2003 Fiscal Year Annual Research Report

酸素含有ラジカルによる微生物の遺伝子多型性獲得と持続感染機構の解明

Research Project

Project/Area Number	14570127
Research Institution	Osaka City University
Principal Investigator	佐藤英介大阪市立大学, 大学院・医学研究科, 講師 (60211942)
Keywords	活性酸素 / 一酸化窒素 / NADH酸化酵素 / 酸素濃度 / 突然変異 / 亜硝酸還元酵素
Research Abstract	本年度の解析により以下のことを明らかにした。 1)活性酸素産生能については化学発光試薬を使い分けることによりH.pyloriはbacillary型はMCLAで検出できるスーパーオキシド、coccoid型ではL-012で検出できるOHラジカルを産生することが判明した。さらに、S.mutansは、これまで過酸化水素を産生すると考えられてきたが、低酸素環境下ではNADH oxidaseの1型によりスーパーオキシドを産生することを組み換えタンパク質を用いた電子スピン共鳴装置により明らかにした。さらに、NADH oxidaseをノックアウトしたS.mutansは培地中に過酸化水素を放出できなくなることも明らかにした。 2)8-OH-GとDNAの断片化を電気泳動法により解析した結果、H.pyloriでは低酸素環境下では遺伝子の酸化傷害は起こりにくいが嫌気あるいは高酸素では著明な酸化傷害が生じ、遺伝子変異を惹起する可能性が考えられ、論文に発表した。 3)菌体の抗菌剤に対する耐性株の出現は、薬剤耐性遺伝子の変異と耐性株の選択という微生物進化によるが、それが酸素環境の変化や酸化ストレスにより引き起こされているか否かをマクロイド系抗生剤に対する耐性株の出現率で解析した結果。H.pyloriは、低酸素環境下では突然変異をおこさないが、嫌気あるいは高酸素で著明な突然変異を起こすことが判明した。 4)S.mutansの一酸化窒素による代謝の実験の途中で、NOの代謝産物であり、口腔内に多量に存在する亜硝酸塩を菌体と共存させると酸素濃度にかかわらず、NOが菌体より産生することが明らかになった。亜硝酸還元酵素が存在すると考えられるが、これまで、本菌での亜硝酸還元酵素の存在は知られていない。データーベースから亜硝酸還元酵素の候補を2種拾い上げ、現在PCRクローニングに成功し塩基配列を明らかにしている。

Research Products

(18 results)

All Other

All Publications (18 results)

[Publications] K.Hiramoto, Y.Yanagihara, EF.Sato, M.Inoue: "Activation of a nitric oxide-dependent neuroendocrinological pathway by the eye protects against ultraviolet B toxicity in the skin"J.Invest.Dermatol.. 120・1. 123-127 (2003)
[Publications] M.Miyoshi, Y.Minamiyama, T, S.Taketani, K, Hiramoto, E, Kasahara, EF.: "Dietary nitrate inhibits stress-induced gastric mucosal injury in the rat"Free Radical Research. 37・1. 85-90 (2003)
[Publications] AM Park, K Nagata, EF Sato, T Tamura, M Inoue: "Different sensitvity to nitric oxide in Helicobactor pylori and Eschelichia coli is due to the subtype of cytochrome c oxidase"Aech.Biochem.Biophys.. 411・1. 129-135 (2003)
[Publications] Sato, EF., Higashino, M., Ikeda, K., Wake, R., Matsuo, M., Utsumi, K., Inoue, M.: "Oxidative stress-induced cell death in oral neutrophils"Am.J.Phyiol.-Cell Physiol.. 284. C1048-C1053 (2003)
[Publications] Bandoh T, Sato EF, Mitani H, Nakashima A, Hoshi K, Inoue M: "Antioxidative potential of fluvastatin via the inhibition of NADPH oxidase activity"Biological & Pharmaceutical Bulletin. 26・6. 818-822 (2003)
[Publications] K.Maeda, K.Yasunari, EF Sato, J.Yoshikawa, M.Inoue: "Activation of protein kinase C and NADPH oxidase in leukocytes of spontaneously hypertensive rats"Hypertension Research. 26・12. 999-1006 (2003)
[Publications] Chang BJ, Nishikawa M, Sato EF, Inoue M: "Mice lacking inducible nitric oxide synthase show strong resistance to anti-Fas antibody-induced fulminant hepatitis"Arch.Biochem.Biophys.. 411・1. 63-72 (2003)
[Publications] Tsuchiya M, Asada A, Ryo K, Noda K, Hashino T, Sato Y, Sato EF, Inoue M: "Relaxing intraoperative natural sound blunts haemodynamic change at the emergence from propfol general anaesthesia and increases the acceptability of anaesthesia to the patient"Acta Anaesthesiologica Scandinavica. 47・8. 939-943 (2003)
[Publications] H.Hanada, K.Katsu, T.Kanno E.F.Sato, A.Kashiwagi J.Sasaki, M.Inoue, K.Utsumi: "Cyclosporin A inhibits thyroid hormone-induced shortening of the tadpole tail through membrane permeability transition"Comparative Biochemistry & Physiology. 135. 473-483 (2003)
[Publications] Inoue M, Sato EF, Nishikawa M, Park AM, Kira Y, Imada I, Utsumi K.: "Cross talk of nitric oxide, oxygen radicals, and superoxide dismutase regulates the energy metabolism and cell death and determines the fates of aerobic life"Antioxid Redox Signal. 5・4. 475-484 (2003)
[Publications] Inoue M, Sato EF, Nishikawa M, Park AM, Kira Y, Imada I, Utsumi K: "Mitochondrial generation of reactive oxygen species and its role in aerobic life."Curr Med Chem.. 23・10. 2495-2505 (2003)
[Publications] Miyamoto, M., Sato, EF., Nishikawa, M., Nishizawa Y., Morii, H., Inoue, M.: "Effect of Endogenously Generated Nitric Oxide on The Energy Metabolism of Peritoneal Macrophages"Physiol.Chem.Phys. & Med.NMR. 36・2. 1-11 (2004)
[Publications] Kanno T, Sato EF, Utsumi T, Muranaka, S., Fujita, H, Fujiwara, T., Utsumi: "Oxidative stress underlies the mechanism for Ca2+-induced permeability trasition of mitochondria"Free Radic Res. 38・1. 27-35 (2004)
[Publications] Yasuji Okai, Eisuke F.Sato, Kiyoka Higashi-Okai, Masayasu Inoue: "Enhancing Effect of an Endocrine Disruptor, Para-Nonylphenol on the Generation of Reactive Oxygen Species in Human Blood Cells"Environ Health Persp. 112・5(in press). (2004)
[Publications] Iguchi T., Nishikawa M., Muroya O, Sato EF., Nakatani S., Inoue M.: "Edaravone inhibits aute injury and cisplatin-induced cyst formation in rat kidney"Free Radic Res. (in press). (2004)
[Publications] K.Hiramoto, H.Tanaka, M.Yanagihara, E.F.Sato, M.Inoue: "Effect of 17β-estradiol on immunosuppression induced by ultraviolet B irradiation"Archives of Dermatological Research. 295・8-9. 307-311 (2004)
[Publications] Eisuke J.Sato, Eri Nakagawa, Keiichi Hiramoto, Seiichi Yamamasu, Ikuko: "Oxidative stress promotes the regression of fetal liver hemopoiesis"Biochemistry(Moscow). 69・1. 18-22 (2004)
[Publications] Am.Park, Q.Li, K.Nagata, T.Tamura, K.Shimono, EF.Sato, M.Inoue: "Oxygen tension regulates reactive oxygen generation and mutation of Helicobacter pylori"Free Radical Biology & Medicine. (in press). (2004)

2003 Fiscal Year Annual Research Report

酸素含有ラジカルによる微生物の遺伝子多型性獲得と持続感染機構の解明

Principal Investigator

佐藤 英介 大阪市立大学, 大学院・医学研究科, 講師 (60211942)

Research Products

[Publications] K.Hiramoto, Y.Yanagihara, EF.Sato, M.Inoue: "Activation of a nitric oxide-dependent neuroendocrinological pathway by the eye protects against ultraviolet B toxicity in the skin"J.Invest.Dermatol.. 120・1. 123-127 (2003)

[Publications] M.Miyoshi, Y.Minamiyama, T, S.Taketani, K, Hiramoto, E, Kasahara, EF.: "Dietary nitrate inhibits stress-induced gastric mucosal injury in the rat"Free Radical Research. 37・1. 85-90 (2003)

[Publications] AM Park, K Nagata, EF Sato, T Tamura, M Inoue: "Different sensitvity to nitric oxide in Helicobactor pylori and Eschelichia coli is due to the subtype of cytochrome c oxidase"Aech.Biochem.Biophys.. 411・1. 129-135 (2003)

[Publications] Sato, EF., Higashino, M., Ikeda, K., Wake, R., Matsuo, M., Utsumi, K., Inoue, M.: "Oxidative stress-induced cell death in oral neutrophils"Am.J.Phyiol.-Cell Physiol.. 284. C1048-C1053 (2003)

[Publications] Bandoh T, Sato EF, Mitani H, Nakashima A, Hoshi K, Inoue M: "Antioxidative potential of fluvastatin via the inhibition of NADPH oxidase activity"Biological & Pharmaceutical Bulletin. 26・6. 818-822 (2003)

[Publications] K.Maeda, K.Yasunari, EF Sato, J.Yoshikawa, M.Inoue: "Activation of protein kinase C and NADPH oxidase in leukocytes of spontaneously hypertensive rats"Hypertension Research. 26・12. 999-1006 (2003)

[Publications] Chang BJ, Nishikawa M, Sato EF, Inoue M: "Mice lacking inducible nitric oxide synthase show strong resistance to anti-Fas antibody-induced fulminant hepatitis"Arch.Biochem.Biophys.. 411・1. 63-72 (2003)

[Publications] H.Hanada, K.Katsu, T.Kanno E.F.Sato, A.Kashiwagi J.Sasaki, M.Inoue, K.Utsumi: "Cyclosporin A inhibits thyroid hormone-induced shortening of the tadpole tail through membrane permeability transition"Comparative Biochemistry & Physiology. 135. 473-483 (2003)

[Publications] Inoue M, Sato EF, Nishikawa M, Park AM, Kira Y, Imada I, Utsumi K.: "Cross talk of nitric oxide, oxygen radicals, and superoxide dismutase regulates the energy metabolism and cell death and determines the fates of aerobic life"Antioxid Redox Signal. 5・4. 475-484 (2003)

[Publications] Inoue M, Sato EF, Nishikawa M, Park AM, Kira Y, Imada I, Utsumi K: "Mitochondrial generation of reactive oxygen species and its role in aerobic life."Curr Med Chem.. 23・10. 2495-2505 (2003)

[Publications] Miyamoto, M., Sato, EF., Nishikawa, M., Nishizawa Y., Morii, H., Inoue, M.: "Effect of Endogenously Generated Nitric Oxide on The Energy Metabolism of Peritoneal Macrophages"Physiol.Chem.Phys. & Med.NMR. 36・2. 1-11 (2004)

[Publications] Kanno T, Sato EF, Utsumi T, Muranaka, S., Fujita, H, Fujiwara, T., Utsumi: "Oxidative stress underlies the mechanism for Ca2+-induced permeability trasition of mitochondria"Free Radic Res. 38・1. 27-35 (2004)

[Publications] Yasuji Okai, Eisuke F.Sato, Kiyoka Higashi-Okai, Masayasu Inoue: "Enhancing Effect of an Endocrine Disruptor, Para-Nonylphenol on the Generation of Reactive Oxygen Species in Human Blood Cells"Environ Health Persp. 112・5(in press). (2004)

[Publications] Iguchi T., Nishikawa M., Muroya O, Sato EF., Nakatani S., Inoue M.: "Edaravone inhibits aute injury and cisplatin-induced cyst formation in rat kidney"Free Radic Res. (in press). (2004)

[Publications] K.Hiramoto, H.Tanaka, M.Yanagihara, E.F.Sato, M.Inoue: "Effect of 17β-estradiol on immunosuppression induced by ultraviolet B irradiation"Archives of Dermatological Research. 295・8-9. 307-311 (2004)

[Publications] Eisuke J.Sato, Eri Nakagawa, Keiichi Hiramoto, Seiichi Yamamasu, Ikuko: "Oxidative stress promotes the regression of fetal liver hemopoiesis"Biochemistry(Moscow). 69・1. 18-22 (2004)

[Publications] Am.Park, Q.Li, K.Nagata, T.Tamura, K.Shimono, EF.Sato, M.Inoue: "Oxygen tension regulates reactive oxygen generation and mutation of Helicobacter pylori"Free Radical Biology & Medicine. (in press). (2004)

佐藤英介大阪市立大学, 大学院・医学研究科, 講師 (60211942)