Mechanism of glutathione-mediated regulation of nitrative signal in cells

• Project/Area Number: 19590253
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Kumamoto University
• Principal Investigator: FUJII Shigemoto Kumamoto University, 大学院・医学薬学研究部, 助教 (00325333)
• Co-Investigator(Kenkyū-buntansha): AKAIKE Takaaki 熊本大学, 大学院・医学薬学研究部, 教授 (20231798)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 一酸化窒素 / 活性酸素 / 酸化ストレス / グルタチオン / ニトロ化 / サイクリックGMP / 8-ニトロcGMP / S-グアニル化

Research Abstract

活性酸素や一酸化窒素によってもたらされる酸化ストレスは、様々な細胞機能変化をもたらす。その機序の一つである細胞内ニトロ化シグナルについて、グルタチオンによる制御機構に焦点をあて解析を行った。その結果、グルタチオンは、ニトロ化シグナルを担う8-ニトロcGMPの生成とこの分子による蛋白質の翻訳後修飾を調節し、ヘムオキシゲナーゼ-1などの抗酸化蛋白質の発現を介した酸化ストレスに対する適応反応の制御に関与していることが示唆された。

Research Products

• [Journal Article] Cytoprotective function of heme oxygenase1 induced by a nitrated cyclic nucleotide formed during murine salmonellosis (2009)
  • Author(s): Zaki MH, Fujii S, Okamoto T, Islam S, Khan S, Ahmed KA, Sawa T, and Akaike T.
  • Journal Title: JImmunol 182 Pages: 3746-56
  • Peer Reviewed
• [Journal Article] NOによる細胞内感染防御の新しい展開 (2009)
  • Author(s): 赤池孝章、岡本竜哉、Zaki MH、藤井重元、澤智裕
  • Journal Title: 日本ハンセン病学会雑誌 78 Pages: 41-47
  • NAID: 10024786455
• [Journal Article] 活性酸素・NOによる感染防御シグナルの新展開 (2009)
  • Author(s): 岡本竜哉, 澤智裕, 藤井重元, 赤池孝章
  • Journal Title: 細胞 41 Pages: 51-55
• [Journal Article] Cytoprotective function of heme oxygenase 1 induced by a nitrated cyclic nucleotide formed during murine salmonellosis. (2009)
  • Author(s): Zaki, et al
  • Journal Title: J Immunol 182 Pages: 3746-3756
  • Peer Reviewed
• [Journal Article] 8-Nitroguanosines as chemical probes of the protein S-guanylation (2008)
  • Author(s): Saito Y, Taguchi H, Fujii S, Sawa T, Kida E, Kabuto C, Akaike T, Arimoto T.
  • Journal Title: Chem Commun Pages: 5984-5986
  • Peer Reviewed
• [Journal Article] S-nitrosylated human serum albumin-mediated cytoprotective activity is enhanced by fatty acid binding (2008)
  • Author(s): Ishima Y, Akaike T, Kragh-Hansen U, Hiroyama S, Sawa T, Suenaga A, Maruyama T, and Otagiri M.
  • Journal Title: J Biol Chem 283 Pages: 34966-34975
  • Peer Reviewed
• [Journal Article] Nitric oxide regulation of MMP-9 activation and its relationship to modifications of the cysteine switch (2008)
  • Author(s): McCarthy SM, Bove PF, Matthews DE, Akaike T, and van der Vliet A.
  • Journal Title: Biochemistry 47 Pages: 5832-5840
  • Peer Reviewed
• [Journal Article] Suppression of NO production and 8-nitroguanosine formation byphenol-containing endocrine-disrupting chemicals in LPS-stimulated macrophages : Involvement of estrogen receptor-dependent or -independent pathways (2008)
  • Author(s): Yoshitake J, Kato K, Yoshioka D, Sueishi Y, Sawa T, Akaike T, and Yoshimura T.
  • Journal Title: Nitric Oxide 18 Pages: 223-228
  • Peer Reviewed
• [Journal Article] Angiopoietin-related growth factor enhances blood flow via activation of the ERK1/2-eNOS-NO pathway in a mouse hind-limb ischemia model (2008)
  • Author(s): Urano T, Ito Y, Akao M, Sawa T, Miyata K, Tabata M, Morisada T, Hato T, Yano M, Kadomatsu T, Yasunaga K, Shibata R, Murohara T, Akaike T, Tanihara H, Suda T, and Oike Y.
  • Journal Title: Arterioscler Thromb Vasc Biol. 28 Pages: 827-834
  • Peer Reviewed
• [Journal Article] Nitric oxide produced in Peyer's patches exhibits antiapoptotic activity contributing to an antimicrobial effect in murine salmonellosis (2008)
  • Author(s): Alam MS, Zaki MH, Sawa T, Islam S, Ahmed KA, Fujii S, Okamoto T, and Akaike T.
  • Journal Title: Microbiol Immunol 52 Pages: 197-208
  • NAID: 10025691687
  • Peer Reviewed
• [Journal Article] Mutagenicity of 8-nitroguanosine, a product of nitrative nucleoside modification by reactive nitrogen oxides in mammalian cells (2008)
  • Author(s): Kaneko K, Akuta T, Sawa T, Kim HW, Fujii S, Okamoto T, Nakayama H, Ohigashi H, Murakami A, and Akaike T.
  • Journal Title: Cancer Lett 262 Pages: 239-47
  • Peer Reviewed
• [Journal Article] 肺の感染炎症病態におけるニトロ化ストレスとそのバイオマーカー (2008)
  • Author(s): 岡本竜哉, 赤池孝章
  • Journal Title: 医学のあゆみ 224 Pages: 851-6
• [Journal Article] 感染病態におけるNO・活性酸素のシグナル伝達機能 : 酸化ストレスとその適応応答の分子メカニズム (2008)
  • Author(s): 岡本竜哉, 藤井重元, 澤智裕, 赤池孝章
  • Journal Title: Allergy From the Nose to the Lung 6 Pages: 12-7
• [Journal Article] 活性酸素を消去する物質8-ニトロcGMP (2008)
  • Author(s): 澤智裕、赤池孝章
  • Journal Title: 検査と技術 36 Pages: 678-679
• [Journal Article] Nitric oxide produced in Peyer's patches exhibits antiapoptotic activity contributing to an antimicrobial effect in murine salmonellosis. (2008)
  • Author(s): Alam, et al
  • Journal Title: Microbiol Immunol 52 Pages: 197-208
  • Peer Reviewed
• [Journal Article] Mutagenicity of 8-nitroguanosine, a product of nitrative nucleoside modification by reactive nitrogen oxides, in mammalian cells. (2008)
  • Author(s): Kaneko, et al
  • Journal Title: Cancer Lett 262 Pages: 239-247
  • Peer Reviewed
• [Journal Article] 8-Nitroguanosines as chemical probes of the protein S-guanylation. (2008)
  • Author(s): Saito, et al
  • Journal Title: Chem Commun Pages: 5984-5986
  • Peer Reviewed
• [Journal Article] Mutagenicity of 8-nitroguanosine, a product of nitrative nucleotide modification by reactive nitrogen oxides, in mammalian cells. (2008)
  • Author(s): Kaneko, et. al.
  • Journal Title: Cancer Lett 262 Pages: 239-247
  • Peer Reviewed
• [Journal Article] Nitric oxide produced in Peyer's patches exhibits antiapoptotic activity contributing to an antimicrobial effect in murine salmonellosis. (2008)
  • Author(s): Alam, et. al.
  • Journal Title: Microbiol Immunol (In press)
  • Peer Reviewed
• [Journal Article] Effect of Endogenous ligands on the biological role of human serum albumin in S-nitrosylation (2007)
  • Author(s): Ishima Y, Akaike T, Kragh-Hansen U, Hiroyama S, Sawa T, Maruyama T, Kai T, and Otagiri M.
  • Journal Title: Biochem Biophys Res Commun 364 Pages: 790-795
  • Peer Reviewed
• [Journal Article] Protein S-guanylation by the biological signal 8-nitroguanosine 3', 5'-cyclic monophosphate (2007)
  • Author(s): Sawa T, Zaki MH, Okamoto T, Akuta T, Tokutomi Y, Kim-Mitsuyama S, Ihara H, Kobayashi A, Yamamoto M, Fujii S, Arimoto H, and Akaike T.
  • Journal Title: Nature Chem Biol 3 Pages: 727-35
  • NAID: 120002467822
  • Peer Reviewed
• [Journal Article] Albuminuria, expression of nitotinamide adenine dinucleotide phosphate oxidase and monocyte chemoattractant protein-1 in therenal tubules of hypertensive Dahl salt-sensitive rats (2007)
  • Author(s): Fujii S, Zhang L, and Kosaka H.
  • Journal Title: Hypertens Res. 30 Pages: 991-8
  • Peer Reviewed
• [Journal Article] Nitrative stress in respiratory inflammation caused by influenza virusinfection (2007)
  • Author(s): Zaki MH, Okamoto T, Sawa T, Fujii S, and Akaike T.
  • Journal Title: Clin Exp Allergy Rev 7 Pages: 19-26
  • Peer Reviewed
• [Journal Article] Protein S-guanylation by the biological signal 8-nitroguanosin 3',5'-cyclic monophosphate. (2007)
  • Author(s): Sawa T., et. al.
  • Journal Title: Nature Chemical Biology 3 Pages: 727-735
  • Peer Reviewed
• [Journal Article] Nitrative stress in respiratory inflammation caused by influenza virus infection. (2007)
  • Author(s): Zaki M. H., et. al.
  • Journal Title: Clinical and Experimental Allergy Reviews 7 Pages: 19-26
• [Presentation] サルモネラ感染におけるニトロ化環状ヌクレオチドを介する生体防御機構 (2009)
  • Author(s): 藤井重元
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2009-03-12
• [Presentation] サルモネラ感染におけるニトロ化環状ヌクレオチドを介する生体防御機構 (2009)
  • Author(s): 藤井重元、岡本竜哉、澤智裕、赤池孝章
  • Organizer: 第82回日本細菌学会総会
  • Place of Presentation: 名古屋市
• [Presentation] 新規環状ヌクレオチド8-ニトログアノシン-3', 5'-環状1リン酸による転写制御因子Keap1のs-グアニル化とその酸化ストレス応答における役割 (2008)
  • Author(s): 藤井重元
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-10
• [Presentation] Keap1のS-グアニル化を介する環状ヌクレオチド8-ニトログアノシン-3', 5'-環状1リン酸のシグナル伝達機序 (2008)
  • Author(s): 藤井重元
  • Organizer: 第61回日本酸化ストレス学会学術集会
  • Place of Presentation: 国立京都国際会館アネックスホール
  • Year and Date: 2008-06-20
• [Presentation] 新規環状ヌクレオチド8-ニトログアノシン-3', 5'-環状1リン酸による転写制御因子Keap1のS-グアニル化とそのシグナル伝達機構 (2008)
  • Author(s): 藤井重元
  • Organizer: 第8回日本NO学会学術集会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2008-05-10
• [Presentation] 新規環状ヌクレオチド8-ニトログアノシン3', 5'-環状1リン酸による転写制御因子Keap1のS-グアニル化とその酸化ストレス応答における役割 (2008)
  • Author(s): 藤井重元、澤智裕、岡本竜哉、居原秀、本橋ほづみ、山本雅之、赤池孝章
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸市
• [Presentation] サルモネラ感染病態における8-ニトログアノシン3', 5'-環状1リン酸を介したNO誘導性生体防御機構 (2008)
  • Author(s): 藤井重元、Md. H. Zaki、岡本竜哉、澤智裕、赤池孝章
  • Organizer: 第61回日本細菌学会九州支部総会
  • Place of Presentation: 熊本市
• [Presentation] Signal transduction by 8-nitro-cGMP via its unique redox property and post-translational modification (2008)
  • Author(s): Akaike T, and Sawa T.
  • Organizer: A Joint Conference of 13th In Vivo EPR Spectroscopy and Imaging and 10th International EPR Spin Trapping/Spin Labeling
  • Place of Presentation: 福岡市
• [Presentation] Protein S-guanylation induced by 8-nitro-cGMP (2008)
  • Author(s): Akaike T.
  • Organizer: 5^<th> Internal conference on biology, chemistry and therapeutic applications of NO
  • Place of Presentation: Bregenz, Austria
• [Presentation] Physiological role of Keap1 S-guanylation by 8-nitroguanosine 3', 5'-cyclic moophosphate formed in C6 glioma cells (2008)
  • Author(s): Fujii S, Sawa T, Okamoto T, Ihara H, Motohashi H, Yamamoto M, and Akaike T.
  • Organizer: 5^<th> Internal conference on biology, chemistry and therapeutic applications of NO
  • Place of Presentation: Bregenz, Austria
• [Presentation] Keap1のS-グアニル化を介する環状ヌクレオチド8-ニトログアノシン3', 5'-環状1リン酸のシグナル伝達機序 (2008)
  • Author(s): 藤井重元、澤智裕、岡本竜哉、居原秀、小林聡、山本雅之、赤池孝章
  • Organizer: 第61回日本酸化ストレス学会学術集会
  • Place of Presentation: 京都市
• [Presentation] 新規環状ヌクレオチド8-ニトログアノシン3', 5'-環状1リン酸による転写制御因子Keap1のS-グアニル化とそのシグナル伝達機構 (2008)
  • Author(s): 藤井重元、澤智裕、岡本竜哉、居原秀、小林聡、山本雅之、赤池孝章
  • Organizer: 第8回日本NO学会学術集会
  • Place of Presentation: 仙台市
• [Presentation] Physiological role of Keap 1 S-guanylation by 8-nitroguanosine 3', 5'-cyclic monophosphate formed in C6 glioma cells (2008)
  • Author(s): Shigemoto Fujii
  • Organizer: 5th International Conference : □ Biology, Chemistry and Therapeutic □ Applieations of Nitric Oxide
  • Place of Presentation: Bregenz, Austria
• [Presentation] 新規環状ヌクレオチド8-ニトログアノシン-3',5'-環状1リン酸による転写制御因子Keap1のS-グアニル化とその生理作用 (2007)
  • Author(s): 藤井 重元
  • Organizer: 第29回日本フリーラジカル学会学術集会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2007-06-10
• [Presentation] 転写制御因子Keap1のS-グアニル化を介した新規環状ヌクレオチド8-ニトログアノシン-3',5'-環状1リン酸による細胞保護作用 (2007)
  • Author(s): 藤井 重元
  • Organizer: 第7回日本NO学会学術集会
  • Place of Presentation: 滋賀県大津市ピアザ淡海
  • Year and Date: 2007-05-17
• [Presentation] A new second messenger, 8-nitroguanosine 3', 5'-cyclic monophosphate involved in NO-induced signal transduction via a unique post-translational modification, protein S-guanylation (2007)
  • Author(s): Akaike T. Sawa T, Fujii S, Okamoto T, Ihara H, and Arimoto H.
  • Organizer: 4th Joint Meeting of the Society for Free Radical Research, Australasia and Japan
  • Place of Presentation: 京都市
• [Presentation] 新規環状ヌクレオチド8-ニトログアノシン3', 5'-環状1リン酸による転写制御因子Keap1のS-グアニル化とその生理作用 (2007)
  • Author(s): 藤井重元、澤智裕、Mohammad Hasan Zaki、赤池孝章
  • Organizer: 第29回日本フリーラジカル学会学術集
  • Place of Presentation: 名古屋市
• [Presentation] 転写制御因子Keap1のS-グアニル化を介した新規環状ヌクレオチド8-ニトログアノシン3', 5'-環状1リン酸による細胞保護作用 (2007)
  • Author(s): 藤井重元、澤智裕、岡本竜哉、HASAN ZAKI MUHAMMAD、赤池孝章
  • Organizer: 第7回日本NO学会学術集会
  • Place of Presentation: 大津市
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