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

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(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