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EXPRESSION AND CYTOPROTECTIVE FUNCTION OF HEAT SHOCK PROTEINS IN THE GASTRIC MUCOSA MEDIATED BY CENTRAL NERVOUS SYSTEM-RELATED NEUROPEPTIDES.

Research Project

Project/Area Number 10670445
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionAkita University

Principal Investigator

OTAKA Michiro  Akita University, School of Medicine Lecturer, 医学部, 講師 (30250872)

Co-Investigator(Kenkyū-buntansha) ITOH Hideaki  Akita University,.School of Medicine associate proffessor, 医学部, 助教授 (80168369)
Project Period (FY) 1998 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsheat shock protein / stress protein / gastric mucosal damage / neuro peptide / TRH / 5-HT / molecular chaperon / ストレス / 胃潰瘍 / NSAID
Research Abstract

We have studied the expression and cytoprotective function of heat shock protein (HSP) in the gastric mucosa supported by this grant. We have found that systemic stress, such as water-immersion stress, induces 72-kDa heat shock protein (HSP72) and 60-kDa heat shock protein (HSP60) in the gastric mucosa. Induction of these HSPs in the gastric mucosa enhances cytoprotective ability against cytotoxic agents including 0.6N HC1, aspirin and ethanol. Also, we found that administration of tyhrotropin releasing hormone (TRH) specifically induces gastric mucosal HSP72 expression. On the other hand, serotonin (5-HT) specifically induces gastric mucosal HSP60 expression. Using these specific induction methods, we could compare the cytoprotective ability of these HSPs. Whereas HSP72 induction in the gastric mucosa showed strong mucosal protective ability, HSP60 did not have mucosal protective ability against cytotoxic agents. Our results indicate that HSP72 could be endogenous cytoprotectant in the gastric mucosa mediated by the function of molecular chaperon. We concluded that HSP72-induction therapy might be useful for peptic ulcers or drag-induced gastric mucosal damages.

Report

(5 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (46 results)

All Other

All Publications (46 results)

  • [Publications] Sasahara H, Otaka M, Itho H. et al.: "Effect of pre-induction of heat shock proteins on acetic acid-induced small intestinal lesion in rats"Dig Dis Sci. 43. 2117-2130 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Otaka M, Osashima M, Itho H, et al.: "Role of calcineurin, protein phosphatase 2B, in gastric acid secretion"Molecular Biological Approach to Gastrointestinal Disease. Axel Springer Japan Publishing Inc.. 13-16 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jin M, Otaka M, Itoh H, et al.: "Associatiation of a 72-kDa heat shock protein expression with adaptation to aspirin in rat gastric mucosa"Dig Dis Sci. 44. 1401-1407 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Odashima M, Otaka M, et al.: "Effects of Cyclosporin A on water-induced gastric lesion and gastric secretion in rats"J Gastroenterol. 35. 369-371 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iwabuchi A, Otaka M, Itoh H, et al.: "Specific pre-induction of a 60-kDa heat shock protein (chaperonin homolog) by TRH does not protect colonic mucosa against acetic acid-induced lesion in rats"Dig Dis Sci. 45. 1480-1489 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Pacheco I, Otaka M, et al.: "Corticosteroid pretreatment prevents small intestinal mucosal lesion induced by acetic acid-perfusion model in rats"Dig Dis Sci. 45. 2337-2346 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Otaka M: "Stress-related events regulate serum leptin level"Molecular Biological Approach to Gastrointestinal Disease. Axel Springer Japan Publishing Inc.. 13-16 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Pacheco I, Otaka M, et al.: "ER167653, a potent suppressant of interleukin-1 and tumor necrosis factor-α production, ameliorates colonic lesions in experimentally induced acute colitis"J Gastroenterol Hepatol. 16. 1105-1111 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Otaka M, Watanabe S.: "Role of mucosal mast cells in Helicobacter pylori infection(Editorial)"Gastroenterol. 37. 70-72 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoh S, Otaka M, et al.: "Inhibition of CN(protein phosphatase-2B) suppresses Ca^<2+>-mediated acid secretion in rtas"Ailment Pharmacol Ther. 16. S26-S28 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 大高道郎: "今日の治療指針 2002 急性胃炎、急性胃潰瘍"医学書院、東京. 1527(296-297) (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sasahara H, Otaka M, Itho H, et al.: "Effect of pre-induction of heat shock proteins acetic acid-induced small intestinal lesion in rats"Dig Dis Sci. 43. 2117-2130 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Otaka M, Odashima M, Itho S.: "Role of calcineurin, protein phosphatase 2B, in gastric acid secretion"Molecular Biological Approach to Gastrointestinal Disease. Axel Springer Japan Publishing Inc.. 13-16 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jin M, Otaka M, Itoh H. et al.: "Association of a 72-kDa heat shock protein expression with adaptation to aspirin in rat gastric mucosa"Dig Dis Sci. 44. 1401-1407 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Odashima M, Otaka M, et al.: "Effects of Cyclosporin A on water-immersion stress-induced gastric lesion and gastric secretion inrats"J Gastroenterol. 35. 369-371 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iwabuchi A, Otaka M, Itoh H, et al.: "Specific pre-induction of a 60-kDa heat shock protein (cnaperonin homolog) by TRH does not protect colonic mucosa against acetic acid-induced lesion in rats"Dig Dis Sci. 45. 1480-1489 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Pacheco I, Otaka M et al.: "Corticosteroid pretreatment prevents small intestinal mucosal lesion induced by acetic acidperfusion model in rats"Dig Dis Sci. 45. 2337-2346 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Otaka M.: "stress-related events regulate serum leptin level"Molecular Biological Approach to Gastrointestinal Disease. Axel Springer Japan Publishing Inc.. 13-16 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Pacheco I, Otaka M, et al.: "FR167653, a potent suppressant of interleukin-1 and tumor necrosis factor-aproduction, ameliorates colonic lesions in experimentally induced acute colitis"J Gastroenterol Hepatol. 16. 1105-1111 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Otaka M, Watanabe S.: "Role of mucosal mast cells in Helicobacter pylori infection. (Editorial)"J Gastroenterol. 37. 70-72 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itoh S. Otaka M, et al.: "Inhibition of CN(protein phosphatase-2B) suppresses Ca2+-mediated acid secretion in rats"Aliment Pharmacol Ther. 16. S26-28 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Otaka M.: "Acute gastritis, Acute gastric ulcer"Today's therapy 2002. Igakusyoin, Tokyo. 1527(in Japanese) (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Pacheco I, Otaka M, et al.: "FR167653, a potent suppressant of interleukin-1 and tumor necrosis factor-α production,ameliorates colonic lesions in experimentally induced acute colitis"J. Gastroenterol Hepatol. 16. 1105-1111 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 大高道郎: "消化器系臓器におけるストレス蛋白質の発現と機能"アレルギー・免疫. 8. 81-84 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Otaka M, Watanabe S.: "Role of mucosal mast cells in Helicobacter pylori infection. (Editorial)"J. Gastroenterol. 37. 70-72 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Itoh S, Otaka M, et al.: "Inhibition of CN(protein phosphatase-2B)suppresses Ca2+-medeated acid secretion in rtas"Aliment Pharmacol Ther. 16. S26-S28 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 大高道郎: "NSAIDs潰瘍-シャペロン誘導療法-"日本臨床. 60(増刊号2). 572-576 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 神 万里夫, 大高道郎, 渡辺純夫: "消化性潰瘍治療-防御因子製剤の新しい使い方-"日本臨床. 60(増刊号2). 377-381 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 大高道郎: "Annual review消化器2002(消化器疾患と自律神経)"中外医学社、東京. 368 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 大高道郎,小西永晃 他: "5-HTが血清および胃粘膜leptin濃度に及ぼす影響-CCK-8の作用との差異を含めて-"Prog Med. 20. 1695-1700 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Otaka M.: "Stress-related events regulate serum leptin level."Molecular Biological Approach to Gastrointestinal Disease. 13-16 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Pacheco I,Otaka M et al.: "Corticosteroid pretreatment prevents small intestinal mucosal damage induced by acetic acid-perfusion model without lipid peroxidation."Ulcer Res. 27. 183-187 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Odashima M,Otaka M et al.: "Effects of Cyclosporin A on water-immersion stress-induced gastric lesion and gastric secretion in rats."J Gastroenterol. 35. 369-371 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Iwabuchi A,Otaka M et al.: "Specific pre-induction of a 60-kDa heat shock protein (chaperonin homolog) by TRH does not protect colonic mucosa against acetic acid-induced lesion in rats."Dig Dis Sci. 45. 1480-1489 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Pacheco I,Otaka M et al.: "Corticosteroid pretreatment prevents small intestinal mucosal lesion induced by acetic acid-perfusion model in rats."Dig Dis Sci. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 大高道郎: "胃粘膜傷害とケモカイン「ケモカインと疾患」"医薬ジャーナル社、大阪. 238(184-188) (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Jin M,Otaka M, et al.: "Association of a 72-kDa heat shock protein expression with adaptation to aspirin in rat gastric mucosa"Dig Dis Sci. 44. 1401-1407 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Konishi N,Otaka M, et al.: "Role of calcineurin (protein phosphatase 2B) in gastric acid secretion"Gastroenterology. 116. A617 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Wada I, Otaka M, et al.: "Effect of preinduction of a 72-kDa heat shock protein by zinc and its derivatives on water-immersion stress-induced gastric lesion in rats"Gestroenterology. 116. A347 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 小田嶋 傑、大高道郎 他: "Cyclosporin Aは胃壁細胞のcalcineurin(protein phosphatase-2B)活性を抑制する"Progress in Mesicine. 19. 1308-1311 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 小田嶋 傑、大高道郎 他: "胃壁細胞のcalcineurin(protein phosphatase-2B)活性抑制による胃酸分泌抑制"Ulcer research. 26. 34-37 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 大高 道郎、渡辺 純夫: "胃粘膜防御機構におけるカプサイシン感受性知覚神経の役割"医薬ジャーナル(株). 131 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sssahara H,Otaka M,Itoh H et al.: "Effect of pre-induction of heat shock proteins on acetic acid-induced small intestinal lesion in rats." Dig Dis Sci. 43. 2117-2130 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Jin M,Otaka M,Itoh H et al.: "Association of a 72-kDa heat shock protein expression with adaptation to aspirin in rat gastric mucosa." Dig Dis Sci. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Otaka M,Jin M,Itoh H et al.: "Differential induction and function of heat shock proteins in rat gastric mucosa regulated by neuropeptides." Gastroenterology. 114. A 250 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Otaka M,Odashima M,Itho H et al.: "Molecular Biological Approach to Gastrointestinal Disease" Axel Springer Japan Publishing Inc., 64 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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