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Updated: Jun 14, 2025

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

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mTORC1 and mTORC2 Co-Protect against Cadmium-Induced Renal Tubular Epithelial Cell Apoptosis and Acute Kidney Injury

Jiaqiao Zhu1,2,3, Zhonggui Gong1,4,5, Xueru Wang1,2,3

  • 1College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China.

Journal of Agricultural and Food Chemistry
|September 2, 2024
PubMed

Insights

Cadmium exposure causes kidney injury. This study shows that mTORC1 and mTORC2 complexes protect kidney cells from apoptosis by regulating AKT activity and autophagy, offering therapeutic targets for renal disease.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cellular Biology

Background:

  • Cadmium (Cd) exposure poses a growing threat, leading to acute kidney injury (AKI).
  • Understanding the molecular mechanisms underlying Cd-induced kidney cell apoptosis is crucial for developing effective treatments.
  • The mechanistic target of rapamycin (mTOR) pathway is implicated in cellular stress responses and survival.

Purpose of the Study:

  • To investigate the distinct roles of mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) in cadmium-induced apoptosis in mouse kidney cells.
  • To elucidate the involvement of protein kinase B (AKT) activation and autophagy in these processes.
  • To explore the therapeutic potential of modulating mTOR activity in cadmium nephrotoxicity.

Main Methods:

  • Construction of a mouse model with specific deletion of Raptor/Rictor in renal cells.
  • Application of specific inhibitors and activators for mTORC1 and mTORC2.
  • Assessment of AKT activation and autophagy levels.
  • Evaluation of kidney cell apoptosis following cadmium exposure.

Main Results:

  • Both mTORC1 and mTORC2 were found to mediate an antiapoptotic mechanism in renal cells by regulating AKT activity.
  • Inhibition of mTORC1 or mTORC2 significantly exacerbated cadmium-induced kidney cell apoptosis.
  • AKT activation was identified as a key mediator in mTORC1/mTORC2-driven antiapoptosis.
  • mTOR activators were observed to inhibit excessive autophagy, alleviate apoptosis, and promote cell survival.

Conclusions:

  • mTORC1 and mTORC2 play critical antiapoptotic roles in cadmium-exposed kidney cells.
  • The mTOR-AKT signaling pathway is essential for protecting renal cells against cadmium toxicity.
  • Modulating mTOR activity presents a promising therapeutic strategy for mitigating cadmium-induced kidney injury and related renal diseases.
Keywords:
AKTapoptosisautophagycadmiumkidneymTORC

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