Effects of PGC-1α on mitochondrial oxidative stress and pyroptosi-sin human renal cortical proximal tubular epithelial cells
Objective To investigate the effects of PGC-1α on mitochondrial oxidative stress and human re-nal tubular epithelial(HK-2)cell pyroptosis.Methods HK-2 cells were divided into control group(Con group,21％oxygen),hypoxia/reoxygenation group(Hyp-R group,incubated with 1％oxygen for 12 h and immediately in-cubated with 21％oxygen for 12 h),hypoxia/reoxygenation plus solvent control group(Hyp-R+S group,incubate with 1％oxygen for 12 h and immediately after addition of DMSO solution,incubate with 21％oxygen for 12 h)and hypoxia/reoxygenation plus drug intervention group(Hyp-R+ZLN group,incubated with 1％oxygen for 12 h and in-cubated with 21％oxygen for 12 h immediately after the addition of PGC-1α agonist ZLN005).The apoptosis rate,ROS content,mitochondrial membrane potential level and cellular serum IL-10 and IL-18 content,as well as the expression level of cellular pyroptosis-related proteins and the expression level of mitochondrial dynamics-related proteins were detected in each group.The morphologies and structures of cells and mitochondria were observed in each group.Results 1.Compared with the Con group,the Hyp-R group showed increased expression of Caspase-1,Nlrp3,GSDMD-N and Drp1 proteins(P＜0.05),increased secretion of IL-18 in the cell supernatant,increased late apoptosis,increased ROS content and increased fluorescent content of JC-1 monomers(P＜0.05).2.Compared with the Hyp-R group,the expression of cellular pyroptosis-related proteins in the Hyp-R group was reduced,the secre-tion of IL-18 in the cell supernatant was reduced,the content of ROS was reduced,and the fluorescence content of JC-1 monomer was reduced(P＜0.05).3.The mitochondria in the Hyp-R group were swollen,the mitochondrial ridges were lysed,and the cells had the characteristics of partially suspected pyroptosis.The damaged cellular and mitochondrial structures in the Hyp-R+ZLN group were repaired.Conclusion PGC-1α alleviates renal tubular ep-ithelial pyroptosis by regulating mitochondrial biosynthesis,thereby affecting pyroptosis in HK-2 cells.
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