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Molecular and cellular basis of septic shock : Involvement of anandamide and HMG-1

Research Project

Project/Area Number 13470324
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionKagoshima University

Principal Investigator

MARUYAMA Ikuro  Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (20082282)

Co-Investigator(Kenkyū-buntansha) YAMAKUCHI Munekazu  Kagoshima University, Faculty of Medicine, Research Associate, 医学部, 助手 (20325814)
HASHIGUCHI Teruto  Kagoshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (70250917)
KANMURA Yuichi  Kagoshima University, Faculty of Medicine, Professor, 医学部, 教授 (30211189)
NAKAJIMA Toshihiro  St. Marianna University, Department of Genome Science, Associate Professor, 難病治療研究センター, 助教授 (90260752)
IMAIZUMI Hitoshi  Sapporo Medical University, Intensive Care Unit, Associate Professor, 集中治療部, 助教授 (70203304)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
KeywordsHMG-1 / anandamide / endocannabinoids / 2-arachidonylflyceorol / septic shock / polymyxin B / アナンダマイド / エンドトキシンショック / ポリミキシンB / アポトーシス
Research Abstract

Bacterial septicemia results hypotensive shock in severe cases. Various mediators have been proposed as causative factors in this hypotensive shock. These include inflammatory cytokines, PAF, NO and so on. However the inhibitors or antibodies against the mediators failed to improve hypotensive shock in clinical studies. Thus the other mediators may exist to cause septic shock.
In the present investigations, we identified that endocannabinoids, anandamide and 2-arachidonylglycerol which axe produced and secreted from stimulated macrophages and platelets induce hypotension, and act as an early hypotensive mediators. We also identified that polymyxin B selectively binds these endocannabinoids. Hemo-perfusion through polymyxin B-coated biomembrane column efficiently removed the circulating endocannabinoids and results rapid improvement of the hypotension.
Then we investigated the role of HMG-1 on the pathogenesis of septic shock, and showed that HMG-1 may act as a late phase mediator in septic shock.

Report

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

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Noboru Taniguchi, Ko-ichi Kawahara, Kazunori Yone, et al.: "High mobility group 1 box chromosomal protein 1 plays a role in the Pathogenesis of rheumatoid arthritis as a novel cytokine"Arthritis and Rheumatism. 48. 971-981 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazuyo Ymaji, Krishna Pada Sarker, Koichi Kawahara, et al.: "Anandamide induces apoptosis in humanendothelial cells : its regulation system and clinical implication"Thromb Haemost. 89. 875-884 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sarker KP, Biswas KK, Yamakuchi M, et al.: "ASK1-p38 MAPK/JNK signaling cascade mediates anandamide-induced PC12 cell death"J Neurochem.. 85. 50-61 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Liu Y, Wang Y, Yamakuchi M, Isowaki S, et al.: "Up-regulation of Toll-like receptor 2 gene expression in macrophage response to peptidoglycan and high concentration of lipopolysaccharide is involved in NF-κB activation. Infection"Immunity. 60. 2788-2796 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yin Wang, Yasuhiko Ito, Teruto Hashiguchi, et al.: "Simultaneous Measurement of Anandamide and 2-Arachidonoylglycerol by Polymyxin B-Selective Adsorption and Subsequent High-Performance Liquid Chromatography Analysis : Increase in Endogenous Cannabinoids in the Sera of Patients with Endotoxic Shock"Analytical Biochemistry. 294. 73-82 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Wang, Y.Liu, K.P.Sarker, M.Nakashima, et al.: "Polymixi B binds to anandamide and inhibits its cytotoxic effect"FEBS Lett.. 470. 151-155 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noboru Taniguchi, Ko-ichi Kawahara, Kazunori Yone, Teruto Hashiguchi, Munekazu Yamakuchi, Masamichi Goto, Keiichi Inoue, Shingo Yamada, Kosei Ijiri, Shunji Matsunaga, Toshihiro Nakajima, Setsuro Komiya, and Ikuro Maruyama: "High Mobility Group Box Chromosomal Protein 1 Plays a Role in the Pathogenesis of Rheumatoid Arthritis as a Novel Cytokine."Arthritis & Rheumatism. 48(4). 971-981 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazuyo Yamaji, Krishna Pada Sarker, Koichi Kawahara, Satoshi Iino, Munekazu Yamakuchi, Kazuhiro Abeyama, Teruto Hashiguchi, Ikuro Maruyama: "Anandamide induces apotosis in human endothelial cells : its regulation system and clinical implication."Thromb Haemost.. 89. 875-884 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sarker KP, Biswas KK, Yamakuchi M, Lee KY, Hashiguchi T, Kracht M, Kitajima I, Maruyama I.: "ASK1-p38 MAPK/JNK signaling cascade mediates anandamide-induced PC12 cell death."J Neurochem.. 85(1). 50-61 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Liu Y, Wang Y, Yamakuchi M, Isowaki S, Nagata E, Kannura Y, Kitajima I, Maruyama I.: "Up-regulation of Toll-like receptor 2 gene expression in macrophage response to peptidoglycan and high concentration of lipopolysacchartide is involved in NF-_B activation Infection."Immunity. 60. 2788-2796 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yin Wang, Yasuhiko Ito, Teruto Hashiguchi, Isao Kitajima, Munekazu Yamakuchi, Hideaki Shimizu, Seiichi Matsuo, Hitoshi Imaizumi, and Ikuro Maruyama: "Simultaneous Measurement of Anandamide and 2-Arachidonoylglycerol by Polymyxin B-Selective Adsorption and Subsequent High-Performance Liquid Chromatography Analysis : Increase in Endogenous Cannabinoids in the Sera of Patients with Endotoxic Shock."Analytical Biochemistry. 294. 73-82 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y Wang, Y Liu, K.P. Sarker, M. Nakashima, T. Seizawa, A. Kishida, M. Nakata, I. Kitajima and I. Maruyama: "Polymyxin B binds to anandamide and inhibits its cytotoxic effect."FEBS Lett.. 470. 151-155 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Taniguchi, N.Kawahara, K., Yone, K, et al.: "High mobility group 1 box chromosomal protein II plays a role in the Pahtogenesis of rheumatoid arthritis as a novel cytokine"Arthritis and Rheumatism. 48(未定). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Krisima, P.Sarker, Maruyama, I.: "Depletion of membrane cholesterol by methyl-□cyclodextrin inhibits ananndamide-induced apoptotic cell death"Eur J Biocehem. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Kanekura, T., Maruyama, I., Kanzaki et al.: "Granulocyte and monocyte adsorption apheresis for pyoderma gangreosum"J. Am Acad. Dermatol.. 47. 320-321 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Niiyama, T., Higuchi, I., Suehara, M.et al.: "Electron microscopic abnormalities of skeletal muscle in patients with collagen VI deficiency in Ullrich's disease"Acta Neuropathol.. 104. 67-71 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamaji, K., Krishna P.Sarker, Hashiguchi, T., et al.: "Endocannabinoids induces apoptotic cell death in cultured endothelial cells"Thromb. Haemost. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishimura, S., Maeno, N., Matsuo K.et al.: "Human lactriferous mammary gland cells produce vascular endothelial grouth factor(VEGF) and express the VEGF receplors, Flt-1 and KFR/Flk-1"Cytokine. 21. 191-198 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Liu Y, .Murayama.I.: "Phosphoinositide-3 kinase-PKB/Akt pathway activation is involved in fibroblast Rat-1 transformation by human T-cell leukemia virus type-I tax"Oncogene. 20. 2514-2526 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Liu Y., Maruyama.I.: "Upregulation of Toll-like receptor 2 gene expression in macrophages response to peptidoglycan an high concerntration of lipopolysaccharide is involved in NFκB activation. Infect Immun."Infect Immun. 69・5. 2788-2796 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Wang Y., Maruyama.I.: "ISimultaneous measurement of anandamide and 2-arachidonoylglycerol by polymyxin B selective absorption and subsequent HPLC analysis : Increase in endogenous cannabinoids in the sera of patients with endotoxic shock"Anal Biochemistry. 294. 73-82 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tezono K., Maruyama.I.: "Bioactivity of the vascular endothelial growth factor trapped in fibrin clots : production of IL-6 and IL-8 in monocytes by fibrin clots"Haemostasis. 31・2. 71-79 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawabata H., Maruyama.I.: "Possible role of transcriptional coactivator P/CAF and nuclear acetylation in calcium-induced kerationcyte differentiation"J Biol Chem. 277・10. 8099-8105 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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