2000 Fiscal Year Annual Research Report

グルタチオンによるレドックス制御と活性酸素および活性窒素種の役割

Research Project

Project/Area Number	10044286
Research Institution	Osaka University
Principal Investigator	谷口直之大阪大学, 医学系研究科, 教授 (90002188)
Co-Investigator(Kenkyū-buntansha)	東山繁樹大阪大学, 医学部, 助教授 (60202272) 鈴木敬一郎兵庫医科大学, 教授 (70221322) 藤井順逸山形大学, 医学部, 教授 (00222258) 高橋素子大阪大学, 医学系研究科, 助手 (00303941) 鄭文玉大阪大学, 医学系研究科, 助手 (60252657)
Keywords	活性酸素 / グルタチオン / 一酸化窒素 / セルロプラスミン / チオレドキシン / ペルオキシレドキシン / NO合成酵素
Research Abstract	活性酸素は、老化や癌をはじめとする様々な疾患に関わっていることはよく知られている。過剰に産生された活性酸素は生体にとって有害で、様々な障害をおこすことがよく知られている。しかし近年、生体は微量ではあるが積極的に活性酸素や活性窒素種を生合成し、増殖因子をはじめとした様々な細胞外ならびに細胞内の情報伝達因子としても利用していることが明らかになってきている。本研究計画では国内外の第一線の研究者を組織して活性酸素の生成とその消去に関わる酵素系のコントロールやこうしたレドックスシグナルがどのようにして伝わり遺伝子の転写制御に関わるか、そしてその結果もたらされる細胞の分化、増殖、死の機構などを明らかにした。具体的には以下の事項について明らかにした。 1)グルタチオンペルオキシダーゼが還元糖やジカルボニル化合物によって不活性化されるメカニズム 2)ペルオキシレドキシンファミリーの生理的役割の解明:新しい細胞外の抗酸化作用を示す物質としてペルオキシレドキシンIVの精製クローニングならびに生理的役割 3)活性酸素代謝の面で重要な働きを行うフェロキシダーゼ活性を持つセルロプラスミンと殺菌に重要なミエロペルオキシダーゼとの結合と相互作用 4)活性酸素による細胞表面glycocalyx修飾を介した細胞接着亢進メカニズム 5)グルタチオン、ならびにグルタチオンペルオキシダーゼ、γ-GCSの各酵素の酸化ストレスに対する防御作用の生理的役割の解析 6)酸化ストレスによって誘導される細胞保護因子であるヘパリン結合性EGF様増殖因子の誘導経路とメカニズムおよびアポトーシス耐性のメカニズムまた本研究グループが中心となって活性酸素ならびに活性窒素、グルタチオンなどについての英文実験マニュアルの出版も行った。

Research Products

(19 results)

All Other

All Publications (19 results)

[Publications] Fujii,J. et al.: "A defect in the mitochondrial import of mutant Mn-superoxide dismutase produced in Sf21 cells."J.Biochem.. 124. 340-346 (1998)
[Publications] Meng,J. et al.: "Glycoxidation in aortic collagen from ATZ-incuced diabetic rats and its relevance to vascular dasmage."Atherosclerosis. 136. 355-365 (1998)
[Publications] Suzuki,K. et al.: "Overexpression of aldehyde reductase protects PC12 cells from the cytotoxicity of methylglyoxal or 3-deoxyglucosone.,"J.Biochem.. 123. 354-358 (1998)
[Publications] Chen,ZS. et al.: "An active efflux system for heavy metals in cisplatin-resistant human KB carcinoma cells."Exp Cell Res.. 240. 312-320 (1998)
[Publications] Ookawara,T. et al.: "Tissue distribution of immunoreactive mouse extracellular superoxide dismutase."Am J Physiol.. 275(3P+1). C840-C847 (1998)
[Publications] Fujiwara,N. et al.: "Functional expression of rat thioredoxin reductase : selenocy insertion sequence element is essential for the active enzyme."Biochem.J.. 340. 439-444 (1999)
[Publications] Park,Y.S. et al.: "Glutathione Peroxidase-like activity of caeruloplasmin as an important lung antioxidant."FEBS Lett.. 458. 133-136 (1999)
[Publications] Iida,T. et al.: "Co-expression of gamma-glutamylcysteine synthetase sub-units in response to cisplatin and doxorubicin in human cancer cells."Int J Cancer. 82. 405-411 (1999)
[Publications] Sakamaki,H. et al.: "Significance of glutathione-dependent antioxidant system in diabetes-induced embryonic malformations."Diabetes.. 48. 1138-1144 (1999)
[Publications] Beutler,E. et al.: "The molecular basis of a case of gamma-glutamylcysteine synthetase deficiency."Blood.. 94. 2890-2894 (1999)
[Publications] Ihara,Y. et al.: "Calnexin discriminates between protein conformational states and functions as a molecular chaperone in vitro."Mol Cell.. 4. 331-341 (1999)
[Publications] Hollander,J. et al.: "Superoxide dismutase gene expression in skeletal muscle : fiber-specific adaptation to endurance training."Am J Physiol.. 277(3P+2). R856-R862 (1999)
[Publications] Okado-Matsumoto,A. et al.: "Peroxiredoxin IV is a secretable protein with heparin-binding properties under reduced conditions."J.Biochem.. 127. 493-501 (2000)
[Publications] Fujii,T. et al.: "Redox capacity of cells affects inactivation of glutathione reductase by nitrosative stress."Archives of Biochemistry and Biophysics. 378. 123-130 (2000)
[Publications] Fujii,T. et al.: "Augmented expression of peroxiredoxinVI in rat lung and kidney after birth implies an antioxidative role."Eur.J.Biochem.. 268. 218-224 (2001)
[Publications] Koh,YH. et al.: "Inactivation of glutathione peroxidase by NO leads to the accumulation of H2O2 and the induction of HB-EGF via c-Jun NH2-terminal kinase in rat aortic smooth muscle cells."FASEB J.. (in press). (2001)
[Publications] Radak,Z. et al.: "Regular training modulates the accumulation of reactive carbonyl derivatives in mitochondrial and cytosolic fractions of rat skeletal muscle."Arch Biochem Biophys.. 383. 114-118 (2000)
[Publications] Taniguchi,N.and Gutteridge,J.M.C.: "Experimental protocols for reactive oxygen and nitrogen species."Oxford Univ.Press. 337 (2000)
[Publications] Suzuki,K. et al.: "Superoxide dismutases in exercise and disease. In : Handbook of Oxidants and Antioxidants in Exercise."Elsevier. (2000)

2000 Fiscal Year Annual Research Report

グルタチオンによるレドックス制御と活性酸素および活性窒素種の役割

Principal Investigator

谷口 直之 大阪大学, 医学系研究科, 教授 (90002188)

Research Products

[Publications] Fujii,J. et al.: "A defect in the mitochondrial import of mutant Mn-superoxide dismutase produced in Sf21 cells."J.Biochem.. 124. 340-346 (1998)

[Publications] Meng,J. et al.: "Glycoxidation in aortic collagen from ATZ-incuced diabetic rats and its relevance to vascular dasmage."Atherosclerosis. 136. 355-365 (1998)

[Publications] Suzuki,K. et al.: "Overexpression of aldehyde reductase protects PC12 cells from the cytotoxicity of methylglyoxal or 3-deoxyglucosone.,"J.Biochem.. 123. 354-358 (1998)

[Publications] Chen,ZS. et al.: "An active efflux system for heavy metals in cisplatin-resistant human KB carcinoma cells."Exp Cell Res.. 240. 312-320 (1998)

[Publications] Ookawara,T. et al.: "Tissue distribution of immunoreactive mouse extracellular superoxide dismutase."Am J Physiol.. 275(3P+1). C840-C847 (1998)

[Publications] Fujiwara,N. et al.: "Functional expression of rat thioredoxin reductase : selenocy insertion sequence element is essential for the active enzyme."Biochem.J.. 340. 439-444 (1999)

[Publications] Park,Y.S. et al.: "Glutathione Peroxidase-like activity of caeruloplasmin as an important lung antioxidant."FEBS Lett.. 458. 133-136 (1999)

[Publications] Iida,T. et al.: "Co-expression of gamma-glutamylcysteine synthetase sub-units in response to cisplatin and doxorubicin in human cancer cells."Int J Cancer. 82. 405-411 (1999)

[Publications] Sakamaki,H. et al.: "Significance of glutathione-dependent antioxidant system in diabetes-induced embryonic malformations."Diabetes.. 48. 1138-1144 (1999)

[Publications] Beutler,E. et al.: "The molecular basis of a case of gamma-glutamylcysteine synthetase deficiency."Blood.. 94. 2890-2894 (1999)

[Publications] Ihara,Y. et al.: "Calnexin discriminates between protein conformational states and functions as a molecular chaperone in vitro."Mol Cell.. 4. 331-341 (1999)

[Publications] Hollander,J. et al.: "Superoxide dismutase gene expression in skeletal muscle : fiber-specific adaptation to endurance training."Am J Physiol.. 277(3P+2). R856-R862 (1999)

[Publications] Okado-Matsumoto,A. et al.: "Peroxiredoxin IV is a secretable protein with heparin-binding properties under reduced conditions."J.Biochem.. 127. 493-501 (2000)

[Publications] Fujii,T. et al.: "Redox capacity of cells affects inactivation of glutathione reductase by nitrosative stress."Archives of Biochemistry and Biophysics. 378. 123-130 (2000)

[Publications] Fujii,T. et al.: "Augmented expression of peroxiredoxinVI in rat lung and kidney after birth implies an antioxidative role."Eur.J.Biochem.. 268. 218-224 (2001)

[Publications] Koh,YH. et al.: "Inactivation of glutathione peroxidase by NO leads to the accumulation of H2O2 and the induction of HB-EGF via c-Jun NH2-terminal kinase in rat aortic smooth muscle cells."FASEB J.. (in press). (2001)

[Publications] Radak,Z. et al.: "Regular training modulates the accumulation of reactive carbonyl derivatives in mitochondrial and cytosolic fractions of rat skeletal muscle."Arch Biochem Biophys.. 383. 114-118 (2000)

[Publications] Taniguchi,N.and Gutteridge,J.M.C.: "Experimental protocols for reactive oxygen and nitrogen species."Oxford Univ.Press. 337 (2000)

[Publications] Suzuki,K. et al.: "Superoxide dismutases in exercise and disease. In : Handbook of Oxidants and Antioxidants in Exercise."Elsevier. (2000)

谷口直之大阪大学, 医学系研究科, 教授 (90002188)