A Compensatory Mechanism for Acute Hyperglycemia Induced Apoptosis

Abstract

Studies have shown that prolonged exposure of hyperglycemia may injure cells and contribute in the development of renal diseases in diabetes. In a recent study, we have demonstrated that acute (10–20 min) exposure of human proximal tubule epithelial cells (hPTECs) to 25 mM high glucose (HG) induces a time‐dependent dual effect, involving an early proliferation and a late apoptosis. Acute exposure of HG initiated intrinsic apoptotic pathway activated by reactive oxygen species (ROS). Furthermore, we observed increased protein expression of p53 that was inhibited by ROS inhibitor NAC. Under similar conditions we observed changes in Bcl‐2 and Bax proteins expression. Chronic HG exposure characteristic of diabetes induces a high Bax to Bcl‐2 ratio indicative of cellular apoptosis. However, acute HG exposure reversed the Bax to Bcl‐2 ratio indicating a possible physiological regulatory and recovery phase in which the hPTECs attempt to overcome damage caused by the reactive oxygen species produced by HG exposure. Consistent with these observations, we identified time‐dependent increase in caspase‐3 protein expression. Our study demonstrates for the first time that a single HG exposure for 10–20 min alone is sufficient to elicit cellular apoptosis inducing epithelial cell injury. However hPTECs may initiate intrinsic physiological machinery towards a recovery phase. Supported by NIH Grant DK072140