2000 Fiscal Year Annual Research Report

活性酸素産生によるH.pyloriの生存戦略と遺伝子変異

Research Project

Project/Area Number	11877031
Research Institution	Osaka City University
Principal Investigator	井上正康大阪市立大学, 医学部, 教授 (80040278)
Co-Investigator(Kenkyū-buntansha)	佐藤英介大阪市立大学, 医学部, 助手 (60211942)
Keywords	H.pylori / 活性酸素 / NO / 感染防御系 / 能動輸送単体 / 酸化ストレス / 胃癌 / 遺伝子変異
Research Abstract	生理的低酸素下ではNOがミトコンドリア、細胞、および大腸菌などの電子伝達系を強く抑制し、食物中の病原微生物に対する防御因子としても作用している。H.pyloriは胃液内でも生息でき、胃粘膜病態因子の可能性がある。本年度の研究により、以下の点が明らかになった。 1)H.pyloriは電子伝達系を介してスーパーオキシドやヒドロキシラジカルを産生するが、これに本菌の形質転換が深く関与している。 2)本菌のNO低感受性は、本菌のスーパーオキシド産生能に加え、チトクロム酸化酵素の膜内存在様式特性にも起因する。 3)NOとスーパーオキシドから生じるONOO^-や^*OHが本菌のDNAを酸化修飾してニトログアニンや8-OHグアノシンなどを生じ、これが本菌の遺伝子多形や発ガンに関与する可能性が示唆された。 4)胃粘膜層は低酸素低pH環境であり、NOや亜硝酸は強い殺菌能を示すが、粘膜細胞に対しては著明な保護作用を示すことが判明した。 5)硝酸イオンは胃腸の粘膜細胞で吸収され、血中から唾液中に能動分泌され、口腔内細菌により亜硝酸に還元されて胃液内でNOに変換されること、及びNO関連分子群の口腔・胃腸・唾液腺間輸送変換サイクルが病原微生物に対する強力な防御システムを形成していることが判明した。また唾液腺に硝酸イオンの能動輸送担体が局在することが判明し、その遺伝子のクローニングに成功した。現在、その構造と機能を解明しつつある。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] C.Sakuta,H.Tanaka,S.Takemura,K.Hirohashi,Y.Minamiyama,A.Nakamura,M.Inoue,H.Kinoshita: "Post-ischemic intraportal adenosine administration protects against reperfusion injury of canine liver."J.Hepatobiliary Pancreat Surg. 7・1. 78-85 (2000)
[Publications] M.Kashiba,M.Inoue: "Nitric oxide-independent effects of nitric oxide donors on energy metabolism in erythrocytes."Biochemical Pharmacology. 59・. 557-561 (2000)
[Publications] Y.Takada,E.Sato,T.Nakajima,M.Hosono,M.Tsumura,M.Inoue,R.Yamada: "Granulocyte-colony stimulating factor enhances anti-tumour effect of hyperthermia."Int.J.Hyperthermia. 16・. 275-286 (2000)
[Publications] K.Suzumura,E.Kasahara,Y.Ohnishi,K.C.Chien,M.Inoue: "Fluvastatin normalizes the decreased turnovers of glutathione and ascorbic acid in Watanabe heritable hyperlipidemic rabbits."Clin.Exp.Pharmacol.Physiol.. 27・. 709-714 (2000)
[Publications] K.Suzumura,E.Kasahara,Yi Wang,K.C.Chien.M.Inoue: "Decreased turnovers of glutathione and ascorbic acid in Watanabe heritable hyperlipidemic rabbits."J.Nutr.Sci.Vitaminol.. 46・. 205-209 (2000)
[Publications] A.Nakamura,A.M.Park,K.Nagata,E.Sato,M.Kashiba,T.Tamura,M.Inoue: "Oxidative cellular damage associated with transformation of helicobacter pylori from a bacillar to a coccoid form."Free Radical Biology Medicine. 28・. 1611-1618 (2000)
[Publications] M.Tsuchiya,H.Tokai,Y.Takehara,Y.Haraguchi,A.Asada,K.Utsumi,M.Inoue: "Interrlation betwwen oxygen tension and nitric oxide in the respiratory system."Am J Respir Crit Care Med. 162・. 1257-1261 (2000)
[Publications] M.Kashiba,J.Oka,R.Ichikawa,A.Kageyama,T.Inayama,H.Kageyama,T.Ishikawa,M.Nishikimi,M.Inoue,s.Inoue: "Impaired reductive regeneration of ascorbic acid in the Goto-Kakizaki diabetic rat."Biochem.J.. 351・. 313-318 (2000)
[Publications] M.Tsuchiya,A.Asada,K.Maeda,Y.Ueda,E.Sato,M.Shindo,M.Inoue: "Propofol versus midazolam regarading their antioxidant activities."American Journal of Respiratory and Critical Care Medicine. 163・. 1-6 (2001)
[Publications] Tomita,M.,Sato,EF.,Nishikawa,M.,Yamano,Y.,Inoue,M.: "Nitric oxide regulates mitochondrial respiration and fanctions of articular chondrocytes"Arthritis & Rheumatism. 44・. 96-104 (2001)
[Publications] Takemura,S.,Minamiyama Y., Inoue,M.,Kubo,S.,Hirohashi,K.,Kinoshita,H.: "Nitric oxide synthase inhibitor increases hepatic injury with formation of oxidative DNA damage and microcirculatory disturbance in endotoxemic rats"Hepato-Gastroenterology. 47・. 1364-1370 (2000)
[Publications] Nishikawa,M.,Nagatomi,H.,Bao-Jun Chang,Sato,E.F.,Inoue,M.: "Targeting superoxide dismutase to renal proximal tuble cells inhibits mitochondrial injury and renal dysfunction induced by cisplatin"Arch.Biochem.& Biophys.. 386・2(in press). (2001)
[Publications] Nishikawa,M.,Nishiguchi,S.,Tamori,A.,Koh,N.,Takeda,T.,Shiomi,S.,Kubo,S.,Hirohashi,K.,Kinoshita,H.,Sato,E.F.,Inoue,M.: "Somatic mutation of mitochondrial DNA in cancerous and noncancerous liver tissue in individuals with hepatocellular carcinoma"Cancer Res. (in press). (2001)
[Publications] Nishikimi,A.,Kira,Y.,Kasahara,E.,Sato,EF.,Kanno,T.,Utsumi,K.,Inoue,: "Tributyltin interacts with thiol groups in adenine nucleotide translocator therby inducing cytochrome c release"Biochem J. (in press). (2001)

2000 Fiscal Year Annual Research Report

活性酸素産生によるH.pyloriの生存戦略と遺伝子変異

Principal Investigator

井上 正康 大阪市立大学, 医学部, 教授 (80040278)

Research Products

[Publications] C.Sakuta,H.Tanaka,S.Takemura,K.Hirohashi,Y.Minamiyama,A.Nakamura,M.Inoue,H.Kinoshita: "Post-ischemic intraportal adenosine administration protects against reperfusion injury of canine liver."J.Hepatobiliary Pancreat Surg. 7・1. 78-85 (2000)

[Publications] M.Kashiba,M.Inoue: "Nitric oxide-independent effects of nitric oxide donors on energy metabolism in erythrocytes."Biochemical Pharmacology. 59・. 557-561 (2000)

[Publications] Y.Takada,E.Sato,T.Nakajima,M.Hosono,M.Tsumura,M.Inoue,R.Yamada: "Granulocyte-colony stimulating factor enhances anti-tumour effect of hyperthermia."Int.J.Hyperthermia. 16・. 275-286 (2000)

[Publications] K.Suzumura,E.Kasahara,Y.Ohnishi,K.C.Chien,M.Inoue: "Fluvastatin normalizes the decreased turnovers of glutathione and ascorbic acid in Watanabe heritable hyperlipidemic rabbits."Clin.Exp.Pharmacol.Physiol.. 27・. 709-714 (2000)

[Publications] K.Suzumura,E.Kasahara,Yi Wang,K.C.Chien.M.Inoue: "Decreased turnovers of glutathione and ascorbic acid in Watanabe heritable hyperlipidemic rabbits."J.Nutr.Sci.Vitaminol.. 46・. 205-209 (2000)

[Publications] A.Nakamura,A.M.Park,K.Nagata,E.Sato,M.Kashiba,T.Tamura,M.Inoue: "Oxidative cellular damage associated with transformation of helicobacter pylori from a bacillar to a coccoid form."Free Radical Biology Medicine. 28・. 1611-1618 (2000)

[Publications] M.Tsuchiya,H.Tokai,Y.Takehara,Y.Haraguchi,A.Asada,K.Utsumi,M.Inoue: "Interrlation betwwen oxygen tension and nitric oxide in the respiratory system."Am J Respir Crit Care Med. 162・. 1257-1261 (2000)

[Publications] M.Kashiba,J.Oka,R.Ichikawa,A.Kageyama,T.Inayama,H.Kageyama,T.Ishikawa,M.Nishikimi,M.Inoue,s.Inoue: "Impaired reductive regeneration of ascorbic acid in the Goto-Kakizaki diabetic rat."Biochem.J.. 351・. 313-318 (2000)

[Publications] M.Tsuchiya,A.Asada,K.Maeda,Y.Ueda,E.Sato,M.Shindo,M.Inoue: "Propofol versus midazolam regarading their antioxidant activities."American Journal of Respiratory and Critical Care Medicine. 163・. 1-6 (2001)

[Publications] Tomita,M.,Sato,EF.,Nishikawa,M.,Yamano,Y.,Inoue,M.: "Nitric oxide regulates mitochondrial respiration and fanctions of articular chondrocytes"Arthritis & Rheumatism. 44・. 96-104 (2001)

[Publications] Takemura,S.,Minamiyama Y., Inoue,M.,Kubo,S.,Hirohashi,K.,Kinoshita,H.: "Nitric oxide synthase inhibitor increases hepatic injury with formation of oxidative DNA damage and microcirculatory disturbance in endotoxemic rats"Hepato-Gastroenterology. 47・. 1364-1370 (2000)

[Publications] Nishikawa,M.,Nagatomi,H.,Bao-Jun Chang,Sato,E.F.,Inoue,M.: "Targeting superoxide dismutase to renal proximal tuble cells inhibits mitochondrial injury and renal dysfunction induced by cisplatin"Arch.Biochem.& Biophys.. 386・2(in press). (2001)

[Publications] Nishikawa,M.,Nishiguchi,S.,Tamori,A.,Koh,N.,Takeda,T.,Shiomi,S.,Kubo,S.,Hirohashi,K.,Kinoshita,H.,Sato,E.F.,Inoue,M.: "Somatic mutation of mitochondrial DNA in cancerous and noncancerous liver tissue in individuals with hepatocellular carcinoma"Cancer Res. (in press). (2001)

[Publications] Nishikimi,A.,Kira,Y.,Kasahara,E.,Sato,EF.,Kanno,T.,Utsumi,K.,Inoue,: "Tributyltin interacts with thiol groups in adenine nucleotide translocator therby inducing cytochrome c release"Biochem J. (in press). (2001)

井上正康大阪市立大学, 医学部, 教授 (80040278)