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Tributyltin induces epigenetic changes and decreases the expression of nuclear respiratory factor-1

Abstract

Tributyltin (TBT), a common organotin environmental pollutant, has been widely used as a component of marine antifouling paints. We previously reported that exposure to TBT inhibits the expression and DNA binding of nuclear respiratory factor-1 (NRF-1) and causes neurotoxicity. In the present study, we focused on the epigenetic effects of TBT and investigated whether TBT decreases NRF-1 expression via epigenetic modifications in SH-SY5Y human neuroblastoma cells. First, we found that exposure to 300 nM TBT decreases NRF-1 expression. We examined epigenetic changes induced by TBT, and showed that TBT causes hypermethylation of the NRF-1 promoter region, increases the amount of methyl-CpG-binding protein 2 (MeCP2) bound to the NRF-1 promoter, and alters the expression of DNA methyltransferases and ten-eleven translocation (TET) demethylation enzymes. These results suggest that epigenetic changes play an important role in regulation of NRF-1 expression. Next, we investigated effect of NRF-1 expression decrease on cells, and TBT reduces mitochondrial membrane potential and overexpression of NRF-1 rescued this reduction in membrane potential. Thus, we suggested that NRF-1 is important for maintaining mitochondrial membrane potential. Our study indicates that TBT causes epigenetic changes such as hypermethylation, which increases recruitment of MeCP2 to the NRF-1 promoter and probably lead to decreased of NRF-1 expression and mitochondrial membrane potential. Therefore, this research provides new evidence of the epigenetic action caused by organotin.

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Publication details

The article was received on 17 Oct 2017, accepted on 04 Jan 2018 and first published on 04 Jan 2018


Article type: Paper
DOI: 10.1039/C7MT00290D
Citation: Metallomics, 2018, Accepted Manuscript
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    Tributyltin induces epigenetic changes and decreases the expression of nuclear respiratory factor-1

    S. Hanaoka, K. Ishida, S. Tanaka, S. Sakamoto, K. Okuda, S. Sanoh, S. Ohta and Y. Kotake, Metallomics, 2018, Accepted Manuscript , DOI: 10.1039/C7MT00290D

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