The control of S-thiolation by cysteine via gamma-glutamyltranspeptidase and thiol exchanges in erythrocytes and plasma of diamide-treated rats
| Autor: | Lucia Coppo, Paolo Di Simplicio, Simona Frosali, Antonios Margaritis, Raffaella Priora, Jongyun Heo, Domenico Summa, Danila Di Giuseppe |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Erythrocytes Time Factors DTNB Cystine Kidney Toxicology Protein glutathionylation Rats Sprague-Dawley chemistry.chemical_compound Animals Cysteine Sulfhydryl Compounds Enzyme Inhibitors Acivicin Diamide Pharmacology chemistry.chemical_classification biology Sulfhydryl Reagents Isoxazoles gamma-Glutamyltransferase Glutathione Rats Liver chemistry Biochemistry Enzyme inhibitor biology.protein Thiol Oxidation-Reduction |
| Zdroj: | Toxicology and Applied Pharmacology. 242:333-343 |
| ISSN: | 0041-008X |
| Popis: | Protein thiol modifications including cysteinylation (CSSP) and glutathionylation (GSSP) in erythrocytes of rat treated with diamide have been reported, but mechanism and origin of CSSP formation are unknown. Experiments were performed to relate CSSP formation to GSH hydrolysis via gamma-glutamyltranspeptidase (gamma-GT) and know whether cysteine may act as deglutathionylation factor. Time-dependent variations of redox forms of glutathione and cysteine were investigated in erythrocytes, plasma, liver and kidney of diamide-treated rats (0.4 mmol/kg by infusion for 45 min followed by 135 min of washout) in the presence and absence of acivicin (10 mg/kg administered twice 1 h before diamide) a known gamma-GT inhibitor. Diamide-treated rats showed decreased concentrations of erythrocyte GSH and increased levels of GSSP and CSSP. The rate of CSSP formation was slower than that of GSSP. Besides the entity of CSSP accumulation of erythrocytes was high and equivalent to approx 3-fold of the normal plasma content of total cysteine. The result was paradoxically poorly related to gamma-GT activity because the gamma-GT inhibition only partially reduced erythrocyte CSSP. After gamma-GT inhibition, a large concentration fluctuation of glutathione (increased) and cysteine (decreased) was observed in plasma of diamide-treated rats, while little changes were seen in liver and kidney. There weremore » indications from in vitro experiments that the CSSP accumulation in erythrocytes of diamide-treated rats derives from the coexistence of GSH hydrolysis via gamma-GT and production of reduced cysteine via plasma thiol exchanges. Moreover, reduced cysteine was found to be involved in deglutathionylation processes. Mechanisms of protein glutathionylation by diamide and deglutathionylation by cysteine were proposed.« less |
| Databáze: | OpenAIRE |
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