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Role of antioxidant defense mechanisms in protecting gastrointestinal mucosal cclls

Research Project

Project/Area Number 06670581
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionDokkyo University

Principal Investigator

HIRAISHI Hideyuki  Dokkyo University, School of Medicine Associate Professor, 医学部, 助教授 (00199035)

Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1995: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
KeywordsReactive oxygen species / Superoxide dismutase / Glutathione / Lipid peroxidation / Cytolysis / Iron / Monochloramine / 過酸化脂質
Research Abstract

In studies with the use of cultured rat gastric mucosal and endothelial cells, we have demonstrated that (1) diethyldithiocarbamate dose-dependently enhanced hydrogen peroxide (H_2O_2) -induced damage to gastric cells, corresponding with inhibition of endogenoud SOD activity ; (2) extracellular glutahione (GSH) potects gastric cells from H_2O_2by accelerating intracellular GSH synthesis ; this is mediated by gamma-glutamyl transpcptidase acting on extracellular GSH (which supplies these cells with cysteine) and then by intracellular gamma-glutamylcysteine synthelase, a mechanism of GSH uptake distinctly different from that of intestinal cells ; (3) oxidant stress causes lipid peroxidation of gastric cells, which is then followed by cytolysis, and iron chelation protccls cells from oxidant stress presumably through inhibition of lipid peroxidation ; (4) GSH isopropylester also protccts gastric cclls from oxidant throuhg inihibition of lipid peroxidation, by an uptake mechanism similar to that of native GSH ; (5) monochloramine (NH_2Cl), which could be threoretically produced in Helicobacter pylori infection-associated inflammation, is more toxic to gastric cells than H_2O_2, and intracellular GSH plays a role as a potent defense system against NH_2Cl ; and (6) ethanol induces superoxide generation by gastric cells, and inhibition of the GSH-redox cycle aggravates ethanol damage ; such phenomena cannot be observed in endothelial cells, and (7) the mechanisms by which oxidant stress induces cytolysis of gastric cells, postulated by the prineipal investigator, is essentially similar to those of endothelial cells.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Hideyuki Hiraishi et al.: "Protective vole of intracellular superoxide dismutase against extracellular cxidants in cultured rat gastric cells" Journal of Clinical Investigation. 93. 331-338 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hideyuki Hiraishi et al.: "Protection of cultured rat gastric cells against oxidant-induced damage by exogenous glutathione" Gastroenterology. 106. 1199-1207 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shinichi Ota,Hideyuki Hiraishi et al.: "P2 purinergic veceptcr regulation of mucus secretion by rabbit gastric mucous cells in a primary culture" Gastroenterology. 106. 1485-1492 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hideyuki Hiraishi et al.: "Reactive oxygen metabolite-induced tcxicity to cuttured Dovine endothelial cells: status of cellulariron in mediating injury" Journal of Cellular Physiology. 160. 132-140 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nariaki Yajima Hideyuki Hiraishi et al.: "Protection of cultured rat gastric cells against oxidant stress by iron chelation: role of lipid peroxidation" Digestive Diseases and Sciences. 40. 879-886 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 平石秀幸,寺野彰: "胃粘膜病変とフリーラジカル" 日本消化器病学会雑誌. 92. 1817-1824 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 寺野彰,平石秀幸: "胃-形態とその機能(第二版)" 医学書院, 354 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 平石秀幸,寺野彰: "キーワード1995-'96(消化器系)" 先端医学社, 233 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hideyuki Hiraishi H et al: "Protective role olimtracellular superoxide dismutase against extmaccllular oxidants in culturcd rat gastric cclls." Journal of Clinical lnvesigation. 93. 331-338 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hideyuki Hiraishi H et al: "Protcction of cultured rat gastric cclls against oxidant-induced danagc by exogcnous glutathione" Gnshoenterology. 106. 1199-1207 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shinichi Ota S,Hideyuki Hiraishi et al: "P_2 purinergic reccptor regulation of mucus secrction by rabbit gastric mucous cells in a primary culture" Gnstroentcrology. 106. 1485-1492 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hideyuki Hiraishi H et al: "Renctive oxygen mctabolitc-induced loxicity to cultured bovine indothelial cells : status of ccllular iron in mcdiationg injury" Journal of Cellular Physiology. 160. 132-140 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yasuaki Itoh, Hideyuki Hiraishi et al: "Role of iron and glutathione redox cyclc in acctaminophcn-induccd cytotoxicity to cultured rat hepatocylcs" Digestive Discascs and Sciences. 39. 1257-1264 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kenta Yoshiura, Hideyuki Hiraishi: "Growth regulation of rabbit gastric epithclial cells and protooncogene expression" Digcstive Discases and Sciences. 39. 1454-1463 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Noriaki Yajima N,Hideyiki Hiraishi H et al.: "Protection of cultured rat gastric cells aganist oxidant stress by iron chclation : role of lipid peroxidation" Digestive Diseases and Sciences. 40. 879-886 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hiroyuki Mutoh H.Hideyiki Hiraishi H et al.: "Adaptivec cytoprotcction in culturcd rat gastric mucus-producing cells : role of mucus and prostaglandin synthesis" Digestive Discases and Sciences. 40. 887-891 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hideyuki Hiraishi, Akira Terano: "Gastric mucosal lcsions and frcc radicls" Japanese Journal of Gastroentcrology. 92(in Japanese). 1817-1824 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Akira Terano: "Hideyuki Hiraishi" Stomach-morphology and function (2nd cdition). lgakushoin. (in Japanese). 354 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hideyuki Hiraishi: "Akira Terano" Key words 1995-'96 (Gastrointestinal tract, Scntan-lgakusha. (in Japanese). 233 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nariaki Yajima, Hideyuki Hiraishi et al.: "Protection of cultured rat gastric cells against oxidant stress by iron chelation: role of lipid peroxidation." Digestive Diseases and Sciences. 40. 879-886 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hiroyuki Mutoh, Hideyuki Hiraishi et al.: "Adaptive cytoprotection in cultured rat gastric mucus-producing cells: role of mucus and prostaglandin synthesis" Digestive Diseases and Sciences. 40. 887-891 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 平石秀幸,寺野彰: "胃粘膜病変とフリーラジカル" 日本消化器病学会雑誌. 92. 1817-1824 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 平石秀幸ら: "活性酸素と消化性潰瘍" 治療の最前線. 2. 571-574 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 平石秀幸ら: "酸化的ストレスによる培養胃粘膜細胞傷害" GI Research. 3. 245-240 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 平石秀幸ら: "フリーラジカルの胃粘膜細胞傷害機序" 消化器科. 21. 389-398 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 平石秀幸,寺野彰: "キーワード1995-'96(消化器系)" 先端医学社, 2 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Hideyuki Hiraishi et al.: "Protective role of intracellular superoxide dismutase against extracellular oxldants in cultured rat gastric cells" Journal of Clinical Investigation. 93. 331-338 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hideyuki Hiraishi et al.: "Protection of cultured rat gastric cells against oxidant-induced damage by exogenous glutathione" Gastroenterology. 106. 1199-1207 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hideyuki Hiraishi et al.: "Reactive oxygen metabolite-induced toxicity to cultured bovine endothelial cells:Status of cellular iron in mediating injury" Journal of Cellular Physiology. 160. 132-140 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Noriaki Yajima,Hideyuki Hiraishi et al.: "Protection of cultured rat gastric cells against oxidant stress by iron chetation:Role of lipid peroxidation" Digestive Diseases and Sciences. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] 平石秀幸ら: "障害修復とフリーラジカル" Mebio. 11. 86-91 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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