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Molecular mechanisms underlying HIF-1 activation by fatty acid-bearing albumin and renal protective effect by its regulation

Research Project

Project/Area Number 26460218
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Medical pharmacy
Research InstitutionOsaka University of Pharmaceutical Sciences

Principal Investigator

NAGAI Junya  大阪薬科大学, 薬学部, 教授 (20301301)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords脂肪酸 / アルブミン / 尿細管上皮細胞 / HIF-1 / GLUT1 / BCRP / 低酸素誘導因子 / 腎尿細管 / トランスポーター / 腎近位尿細管上皮細胞 / 低酸素誘導因子HIF-1 / 乳癌耐性タンパク質BCRP / エンドサイトーシス
Outline of Final Research Achievements

In this study, we performed analysis to identify fatty acid which plays an important role in HIF-1 activation by fatty acid-bearing albumin exposure and to examine an involvement of PPAR gamma in fatty acid-bearing albumin-induced HIF-1 activation in HK-2 cells.
Treatment with palmitic acid and oleic acid had no significant effect on GLUT-mediated transport activity, which is enhanced by HIF-1 activation, while the activity of GLUT was increased by treatment with arachidonic acid. These results indicated that arachidonic acid is involved in albumin-induced HIF-1 activation. We also observed induction of HIF-1 alpha, GLUT1 and BCRP mRNA expression by treatment with a PPAR gamma agonist pioglitazone. In addition, pioglitazone increased transport activity of GLUT and BCRP in a concentration-dependent manner. These findings suggested that PPAR gamma induced HIF-1 activation, resulting in enhanced transporter activity of GLUT and BCRP, HIF-1 target gene products.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (19 results)

All 2017 2016 2015 2014 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (2 results)

  • [Journal Article] Cobalt Chloride Induces Expression and Function of Breast Cancer Resistance Protein (BCRP/ABCG2) in Human Renal Proximal Tubular Epithelial Cell Line HK-22017

    • Author(s)
      Nishihashi K, Kawashima K, Nomura T, Urakami-Takebayashi Y, Miyazaki M, Takano M, Nagai J.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 1 Pages: 82-87

    • DOI

      10.1248/bpb.b16-00684

    • NAID

      130005188900

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Basic knowledge of drug transporters described on package inserts for prescription drugs2016

    • Author(s)
      Junya Nagai
    • Journal Title

      Bulletin of Osaka University of Pharmaceutical Sciences

      Volume: 10 Pages: 87-95

    • NAID

      40020804718

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fatty acid-bearing albumin but not fatty acid-depleted albumin induces HIF-1 activation in human renal proximal tubular epithelial cell line HK-2.2014

    • Author(s)
      Nagai, J., Yamamoto, A., Katagiri, Y., Yumoto, R., Takano, M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 450 Issue: 1 Pages: 476-481

    • DOI

      10.1016/j.bbrc.2014.05.146

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 腎近位尿細管上皮細胞へのアルブミン負荷に伴うHIF-1活性化を導く脂肪酸の同定:GULT輸送活性を指標とした解析2017

    • Author(s)
      竹原一揮、仲川直輝、竹林裕美子、宮崎 誠、永井純也
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター、仙台市
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 腎近位尿細管上皮細胞におけるHIF-1標的遺伝子産物GLUT1およびBCRPの発現・機能に及ぼすPPARγアゴニストの影響2017

    • Author(s)
      村田 匡、黒田幸美、柴田 葵、竹林裕美子、宮崎 誠、永井純也
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター、仙台市
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] 腎近位尿細管上皮細胞におけるアルブミン誘発HIF-1活性化の分子機構解析―PPARγ作動薬ピオグリタゾンによるHIF-1誘導について―2016

    • Author(s)
      黒田幸美、竹林裕美子、宮崎 誠、永井純也
    • Organizer
      第66回 日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪薬科大学、高槻市
    • Year and Date
      2016-10-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] 腎近位尿細管上皮細胞におけるアルブミン結合脂肪酸の細胞内移行特性2016

    • Author(s)
      大久保佐和子、竹林裕美子、宮崎 誠、永井純也
    • Organizer
      第66回 日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪薬科大学、高槻市
    • Year and Date
      2016-10-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] HIF-1活性化によるABCトランスポーター発現と抗がん剤による細胞障害性の変動解析2016

    • Author(s)
      西橋佳津希、川嶋 圭、宮崎 誠、岩永一範、永井純也
    • Organizer
      日本薬剤学会第31年会
    • Place of Presentation
      長良川国際会議場、岐阜市
    • Year and Date
      2016-05-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] Fatty acid-bearing Albumin Enhances the Expression and Function of BCRP Transporter via HIF-1 Activation in Renal Proximal Tubular Epithelial Cells2016

    • Author(s)
      Junya Nagai
    • Organizer
      BIT’s 9th Annual World Protein & Peptide Conference 2016
    • Place of Presentation
      International Conference Center, Dalian, China
    • Year and Date
      2016-04-25
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 腎近位尿細管上皮細胞におけるHIF-1活性化に伴うBCRP機能亢進と薬剤性細胞障害に及ぼす影響2016

    • Author(s)
      川嶋 圭、野村 嶺、西橋佳津希、宮崎 誠、岩永一範、永井純也
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] 腎近位尿細管上皮細胞におけるBCRPおよびP-糖タンパク質活性に及ぼす脂肪酸結合アルブミンの影響2015

    • Author(s)
      永井純也、野村 嶺、田中千尋、岩永一範、宮崎 誠、高野幹久
    • Organizer
      日本薬物動態学会第30回年会
    • Place of Presentation
      タワーホール船堀
    • Year and Date
      2015-11-12
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒト腎近位尿細管上皮細胞株におけるアルブミン誘発BCRP 輸送活性の上昇:脂肪酸の関与2015

    • Author(s)
      野村 嶺、田中千尋、宮崎 誠、岩永一範、永井純也
    • Organizer
      第65回 日本薬学会近畿支部総会・大会
    • Place of Presentation
      大阪大谷大学
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report
  • [Presentation] アルブミン共存下におけるBODIPY® FL C16の尿細管上皮細胞内移行特性2015

    • Author(s)
      松村 里子、坂上 弘恵、宮崎 誠、岩永 一範、永井 純也
    • Organizer
      日本薬剤学会第30年会
    • Place of Presentation
      長崎ブリックホール
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒト肝由来HepG2細胞におけるBODIPY® FL C16の細胞内取り込みに及ぼすアルブミン共存の影響2015

    • Author(s)
      坂上 弘恵、松村 里子、宮崎 誠、岩永 一範、永井 純也
    • Organizer
      日本薬剤学会第30年会
    • Place of Presentation
      長崎ブリックホール
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] 腎尿細管上皮細胞におけるアルブミン再取り込みと薬物トランスポーターの発現変動2014

    • Author(s)
      永井純也
    • Organizer
      日本薬学会東海支部特別講演会
    • Place of Presentation
      愛知学院大学
    • Year and Date
      2014-11-17
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Activation of HIF-1 by albumin overload in renal proximal tubular epithelial cells2014

    • Author(s)
      Junya Nagai, Mikihisa Takano
    • Organizer
      International Symposium on Epithelial Barrier and Transport 2014
    • Place of Presentation
      Biwako-Kusatsu campus, Ritsumeikan University
    • Year and Date
      2014-11-01 – 2014-11-02
    • Related Report
      2014 Research-status Report
  • [Presentation] Cyclic AMP-dependent upregulation of MRP2 messenger RNA expression in HK-2 human renal proximal tubular cells: involvement of EPAC2014

    • Author(s)
      Junya Nagai, Machi Nagahiro, Takaaki Tanabe, Ryoko Yumoto, Mikihisa Takano
    • Organizer
      19th North American ISSX Meeting / 29th JSSX Meeting
    • Place of Presentation
      Hilton San Francisco Union Square Hotel
    • Year and Date
      2014-10-18 – 2014-10-23
    • Related Report
      2014 Research-status Report
  • [Remarks]

    • URL

      http://www.oups.ac.jp/kenkyu/kenkyuushitu/yakuzai.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 大阪薬科大学 薬剤学研究室

    • URL

      http://www.oups.ac.jp/kenkyu/kenkyuushitu/yakuzai.html

    • Related Report
      2015 Research-status Report 2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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