MiR-24–3p/Dio3 axis is essential for BDE47 to induce local thyroid hormone disorder and neurotoxicity. (1st June 2023)

• Record Type: Journal Article
• Authors: Liu, Min; Yu, Zhenlong; Zhao, Zikuang; Yang, Fangyu; Zhou, Meirong; Wang, Chao; Tian, Xiangge; Zhang, Baojing; Liang, Guobiao; Liu, Xiaohui; Shao, Jing
• Is Part Of: Toxicology. Volume 491(2023)
• Publication Date: 2023-06-01
• Subjects: BDE47 (2, 2, 4, 4-tetrabromodiphenyl ether) -- Human type III iodothyronine deiodinase (Dio3) -- MiR-24–3p -- Thyroid hormone; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2023.153527
• Languages: English
• ISSNs: 0300-483X

Abstract

Abstract: BDE47 (2, 2, 4, 4-tetrabromodiphenyl ether) is a member of the most important congeners of polybrominated diphenyl ethers (PBDEs) and has been identified as a developmental, reproductive and nervous system toxicant and endocrine system disruptor due to its frequent detection in human tissue and environmental samples. Our preliminary work suggested that high- and low-level of bromodiphenyl ethers have different effects on neuronal cells with differential targets of actions on neural tissues. In this study, we presented the underlying mechanism of BDE47 neurotoxicity from the perspective of thyroid hormone (TH) metabolism using in vitro model of human SK-N-AS neuronal cells. BDE47 could induce local TH metabolism disorder in neuronal cells by inhibiting the expression of the main enzyme, human type III iodothyronine deiodinase (Dio3). Further elucidation revealed that BDE47 effectively up-regulating miR-24–3p, which binds to the 3′-UTR of Dio3 and inhibits its expression. In addition, BDE47 could also inhibit the deiodinase activity of Dio3. Collectively, our study demonstrates the molecular mechanism of BDE47 regulating Dio3-induced TH metabolism disorder through inducing miR-24–3p, providing new clues for the role of miRNAs in neurodevelopmental toxicity mediated by environmental pollutants. Graphical Abstract: ga1 Highlights: BDE47 inhibits Dio3 expression by targeting miR-24–3p to result in a disorder of TH metabolism in neuronal cells. BDE47 causing TH metabolism disorder and neurotoxicity largely in a miR-24–3p dependent manner. BDE47 inhibit Dio3 catalytic activity and further aggravate the local TH metabolism disorder in neuronal cells.