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Functional analysis of low molecular weight stress protein in the central nerves

Research Project

Project/Area Number 11672181
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionSHOWA UNIVERSITY

Principal Investigator

NUMAZAWA Satoshi  School of pharmaceutical Sciences, SHOWA UNIVERSITY Associate Professor, 薬学部, 助教授 (80180686)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsHeme Oxygenase / HSP27 / Neural Cell Death / Oxidative Stress / PC12 / ストレス / 熱ショックタンパク質 / 中枢神経 / 4-ヒドロキシノネナール / プロティンキナーゼC
Research Abstract

The aim of this research was to clarify the function of the low molecular weight stress protein, such as heme oxygenase-1 (HO-1) and 27 kD heat shocking protein (HSP27), in the central nervous. The cell protection function of these low molecular weight stress proteins was investigated using rat pheochromocytoma PC12 cells, which conditionally express HO-1 and HSP27 in response to doxycycline. The apoptotic cell death induced by serum removal was suppressed by HSP27, whereas HO-1 showed no effect. Moreover, expression of these low molecular weight stress proteins showed no protective function in cells treated with compounds that induce oxidative stress and genotoxicity. Differentiated cells induced by nerve growth factor (NGF), on the other hand, showed increased susceptibility to hydrogen peroxide, most provably by reduced contents of cellular glutathione. Forced expression of HO-1 in these cells induced cell death, which was further increased by the low concentration of an HO-1 substrate hemin. This effect of hemin was canceled by deferoxamine, an iron-chelating agent. These results indicate that a molecular chaperon HSP27 counteracts apoptosis induced by growth factor starvation in PC12 cells. On the other hand, it is suggested that HO-1 induced by oxidative stress not only shows no a protection function in undifferentiated cells but also promotes cell death in differentiated cells through iron production by the enzyme reaction.

Report

(2 results)
  • 2000 Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Kurosawa M,Tani Y,Nishimura S,Numazawa S and Yoshida T: "Distinct PKC isozymes regulate bufalin-induced differentiation and apoptosis in human monocytic cells"Am J Physiol Cell Physiol. 280. C459-C464 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kobayashi K,Kogo M,Tani M,Shimada N,Ishizaki T,Numazawa S,Yoshida T,Yamamoto T,Kuroiwa Y,Chiba K.: "Role of CYP2C19 in stereoselective hydroxylation of mephobarbital by human liver microsomes"Drug Metab Dispos. 29. 36-40 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Oda M,Kurosawa M,Numazawa S,Tanaka S,Akizawa T,Ito K,Maeda M,Yoshida T: "Determination of bufalin-like immunoreactivity in serum of humans and rats by time-resolved fluoroimmunoassay using a monoclonal antibody"Life Sci. 68. 1107-1117 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Numazawa S,Shibata M,Imaoka S,Funae Y,Yoshida T: "Induction of hepatic CYP2B1/2 by a teratogenic compound cis-1-[-4-(p-menthane-8-yloxy)phenyl]piperadine"J Toxicol Sci. 25. 57-61 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Kurosawa,S.Numazawa,Y.Tani and T.Yoshida: "ERK signaling mediates the induction of inflammatory cytokines by bufalin in human monocytic cells"Am J Physiol Cell Physiol. 278. C500-C508 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurosawa M, Tani Y, Nishimura S, Numazawa S and Yoshida T: "Distinct PKC isozymes regulate bufalin-induced differentiation and apoptosis in human monocytic cells."Am J Physiol Cell Physiol. 280. C459-C464 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kobayashi K, Kogo M, Tani M, Shimada N, Ishizaki T, Numazawa S, Yoshida T, Yamamoto T, Kuroiwa Y, Chiba K: "Role of CYP2C19 in stereoselective hydroxylation of mephobarbital by human liver microsomes."Drug Metab Dispos. 29. 36-40 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Oda M, Kurosawa M, Numazawa S, Tanaka S, Akizawa T, Ito K, Maeda M, Yoshida T: "Determination of bufalin-like immunoreactivity in serum of humans and rats by time-resolved fluoroimmunoassay using a monoclonal antibody."Life Sci. 68. 1107-1117 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Numazawa S, Shibata M, Imaoka S, Funae Y, Yoshida T: "Induction of hepatic CYP2B1/2 by a teratogenic compound cis-1-[-4-(p-menthane-8-yloxy) phenyl] piperadine."J Toxicol Sci. 25. 57-61 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Kurosawa, S.Numazawa, Y.Tani and T.Yoshida: "ERK signaling mediates the induction of inflammatory cytokines by bufalin in human monocytic cells."Am J Physiol Cell Physiol. 278. C500-C508 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M. Kurosawa: "ERK signaling mediates the induction of inflammatory cytokines by bufalin in human monocytic cells"Am. J. Physiol.. (in press).

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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