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Elucidation of physiological significance of a novel regulator of neuronal functions and its application to functional regeneration of brain

Research Project

Project/Area Number 16590041
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionTohoku University

Principal Investigator

YAMAKUNI Tohru  Tohoku University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学研究科, 助教授 (30333793)

Co-Investigator(Kenkyū-buntansha) OHIZUMI Yasushi  Tohoku University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (00006355)
NAKAJIMA Akira  Tohoku University, Graduate School of Pharmaceutical Sciences, Instructor, 大学院・薬学研究科, 助手 (20419237)
SAITO Shin-ya  Tohoku University, Graduate School of Medicine, Instructor, 大学院・医学系研究科, 助手 (80271849)
李 玉山  東北大学, 大学院・薬学研究科, 教務職員 (50344685)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsV-1 / CapZ / Actin dynamics / Transcriptional regulation / TH gene / Neurogenesis / Regeneratin of brain function / CNS neurodegeneration / レトロウイルスベクター / アクチンフィラメント形成 / 神経機能制御 / 神経再生 / 脳神経幹細胞 / 天然ハーブエキス / 蛋白質相互作用 / neurosphere
Research Abstract

V-1 has been identified as a novel ankyrin repeat protein which exhibits a transient increase in the protein expression level during the postnatal brain development. This protein also has the activity to control both tyrosine hydroxylase (TH) gene expression and catecholamine release in PC12D cells, and associates with CapZ, an actin capping protein to regulate actin polymerization in vitro. However the physiological significance of V-1 in controlling actin dynamics remains unknown. In this study, we for the first time showed that in V-1-overexpressing PC12D transfectant, the amount of CapZ in the cytoskeletal fraction was decreased, whereas that in the cytoplasmic fraction was increased, as compared with of vector control transfectant. The amount of CapZ-associated actin filaments was also decreased to produce an increment of the ratio of F-/G-actin in V-1 transfectant. Moreover the capping activity of CapZ was stimulated at 5 min after treatment with forskolin, accompanied by its translocation from the cytoplasmic to cytoskeletal fractions in PC12D cells. It is thus suggested that V-1 serves as a novel cytoplasmic anchor of CapZ and that control of CapZ activity by its interaction with V-1 probably acts as a novel PKA-dependent regulatory mechanism of actin dynamics in vivo. Furthermore, as the first step to searching for natural products with the activity to positively or negatively control the interaction between V-1 and CapZ in vivo, we screened twenty natural herbal extracts to examine whether these herbs affected the interaction between V-1 and CapZ. Consequently several herbs showed such a pharmacological actin.
Also we constructed a retrovirus vector for expression of V-1 to successfully overexpress its protein in neural stem cells. Notably overexpression of V-1 in neural stem cells appreciably produced astrocytes and neurons in the growth medium. In addition the V-1 retrovirus inhibited differentiation of a preadipocyte cell line to adipocytes.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (38 results)

All 2006 2005 2004 Other

All Journal Article (38 results)

  • [Journal Article] V-1 enhances PMA-induced activation of NF-κB-dependent transcription in PC12D cells2006

    • Author(s)
      Y.Hiwatashi, T.Yamakuni et al.
    • Journal Title

      Pharmacometrics 70

      Pages: 17-20

    • NAID

      10020344516

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Garcinone B reduces prostaglandin E2 release and NF-κB-mediated transcription in C6 cells2006

    • Author(s)
      T.Yamakuni, K.Aoki et al.
    • Journal Title

      Neurosci. Lett. 394

      Pages: 206-210

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nobiletin restoring β-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer's disease model rats2006

    • Author(s)
      K.Matsuzaki, T.Yamakuni et al.
    • Journal Title

      Neurosci. Lett. 400

      Pages: 230-234

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Proinsulin C-peptide stimulates a PKC/IκB/NF-κB signaling pathway2006

    • Author(s)
      M.Kitazawa, T.Yamakuni et al.
    • Journal Title

      J. Biochem. (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] V-1 enhances PMA-induced activation of NF-κB-dependent transcription in PC12D cells.2006

    • Author(s)
      Hiwatashi, Y., Yamakuni, T., Ohizumi, Y.
    • Journal Title

      Pharmacometrics 70

      Pages: 17-20

    • NAID

      10020344516

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Garcinone B reduces prostaglandin E_2 release and NF-κB-mediated transcription in C_6 cells.2006

    • Author(s)
      Yamakuni, T., Aoki, K., Nakatani, K., Kondo, N., Oku, H., Ishiguro, K., Ohizumi, Y.
    • Journal Title

      Neurosci.Lett. 394

      Pages: 206-210

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nobiletin restoring β-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer's disease model rats2006

    • Author(s)
      Matsuzaki, K., Yamakuni, T., Hashimoto, M., Haque, A.M., Shido, O., Mimaki, Y., Sashida, Y., Ohizumi, Y.
    • Journal Title

      Neurosci.Lett. 400

      Pages: 230-234

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Garcinone B reduces prostaglandin E_2 release and NF-κB-mediated transcription in C6 rat glioma cells.2006

    • Author(s)
      T.Yamakuni, Y.Ohizumi et al.
    • Journal Title

      Neuroscience Letters (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Nobiletin restoring β-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer's disease model rats2006

    • Author(s)
      K.Matsuzaki, T.Yamakuni et al.
    • Journal Title

      Neuroscience Letters (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] PKA-dependent signaling regulates CapZ by promoting its dissociation from V-1 with anti-capping activity in PC12D cells2006

    • Author(s)
      M.Kitazawa, M., T.Yamakuni et al.
    • Journal Title

      Journal of Biological Chemistry (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intracellular cAMP controls a physical association of V-1 with Cap Z in cultured mammalian endocrine cells2005

    • Author(s)
      M.Kitazawa, T.Yamakuni et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 331

      Pages: 181-186

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ephedorae herba decreases lipopolysaccharide-induced cyclooxgenase-2 protein expression and NF-κB-dependent transcription in C6 rat glioma cells2005

    • Author(s)
      K.Aoki, T.Yamakuni et al.
    • Journal Title

      J. Pharmacol. Sci. 98

      Pages: 327-330

    • NAID

      10025729227

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mechanism of neurotropic action of nobiletin in PC12D cells2005

    • Author(s)
      H.Nagase, T.Yamakuni et al.
    • Journal Title

      Biochemistry 44

      Pages: 13683-13691

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Nobiletin and its related flavonoids with CRE-dependent transcription-stimulating and neuritegenic activities2005

    • Author(s)
      H.Nagase, T.Yamakuni et al.
    • Journal Title

      Biochem. Biophys. Res. Commun. 377

      Pages: 1330-1336

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 新たな創薬研究のターゲット-新規カテコラミン合成制御因子 V-12005

    • Author(s)
      山國 徹
    • Journal Title

      応用薬理 69

      Pages: 89-94

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intracellular cAMP controls a physical association of V-1 with Cap Z in cultured mammalian endocrine cells.2005

    • Author(s)
      Kitazawa, M., Yamakuni, T., Song, S.-Y., Kato, C., Tsuchiya, R., Ishida, M., Suzuki, N., Adachi, E., Iwashita, S., Ueno, S., Yanagihara, N., Taoka, M., Isobe, T., Ohizumi, Y.
    • Journal Title

      Biochem.Biophys.Res.Commun. 331

      Pages: 181-186

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ephedorae herba decreases lipopolysaccharide-induced cyclooxgenase-2 protein expression and NF-κB-dependent transcription in C6 rat glioma cells.2005

    • Author(s)
      Aoki, K., Yamakuni, T., Yoshida, M., Ohizumi, Y.
    • Journal Title

      J.Pharmacol.Sci. 98

      Pages: 327-330

    • NAID

      10025729227

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mechanism of neurotropic action of nobiletin in PC12D cells.2005

    • Author(s)
      Nagase, H., Yamakuni, T., Matsuzaki, K., Maruyama, Y., Kasahara, J., Fukunaga, K., Hinohara, Y., Kondo, S., Mimaki, Y., Sashida, Y., Tank, A.W., Ohizumi, Y.
    • Journal Title

      Biochemistry 44

      Pages: 13683-13691

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nobiletin and its related flavonoids with CRE-dependent transcription- stimulating and neuritegenic activities.2005

    • Author(s)
      Nagase, H., Omae, N., Omori, A., Nakagawasai, O., Tadano, T., Yokosuka, A., Sashida, Y., Mimaki, Y., Yamakuni, T., Ohizumi, Y.
    • Journal Title

      Biochem.Biophys.Res.Commun. 377

      Pages: 1330-1336

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Target for new drug development-a novel regulatory factor of catecholamine synthesis2005

    • Author(s)
      Yamakuni, T.
    • Journal Title

      Pharmacometrics 69

      Pages: 89-94

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intracellular cAMP controls a physical association of V-1 with CapZ in cultured mammalian endocrine cells2005

    • Author(s)
      M.Kitazawa, M., T.Yamakuni et al.
    • Journal Title

      Biochemical and Biophysical Research. Communications 331

      Pages: 181-186

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Nobiletin and its related flavonoids with CRE-dependent transcription-stimulating and neuritegenic activities.2005

    • Author(s)
      H.Nagase, T.Yamakuni et al.
    • Journal Title

      Biochemical and Biophysical Research. Communications 377

      Pages: 1330-1336

    • Related Report
      2005 Annual Research Report
  • [Journal Article] γ-Mangostin inhibits inhibitor-κB kinase activity and decreases lipopolysaccharide-induced cyclooxygenase-2 gene expression in C6 rat glioma cells2004

    • Author(s)
      K.Nakatani, T.Yamakuni et al.
    • Journal Title

      Mol. Pharmacol. 66

      Pages: 667-674

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] IC101 induces apotosis by Akt dephosphorylation via an inhibition of heat shock protein 90-ATP binding activity accompanied by preventing the interaction with Akt in L12210 cells2004

    • Author(s)
      H.Fujiwara, T.Yamakuni et al.
    • Journal Title

      J. Pharmacol. Exp. Ther. 310

      Pages: 1288-1295

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Potent antioxidative activity of unripe fruits of Garcinia mangostana L2004

    • Author(s)
      J.Feng, T.Yamakuni et al.
    • Journal Title

      Natural Medicines, 58

      Pages: 156-159

    • NAID

      80016842507

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Acidosis-induced protein tyrosine phosphorylation depends on Ca~<2+> influx via voltage-dependent Ca~<2+> channels in SHR aorta2004

    • Author(s)
      D.K.Rohra, T.Yamakuni et al.
    • Journal Title

      Eur. J. Pharmacol. 504

      Pages: 105-111

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Evidence for the involvement of protein kinase C in acidic pH-induced contraction in spontaneously hypertensive rat aorta2004

    • Author(s)
      D.K.Rohra, T.Yamakuni et al.
    • Journal Title

      Pharmacology 71

      Pages: 10-16

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] _Y-Mangostin inhibits inhibitor-κB kinase activity and decreases lipopolysaccharide-induced cyclooxygenase-2 gene expression in C6 rat glioma cells.2004

    • Author(s)
      Nakatani, K., Yamakuni, T., Kondo, N., Arakawa, T., Oosawa, K., Shimura, S., Ohizumi, Y.
    • Journal Title

      Mol.Pharmacol. 66

      Pages: 667-674

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] IC101 induces apotosis by Akt dephosphorylation via an inhibition of heat shock protein 90-ATP binding activity accompanied by preventing the interaction with Akt in L1210 cells.2004

    • Author(s)
      Fujiwara, H., Yamakuni, T., Ueno, M., Ishizuka, M., Shinkawa, T., Isobe, T., Ohizumi, Y.
    • Journal Title

      J.Pharmacol.Exp.Ther. 310

      Pages: 1288-1295

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Potent antioxidative activity of unripe fruits of Garcinia mangostana L.2004

    • Author(s)
      Feng.J., Yamakuni, T., Katoh, E., Hosoda, S., Ohizumi, Y.
    • Journal Title

      Natural Medicines 58

      Pages: 156-159

    • NAID

      80016842507

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Acidosis-induced protein tyrosine phosphorylation depends on Ca^<2+> influx via voltage-dependent Ca^<2+> channels in SHR aorta.2004

    • Author(s)
      Rohra, D.K., Yamakuni, T., Ohizumi, Y.
    • Journal Title

      Eur.J.Pharmacol. 504

      Pages: 105-111

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Evidence for the involvement of protein kinase C in acidic pH-induced contraction in spontaneously hypertensive rat aorta.2004

    • Author(s)
      Rohra, D.K., Yamakuni, T., Ito, S., Saito, S., Ohizumi, Y.
    • Journal Title

      Pharmacology 71

      Pages: 10-16

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] IC101 induces apoptosis by akt dephosphorylation via an inhibition of heat shock protein 90-ATP binding activity accompanied by preventing the interaction with akt in L1210 cells.2004

    • Author(s)
      H.Fujiwara, T.Yamakuni et al.
    • Journal Title

      Journal of Pharmacology and Experimental Therapeutics 310

      Pages: 1288-1295

    • Related Report
      2004 Annual Research Report
  • [Journal Article] γ-Mangostin inhibits IκB kinase activity and decreases lipopolysaccharide-induced cyclooxygenase-2 gene expression in C6 rat glioma cells.2004

    • Author(s)
      K.Nakatani, T.Yamakuni et al.
    • Journal Title

      Molecular Pharmacology 66

      Pages: 667-674

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Acidosis-induced protein tyrosine phosphorylation depends on Ca^<2+> influx via voltage-dependent Ca^<2+> channels in SHR aorta2004

    • Author(s)
      D.K.Rohra, T.Yamakimi, Y.Ohizumi
    • Journal Title

      European Journal of Pharmacology 504

      Pages: 105-111

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Potent antioxidative activity of unripe fruits of Garcinia mangostana L.2004

    • Author(s)
      J.Feng, T.Yamakuni, et al.
    • Journal Title

      Natural Medicines 58

      Pages: 156-159

    • NAID

      80016842507

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Proinsulin C-peptide stimulates a PKC/Iκ B/NF-κ B signaling pathway

    • Author(s)
      Kitazawa, M., Shibata, Y., Hashimoto, S., Ohizumi, Y., T., Yamakuni
    • Journal Title

      J.Biochemi. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intracellular cAMP controls a physical association of V-1 with CapZ in cultured mammalian endocrine cells

    • Author(s)
      M.Kitazawa, M., T.Yamakuni, et al.
    • Journal Title

      Biochemical and Biophysical Research. Communications (印刷中)

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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