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Functional characterization of folate transport in osteoclast

Research Project

Project/Area Number 20790141
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Medical pharmacy
Research InstitutionNagoya City University

Principal Investigator

INOUE Katsuhisa  Nagoya City University, 大学院・薬学研究科, 准教授 (50315892)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords葉酸 / トランスポーター / 破骨細胞 / リソソーム / メトトレキサート / 担体輸送 / ビタミン / 吸収
Research Abstract

In order to explore the possibility that the carrier-mediated folate transport system could be involved in the accumulation of methotrexate in osteoclasts, we examined the transport of folate in lysosomes isolated from the rat kidney, since lysosomal membrane has functional similarities of the ruffled border in osteoclasts. It was found that the lysosomal folate transport occurred at an acidic pH (pH 5.0 - 6.0), and was saturable with the Michaelis constant of 0.073 μM. When we examined the effect of various inhibitors for RFC1 (reduced folate carrier 1) and PCFT (proton-coupled folate transporter) on the lysosomal folate transport, the inhibition profile was found to be different from those of RFC1 and PCFT. These results suggest that lysosomes have a specific folate transport system, which has not been identified, and this transport system may be involved in methotrexate accumulation in osteoclasts.

Report

(3 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • Research Products

    (16 results)

All 2010 2009 2008

All Journal Article (13 results) (of which Peer Reviewed: 6 results) Presentation (3 results)

  • [Journal Article] Evaluation of 4', 6-diamidino-2- phenylindole as a fluorescent probe substrate for rapid assays of the functionality of human multidrug and toxin extrusion proteins.2010

    • Author(s)
      Yasujima T, Ohta K, Inoue K, Ishimaru M, Yuasa H
    • Journal Title

      Drug Metab Dispos 38

      Pages: 715-721

    • Related Report
      2009 Final Research Report
  • [Journal Article] Identification and functional characterization of the first nucleobase transporter in mammals.2010

    • Author(s)
      Yamamoto S, Inoue K, Murata T, Kamigaso S, Yasujima T, Maeda JY, Yoshida Y, Ohta K, Yuasa H
    • Journal Title

      J Biol Chem 285

      Pages: 522-531

    • Related Report
      2009 Final Research Report
  • [Journal Article] Identification and functioal characterization of the first nucleobase transpo rters in mammals : implication in the species difference in the intestinal absorption mechanism of mucleobases and their analogs between higher frimates and other mammals.2010

    • Author(s)
      Syunsuke, S., et al.
    • Journal Title

      J.Biol.Chem. 285

      Pages: 6522-6531

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of 4, 6-diamidino-2-phenylindole as a fluorescent probe substrate for rapid assays of the functionality of human multidrug nad toxin extrusion proteins.2010

    • Author(s)
      Yasujima, T., et al.
    • Journal Title

      Drug Metab.Dispos. 38

      Pages: 715-721

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional characteristics of two human MATE transporters: Kinetics of cimetidine transport and profiles of inhibition by various compounds.2009

    • Author(s)
      Ohta K, Inoue K, Yasujima T, Ishimaru M, Yuasa H
    • Journal Title

      J Pharm Pharm Sci 12

      Pages: 388-396

    • Related Report
      2009 Final Research Report
  • [Journal Article] Identification and functional characterization of rat riboflavin transporter 2.2009

    • Author(s)
      Yamamoto S, Inoue K, Ohta K, Fukatsu R, Maeda J, Yoshida Y, Yuasa H
    • Journal Title

      J Biochem 145

      Pages: 437-443

    • NAID

      10026301970

    • Related Report
      2009 Final Research Report
  • [Journal Article] Molecular and functional characteristics of proton-coupled folate transporter.2009

    • Author(s)
      Yuasa Y., Inoue K, Hayashi Y
    • Journal Title

      J Pharm Sci 98

      Pages: 1608-1616

    • Related Report
      2009 Final Research Report
  • [Journal Article] Functional characterization of multidrug and toxin extrusion protein 1 as a facilitative transporter for fluoroquinolones.2009

    • Author(s)
      Ohta K, Imamura Y, Okudaira N, Atsumi R, Inoue K, Yuasa H
    • Journal Title

      J Pharmacol Exp Ther 328

      Pages: 628-634

    • Related Report
      2009 Final Research Report
  • [Journal Article] Functional characteristics of two human MATE transporters : kinetics of cimetidine transport and profiles of inhibition by various compunds.2009

    • Author(s)
      Ohta, K., et al.
    • Journal Title

      J.Pharm.Pharmaceut.Sci. 12

      Pages: 388-396

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional characterization of multidrug and toxin extrusion protein 1 as a facilitative transporter for fluoroquinolones2009

    • Author(s)
      Ohta, K
    • Journal Title

      J. Pharmacol. Exp. Ther 328

      Pages: 628-634

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional characterization of PCFT/HCP1 as the molecular entity of the carrier-mediated intestinal folate transport system in the rat model.2008

    • Author(s)
      Inoue K, Nakai Y, Ueda S, Kamigaso S, Ohta K, Hatakeya M., Hayashi Y, Otagiri M, Yuasa H
    • Journal Title

      Am J Physiol 294

    • Related Report
      2009 Final Research Report
  • [Journal Article] Identification and functional characterization of rat riboflavin transporter 22008

    • Author(s)
      Yamamoto, S., et.al.
    • Journal Title

      J. Biochem 145

      Pages: 437-443

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional characterization of PCFT/HCP1 as the molecular entity of the carrier-mediated intestinal folate transport system in the rat model2008

    • Author(s)
      Inoue, K., et.al.
    • Journal Title

      Am. J. Physiol 294

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 葉酸吸収におけるPCFT/SLC46A1の役割2010

    • Author(s)
      井上勝央、湯浅博昭
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Year and Date
      2010-03-29
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] ラット腎リソソームにおけるfolate輸送系の機能解析2009

    • Author(s)
      井上勝央、石谷治男、太田欣哉、湯浅博昭
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-26
    • Related Report
      2009 Final Research Report
  • [Presentation] ラット腎リソソームにおけるfblate輸送系の機能解析2009

    • Author(s)
      井上勝央, 他
    • Organizer
      日本薬学会第129年会
    • Place of Presentation
      京都
    • Year and Date
      2009-03-26
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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