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  3. Arsenic Exposure-Induced Acute Kidney Injury by Regulating SIRT1/PINK1/Mitophagy Axis in Mice and in HK-2 Cells

Arsenic Exposure-Induced Acute Kidney Injury by Regulating SIRT1/PINK1/Mitophagy Axis in Mice and in HK-2 Cells

  • J Agric Food Chem. 2023 Oct 16. doi: 10.1021/acs.jafc.3c05341.
Shuiping Liu 1 2 3 4,  Yunhuan Liu 2 3 4,  Jinyan Li 2 3 4,  Mengmeng Wang 2 3 4,  Xingxiang Chen 2 3 4,  Fang Gan 2 3 4,  Lixin Wen 1,  Kehe Huang 2 3 4,  Dandan Liu 2 3 4
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan Province 410128, China.
  • 2 College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province 210095, China.
  • 3 Institute of Animal Nutritional Health, Nanjing Agricultural University, Nanjing, Jiangsu Province 210095, China.
  • 4 MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province 210095, China.
PMID: 37843077 DOI: 10.1021/acs.jafc.3c05341
Abstract

Groundwater resources are often contaminated by arsenic, which poses a serious threat to human and animal's health. Some studies have demonstrated that acute arsenic exposure could induce kidney injury because the kidney is a key target organ for toxicity, but the exact mechanism remains unclear. Hence, we investigated the effect of SIRT1-/PINK1-mediated Mitophagy on NaAsO2-induced kidney injury in vivo and in vitro. In our study, NaAsO2 exposure obviously induced renal tubule injury and mitochondrial dysfunction. Meanwhile, NaAsO2 exposure could inhibit the mRNA/protein level of SIRT1 and activate the mitophagy-related mRNA/protein levels in the kidney of mice. In HK-2 cells, we also confirmed that NaAsO2-induced nephrotoxicity depended on the activation of Mitophagy. Moreover, the activation of SIRT1 by resveratrol alleviated NaAsO2-induced acute kidney injury via the activation of Mitophagy in vivo and in vitro. Interestingly, the inhibition of Mitophagy by cyclosporin A (CsA) further exacerbated NaAsO2-induced nephrotoxicity and inflammation in HK-2 cells. Taken together, our study found that SIRT1-regulated PINK1-/Parkin-dependent Mitophagy was implicated in NaAsO2-induced acute kidney injury. In addition, we confirmed that PINK1-/Parkin-dependent Mitophagy played a protective role against NaAsO2-induced acute kidney injury. Therefore, activation of SIRT1 and Mitophagy may represent a novel therapeutic target for the prevention and treatment of NaAsO2-induced acute renal injury.

Keywords

PINK1; SIRT1; acute kidney injury; arsenic; mitophagy.

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