Protective effects of the AKT activator SC79 on renal ischemia-reperfusion injury

Background and Aims: SC79, an AKT activator, has been reported to protect experimental ischemia-elicited neuronal death, brain injury, and myocardiocyte hypoxia/reoxygenation (H/R) injury. However, the protection of SC79 from renal ischemia-reperfusion (I/R) injury and the precise mechanisms involved are unknown. Here, we investigated the effects of SC79 in renal tubular epithelial cells in vitro and in mouse kidney in vivo following hypoxia-reoxygenation (H/R) and renal I/R injury. Methods: The kidneys of Sprague-Dawley rats were subjected to 30 min of warm ischemia followed by 24 h of reperfusion. Murine renal tubular epithelial NRK-52E cells were subjected to hypoxia for 6 h and reoxygenation for 24 h. The NRK-52E cells and the renal I/R injury model were treated with SC79 and/or LY294002 at different times and concentrations. Serum creatinine (Cr) concentration, renal histology, cellular viability, and cell apoptosis were assessed. Levels of phospho-Akt, bad, Bim, bax, bcl-2, and bcl-XL in NRK-52E cells and renal tissues were determined by western blotting. Results: SC79 improved viability and inhibited apoptosis in NRK-52E cells following H/R. SC79 decreased serum Cr and markedly improved pathology and decreased cell apoptosis in kidneys following I/R. In addition, SC79 promoted the expression of phospho-Akt, bcl-2, and bcl-XL, and decreased the expression levels of bid, bax, and bim. PI3K inhibitor (LY294002) pre-treatment completely abolished these effects of SC79. Conclusions: The protective role of SC79 against H/R of NRK-52E cells or renal I/R injury is related to activation of phosphorylation of AKT, resulting in a decrease in the pro-apoptotic proteins bim, bax, and bad and an increase in the anti-apoptotic proteins bcl-2 and bcl-XL induced by cell H/R and renal I/R injury.