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Regulatory mechanisms for heme biosynthesis in response to the change of regulatory heme pool.

Research Project

Project/Area Number 23590353
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionIwate Medical University (2013)
Tohoku University (2011-2012)

Principal Investigator

FURUYAMA Kazumichi  岩手医科大学, 医学部, 教授 (80280874)

Co-Investigator(Kenkyū-buntansha) SHIBAHARA Shigeki  東北大学, 大学院医学系研究科, 教授 (00154253)
KANEKO Kiriko  東北大学, 大学院医学系研究科, 助教 (10545784)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsヘム / 翻訳後修飾 / ミトコンドリア / 5-アミノレブリン酸合成酵素 / 5-アミノレブリン酸合成酵素 / 翻訳後調節 / 質量分析 / アミノレブリン酸合成酵素
Research Abstract

Heme is an essential prosthetic group of several proteins, and is synthesized in all living cells. On the other hand, production of heme was strictly regulated in each cells, since excess amount of heme produces reactive oxygen spices. It has been well known that the expression of non-specific 5-aminolevulinate synthase (ALAS1), which is the first and the rate limiting enzyme of heme biosynthetic pathway in non-erythroid cells, is regulated at transcriptional, as well as at several post-transcriptional levels for the strict regulation of heme biosynthesis. In the present project, we have challenged to determine the novel mechanisms, which is involved in the precise and quick response of ALAS1 expression to the change of heme contents in the cells.As a result, we have successfully identified novel mechanisms for post-translational regulation of ALAS1 protein in mitochondria.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (24 results)

All 2014 2013 2012 2011 Other

All Journal Article (8 results) (of which Peer Reviewed: 6 results) Presentation (12 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Identification of a novel erythroid-specific enhancer for the ALAS2 gene and its loss-of-function mutation which is associated with congenital sideroblastic anemia2014

    • Author(s)
      Kaneko K, Furuyama K, Fujiwara T, Kobayashi R, Ishida H, Harigae H, Shibahara S
    • Journal Title

      Haematologica

      Volume: 99(2)(PubMed PMID : 23935018; PMCID : PMC3912954) Issue: 2 Pages: 252-261

    • DOI

      10.3324/haematol.2013.085449

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Journal Article] Clinical and genetic characteristics of congenital sideroblastic anemia: comparison with myelodysplastic syndrome with ring sideroblast (MDS-RS)2013

    • Author(s)
      大場理恵、吉田健一
    • Journal Title

      Ann Hematol

      Volume: 92 Issue: 1 Pages: 1-9

    • DOI

      10.1007/s00277-012-1564-5

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Depletion of glutamine enhances sodium butyrate-induced erythroid differentiation of K562 cells.Depletion of glutamine enhances sodium butyrate-induced erythroid differentiation of K562 cells.2012

    • Author(s)
      Hiep,N. C., Kinohira, S., Furuyama, K and Taketani S
    • Journal Title

      J. Biochem

      Volume: 152(6) Issue: 6 Pages: 509-519

    • DOI

      10.1093/jb/mvs097

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Coordinated expression of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 4 and heme oxygenase 2: evidence for a regulatory link between glycolysis and heme catabolism2012

    • Author(s)
      Li B, Takeda K, Ishikawa K, Yoshizawa M, Sato M, Shibahara S, Furuyama K
    • Journal Title

      Tohoku J Exp Med

      Volume: 228(1)(PMID : 22892400) Pages: 27-41

    • NAID

      10031025395

    • Related Report
      2013 Final Research Report
  • [Journal Article] Expression of (pro)renin receptor in human erythroid cell lines and its increased protein accumulation by interferon-γ2012

    • Author(s)
      Kaneko K, Nishiyama H, Ohba K, Shibasaki A, Hirose T, Totsune K, Furuyama K, Takahashi K
    • Journal Title

      Peptides

      Volume: 37 Issue: 2 Pages: 285-289

    • DOI

      10.1016/j.peptides.2012.07.015

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The carboxyl-terminal region of erythroid-specific 5-aminolevulinate synthase acts as an intrinsic modifier for its catalytic activity and protein stability.2012

    • Author(s)
      Kadirvel S, Furuyama K, Harigae H, Kaneko K, Tamai Y, Ishida Y, Shibahara S.
    • Journal Title

      Exp Hematol

      Volume: 40 Issue: 6 Pages: 477-486

    • DOI

      10.1016/j.exphem.2012.01.013

    • Related Report
      2013 Final Research Report 2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Coordinated expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 and heme oxygenase 2: evidence for a regulatory link between glycolysis and heme catabolism.2012

    • Author(s)
      Li B, Takeda K, Ishikawa K, Yoshizawa M, Sato M, Shibahara S, Furuyama K.
    • Journal Title

      Tohoku J Exp Med.

      Volume: 228 Pages: 27-41

    • NAID

      10031025395

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Roles of porphyrin and iron metabolisms in the δ-aminolevulinic acid (ALA)-induced accumulation of protoporphyrin and photodamage of tumor cells2011

    • Author(s)
      Yoshiko Ohgari
    • Journal Title

      Photochemistry and Photobiology

      Volume: 87 Issue: 5 Pages: 1138-1145

    • DOI

      10.1111/j.1751-1097.2011.00950.x

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 「ヘム鉄—プロトポルフィリンIX」が関与する細胞内クロストーク機構2013

    • Author(s)
      古山和道
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] ヘム(鉄-プロトポルフィリンIX)が関与する細胞内クロストーク機構2013

    • Author(s)
      古山和道
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] ヒト赤芽球特異的5−アミノレブリン酸合成酵素遺伝子における新たな赤芽球特異的エンハンサーの同定2012

    • Author(s)
      古山和道, 金子桐子, 藤原亨, 張替秀郎, 柴原茂樹
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] Identification of the Novel Erythroid-Specific Enhancer in the First Intron of Human ALAS2 Gene;The Mutation Disrupting GATA Transcription Factor-Binding Site in the Enhancer Causes X-Linked Sideroblastic Anemia2012

    • Author(s)
      Furuyama K, Kaneko K, Fujiwara T, Harigae H, Shibahara S
    • Organizer
      54th Annual Meeting of American Society of Hematology
    • Place of Presentation
      Atlanta, U.S.A
    • Related Report
      2013 Final Research Report
  • [Presentation] ヒト赤芽球特異的5-アミノレブリン酸合成酵素遺伝子における新たな赤芽球特異的エンハンサーの同定2012

    • Author(s)
      古山和道、金子桐子、藤原亨、張替秀郎、柴原茂樹.
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Identification of the Novel Erythroid-Specific Enhancer in the First Intron of Human ALAS2 Gene; Tthe Mutation Disrupting GATA Transcription Factor-Binding Site in the Enhancer Causes X-Linked Sideroblastic Anemia.2012

    • Author(s)
      Furuyama K, Kaneko K, Fujiwara T, Harigae H, Shibahara S.
    • Organizer
      54th Annual Meeting of American Society of Hematology
    • Place of Presentation
      Atlanta, U.S.A.
    • Related Report
      2012 Research-status Report
  • [Presentation] 赤芽球特異的5−アミノレブリン酸合成酵素のカルボキシル末端は内因性抑制ドメインとして機能する2011

    • Author(s)
      Senkottubelan Kadirvel,古山和道, 金子桐子, 張替秀郎, 柴原茂樹
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都国際会館
    • Related Report
      2013 Final Research Report
  • [Presentation] haracteristics of sideroblastic anemia in japan–from the analysis of multicenter study2011

    • Author(s)
      Rie Ohba, Kazumichi Furuyama, Atsushi Manaba, Etsuro Ito, Seiji Kojima, Keiya Ozawa, Hideo Harigae
    • Organizer
      第73回日本血液学会総会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2013 Final Research Report
  • [Presentation] Expression of (pro) renin receptor in human erythroid cell lines : the effect of interferon–gamma2011

    • Author(s)
      Kiriko Kaneko, Akiko Shibasaki, Hiroshi Nishiyama, Takuo Hirose, Koji Ohba, Kazuhito Totsune, Kazumichi Furuyama and Kazuhiro Takahashi
    • Organizer
      第53回アメリカ血液学会
    • Place of Presentation
      San Diego, U.S.A
    • Related Report
      2013 Final Research Report
  • [Presentation] 赤芽球特異的5-アミノレブリン酸合成酵素のカルボキシル末端は内因性抑制ドメインとして機能する

    • Author(s)
      Senkottubelan Kadirvel, 古山和道、金子桐子、張替秀郎、柴原茂樹
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都国際会議場
    • Related Report
      2011 Research-status Report
  • [Presentation] Characteristics of sideroblastic anemia in Japan-from the analysis of multicenter study

    • Author(s)
      Rie Ohba, Kazumichi Furuyama, Atsushi Manaba, Etsuro Ito, Seiji Kojima, Keiya Ozawa, Hideo Harigae
    • Organizer
      第73回日本血液学会総会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2011 Research-status Report
  • [Presentation] Expression of (pro)renin receptor in human erythroid cell lines: the effect of interferon- gamma

    • Author(s)
      Kiriko Kaneko, Akiko Shibasaki, Hiroshi Nishiyama, Takuo Hirose, Koji Ohba, Kazuhito Totsune, Kazumichi Furuyama and Kazuhiro Takahashi
    • Organizer
      第53回アメリカ血液学会総会
    • Place of Presentation
      サンディエゴコンベンションセンター、アメリカ合衆国
    • Related Report
      2011 Research-status Report
  • [Book] Handbook of Porphyrin Science, Volume 27 p 1-392013

    • Author(s)
      Kazumichi Furuyama and Masayuki Yamamoto
    • Total Pages
      39
    • Publisher
      World Scientific Publishing Co. Pte. Ltd.
    • Related Report
      2013 Annual Research Report
  • [Book] Handbook of porphyrin science(volume 27)

    • Author(s)
      Furuyama K, Yamamoto M(Ferreira G.C. edited)
    • Publisher
      World Scientific Publishing Co.Ltd
    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://www.iwate-med.ac.jp/education/gakubu_in/basic_kouza/seika/

    • Related Report
      2013 Final Research Report
  • [Remarks]

    • URL

      http://www.mbap.med.tohoku.ac.jp/thema.html

    • Related Report
      2011 Research-status Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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