Investigation of disease biomarkers using metabolome analysis targeted to transporters

2018 Fiscal Year Final Research Report

• Project/Area Number: 15H04664
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kanazawa University
• Principal Investigator: KATO YUKIO 金沢大学, 薬学系, 教授 (30251440)
• Research Collaborator: Nakamichi Noritaka ; MASUO Yusuke ; Sakai Yoshio ; Kagaya Takashi
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 膜輸送体 / メタボロミクス / 薬物動態 / 薬物相互作用 / 医薬品開発

Outline of Final Research Achievements

Transporters are involved in influx and efflux of endogenous compounds through cellular plasma membranes. The present study focused on one of such transporters OCTN1. OCTN1 is a unique transporter since its expression is known to be up-regulated in inflammatory conditions in certain organs such as gut and liver. The aim of the present study is to understand pathophysiological roles of OCTN1, to clarify its endogenous substrates, and to establish methodology to identify endogenous substrates. In the present study we have constructed structure-selective metabolomics in which endogenous compounds are first concentrated using transporter function, and amino group in endogenous compounds are comprehensively derivatized, followed by quantification of the compounds using LC-TOFMS. Based on this technique, we identified endogenous substrate of OCTN1. In addition, we also clarified that OCTN1 and its endogenous substrate may play a protective role in chronic kidney disease mice and patients.

Free Research Field

薬物治療学

Academic Significance and Societal Importance of the Research Achievements

膜輸送体はさまざまな疾患に関係する。実際、本研究でもOCTN1と慢性腎臓病の関連が示唆されたが、多くの遺伝子レベルの研究からも、疾患と膜輸送体との関係が示されつつある。一方、本研究では膜輸送体の生体内基質を解明するための新たな手法として構造選択的メタボロミクスを確立した。よって、この手法を今後応用・発展させることにより、さまざまな膜輸送体と疾患との間に働く生体内物質を解明する手段となることが期待される。このことは、疾患の原因の解明につながるばかりでなく、見つけられた物質を疾患の診断や予後の予測、さらには治療に使うことができるかもしれない。このように病気の研究、診断、治療に有意義な知見を得た。