mTORC1 and mTORC2\nCo-Protect against Cadmium-Induced\nRenal Tubular Epithelial Cell Apoptosis and Acute Kidney Injury by\nRegulating Protein Kinase B

The potential threat of cadmium (Cd)-induced acute kidney\ninjury\n(AKI) is increasing. In this study, our primary goal was to investigate\nthe individual roles played by mTOR complexes, specifically mTORC1\nand mTORC2, in Cd-induced apoptosis in mouse kidney cells. We constructed\na mouse model with specific deletion of Raptor/Rictor renal cells.\nInhibitors and activators of mTORC1 or mTORC2 were also applied. The\neffects of protein kinase B (AKT) activation and autophagy were studied.\nBoth mTORC1 and mTORC2 were found to mediate the antiapoptotic mechanism\nof renal cells by regulating the AKT activity. Inhibition of mTORC1\nor mTORC2 exacerbated Cd-induced kidney cell apoptosis, suggesting\nthat both proteins exert antiapoptotic effects under Cd exposure.\nWe further found that the AKT activation plays a key role in mTORC1/TORC2-mediated\nantiapoptosis, protecting Cd-exposed kidney cells from apoptosis.\nWe also found that mTOR activators inhibited excessive autophagy,\nalleviated apoptosis, and promoted cell survival. These findings provide\nnew insights into the regulatory mechanisms of mTOR in renal diseases\nand provide a theoretical basis for the development of novel therapeutic\nstrategies to treat renal injury.