Low-dose hexavalent chromium induces mitophagy in rat liver via the AMPK-related PINK1/Parkin signaling pathway.

Publisher: PeerJ Inc Country of Publication: United States NLM ID: 101603425 Publication Model: eCollection Cited Medium: Internet ISSN: 2167-8359 (Electronic) Linking ISSN: 21678359 NLM ISO Abbreviation: PeerJ Subsets: MEDLINE

Original Publication: Corte Madera, CA : PeerJ Inc.

Chromium*/toxicity ; Mitophagy*/drug effects ; Protein Kinases*/metabolism ; Ubiquitin-Protein Ligases*/metabolism ; Signal Transduction*/drug effects ; Liver*/drug effects ; Liver*/metabolism ; Liver*/pathology; Animals ; Rats ; Male ; Potassium Dichromate/toxicity ; AMP-Activated Protein Kinases/metabolism ; Rats, Sprague-Dawley ; Malondialdehyde/metabolism

Hexavalent chromium (Cr(VI)) is a hazardous metallic compound commonly used in industrial processes. The liver, responsible for metabolism and detoxification, is the main target organ of Cr(VI). Toxicity experiments were performed to investigate the impacts of low-dose exposure to Cr(VI) on rat livers. It was revealed that exposure of 0.05 mg/kg potassium dichromate (K 2 Cr 2 O 7 ) and 0.25 mg/kg K 2 Cr 2 O 7 notably increased malondialdehyde (MDA) levels and the expressions of P-AMPK, P-ULK, PINK1, P-Parkin, and LC3II/LC3I, and significantly reduced SOD activity and P-mTOR and P62 expression levels in liver. Electron microscopy showed that CR(VI) exposure significantly increased mitophagy and the destruction of mitochondrial structure. This study simulates the respiratory exposure mode of CR(VI) workers through intratracheal instillation of CR(VI) in rats. It confirms that autophagy in hepatocytes is induced by low concentrations of CR(VI) and suggest that the liver damage caused by CR(VI) may be associated with the AMPK-related PINK/Parkin signaling pathway.
Competing Interests: The authors declare there are no competing interests.
(©2024 Li et al.)

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Keywords: AMPK; Chromium; Liver injury; Mitophagy; PINK; Parkin

EC 2.3.2.27 (parkin protein)
0R0008Q3JB (Chromium)
18540-29-9 (chromium hexavalent ion)
EC 2.7.- (Protein Kinases)
EC 2.3.2.27 (Ubiquitin-Protein Ligases)
EC 2.7.11.1 (PTEN-induced putative kinase)
T4423S18FM (Potassium Dichromate)
EC 2.7.11.31 (AMP-Activated Protein Kinases)
4Y8F71G49Q (Malondialdehyde)

Date Created: 20240805 Date Completed: 20240805 Latest Revision: 20240806

20240806

PMC11296300

10.7717/peerj.17837

39099653