Oxidative stress and P53 involve in fluctuant high glucose-induced apoptosis of renal tubular epithelial cells

AIM: To explore the mechanism of fluctuant high blood glucose-induced apoptosis of renal tubular epithelial cells. METHODS: Cultured human renal tubular epithelial cells (HK-2) were treated with stable high glucose or fluctuant high glucose. Antioxidant and specific inhibitor of P53 were applied for identifying the role of oxidative stress and P53 in fluctuant high glucose-induced apoptosis of renal tubular epithelial cells. Additionally, SD rats were randomly divided into normal control group (A), stable high blood glucose group (B) and fluctuant high blood glucose group (C). Diabetic rats were induced by intraperitoneal injection of streptozocin(STZ,65 mg/kg), and the fluctuant high blood glucose animal model was induced by intraperitoneal injection of ordinary insulin and glucose at different time points every day. The activity of superoxide dismutase (SOD) and the content of malonaldehyde (MDA) were detected by the method of colorimetry. The protein expression of NADPH oxidase 4(Nox4) and P53 were examined by immunohistochemistry and Western blotting. Apoptosis was assessed by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). RESULTS: The cultured HK-2 cells treated with fluctuant high glucose had significantly higher apoptotic rate and expression level of P53 protein than those in the cells treated with stable high glucose. Compared with the culture solution of the cels treated with stable high glucose, the SOD activity was decreased and the concentration of MDA was increased in the culture solution of the cells treated with fluctuant high glucose. The antioxidant and specific inhibitor of P53 significantly inhibited the p-P53 expression and decreased the apoptotic rate. After 12 experimental weeks, the cell apoptotic index and protein expression of Nox4 and p-P53 in the kidney tubular epithelial cells isolated from the diabetic rats were significantly increased in C group as compared with B group. CONCLUSION: Oxidative stress and P53 are involved in fluctuant high glucose-induced apoptosis of renal tubular epithelial cells.