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  2. The mechanism of nickel-induced autophagy and its role in nephrotoxicity

The mechanism of nickel-induced autophagy and its role in nephrotoxicity

  • Ecotoxicol Environ Saf. 2024 Mar 1:273:116150. doi: 10.1016/j.ecoenv.2024.116150.
Heng Yin 1 Chengbi Wang 1 Hongrui Guo 2 Xiaocong Li 1 Jingbo Liu 3
Affiliations

Affiliations

  • 1 School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan 621010, China.
  • 2 College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
  • 3 School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang, Sichuan 621010, China. Electronic address: jingboliu@swust.edu.cn.
Abstract

Nickel (Ni), an environmental health hazard, is nephrotoxic to humans, but the exact mechanism is unknown. This study aims to identify whether nephrotoxicity is associated with Autophagy. Here, nickel chloride (NiCl2) increased Autophagy in TCMK-1 cells. NiCl2 induces Autophagy through Akt and AMPK/mTOR pathways. Next, oxidative stress was investigated in NiCl2-induced Autophagy. The findings demonstrated that the antioxidant (NAC) or mitochondrial targeted antioxidant (Mito-TEMPO) attenuated NiCl2-induced Autophagy, reversed the influence on AMPK-mTOR and Akt pathways. Additionally, our study examined the role of Autophagy in NiCl2-induced nephrotoxicity. Autophagy inhibition with 3-MA could inhibit cell viability and increase Apoptosis in the TCMK-1 cells, however, Autophagy promotion with rapamycin relieved cytotoxicity and decreased Apoptosis. Additionally, co-treatment with Z-VAD-FMK reduced cytotoxicity, but did not affect Autophagy. Besides, NiCl2 can increase the level of Mitophagy in vivo and vitro. Mitophagy inhibition could inhibit cell viability and increase Apoptosis in the TCMK-1 cells, whereas, promotion of Mitophagy could increase cell viability and decrease Apoptosis. In summary, above-mentioned results showed that NiCl2 induces Autophagy in TCMK-1 cells through oxidative stress-dependent AMPK/AKT-mTOR pathway, Autophagy plays a role in reducing NiCl2-induced renal toxicity, and a major mechanism in autophagy's inhibitory effect on NiCl2-induced Apoptosis may be Mitophagy.

Keywords

Apoptosis; Autophagy; Kidney; Mitophagy; Nickel.

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