Disease relevance of Gss

• Kidney and plasma GSH and GSSG were measured 1) in bile duct-ligated (BDL) rats; 2) in healthy rats after bile acid loading to mimic cholestasis; and 3) after irreversible inhibition of glutathione synthetase with buthionine-sulfoximine (BSO), where glutathione consumption, urinary volume, and sodium excretion were also estimated [1].
• In Yoshida AH-130 hepatoma, the gamma-glutamylcysteine synthetase and glutathione synthetase activities are lower in respect to normal liver [2].
• Diabetes or experimental galactosemia of 2 months duration significantly decreased the activities of glutathione reductase and glutathione peroxidase in the retina while having no effect on the glutathione synthesizing enzymes glutathione synthetase and gamma-glutamyl cysteine synthetase [3].
• Nitric oxide synthase expression in hypertension induced by inhibition of glutathione synthase [4].

High impact information on Gss

• The effects of H(2)O(2) were completely inhibited by dialysis of the cell interior with reduced glutathione, and were markedly enhanced by inhibition of glutathione synthase [5].
• Amino acid sequence of rat kidney glutathione synthetase [6].
• The cDNA encoding rat kidney GSH synthetase was isolated from a rat kidney lambda gt11 cDNA library by immunoscreening with an antibody prepared against the isolated enzyme [6].
• In examining possible mechanisms for increased liver GSH, both cysteine level and gamma-glutamylcysteine synthetase (GCS) activity were significantly higher than controls, while the activity of GSH synthetase was unchanged [7].
• Role of AP-1 in the coordinate induction of rat glutamate-cysteine ligase and glutathione synthetase by tert-butylhydroquinone [8].

Chemical compound and disease context of Gss

• In this paper the in vitro activities of two enzymes involved in glutathione synthesis, gamma-glutamylcysteine synthetase and glutathione synthetase, are studied in normal adult rat liver, in regenerating rat liver and in highly anaplastic Yoshida AH-130 hepatoma cells [2].

Biological context of Gss

• Glutathione synthetase. Purification from rat kidney and mapping of the substrate binding sites [9].
• GSH-depleted hepatocytes were incubated with gamma-glutamylcysteinylethyl ester (gamma-ECOEt), which is known to be converted to GSH via glutathione synthetase after its hydrolysis by esterase, at concentrations of 1.0 to 10 mM in order to replenish intracellular GSH [10].
• I/R induced myocardial lipid peroxidation and lactate dehydrogenase release were attenuated with T/GSH-S treatment [11].
• Novel kinetics of mammalian glutathione synthetase: characterization of gamma-glutamyl substrate cooperative binding [12].
• The downregulated genes included glutathione synthetase, lecithin-cholesterol acyltransferase, p55CDC, heart fatty acid binding protein, cell adhesion regulator and endothelial cell selectin ligand [13].

Anatomical context of Gss

• The capacity to synthesize GSH de novo determined in cell-free extracts incubated with GSH precursors was greater (50-70%) in hepatocytes that were treated with TNF; however, the activity of GSH synthetase remained unaltered by TNF treatment indicating that TNF selectively increased the activity of gamma-GCS [14].
• 4. At Vj > 60 mV, Gss was virtually zero, a property that is unique among the gap junctions characterized to date [15].
• METHODS: Buthionine sulfoximine (BSO), an inhibitor of glutathione synthase, was administered to Sprague-Dawley rats and 3T3-L1 adipocytes [16].
• The glutathione synthase inhibitor L-buthionine-(S,R)-sulfoximine markedly decreased the MTP and increased lactate dehydrogenase (LDH) releases in SIN-1-treated astrocytes [17].

Associations of Gss with chemical compounds

• One repressor identified was NF1. tert-Butylhydroquinone (TBH) exerted a dose- and time-dependent increase in the mRNA level and promoter activity of both GCL subunits and GS [8].
• This can be mediated by conjugation with glutathione, which is synthesized by the sequential actions of glutamate-cysteine ligase (GLCL) and glutathione synthetase [18].
• Glutathione synthetase was induced approximately 1.5-fold by coumarin, alpha-angelicalactone, ellagic acid and ethoxyquin [18].
• The glutathione synthetase inhibitor, buthionine sulfoximine, increased SDZ IMM125-mediated caspase-3 action in parallel to chromatin condensation and fragmentation as well as Ca(2+) influx [19].
• There did not appear to be a relationship between the protection by glycine and glutathione concentration of the hepatocytes as shown by the lack of effect of a glutathione synthetase inhibitor (butathionine sulfoximine) on the protective effects of glycine [20].

Other interactions of Gss

• In the liver, activities of the following enzymes were elevated: gamma-glutamylcysteine synthetase, GSH synthetase, gamma-glutamyl transpeptidase, dipeptidase, and microsomal GSH transferase [21].
• Myocardial superoxide dismutase, GSH peroxidase, glutathione reductase, and gamma-glutamyl transpeptidase activities were increased with treadmill training in both GSH-S and C rats [11].
• Buthionine sulfoximine, an inhibitor of glutathione synthase, did not affect the action of MMC. tert-Butylhydroquinone induced DT-diaphorase activity, increased PFM uptake, and enhanced the growth-inhibitory action of MMC in AH130/5A cells [22].

Analytical, diagnostic and therapeutic context of Gss

• Knowledge of this amino acid sequence is expected to facilitate elucidation of the sequence of the corresponding human enzyme and to lead to studies on the biochemical mechanisms involved in human GSH synthetase deficiency as well as to development of improved methods for prenatal diagnosis of these inborn diseases [6].
• Setaria cervi: kinetic studies of filarial glutathione synthetase by high performance liquid chromatography [23].

References