Effects of uric acid on mitochondrial oxidative damage and apoptosis in human renal tubular epithelial cells / 中华肾脏病杂志

ABSTRACT

Objective To observe the effects of uric acid (UA) on mitochondrial oxidative damage and apoptosis in renal tubular epithelial cells (HK-2),and investigate the possible mechanism.Methods HK-2 cells were exposed to UA (480 μmol/L,720 μmol/L) for different time (0 h,24 h,48 h)in vitro.The mitochondrial ROS production was detected by MitoSOX staining.The mitochondrial membrane potential was measured by JC-1 staining.The expressions of prohibitin and AIF were examined by Western blotting and irnmunofluorescence cytochemistry.The cell apoptosis was measured by Annexin V-FITC/PI staining.Results The mitochondrial ROS production in HK-2 cells exposed to 480 μ mol/L UA was increased than that of control group at 24 h (P ＜ 0.05),and increased gradually with UA concentration and incubation time increasing,while the mitochondrial membrane potential was reduced at the same time.There were no significant changes in AIF expression and apoptosis rate of HK -2 cells exposed to 480 μmol/L UA for 24 h compared with that of control group (P ＞ 0.05),while both of them were up-regulated when HK-2 cells were exposed to 480 μmol/L UA for 48 h and 720 μmol/L JA for 24 h and 48 h (P ＜ 0.05).The prohibitin expression in HK-2 cells exposed to 480 μmol/L UA was reduced than that of control group at 24 h (P ＜ 0.05),and down-regulated gradually with UA concentration and incubation time increasing.Conclusion Uric acid can induce the mitochondrial ROS production increased,the mitochondrial membrane potential reduced,the prohibitin expression down-regulated and the mitochondrial apoptosis pathway activated in HK-2 cells.