Low-dose effects of bisphenol A are induced by tandem binding of nuclear receptors on DNA

2015 Fiscal Year Final Research Report

• Project/Area Number: 25701008
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Kyushu University
• Principal Investigator: Matsushima Ayami 九州大学, 理学(系)研究科(研究院), 准教授 (60404050)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 分子認識 / 人体有害物質 / 内分泌撹乱物質 / リスク評価 / タンパク質 / 受容体 / 生理活性物質 / 転写

Outline of Final Research Achievements

An endocrine-disrupting chemical bisphenol A (BPA) induces adverse low-dose effects in reproductive organs and in brains. The molecular mechanisms of low-dose effects are unclear, because the binding of BPA to ERα or ERβ is very weak. We found that the transcription activity of ERα induced by BPA is remarkably reinforced by the co-existence of estrogen-related receptor α (ERRα). We have hypothesized that the ERα dimer binds to estrogen response elements (EREs) on DNA at multiple consecutive sites, which are separated at specific intervals, and induces synergistic activation. We therefore plan to explore the optimized nucleotide spacer length between the hormone response elements for ERα-ERRα synergistic transcriptional function. We found that the greatest ERα-ERRα synergistic transcriptional activation was detected with 11 bp-spacer nucleotides. We also analyzed the ER and ERR mRNA expression levels in several cell lines. Their expression levels were different in each cell.

Free Research Field

生物化学