glucose(HG)group,HG+LI-L group,HG+LI-H group HG+LI-H+3-methyladenine(3MA)group.The cell proliferation ability,the levels of Glu,malondialdehyde(MDA),adenosine triphosphate(ATP),superoxide dismutase(SOD),Cell apoptosis,reactive oxygen species(ROS)level,mitochondrial membrane potential.The expression and localization of microtubule-associated protein 1 light chain 3(LC3B),p62,The expression of phosphatidylinositol 3-kinase(PI3K),p-PI3K,mammalian rapamycin target protein(mTOR)p-mTOR,protein kinase B(Akt)and p-Akt protein were detected.Results:Compared with HG group,the cell proliferation activity in HG+LI(500 nM)group was the most significant,Glu and MDA decreased and SOD increased in HG+LI(500 nM)group,the cell viability,ATP and SOD were increased,and the apoptosis rate,ROS fluorescence intensity,Glu,MDA and JC-1 were decreased in HG+LI-L group and HG+LI-H group,and the cell viability,ATP and SOD in HG+LI-H group were higher than those in HG+LI-L group,and the apoptosis rate,ROS fluorescence intensity,Glu,MDA and JC-1 were lower than those in HG+LI-L group,p-mTOR and p62 proteins expression were decreased,p-PI3K,p-Akt and LC3B proteins expression were increased in the HG+LI-H group(P＜0.05).Compared with control group,Glu,MDA,apoptosis rate,ROS fluorescence intensity,Glu,MDA,JC-1,P-mTOR and p62 protein expression in HG group increased,while SOD,ATP,cell survival rate,p-PI3K,p-Akt and LC3B protein expression decreased(P＜0.05).Compared with HG+LI-H group,the cell viability,ATP,SOD,p-PI3K,p-Akt and LC3B protein expression were decreased,and the apoptosis rate,ROS fluorescence intensity,Glu,MDA JC-1,p-mTOR and p62 protein expression were increased in HG+LI-H+3MA group(P＜0.05).Conclusion:Lira may reduce oxidative stress in SH-SY5Y cells in a dose-dependent manner,improve mitochondrial function and PI3K/AKT/mTOR autophagy pathway,Play a role in resist apoptosis and protect nerve cells.
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