Jump to main content
Jump to site search

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


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.

Back to tab navigation

Supplementary files

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
  •   Request permissions

    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

Search articles by author