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Association and Interaction of Terminal Enzymes of Heme Biosynthesis in Mitochondria.

Research Project

Project/Area Number 07680779
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionKANSAI MEDICAL UNIVERSITY

Principal Investigator

TAKETANI Shigeru  Kansai Medical University, Hygiene, Associate Professor., 医学部, 助教授 (20121949)

Co-Investigator(Kenkyū-buntansha) FURUKAWA Takako  Kansai Medical University, Hygiene, Research Associate, 医学部, 助手 (00221557)
KOHNO Hirao  Kansai Medical University, Hygiene, Assistant Professor., 医学部, 講師 (30148522)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsHeme biosynthesis / Mitochondria / Terminal Enzymes / Ferrochelatase / Protoporphyrinogen Oxidase / Coproporphyrinogen Oxidase / プロトポルフィリノーゲンオキシダーゼ / ポルフィリン合成
Research Abstract

Coproporphyrinogen oxidase (CPOX), protoporphyrinogen oxidase (PPOX) and ferrochelatase (FECH) in terminal steps of heme biosynthesis are located in mitochondria. To clarify association and interaction of three enzymes in mitochondria where transport of porphyrin intermediates occurs, regulation of expressions of cloned CPOX,PPOX and FECH during erythroid differentiation was examined. The induction of CPOX and FECH mRNAs in mouse erythroleukemia cells occurred within 6 h after dimethylsulfoxide treatment, while PPOX mRNA remained constant, indicating that PPOX is not a rate-limiting step of heme biosynthesis. Onset of an increase in heme content of the differentiated cells delayd at least 6h, as compared with the induction of FECH,suggesting that the rate limiting step of heme biosynthesis during erythroid differentiation cannot be ascribed for heme synthesis but iron metabolism in mitochondria. Attempts to isolate iron metabolizing molecules, however, have not been succeeded. Active CPOX of the mouse cloned cDNA was expressed as a soluble form, and histidine residues are essential to maintain the structure as well as to catalytic activity. Otherwise, C-terminus of human FECH contains iron-sulfur cluster which is destroyed by NO,leading to inactivation of the enzyme. Finally we also demonstrated that peripheral-type benzodiazepine receptors exhibit affinity for porphyrins and heme, and suggest that the receptors play a role of transport of porphyrins and heme in mitochondria.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (39 results)

All Other

All Publications (39 results)

  • [Publications] Taketani et al.: "Hemopeein from four species inhibits the association of home with cultured bepatoma or rat hepatocytes・・・" Hepatology. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tanabe et al.: "Involvement of transcriptional factor GATA-1 in the regulation of the expression of coproporphyn" Biochem.Biophys.Res.Commun. 233. 729-736 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Furukawa et al.: "Regulation of the ferrochelatase gene expression during differentiation of mouse erythroleulemia cells" Biochem.Mol.Biol.Intl.41. 1167-1170 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kadota et al.: "Induction of peripheral-type benzodiazepine receptors in mouse brain following thioacetamide-induces・・・" Life Sciences. 58. 953-959 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Furukawa et al.: "Nitric oxide-mediated in activation of the mammalan ferrochelatase in vivo and in vitro" Biochem.J.310. 533-538 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Taketani et al.: "Induction of terminal enzymes for heme biosynthesis during differentiation of mouse erythro." Eur.J.Biochem.230. 760-765 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Taketani & Endo: "Lead Poisoning in Clinical studies in Medical Biochemistry" Oxford University Press,Glew and Ninomiya eds., 237-246 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Taketani: "Measurement of Ferrochelatase Activity current Protocol in Toxicology" John Wiley & Sons Inc.,Maines ed. (in press), (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Taketani, S.Immenschuh, S.Go, P.R.Sinclair, R.Stockert, H.H.Liem, and Eberhard U.: "Hemopexin from Four Species Inhibits the Association of Heme with Cultured Hepatoma Cells or Rat Hepatocytes Exhibiting A Small Number of Species-specific Hemopexin Receptors." Hepatology. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Z.Q.Bonday, S.Taketani and P.D.Gupta et al: "Heme Biosynthesis by the Malarial Parasite : Import of 5-aminolevulinate Dehydratase from the Host Red Cells." J.Biol.Chem.272. 21839-21846 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] A.Tanabe, T.Furukawa, Y.Ogawa, M.Yamamoto, N.Hayashi, R.Tokunaga and S.Taketani: "Involvement of Transcriptional Factor GATA-1 in the Regulation of the Expression of Coproporphyrinogen Oxidase in Mouse Erythroleukemia Cells." Biochem.Biphys.Res.Commun.233. 729-733 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Kadota, A.Niiya, R.Masaki, A.Yamamoto, M.Araki and S.Taketani: "A Newly Identified Membrane Protein Localized Exclusively in Intracellular Organelles of Neurons." Mol.Brain Res.46. 265-273 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Kadota, K.Inoue.R.Tokunaga, and S.Taketani: "Induction of Peripheral-type Benzodiazepine Receptors in Mouse Brain Following Thioacetamide-induced Acute Liver Failure" Life Sciences. 58. 953-959 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Endo-Ichikawa, H.Kohno, T.Furukawa, T.Ueda, Y.Ogawa, R.Tokunaga and S.Taketani: "Requirement of Multiple DNA-Proteins Interactions for Inducible Expression of RNR3 Gene in Saccharomyces cerevisiae in Response to DNA Damage" Biochem.Biophys.Res.Commun. 222. 280-286 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Kohno, T.Furukawa, R.Tokunaga, S.Taketani and T.Yoshinaga: "Mouse Coproporphyrinogen Oxidase is a Coppercontaining Enzyme : Expression in Echerichia coli and Site-directed Mutagenesis." Biochem.Biophys. Acta. 1292. 156-162 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Furukawa, H.Kohno, R.Tokunaga and S.Taketani: "Nitric Oxide-mediatesd Inactivation of the Mammalian Ferrochelatase in vivo and in vitro. Possible Involvement of the Iron-sulphur Cluster." Biochem.J.310. 533-538 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Taketani, J.Inazawa, T.Abe, T.Furukawa, H.Kohno, R.Tokunaga, K.Nishimura and H.Inokuchi: "The Human Protoporphyrinogen Oxidase Gene : Organization and Location to Chromosome 1." Genomics. 29. 698-703 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Taketani, T.Yoshinaga, T.Furukawa, H.Kohno, R.Tokunaga, K.Nishimura and H.Inokuchi: "Induction of Terminal Enzymes for Heme Biosynthesis during Differentiation of Mouse Erythroleukemia Cells." Eur.J.Biochem. 230. 760-765 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Endo-Ichikawa, H.Kohno, R.Tokunaga and S.Taketani: "Induction of the Gene RNR3 in Saccharomyces cerevisiae upon Exposureto Different Agents Related to Carcinogenesis" Biochem.Pharmacol. 50. 1695-1699 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Taketani, et al.: "Hemopexin from four species inhipits the association of heme with cultured bepatoma cells or vat hepatocytes exhibiting a small..." Hepatology. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Bonday.et al.: "Heme biosyuthesis by the on alariol parasife:importof 5-aminolevulinate dehydratase from the host red cells" J.Biol.Chem.272. 21839-21846 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanabe, et al.: "Involvement of transcriptional factor GATA-1 in the rogu lation of the expression of coprapor phyrinogen oxidase..." Biochem.Biophys.Res.Commun. 233. 729-736 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Furulcawa, et al.: "Regulation of the ferrocle latase gene expression during differentiation of mouse erythroleulcewia cells" Biochem.Mol.Biol.Zntl.41. 1161-1170 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kadota, et al.: "A Newly identified membrane pratein localiqed exclusively in intracellular organelles of neurons." Mol.Brain.Res.46. 265-273 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishihara, et al.: "Molecular Cloning,Seqvencing and exprossion of cDNA encoding lwman trehalase" Gene. 202. 69-74 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Taketani & Endo: "Lead Poisoning in Clinical Studies in Medical Biochemistry" Oxford University Press,Glew and Ninomiya eds., 237-246 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Taketani: "Measuremeut of Ferrochelatase activitl in Current Protocol in Toxicology" John Wiley &Sons Inc.,Maines ed.(in press), (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Kadota: "Induction of Peripheral-type Benzodiazepine Receptors in Mouse Brain Following Thioacetamide-indured Acute Liver Failure" Life Sciences. 58. 953-959 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Sasai-Takedatsu: "Human Trehalase : characterization, Localization, and Its Increase in Urine by Ronal Proximal Tubular Damage" Nephron. 73. 179-185 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Endo-Ichikawa: "Requirement of Multiple DNA-proteins Interaction for Inducible Expression of RNR3 Gene in Saccharomyces cere Uisiae" Biochem. Biohys. Res. Commun.222. 280-286 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] L.Warnich: "Identification of Three Mutations and Associated Haplotypes in Protoporghyrinogen Oxidase Gene in South African Families with VP" Hum. Mol. Genet.5. 981-984 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Narita: "Molecular Cloning and characterization of cDNA that Encodes Protoporphyrinogen Oxidase of Arabidosis thaliana" Gene. 182. 169-175 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Sassa: "Molecular Defects of the coproporphyrinogen Oxidase in Heredi-Tary Coproporphyria" Cell. Mol. Biol.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Taketani Shigeru: "Imvolvement of Peripheral-type Benzodiazepine Reoptors in the Intracellular Transport of Heme and Porphyrins" J. Biochem.117. 875-880 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nishimura Koichi: "Cloning of a Human cDNA for Protoporphyrinogen Oxidase by Complementation in vivo of a HemG Matant of E. co li" J. Biol. Chem.270. 8076-8080 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Furukawa Takako: "Nitric Oxide-mediated Inactivation of the Mammalian Ferrochelatase in vivo and in vitro. Possible Involvement of the Iron Sulpher Chister" Biochem., J.310. 533-538 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Taketani Shigeru: "Induction of Terminal Enzymes for Heme Biosynthesis During Differentiation of Mouse Erythrolenkemia Cells" Eur. J. Biochem.270. 760-765 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ishii Tetsuro: "Inhibition of the Thiol-specific Antioxidant Activity of Rat Liver MSP23 Protein by Hemin" Biochem. Biophys. Res. Commun.216. 970-975 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Taketani Shigeru: "The Human Protoporphyrinogen Oxidase Gene : Orgauization and Location to Chromosome 1" Genomics. 29. 698-703 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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