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Cell signaling of the neuroprotective cytokines

Research Project

Project/Area Number 13671440
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionEhime University

Principal Investigator

HATA Ryuji  Ehime University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (90258153)

Co-Investigator(Kenkyū-buntansha) KUMON Yoshiaki  Ehime University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (80127894)
SAKANAKA Masahiro  Ehime University, Faculty of Medicine, Professor, 医学部, 教授 (60170601)
大田 信介  愛媛大学, 医学部・附属病院, 講師 (50194163)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsStat / Cerebral Ischemia / Cell Death / Bcl-xL / Cytokine
Research Abstract

Introduction : Recently, we reported that Stat3 was activated following cerebral ischemia in mouse [1]. However, little is known about the function of activated Stat3 in the ischemic brain. Here we demonstrate the increased expression of activated Stat3 promotes cell death in clutured astrocytes.
Methods : Astrocytes from the forebrains of newborn rats were cultured as described [2] with some modifications. Recombinant adenovirus expressing Stat3 wild type (St3.Wt), Stat3 dominant negative type (St3.DN) and LacZ were constructed. Astocytes were exposed to adenovirus vector expressing Stat3.Wt, Stat3.DN or LacZ (multiplicity of infection 10) for 2h and incubated with a virus free fresh medium up to 72h. At 72h later, astrocytes were homogenized in lysis buffer and immunoblotted with antibody against Stat3, p-Stat3 (Tyr-705) and beta-actin. Cell death was quantified by LDH assay. Caspase-3 like activity was evaluated at 12h, 24 and 48h after the virus inoculation using a caspase-3 fluorometric protease assay kit.
Results : Western blots analysis revealed feat Ad.St3.wt remarkably induced p-Stat3(Tyr-705) while Ad.St3.DN and Ad-LacZ did not. These results demonstrated that both Ad.St3.Wt and Ad.St3.DN induced Stat3 protein in cultred astrocytes and only Ad.St3.Wt b could phosphorylate Stat3 at Tyr-705 site and activate Stat3. LDH assay revealed that overexpression of St3.wt promoted cell death while overexpression of St3.DN and LacZ did not. In addition, caspase-3 like activity of the St3.Wt treated group was significantly increased than that of the St3.DN group at 2d after virus inoculation.
Conclusion : Our Data have shown that over-expression of Stat3 promotes cell death. Activation of caspase-3 activity may be involved in this cell death mechanism. References : [1] Wen et al.; Neurosci Lett, 303:153-156, (2001), [2] Tanaka J et al.; Glia, 28:85-96 (1999)

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (41 results)

All Other

All Publications (41 results)

  • [Publications] Wen T, Peng H, Hata R, Desaki J, Sakanaka M: "Induction of phosphorylated Stat3 following focal cerebral ischemia in mice"Neurosci Lett. 303. 153-156 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Morita F, Wen TC, Tanaka J, Hata R, Desaki J, Sato K, Nakata K, Ma YJ, Sakanaka M: "Protective effect of a prosaposin-derived, 18-mer Peptide on slowly progressive neuronal degeneration after brief ischemia"J Cereb Blood Flow Metab. 21. 1295-1302 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masumura M, Hata R, Uetsuki T, Nishimura I, Nagai Y, Sawada T: "In vivo gene transfer to cerebral white matter lesions with a recombinant adenovirus vector"Biochem Biophys Res Commun. 287. 440-444 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masumura M, Hata R, Nagai Y, Sawada T: "Oligodendroglial cell death with DNA fragmentation in the white matter under chronic cerebral hypoperfusion: comparison between normotensive and spontaneously hypertensive rats"Neurosci Res. 39. 401-412 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hara T, Mies G, Hata R, Hossmann K-A: "Gene expressions after thrombolytic treatment of middle cerebral artery clot embolism in mice"Stroke. 32. 1912-1919 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda K, Hata R, Gillardon F, Hossmann K-A: "Aggravation of brain injury after transient focal ischemia in p53-deficient mice"Mol Brain Res. 88. 54-61 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hermann DM, Kuroiwa T, Hata R, Gillardon F, Ito U, Mies G: "Expression of redox factor-1, p53-activated gene 608 and caspase-3 messenger RNAs following repeated unilateral common carotid artery occlusion in gerbils-Relationship to delayed cell injury and secondary failure of energy state"Neuroscience. 102. 779-787 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hata R, Masumura M, Akatsu H, Li F, Fujita H, Nagai Y, Yamamoto T, Okada H, Kosaka K, Sakanaka M, Sawada T: "Up-Regulation of Calcineurin Abeta mRNA in the Alzheimer's Disease Brain: Assessment by cDNA Microarray"Biochem Biophys Res Commun. 284. 310-316 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masumura M, Hata R, Akatsu H, Kosaka K, Yamamoto T, Nagai Y, Sawada T: "Increasing in situ nick end labeling of oligodendrocytes in white matter of patients with Binswanger's disease"Stroke Cere Dis. 10. 55-62 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hermann DM, Kilic E, Hata R, Hossmann K-A, Mies G: "Relationship between metabolic dysfunctions, gene responses and delayed cell death after mild focal cerebral ischemia in mice"Neuroscience. 104. 947-955 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Heese K, Nakayama T, Hata R, Masumura M, Akatsu H, Li F, Nagai Y, Yamamoto T, Kosaka K, Suemoto T, Sawada T: "Characterizing CGI-94 (comparative gene identification-94) which is down-regulated in the hippocampus of early stage Alzheimer's disease brain"Eur J Neurosci. 15. 79-86 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Wen TC, Sadamoto Y, Tanaka J, Zhu PX, Nakata K, Ma YJ, Hata R, Sakanaka M: "Erythropoietin protects neurons against chemical hypoxia and cerebral ischemic injury by up-regulating Bcl-xL expression"J Neurosci Res. 67. 795-803 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masumura M, Hata R: "Recent advances in adenovirus-mediated gene therapy for cerebral ischemia"Current Gene Therapy. 3. 43-48 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hossmann K-A, Hata R, Hara T.: "Dynamics of infarct evolution after permanent and transient focal ischemia in mice. In Cerebrovascular disease, 22nd Princeton Conference edited by PH Chan"Cambridge University Press, Cambridge, UK. 192-210 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Wen T, Peng H, Kara K, Desaki J, and Sakanaka M: "Induction of phosphorylated Stat3 following focal cerebral ischemia in mice"Neurosci Lett.. 303. 153-156 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masumura M, Hata R, Nagai Y, and Sawada T: "Oligodendroglial cell death with DNA fragmentation in the white matter under chronic cerebral hypoperfusion : comparison between normotensive and spontaneously hypertensive rats"Neurosci Res.. 39. 401-412 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda K, Hata R, Gillardon F, and Hossmann K-A: "Aggravation of brain injury after transient focal ischemia in p53- deficient mice"Mol Brain Res.. 88. 54-61 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hermann DM, Kuroiwa T, Hata R, Gillardon F, Ito U, and Mies G: "Expression of redox factor-1, p53-activated gene 608 and caspase-3 messenger RNAs following repeated unilateral common carotid artery occlusion in gerbils-Relationship to delayed cell injury and secondary failure of energy state"Neuroscience. 102. 779-787 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hata R, Masumura M, Akats H, Li F, Fujita H, Nagai Y, Yamamoto T, Okada H, Kosaka K, Sakanaka M, and Sawada T: "Up-Regulation of Calcineurin Abeta mRNA in the Alzheimer's Disease Brain : Assessment by cDNA Microarray"Biochem Biophys Res Commun.. 284. 310-316 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hermann DM, Kilic E, Hata R, Hossmann K-A, and Mies G: "Relationship between metabolic dysfunctions, gene responses and delayed cell death after mild focal cerebral ischemia in mice"Neuroscience. 104. 947-955 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hara T, Mies G, Hata R and Hossmann K-A: "Gene expressions after thrombolytic treatment of middle cerebral artery clot embolism in mice"Stroke. 32. 1912-1919 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masumura M, Hata R, Akatsu H, Kosaka K, Yamamoto T, Nagai Y and Sawada T: "Increasing in situ nick end labeling of oligodendrocytes in white matter of patients with Binswanger's disease"J Stroke Cere Dis.. 1055-1062 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masumura M, Hata R, Uetsuki T, Nishimura I, Nagai Y and Sawada T: "In vivo gene transfer to cerebral white matter lesions with a recombinant adenovirus vector"Biochem Biophys Res Commun.. 287. 440-444 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Morita F, Wen TC, Tanaka J, Hata R, Desaki J, Sato K, Nakata K, Ma YJ and Sakanaka M: "Protective effect of a prosaposin-derived, 18-mer Peptide on slowly progressive neuronal degeneration after brief ischemia"J Cereb Blood Flow Metab.. 21. 1295-1302 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Heese K, Nakayama T, Hata R, Masumura M, Akatsu H, Li F, Nagai Y, Yamamoto T, Kosaka K, Suemoto T, and Sawada T: "Characterizing CGI-94 (comparative gene identification-94) which is down-regulated in the hippocampus of early stage Alzheimer's disease brain"Eur J Neurosci.. 15. 79-86 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Wen TC, Sadamoto Y, Tanaka J, Zhu PX, Nakata K, Ma Yj, Hata R, and Sakanaka M: "Erythropoietin protects neurons against chemical hypoxia and cerebral ischemic injury by up-regulating Bcl-xL expression"Neurosci Res.. 67. 795-803 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Masumura M, Hata R.: "Recent advances in adenovirus-mediated gene therapy for cerebral ischemia"Current Gene Therapy. 3. 43-48 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hossmann K-A, Hata R and Hara T., edited by PH Chan: "Dynamics of infarct evolution after permanent and transient focal ischemia in mice. In Cerebrovascular disease, 22nd Princeton Conference"Cambridge University Press. 192-210 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Wen T et al.: "Induction of phosphorylated Stat3 following focal cerebral ischemia in mice."Neurosci Lett. 303. 153-156 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Morita, F., et al.: "Protective effect of a prosaposin-derived, 18-mer Peptide on slowly progressive neuronal degeneration after brief ischemia,"J Cereb Blood Flow Metab. 21. 1295-1302 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masumura, M., et al.: "In vivo gene transfer to cerebral white matter lesions with a recombinant adenovirus vector."Biochem Biophys Res Commun. 287. 440-444 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masumura, M., et al.: "Oligodendroglial cell death with DNA fragmentation in the white matter under chronic cerebral hypoperfusion : comparison between normotensive and spontaneously hypertensive rats."Neurosci Res. 39. 401-412 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hara, T., et al.: "Gene expressions after thrombolytic treatment of middle cerebral artery clot embolism in mice."Stroke. 32. 1912-1919 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hara, T., et al.: "Gene expressions after thrombolytic treatment of middle cerebral artery clot embolism in mice."Stroke. 32. 1912-1919 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hossmann K-A: "Dynamics of infarct evolution after permanent and transient focal ischemia in mice. In Cerebrovascular disease, 22nd Princeton Conference edited by PH Chan"Cambridge University Press, Cambridge, UK. 192-210 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wen T et al.: "Induction of phosphorylated Stat3 following focal cerebral ischemia in mice"Neurosci Lett. 303. 153-156 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Morita F et al.: "Protective effect of a prosaposin-derived, 18-mer Peptide on slowly progressive neuronal degeneration after brief ischemia"J Cereb Blood Flow Metab. 21. 1295-1302 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masumura M et al.: "In vivo gene transfer to cerebral white matter lesions with a recombinant adenovirus vector"Biochem Biophys Res Commun. 287. 440-444 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masumura M et al.: "Oligodendroglial cell death with DNA fragmentation in the white matter under chronic cerebral hypoperfusion : comparison between normotensive and spontaneously hypertensive rats"Neurosci Res. 39. 401-412 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hara T et al.: "Gene expressions after thrombolytic treatment of middle cerebral artery clot embolism in mice"Stroke. 32. 1912-1919 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hermann DM: "Relationship between metabolic dysfunctions, gene responses and delayed cell death after mild focal cerebral ischemia in mice"Neuroscience. 104. 947-955 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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