Search for AhR endogenous ligands by metabolomics

Research Project

Project/Area Number	26460377
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	General medical chemistry
Research Institution	Kyorin University
Principal Investigator	Taniguchi Yoshihito 杏林大学, 医学部, 教授 (00324616)
Project Period (FY)	2014-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000) Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	CYP1A / P450 / 多環芳香族炭化水素 / ダイオキシン / AhR / メダカ / 変異体 / メタボローム / cyp1a / dioxin / medaka / CYP1A1
Outline of Final Research Achievements	Medaka deficient for CYP1A, a highly conserved phase I detoxifying enzyme, was created by TILLING method. This CYP1A 'knockout' medaka reacted to lower (about one tenth) concentrations of polycyclic aromatic hydrocarbons than their wild type littermates. Interestingly, AhR signaling pathway is dramatically activated in unexposed CYP1A knockouts compared to the wild type, suggesting that there are endogenous ligands for AhR that are metabolized by CYP1A in vivo. The metabolome analysis revealed that CYP1A is possibly involved in nucleic acid metabolism.