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

(1)克隆了酵母谷胱甘肽S-转移酶（GST）的cDNA和大肠杆菌γ-谷氨酰转肽酶（γ-GTP）的基因，并测定了它们的序列。(2)已经鉴定了参与GST-P基因表达的顺式元件及其转录因子。(3)已显示GST-P被SH试剂和过氧化氢灭活。第47位半胱氨酸残基已被确定为其失活的靶氨基酸。(4)对羟甲基芳烃硫酸盐有活性的新GST形式已从大鼠肝脏中纯化，这些形式显示构成GST的第四类。(5)γ-GTP在LEC大鼠肝脏中的表达已被证明依赖于DNA的低甲基化。Arg-107和Blu-108已被鉴定为构成人γ-GTP活性位点的残基。(6)克隆了人血浆谷胱甘肽过氧化物酶的cDNA，并测定了其序列。这种酶对磷脂氢过氧化物有活性。(7)胱抑素 ...更多信息 α被磷酸化，而半胱氨酸蛋白酶抑制剂β与谷胱甘肽形成混合二硫化物，从而失去抑制活性。这些翻译后修饰的建议，发挥重要的作用，在这些胱抑素的细胞内易位。(8)建立了一种抗化学致癌物诱发大鼠肝癌的品系。该菌株在药物代谢酶包括GST和醇脱氢酶中表现出与对照菌株不同的表达模式。(9)在肝脏和肾脏之间的GSH运输中，血管中的GSH在血压调节中起着重要作用。(10)在人白血病K562细胞中，顺式二氨二氯铂（II）与谷胱甘肽结合，该复合物由GS-X结合物依赖性ATP酶（GSSG或GS-X结合物的转运蛋白）转运。(11)胱氨酸转运蛋白在维持巨噬细胞或内皮细胞中GSH水平方面起着关键作用，并且这种转运蛋白活性在应激条件下被诱导。少

(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