The mechanism behind the disruption of Thyroid hormone receptor (THR) activity via PDI by BPA

2015 Fiscal Year Final Research Report

• Project/Area Number: 25340053
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Kwansei Gakuin University
• Principal Investigator: Imaoka Susumu 関西学院大学, 理工学部, 教授 (60145795)
• Research Collaborator: OGURO AMI 関西学院大学, 理工学部, 助教 (20634497)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: GH3細胞 / PC12細胞 / プロテインジスルフィドイソメラーゼ / ビスフェノールA / HIF-1alpha / 甲状腺ホルモン受容体

Outline of Final Research Achievements

An endocrine disrupting chemical, bisphenol A (BPA) binds to protein disulfide isomerase (PDI) and inhibits its isomerase activity. In this study, we found the new BPA-binding PDI family proteins. ERp29 revealed 3 times higher affinity than PDI toward BPA.　Furthermore, effects of BPA on growth hormone (GH) release via Thyroid hormone receptor (THR) in GH3 cells. BPA in high concentration induced but low concentration of BPA inhibited the GH expression of GH3 cells. BPA induced nitric oxide in GH3 and PC12 cells and nitrosylation of PDI. NOC7 which is an NO-provider inhibited PDI activity and neurite outgrowth in PC12 cells.

Free Research Field

環境応答制御学