Molecular Mechanism of Defense against Stress and Metabolic Regulation by Glutathione and Its Metabolites

谷胱甘肽及其代谢物抗应激及代谢调节的分子机制

• 批准号: 02304035
• 负责人: KUMAGAI Hidehiko
• 金额: $ 9.73万
• 依托单位: KYOTO UNIVERSITY (1992)Hirosaki University (1990-1991)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Co-operative Research (A)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02304035/
• 关键词: Glutathione; Glutathione S-transferase; Cysteine protease inhibitor; Lipid hydroperoxide; Cell survival; Oxidative stress; Oxido-reduction; Transport system; グルタチオン Sートランスフェラ-ゼ; 酸化還元; グルタチオンSートランスフェラ-ゼ; システィンプロテア-ゼ

(1) A cDNA for glutathione S-transferase (GST) of the yeast and gene for Escherichia coli gamma-glutamyl transpeptidase (gamma-GTP) have been cloned and their sequences have been determined.(2) Cis-elements involved in GST-P gene expression and their transcription factors have been identified.(3) GST-P has been shown to be inactivated by SH-reagents and hydrogen peroxide. The 47th cysteine residue has been identified as the target amino acid in its inactivation.(4) New GST forms active toward hydroxymethylarene sulfate have been purified from rat livers and these forms are shown to constitute the fourth class of GST.(5) Expression of gamma-GTP in LEC rat liver has been shown to be dependent on hypomethylation of DNAs. Arg-107 and Blu-108 have been identified as residues constituting active sites of human gamma-GTP.(6) A cDNA for human plasma glutathione peroxidase has been cloned and its sequence has been determined. This enzyme is active toward phospholipid hydroperoxides.(7) Cystatin … More alpha is phosphorylated while cystatin beta forms mixed disulfide with glutathione to lose the inhibitory activity. These post-translational modifications are suggested to play an important role during the intracellular translocation of these cystatins.(8) A rat strain resistant to hepatocarcinogenesis by chemical carcinogens has been established. This strain has exhibited a different expression pattern in drug-metabolizing enzymes including GST and alcohol dehydrogenase from the control strain.(9) In the tranport of GSH between the liver and kidney, GSH in the blood vessels plays an important role in regulation of blood pressure.(10) In human leukemia K562 cells cis-diamminedichloroplatinum(II) is conjugated to glutathione and the complex is transported by GS-X conjugate-dependent ATPase, a transporter for GSSG or GS-X conjugates.(11) A cystine transporter plays a key role to maintain GSH level in macrophages or endothelial cells, and this transporter activity is induced under stress conditions. Less

(1)克隆了酵母谷胱甘肽S转移酶(Gst)和大肠杆菌γ-谷氨酰转肽酶(Gamma-GTP)基因，并测定了其序列；(2)鉴定了参与GST-P基因表达的顺式元件及其转录因子。(3)GST-P被SH试剂和过氧化氢灭活。47位半胱氨酸残基已被确定为其失活的目标氨基酸。(4)从大鼠肝脏中提纯了对羟甲基亚甲基硫酸盐有活性的新的GST形式，这些形式被证明是第四类GST。(5)LEC大鼠肝脏中γ-GTP的表达依赖于DNA的低甲基化。Arg-107和BLU-108已被鉴定为构成人γ-GTP活性中心的残基。(6)克隆了人血浆谷胱甘肽过氧化物酶的基因，并测定了其序列。该酶对磷脂过氧化氢具有活性。(7)Cystatin…更多的α被磷酸化，而胱抑素β与谷胱甘肽形成混合的二硫化物，从而失去抑制活性。这些翻译后修饰被认为在这些半胱氨酸的细胞内转运过程中发挥了重要作用。(8)建立了一个抵抗化学致癌物诱发肝癌的大鼠品系。该菌株在包括GST和酒精脱氢酶在内的药物代谢酶中表现出与对照菌株不同的表达模式。(9)在肝和肾之间的GSH转运过程中，血管中的GSH在调节血压方面发挥着重要作用。(10)在人白血病K562细胞中，顺式二氯铂(II)与谷胱甘肽结合，该复合体由GS-X结合依赖的ATPase转运，GS-X结合的ATPase是GSSG或GS-X结合的转运体。(11)在巨噬细胞或内皮细胞中，半胱氨酸转运体对维持GSH水平起关键作用，这种转运体活性是在应激条件下诱导的。较少

项目成果

Morimura Shigeru: "Trans-activation of glutathione transferase P gene during chemical hepatocarcinogenesis of the rat" Proceedings of National Academy of Science USA. (1993)

Morimura Shigeru：“大鼠化学性肝癌发生过程中谷胱甘肽转移酶 P 基因的反式激活”美国国家科学院院刊。

Ogura Kenichiro: "Molecular cloning and amino acid sequencing of rat liver class theta glutathione S-transferase Yrs-Yrs inactivating reactive sulfate esters of carcinogenic arylmethanols" Biochemical and Biophysical Research Communications. 181. 1294-130

小仓健一郎：“大鼠肝类 θ 型谷胱甘肽 S 转移酶年灭活致癌芳基甲醇反应性硫酸酯的分子克隆和氨基酸测序”生物化学和生物物理研究通讯。

Takahashi Masae: "Identification of hematoxylin-stainable protein in epidermal keratohyalin granules as phosphorylated cystatin alpha by protein kinase C" FEBS Letters. 287. 178-180 (1991)

Takahashi Masae：“通过蛋白激酶 C 将表皮角质透明蛋白颗粒中的苏木精染色蛋白鉴定为磷酸化半胱氨酸蛋白酶抑制剂 α” FEBS Letters。

Ohno Hideki: "Effects of exercise stress and cold stress on glutathione and γ-glutamyltransferase in rat liver" Biochimica et Biophysica Acta. 1033. 19-22 (1990)

Ohno Hideki：“运动应激和冷应激对大鼠肝脏中谷胱甘肽和 γ-谷氨酰转移酶的影响”Biochimica et Biophysicala Acta。1033. 19-22 (1990)

Takahashi Kazuhiko: "Primary structure of human plasma glutathione peroxidase deduced from cDNA sequences" Journal of Biochemistry. 108. 145-148 (1990)

Takahashi Kazuhiko：“从 cDNA 序列推导出的人血浆谷胱甘肽过氧化物酶的一级结构”《生物化学杂志》。