1997 年度実績報告書

部位指向性SODによるneurovascular networkと血液循環制御機構の解析

研究課題

研究課題/領域番号	08457054
研究機関	大阪市立大学
研究代表者	井上正康大阪市立大学, 医学部, 教授 (80040278)
研究分担者	佐藤英介大阪市立大学, 医学部, 助手 (60211942)
キーワード	活性酸素 / スーパーオキサイド / 一酸化窒素 / 血圧制御 / 高血圧 / 血圧中枢 / 酸化ストレス / マンノース受容体
研究概要	これまでに、長時間作動型SODや血管内皮細胞指向型SODを開発し、特定の組織細胞局所でスーパーオキシドを特異的に消去して解析した結果、高血圧をはじめとする循環病態に活性酸素が深く関与する事が判明した。血管局所で発生する活性酸素が循環制御に重要な役割を果たすことが判明し、末梢組織と脳血圧中枢における活性酸素代謝の意義を解析した。 Mannoseレセプター含有細胞に特異的に集積するMannose結合SOD(MAN-SOD)を合成して静脈内投与したところ、正常動物の血圧が瞬時に低下したことから、Mannoseレセプター含有細胞が全身の血圧維持に重要な役割を担うことが判明した。本降圧作用に関与するMannoseレセプター含有細胞を同定する目的で、放射性標識MAN-SODの組織分布を解析した結果、その90%以上が肝のKupffer細胞と脾臓マクロファージに取り込まれた。しかし、75%肝切除および脾摘出動物でも本降圧反応が認められることから、その責任細胞はこれら以外の細胞であることが判明した。本降圧現象には痲酔剤感受性を示す興奮性細胞が関与することが示唆されたが、アトロピンやアネチジンなどの神経遮断薬では影響されず、自律神経系以外の関与が示唆された。中枢神経系における放射活性は特に顕著な集積性を示さないことから、本責任細胞は比較的小さな領域に局在する可能性が考えられた。さらに、抗ヒトSOD抗体を用いた免疫組織学的解析を行ったが、未だ著明な分布領域を見つけることには成功していない。今後、孤束核や血圧中枢のNO神経などを中心に解析を進めると同時に、マンノースレセプター含有細胞に集積するスーパーオキシド発生系を開発し、これにより特異的昇圧反応が誘起されるか否かを検討つつある。

研究成果
(26件)

すべてその他

すべて文献書誌 (26件)

[文献書誌] Minamiyama,Y.;Takemura,S.;Kawada,N.;Inoue,M.: "Role of nitric oxide Tn extracellular nucleotide-induced contractile status of assorted vessels including parts of portal vasculature" J.Hepatology. 28:314-319. 314-319 (1998)
[文献書誌] Nishikawa,M.;Sato,EF.;Kuroki,T.;Utsumi,K.;Inoue,M.: "Role of glutathione in energy metabolism of tumor cells" Hepatology. (in press). (1998)
[文献書誌] Nakanishi,K.;Nishi,Y.;Sato,EF,;Ishii,M.;Hamada,T.;Inoue,M.: "Termal injury induces thymoyte apoptosis in the rat" J.Trauma. (in press). (1998)
[文献書誌] Nakahara,H.;Sato,EF.;Ishihara,R.;Yabuki,M.;Inoue,M.;Utsumi,K.: "Biochemical properties of human neutrophils" Free Radic.Res.(in press). (1998)
[文献書誌] Nishikawa,M.;Takeda,K.;Sato,EF.;Kuroki,T.;Inoue,M.: "Nitric oxide regulates energy metabolism and bc1-2 expression in rat intestional epithelial cells" Am.J.Physiol.(in press). (1998)
[文献書誌] Morishita,S.;Sato,EF.;Takahashi,YP.;Manabe,M.;Inoue,M.: "Hypoglycemia-induced apoptosis in rat thymocytes in vivo" Dyabetes Res.Clin.Prac.(in press). (1998)
[文献書誌] Nagata,K.;Yu,H.;Sato,EF;Kasahiba,M.;Tamura,T.;Inoue,M.: "Irreversible inhibition of respiration of Helicobacter pylori by nitric oxide" J.Biol.Chem.(in press). (1998)
[文献書誌] Kawada,N.;Seki,S.;Inoue,M.;Kuroki,T.: "Effect of antioxidants,resveratol,quercetin and N-acetyl cysteine on the function of hepatic stellate cells and Kupffer cells" Hepatology. (in press). (1998)
[文献書誌] Dunlap,WC.;Yamamoto,Y.;Inoue,M.;Kashiba,M.;Yamaguchi,M.;Tomita,K.: "Uric acid photo-oxidation assay:in vitro comparison of sunscreening agents" Int.I.Cosmetic Sci.20:1-8. 1-8 (1998)
[文献書誌] I.Shiraishi,;E.F.Sato.;M.Nishikawa.;F.Sendo.;M.Inoue: "Mechanism of hypotensive shock induced by anti-neutrophil monoclonal antibody" Pathopysiology. 4:197-204. 197-204 (1997)
[文献書誌] H.Yu.;E.F.Sato.;T.Arakawa.;K.Kobayashi,.;M.Inoue: "Protective action of lipopolysaccharide against stress-induced gastric mucosal injury" Digestion. 58:311-318. 311-318 (1997)
[文献書誌] Hirai,A.;Minamiyama,Y.;Hamada,T.;Ishii,M.;Inoue,M.: "Dynamic aspects of glutathione metabolism in mice with hapten-induced allergic and irritant contact" J.Invest.Dermatol.109:314-318. 314-318 (1997)
[文献書誌] Minamiyama,Y.;Takemura,S.;Inoue,M.: "Effect of thiol status on nitric oxide metabolism in the circulation" Arch. Biochem.Biophys.341:186-192. 186-192 (1997)
[文献書誌] Yabuki,M.;Inai,Y.;Yoshioka,T.;Hamazaki,K.;Yasuda,T.;Inoue,M.;Utsumi.K.: "Oxygen-dependent fragmentation of cellular DNA by nitric oxide" Free Rad.Res.26:245-255. 245-255 (1997)
[文献書誌] Uno,H.;Arakawa,T.;Fukuda,T.;Yu,H.;Fujiwara,Y.;Higuchi,K.;Inoue,M.;Kobayashi.K.: "Nitric oxide stimulates prostaglandin synthesis in cultured rabbit gastric cells" Prostaglandins. 53:153-162. 153-162 (1997)
[文献書誌] Yu,H.;Sato,EF.;Nagata,K.;Nishikawa,M.;Kashiba,M.;Arakawa,T.;Kobayashi.K.;Inoue.M.: "Oxygen-dependent regulation of the respiration and growth of Escherichia coli by nitric oxide" FEBS Letters. 409:161-165. 161-165 (1997)
[文献書誌] Yamamasu,S.;Sato,EF.;Ogita,S.;Inoue,M.: "Role of glutathione metabolism and apoptosis in the regression of liver hemopoiesis" Free Radical Biol. & Med.23:100-109. 100-109 (1997)
[文献書誌] Kashiba,M.;Miyamoto,M.;Inoue,M.: "Effect of nitric oxide on the ligand binding activity of albumin" Arch.Biochem.Biopjys.345:237-242. 237-242 (1997)
[文献書誌] Morishita,S.;Nishi,Y.;Sato,EF.;Yamaoka,K.Manabe,M.;Inoue,M.: "Cold-stress induces thymocyte apoptosis in the rat" Pathophysiology. 4:213-219. 213-219 (1997)
[文献書誌] Hanada,H.;Kashiwagi,A.Takehara,Y.;Kanno,T.;Yabuki,M.;Sasaki,J.;Inoue.M.;Utsumi.K.: "Do reactive oxygen species underlie the mechanism of apoptosis in the tadpole tail?" Free Radical Biol. & Med. 23:294-301. 294-301 (1997)
[文献書誌] Nishikawa,M.;Sato,EF.;Kuroki,T.;Inoue,M.: "Role glutathione in the energy metabolism of mitochondria" FEBS Letters. 415:341-345. 341-345 (1997)
[文献書誌] Kashiba,M.;Kitoh,K.;Yu,H.;Kasahara,E.;Nishikawa,M.;Matsuo,M.;Inoue,M.: "Ascorbic Acid and reducing agents regulates the fates and functions of S-nitrospthiols" J.Biochem.122:1208-1214. 1208-1214 (1997)
[文献書誌] Minamiyama,Y.;Takemura,S.;Imaoka,S.;Funae,Y.;Tanimoto,Y.;Inoue,M.: "Irreversible inhibition of cytochrome P450 by nitric oxide" J.Phaemacol.Exp.Ther.283:1479-1485. 1479-1485 (1997)
[文献書誌] Yamada,T.;Yukioka,H.;Asada,A.;Inoue,M.: "Effect of inhaled nitric oxide on platelet-activating factor induced pulmonary hypertension in dogs" Acta Anesthesiol. Scand.41. (1997)
[文献書誌] Kashiba-Iwatsuki.M.,Kitoh.K.,Nishikawa.M.,Sato.E.F.Inoue.M.: "Oxygen Homeostasis and its dynamics" Springer-Verlag.Tokyo(Ishimura,Y.,Suematsu,M.,Shimada,H), 7 (1998)
[文献書誌] Utsumi.K.,Takehara.Y.,Inai.Y.Yabuki.M.,Kanno,T.,Nishikawa,M.Sato,EF.,Inoue.M.: "Mitochondria,Oxidants,and Aging" Academic Press (L.Packer Cadenas)(in press), (1998)

1997 年度 実績報告書

部位指向性SODによるneurovascular networkと血液循環制御機構の解析

研究代表者

井上 正康 大阪市立大学, 医学部, 教授 (80040278)

研究成果

[文献書誌] Minamiyama,Y.;Takemura,S.;Kawada,N.;Inoue,M.: "Role of nitric oxide Tn extracellular nucleotide-induced contractile status of assorted vessels including parts of portal vasculature" J.Hepatology. 28:314-319. 314-319 (1998)

[文献書誌] Nishikawa,M.;Sato,EF.;Kuroki,T.;Utsumi,K.;Inoue,M.: "Role of glutathione in energy metabolism of tumor cells" Hepatology. (in press). (1998)

[文献書誌] Nakanishi,K.;Nishi,Y.;Sato,EF,;Ishii,M.;Hamada,T.;Inoue,M.: "Termal injury induces thymoyte apoptosis in the rat" J.Trauma. (in press). (1998)

[文献書誌] Nakahara,H.;Sato,EF.;Ishihara,R.;Yabuki,M.;Inoue,M.;Utsumi,K.: "Biochemical properties of human neutrophils" Free Radic.Res.(in press). (1998)

[文献書誌] Nishikawa,M.;Takeda,K.;Sato,EF.;Kuroki,T.;Inoue,M.: "Nitric oxide regulates energy metabolism and bc1-2 expression in rat intestional epithelial cells" Am.J.Physiol.(in press). (1998)

[文献書誌] Morishita,S.;Sato,EF.;Takahashi,YP.;Manabe,M.;Inoue,M.: "Hypoglycemia-induced apoptosis in rat thymocytes in vivo" Dyabetes Res.Clin.Prac.(in press). (1998)

[文献書誌] Nagata,K.;Yu,H.;Sato,EF;Kasahiba,M.;Tamura,T.;Inoue,M.: "Irreversible inhibition of respiration of Helicobacter pylori by nitric oxide" J.Biol.Chem.(in press). (1998)

[文献書誌] Kawada,N.;Seki,S.;Inoue,M.;Kuroki,T.: "Effect of antioxidants,resveratol,quercetin and N-acetyl cysteine on the function of hepatic stellate cells and Kupffer cells" Hepatology. (in press). (1998)

[文献書誌] Dunlap,WC.;Yamamoto,Y.;Inoue,M.;Kashiba,M.;Yamaguchi,M.;Tomita,K.: "Uric acid photo-oxidation assay:in vitro comparison of sunscreening agents" Int.I.Cosmetic Sci.20:1-8. 1-8 (1998)

[文献書誌] I.Shiraishi,;E.F.Sato.;M.Nishikawa.;F.Sendo.;M.Inoue: "Mechanism of hypotensive shock induced by anti-neutrophil monoclonal antibody" Pathopysiology. 4:197-204. 197-204 (1997)

[文献書誌] H.Yu.;E.F.Sato.;T.Arakawa.;K.Kobayashi,.;M.Inoue: "Protective action of lipopolysaccharide against stress-induced gastric mucosal injury" Digestion. 58:311-318. 311-318 (1997)

[文献書誌] Hirai,A.;Minamiyama,Y.;Hamada,T.;Ishii,M.;Inoue,M.: "Dynamic aspects of glutathione metabolism in mice with hapten-induced allergic and irritant contact" J.Invest.Dermatol.109:314-318. 314-318 (1997)

[文献書誌] Minamiyama,Y.;Takemura,S.;Inoue,M.: "Effect of thiol status on nitric oxide metabolism in the circulation" Arch. Biochem.Biophys.341:186-192. 186-192 (1997)

[文献書誌] Yabuki,M.;Inai,Y.;Yoshioka,T.;Hamazaki,K.;Yasuda,T.;Inoue,M.;Utsumi.K.: "Oxygen-dependent fragmentation of cellular DNA by nitric oxide" Free Rad.Res.26:245-255. 245-255 (1997)

[文献書誌] Uno,H.;Arakawa,T.;Fukuda,T.;Yu,H.;Fujiwara,Y.;Higuchi,K.;Inoue,M.;Kobayashi.K.: "Nitric oxide stimulates prostaglandin synthesis in cultured rabbit gastric cells" Prostaglandins. 53:153-162. 153-162 (1997)

[文献書誌] Yu,H.;Sato,EF.;Nagata,K.;Nishikawa,M.;Kashiba,M.;Arakawa,T.;Kobayashi.K.;Inoue.M.: "Oxygen-dependent regulation of the respiration and growth of Escherichia coli by nitric oxide" FEBS Letters. 409:161-165. 161-165 (1997)

[文献書誌] Yamamasu,S.;Sato,EF.;Ogita,S.;Inoue,M.: "Role of glutathione metabolism and apoptosis in the regression of liver hemopoiesis" Free Radical Biol. & Med.23:100-109. 100-109 (1997)

[文献書誌] Kashiba,M.;Miyamoto,M.;Inoue,M.: "Effect of nitric oxide on the ligand binding activity of albumin" Arch.Biochem.Biopjys.345:237-242. 237-242 (1997)

[文献書誌] Morishita,S.;Nishi,Y.;Sato,EF.;Yamaoka,K.Manabe,M.;Inoue,M.: "Cold-stress induces thymocyte apoptosis in the rat" Pathophysiology. 4:213-219. 213-219 (1997)

[文献書誌] Hanada,H.;Kashiwagi,A.Takehara,Y.;Kanno,T.;Yabuki,M.;Sasaki,J.;Inoue.M.;Utsumi.K.: "Do reactive oxygen species underlie the mechanism of apoptosis in the tadpole tail?" Free Radical Biol. & Med. 23:294-301. 294-301 (1997)

[文献書誌] Nishikawa,M.;Sato,EF.;Kuroki,T.;Inoue,M.: "Role glutathione in the energy metabolism of mitochondria" FEBS Letters. 415:341-345. 341-345 (1997)

[文献書誌] Kashiba,M.;Kitoh,K.;Yu,H.;Kasahara,E.;Nishikawa,M.;Matsuo,M.;Inoue,M.: "Ascorbic Acid and reducing agents regulates the fates and functions of S-nitrospthiols" J.Biochem.122:1208-1214. 1208-1214 (1997)

[文献書誌] Minamiyama,Y.;Takemura,S.;Imaoka,S.;Funae,Y.;Tanimoto,Y.;Inoue,M.: "Irreversible inhibition of cytochrome P450 by nitric oxide" J.Phaemacol.Exp.Ther.283:1479-1485. 1479-1485 (1997)

[文献書誌] Yamada,T.;Yukioka,H.;Asada,A.;Inoue,M.: "Effect of inhaled nitric oxide on platelet-activating factor induced pulmonary hypertension in dogs" Acta Anesthesiol. Scand.41. (1997)

[文献書誌] Kashiba-Iwatsuki.M.,Kitoh.K.,Nishikawa.M.,Sato.E.F.Inoue.M.: "Oxygen Homeostasis and its dynamics" Springer-Verlag.Tokyo(Ishimura,Y.,Suematsu,M.,Shimada,H), 7 (1998)

[文献書誌] Utsumi.K.,Takehara.Y.,Inai.Y.Yabuki.M.,Kanno,T.,Nishikawa,M.Sato,EF.,Inoue.M.: "Mitochondria,Oxidants,and Aging" Academic Press (L.Packer Cadenas)(in press), (1998)

1997 年度実績報告書

井上正康大阪市立大学, 医学部, 教授 (80040278)