Ferritinophagy is involved in hexavalent chromium-induced ferroptosis in Sertoli cells.

Autor: Zhuge R; Department of Toxicology, School of Public Health, Jilin University, Changchun, Jilin Province, China., Zhang L; Department of Toxicology, School of Public Health, Jilin University, Changchun, Jilin Province, China., Xue Q; Department of Toxicology, School of Public Health, Jilin University, Changchun, Jilin Province, China., Wang R; Department of Toxicology, School of Public Health, Jilin University, Changchun, Jilin Province, China., Xu J; Department of Toxicology, School of Public Health, Jilin University, Changchun, Jilin Province, China., Wang C; Department of Toxicology, School of Public Health, Jilin University, Changchun, Jilin Province, China., Meng C; Department of Spine Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China., Lu R; Department of Toxicology, School of Public Health, Jilin University, Changchun, Jilin Province, China., Yin F; Department of Spine Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China., Guo L; Department of Toxicology, School of Public Health, Jilin University, Changchun, Jilin Province, China. Electronic address: gli@jlu.edu.cn.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2024 Nov; Vol. 492, pp. 117139. Date of Electronic Publication: 2024 Oct 30.
DOI: 10.1016/j.taap.2024.117139
Abstrakt: Hexavalent chromium [Cr(VI)] has significant adverse effects on the environment and human health, particularly on the male reproductive system. Previously, we observed ferroptosis and autophagy in rat testicular injury induced by Cr(VI). In the present study, we focused on the association between ferroptosis and autophagy in mouse Sertoli cells (TM4) exposed to concentrations of 2.5 μМ, 5 μМ, and 10 μМ Cr(VI). Cr(VI) exposure altered mitochondrial ultrastructure; increased intracellular iron, malondialdehyde, and reactive oxygen species (ROS) levels; decreased glutathione content; increased TfR1 protein expression; and decreased GPX4, FPN1, and SLC7A11 protein expression, ultimately resulting in ferroptosis. Additionally, we observed ferritinophagy, increased expression of BECLIN1, LC3B, and NCOA4, and decreased expression of FTH1 and P62. Inhibition of autophagy and ferritinophagy via 3-MA and small interfering RNA (siRNA)-mediated silencing of NCOA4 ameliorated changes in ferritinophagy- and ferroptosis-associated protein expression, and reduced ROS levels. Rats exposed to Cr(VI) exhibited atrophy of testicular seminiferous tubules, a reduction in germ and Sertoli cells, and the occurrence of ferritinophagy and ferroptosis in cells of the rat testes. These results indicate that ferroptosis, triggered by NCOA4-mediated ferritinophagy, is one of the mechanisms that contribute to Cr(VI)-induced damage in Sertoli cells.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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