2. Academic Validation
  3. mTORC1 and mTORC2 Co-Protect against Cadmium-Induced Renal Tubular Epithelial Cell Apoptosis and Acute Kidney Injury by Regulating Protein Kinase B

mTORC1 and mTORC2 Co-Protect against Cadmium-Induced Renal Tubular Epithelial Cell Apoptosis and Acute Kidney Injury by Regulating Protein Kinase B

  • J Agric Food Chem. 2024 Sep 11;72(36):19667-19679. doi: 10.1021/acs.jafc.4c05702.
Jiaqiao Zhu 1 2 3,  Zhonggui Gong 1 4 5,  Xueru Wang 1 2 3,  Kanglei Zhang 1 2 3,  Yonggang Ma 1 2 3,  Hui Zou 1 2 3,  Ruilong Song 1 2 3,  Hongyan Zhao 1 2 3,  Zongping Liu 1 2 3,  Wenxuan Dong 1 6
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.
  • 2 Institute of Agricultural Science and Technology Development (Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China), Yangzhou University, Yangzhou, Jiangsu 225009, China.
  • 3 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China.
  • 4 Agricultural High-tech Industrial Demonstration Area of the Yellow River Delta of Shandong Province, Dongying, Shandong 257000, China.
  • 5 National Technological Innovation Center for Comprehensive Utilization of Saline-Alkali Land, Dongying, Shandong 257000, China.
  • 6 Laboratory of Animal Nutrition Metabolic and Poisoning Diseases, College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, Shandong 266109, China.
PMID: 39219293 DOI: 10.1021/acs.jafc.4c05702
Abstract

The potential threat of cadmium (Cd)-induced acute kidney injury (AKI) is increasing. In this study, our primary goal was to investigate the individual roles played by mTOR complexes, specifically mTORC1 and mTORC2, in Cd-induced Apoptosis in mouse kidney cells. We constructed a mouse model with specific deletion of Raptor/Rictor renal cells. Inhibitors and activators of mTORC1 or mTORC2 were also applied. The effects of protein kinase B (Akt) activation and Autophagy were studied. Both mTORC1 and mTORC2 were found to mediate the antiapoptotic mechanism of renal cells by regulating the Akt activity. Inhibition of mTORC1 or mTORC2 exacerbated Cd-induced kidney cell Apoptosis, suggesting that both proteins exert antiapoptotic effects under Cd exposure. We further found that the Akt activation plays a key role in mTORC1/TORC2-mediated antiapoptosis, protecting Cd-exposed kidney cells from Apoptosis. We also found that mTOR activators inhibited excessive Autophagy, alleviated Apoptosis, and promoted cell survival. These findings provide new insights into the regulatory mechanisms of mTOR in renal diseases and provide a theoretical basis for the development of novel therapeutic strategies to treat renal injury.

Keywords

AKT; apoptosis; autophagy; cadmium; kidney; mTORC.

Figures