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Transcription factors insolved in the development of drug abuse and therapeutic drugs.

Research Project

Project/Area Number 09357021
Research Category

Grant-in-Aid for Scientific Research (A).

Allocation TypeSingle-year Grants
Section展開研究
Research Field 応用薬理学・医療系薬学
Research InstitutionOsaka University

Principal Investigator

MIKI Naomasa  Osaka Univ.Graduate Sch.of Med.Professor, 医学系研究科, 教授 (40094445)

Co-Investigator(Kenkyū-buntansha) YAMAGATA Kanato  Tokyo Metropolitan Insti, for Neuroscince, Director, 研究部門長 (20263262)
TAIRA Eiichi  Osaka Univ.Graduate Sch.of Med.Asoc.Prof., 医学系研究科, 助教授 (60263240)
KUO Che-hui  Osaka Univ.Graduate Sch.of Med.Asoc.Prof., 医学系研究科, 助教授 (50126570)
OSUGI Takeshi  Nihon Boehringer Ingelheim Co. group manager Scientist, 主席研究員 (50176880)
入江 康至  大阪大学, 医学部, 助手 (70303948)
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥29,800,000 (Direct Cost: ¥29,800,000)
Fiscal Year 2000: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1998: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1997: ¥18,800,000 (Direct Cost: ¥18,800,000)
Keywordsmorphine / Purα / gene expression / drug dependence / calcium / methamphetamine / methamphetamine-psychosis / Amida / Arc / カルモジュリン / 細胞死 / 依存性 / 耐性 / 依存 / 一本鎖CRE
Research Abstract

We have found that the activity of Purα, a single stranded DNA-binding protein, is changed with chronic morphine treatment. The DNA-binding activity was found to be enhanced by endogenous activator. The activator was purified and identified to be calmodulin (CaM) which enhanced the DNA-binding activity of Purα more than 10 times. CaMIII gene in three CaM genes was only activated by chronic morphine treatment. The enhancer activity of CRE/CREB and neurite outgrowth from PC12 cells were suppressed by Purα. These results suggest that Calcium signaling is involved in the gene expression by morphine.
Arc, an immediate early gene is reported to be induced markedly by methamphetamine in the brain. Amida was isolated by yeast two hybrid system. Amida has two nuclear translation signals and transported to the nuclei and caused cell death. Arc formed a complex with Amida and transported to nuclei and suppressed apoptotic activity of Amida. Amida was phosporylated at serine-180 by Cdc2/cyclin B and changed the DNA-binding activity. The data suggest that the ratio of Amida and Arc is a critical factor for cell death during methamphetamine administration, which may cause the methamphetamine psychosis.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Ding,Y.,Osugi,T. et al.: "Characterization of a nuclear factor that enhances DNA binding activity of ssCRE-BP/pura, a single-stranded DNA binding protein"Neurochem, Int.. 31. 45-54 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamagata,K. et al.: "Arcadlin is a neural activity-regulated cadherin involved in long term potentiation."J.Biol.Chem.. 274. 19473-19479 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kuo,C-H., et al.: "Calmodulin functions as an activator of Purα-binding to single-stranded purine rich DNA elements (PUR elements)"Biochem.Biophys.Res.Commun.. 255. 406-411 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Niu,S.,Kuo,c-H, et al.: "Increase of calmodulin III gene expression by mu-opioid receptor stimulation in PC12 cells."Jpn.J.Pharmacology. 84. 412-417 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sadakata,T., et al.: "Purα, a single-stranded DNA binding protein, suppresses the enhancer activity of cAMP response element (CRE)."Molec.Brain Research. 77. 47-54 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Niu,S.Kuo,C-H. et al.: "Inhibition by neloxone of promoter activity of the neurofilament gene in SK-SH cells."Jpn.J.Pharmacology. 82. 34-39 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ding, Y., Osugi, T., Kuo, C-H., Tanaka, H., et al.: "Characterization of a nuclear factor that enhances DNA binding activity of ssCRE-BP/pur α, a single-stranded DNA binding protein"Neurochem.Int.. 31. 45-54 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] E-Q.Wei, Y.Irie, C-H.Kuo, et al.: "A single stranded DNA-binding protein, ssCRE-BP/Pur α , in rat lung and its increase in allergic airway inflammation."Jpn.J.Pharmacol.. 78. 419-427 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] K.Yamagata, K.I.Andreasson, H.Sugiura, et al.: "Arcadlin is a neural activity-regulated cadherin involved in long term potentiation."J.Biol.Chem.. 274. 19473-19479 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] C-H.Kuo, E.Nishikawa, H.Ichikawa, et al.: "Calmodulin functions as an activator of Pur-alpha binding to single-stranded purine rich DNA elements (PUR elements)."Biochem.Biophys.Res.Comm.. 255. 406-411 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Niu, C.-H.Kuo, Y.Gan et al.: "Increase of calmodulin III gene expression by mu-opioid receptor stimulation in PC12 cells."Jpn.J.Pharmacol.. 84. 412-417 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] T.Sadakata, C-H.Kuo, H.Ichikawa, et al.: "Pur-alpha, a single-stranded DNA binding protein, suppresses the enhancer activity of cAMP response element (CRE)."Molec.Brain Res.. 77. 47-54 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Y.Irie, K.Yamagata, Y.Gan, et al.: "Molecular cloning and characterization of Amida, a novel protein which interacts with a neuron specific immediate early gene product Arc, contains novel nuclear localization signals, and causes cell death in cultured cells."J.Biol.Sci. 275. 2647-2653 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S-Y.Niu, C-H.Kuo, E.Taira, et al.: "Inhibition by naloxone of promoter activity of the neurofilament gene in SK-N-SH cells."Jpn.J.Pharmacol.. 82. 34-39 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S.Niu,C.-H.Kuo,Y.Gan,: "Increase of calmodulin III gene expression by mu-opioid receptor stimulation in PC12 cells."Jpn.J.Pharmacol.. 84. 412-417 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] O.Muraoka,H.Ichikawa,: "Kheper,a novel ZFH/dEF1 family, regulates the development of the neuroectoderm of zebrafish (Danio rerio)."Dev.Biol.. 228. 29-40 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Sadakata,C-H.Kuo,: "Pur-alpha, a single-stranded DNA binding protein, suppresses the enhancer activity of cAMP response element (CRE)."Molec.Brain Res.. 77. 47-54 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Y.Irie,K.Yamagata,Y.Gan,: "Molecular cloning and characterization of Amida, a novel protein which interacts with a neuron specific immediate early gene product Arc, contains novel nuclear localization signals, and causes cell death in cultured cells."J.Biol.Chem.. 275. 2647-2653 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S-Y.Niu,C-H.Kuo,E.Taira: "Inhibition by naloxone of promoter activity of the neurofilament gene in SK-N-SH cells."Jpn.J.Pharmacol.. 82. 34-39 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] T.Sadakata,: "Pur-alpha, a single-stranded DNA binding protein, suppresses the enhancer activity of cAMP response element(CRE)"Molec. Brain Res.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Irie,: "Molecular cloning and characterization of Amida, a novel protein which interacts with a neuron specific immediate early gene product Arc, contains novel nuclear localization signals, and causes cell death in cultured cells"J. Biol.Chem.. 275. 2647-2653 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] S-Y.Niu,: "Inhibition by naloxone of promoter activity of the neurofilament gene in SK-N-SH cells"Jpn. J. Pharmacol.. 82. 34-39 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Yamagata,: "Arcadlin is a neural activity-regulated cadherin involved in long term potentiation"J. Biol. Chem.. 274. 19473-19479 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] C-H.Kuo,: "Calmodulin functions as an activator of Pur-alpha binding to single-stranded purine rich DNA elements (PUR elements)"Biochem. Biophys. Res. Comm.. 255. 406-411 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] C-H.Kuo,E.Nishikawa et al.,: "Calmodulin functions as an activator of Pur α binding to single-stranded purine rich DNA elements(PUR elements)." Biochem.Biophys.Res.Comm.255. 406-411 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] E-Q,Wei,Y.Irie,et al: "A single stranded DNA-binding protein,ssCRE-BP/Pura,in rat lung and its increase in allergic airway inflammation." Japn.J.Pharmacol.78. 419-427 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 三木直正: "医科薬理学(栗山欣弥編) 麻薬性鎮痛薬" 南山堂, (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 三木直正: "神経伝達物質update-基礎から臨床まで(中村重信編)" 中外医学社, (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ding,Y., Osugi, Miki,N., et al.: "Characterization of a nuclear factor that enhances DNA binding activity of ssCRE-BP/pura,a single-stranded DNA binding protein." Neurochem.Int.,. 31. 45-54 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Tanaka, N.Miki, et al.: "Analysis of the Tbr-binding domain of MEKA/phosducin." Neurochem.Int.,. 31. 625-634 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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