Investigation of disease biomarkers using metabolome analysis targeted to transporters
| Project/Area Number |
15H04664
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
KATO YUKIO 金沢大学, 薬学系, 教授 (30251440)
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| Research Collaborator |
Nakamichi Noritaka
MASUO Yusuke
Sakai Yoshio
Kagaya Takashi
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2017: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
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| 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 / メタボローム / バイオマーカー / 炎症性疾患 / 炎症性腸疾患 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(52 results)
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[Journal Article] Increased plasma concentrations of unbound SN-38, the active metabolite of irinotecan, in cancer patients with severe renal failure2016
Author(s)
Ken-ichi Fujita, Yusuke Masuo, Hidenori Okumura, Yusuke Watanabe, Hiromichi Suzuki, Yu Sunakawa, Ken Shimada, Kaori Kawara, Yuko Akiyama, Masanori Kitamura, Munetaka Kunishima, Yasutsuna Sasaki, Yukio Kato
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Journal Title
Pharmaceutical Research
Volume: 33
Issue: 2
Pages: 269-282
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Localizatoin of xenobiotic transporter OCTN1/SLC22A4 in hepatic stellate cells and its protective role in liver fibrosis.2016
Author(s)
Tang Y, Masuo Y, Sakai Y, Wakayama T, Sugiura T, Harada R, Futatsugi A, Komura T, Nakamichi N, Sekiguchi H, Sutoh K, Usumi K, Iseki S, Kaneko S, Kato Y.
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Journal Title
J Pharm Sci
Volume: 印刷中
Issue: 5
Pages: 1779-89
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] A mutation in SLC22A4 encoding an organic cation transporter expressed in the cochlea strial endothelium causes human recessive non-syndromic hearing loss DFNB60.2016
Author(s)
Ben Said M, Grati M, Ishimoto T, Zou B, Chakchouk I, Ma Q, Yao Q, Hammami B, Yan D, Mittal R, Nakamichi N, Ghorbel A, Neng L, Tekin M, Shi XR, Kato Y, Masmoudi S, Lu Z, Hmani M, Liu X.
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Journal Title
Human Genetics
Volume: 135(5)
Issue: 5
Pages: 513-524
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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