2,2',4,4'-四溴联苯醚通过核受体介导神经毒性作用机制的初步研究

doi:10.3969/j.issn.1004-616x.2017.03.003

Abstract

Abstract: OBJECTIVE:To investigate the effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on cell proliferation and expression of the main nuclear receptors of RXRα,TRs and PPARs in human neuroblastoma SK-N-SH cells. METHODS:SK-N-SH cells were treated with different concentrations of BDE-47 and their proliferation was measured by the Cell Counting Kit-8 (CCK-8) assay. In addition,ROS level,SOD vitality,GSH-Px vitality and hOGG1 mRNA expression were analyzed by using the DCFH-DA,WST-1,colorimetric and qPCR assays,respectively. Involvement of the main nuclear receptors on expression of mRNA and protein were determined by qPCR and Western blot,respectively. RESULTS:BDE-47 inhibited cell proliferation and induced significant cytotoxicity in SK-N-SH cells. Dose-and time-dependent responses of the inhibitory effect were concentration-dependent,and the IC₅₀ for 24-hours was 75.94 μmol/L. The expression levels in mRNA and protein of RXRα,TRs and PPARs in the treated cells were significantly increased compared with that in the control group,while induction of the isoforms was not consistent. CONCLUSION:BDE-47 inhibited proliferation of SK-N-SH cells via the induction of oxidative damage and neurotoxicity through up-regulating the expression of nuclear receptors:RXRα,TRs,and PPARs.

Key words: tetrabromo diphenyl ether, retinoid X receptor, thyroid hormone receptors, peroxisome proliferator-activated receptors, oxidative stress

CLC Number:

R994.6

LI Yunxiu, JIANG Yousheng, ZHANG Jianqing, WANG Xiaohui, MEI Shujiang, ZHOU Jian, LIN Xiaoshi, ZHAO Wenjun, WAN Keyan. Preliminary study on mechanisms of neurotoxicity by 2, 2', 4, 4'-tetrabromodiphenyl ether via nuclear receptors[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(3): 172-178.

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Preliminary study on mechanisms of neurotoxicity by 2, 2', 4, 4'-tetrabromodiphenyl ether via nuclear receptors

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