2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) induces mitochondrial dysfunction and related liver injury via eliciting miR-34a-5p-mediated mitophagy impairment.

Autor: Chen F; School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; College of Health Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China., Feng L; School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; College of Health Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China., Zheng YL; School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; College of Health Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China., Lu J; School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; College of Health Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China., Fan SH; School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; College of Health Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China., Shan Q; School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; College of Health Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China., Zheng GH; School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; College of Health Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China., Wang YJ; School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; College of Health Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China., Wu DM; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; College of Health Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China., Li MQ; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; College of Health Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China., Wang QQ; School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China., Zhang ZF; School of Life Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China; College of Health Science, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, PR China. Electronic address: zhangzifengsuper@jsnu.edu.cn.
Jazyk: angličtina
Zdroj: Environmental pollution (Barking, Essex : 1987) [Environ Pollut] 2020 Mar; Vol. 258, pp. 113693. Date of Electronic Publication: 2019 Dec 06.
DOI: 10.1016/j.envpol.2019.113693
Abstrakt: 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) is associated with various adverse human health effects; however, the knowledge of its toxicity is still very limited. Mitochondrial injury has been observed in liver cells exposed to BDE-47 in vitro. Mitophagy impairment causes the accumulation of dysfunctional mitochondria, contributing to the pathological mechanisms of liver injury. The aim of this study was to investigate whether BDE-47 impairs mitophagy to trigger mitochondrial dysfunction-related liver injury and the underlying mechanisms. This study revealed that BDE-47 elicited mitochondrial dysfunction and related oxidative liver injury by impairing mitophagy. Moreover, our results showed that NAD + insufficiency is responsible for BDE-47-mediated mitophagy defect and mitochondrial dysfunction in mouse livers, which was associated with suppression of Sirt3/FoxO3a/PINK1 signaling. Furthermore, our results indicated a potential role of miR-34a-5p in the hepatotoxicity of BDE-47. Mechanistically, BDE-47 dramatically upregulated miR-34a-5p expression in mouse livers. The data from AAV-sponge-mediated miR-34a-5p inhibition suggested that miR-34a-5p diminished NAD + level by directly targeting NAMPT expression in BDE-47-treated mouse livers, which was confirmed by luciferase reporter assay. Consequently, miR-34a-5p markedly abated Sirt3/FoxO3a/PINK1 signaling-mediated mitophagy to promote mitochondrial dysfunction in BDE-47-treated mouse livers. The present study provided in vivo evidence to reveal a potential mechanism for BDE-47-induced mitochondrial dysfunction and related liver injury and indicated that miR-34a-5p-mediated mitophagy impairment might be a therapeutic target for BDE-47 toxicity.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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