细胞核受体RXRα在2,2',4,4'-四溴二苯醚神经毒性中的作用及其机制

doi:10.3969/j.issn.1004-616x.2020.05.002

Abstract

Abstract: OBJECTIVE: To explore interactions between nucleus receptor RXRs and other nuclear receptors in BDE-47-induced cytotoxicity in human neuroblastoma SK-N-SH cells. METHODS: RXRα-knockout cell lines and RXRα high-expression cell lines from human neuroblastoma SK-N-SH cells (named RXR/KO-SK-N-SH and RXR/OE-SK-N-SH cells,respectively) were constructed. The three cell lines were exposed to different concentrations of BDE-47 (1,5,10,20,50,100,150,200 mol/L) for 12,24,48,72 h,and their proliferation rates were determined by the CCK-8 method. mRNA and protein levels of RXR,TR,TR,PPAR and PPAR were measured by qPCR and Western blot,respectively. RESULTS: Proliferation rates of three cell lines which were exposed to BDE-47 for 12,24,48,72 h were significantly different from each other,(P < 0.05). The IC₅₀ of BDE-47 to RXR/KO-SK-N-SH was 1/2 to SK-N-SH and RXR/OE-SK-N-SH. After treatment with BDE-47,the wild-type and RXR/OE-SK-N-SH cell lines showed significant increase of RXRα mRNA and protein expression levels. Their protein expression levels of TRα and PPARα showed the same changes. However,the knockout SK-N-SH cells showed lower expression level in RXRα. The expression levels of TRβ and PPARγ were not dramatically changed in all three SK-N-SH cell lines after the BDE-47 treatment. CONCLUSION: RXRα played a critical role in improving cell viability. After treatment with BDE-47,RXRα mediated the expression of TRα and PPARα in the three SK-N-SH cell lines,but not the expression of TRβ and PPARγ. These data demonstrate that toxicity of BDE-47 on SK-N-SH cells was medicated by activation of RXRα which enhanced TRα and PPARα expression.

Key words: 2,2',4,4'-tetrabromo diphenyl ether, human neuroblastoma cells, retinoid X receptor, thyroid hormone receptors, peroxisome proliferator-activated receptors

CLC Number:

R994.6

XU Yingjian, ZHANG Hang, ZHANG Jianqing. Effect of BDE-47 on nuclear receptor RXRα and toxicity in human neuroblastoma SK-N-SH cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(5): 336-343,349.

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Effect of BDE-47 on nuclear receptor RXRα and toxicity in human neuroblastoma SK-N-SH cells

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