The control of S-thiolation by cysteine via gamma-glutamyltranspeptidase and thiol exchanges in erythrocytes and plasma of diamide-treated rats

Journal Article · Mon Feb 01 00:00:00 EST 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.11.003· OSTI ID:21344856

Priora, Raffaella; Coppo, Lucia; Margaritis, Antonios; Di Giuseppe, Danila; Frosali, Simona; Summa, Domenico ^[1]; Heo, Jongyun ^[2]

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1. Department of Neuroscience, Pharmacology Unit, University of Siena, Via A. Moro no. 4, 53100 Siena (Italy)
2. Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington TX 76019 (United States)

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 were 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.

• OSTI ID: 21344856
• Journal Information: Toxicology and Applied Pharmacology, Vol. 242, Issue 3; Other Information: DOI: 10.1016/j.taap.2009.11.003; PII: S0041-008X(09)00469-4; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
CHLORINATED ALIPHATIC HYDROCARBONS
CYSTEINE
CYSTINE
ERYTHROCYTES
GLUTATHIONE
HEMOGLOBIN
KIDNEYS
LIVER
RATS
TIME DEPENDENCE
AMINO ACIDS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARBOXYLIC ACIDS
DIGESTIVE SYSTEM
DISULFIDES
DRUGS
GLANDS
GLOBINS
HALOGENATED ALIPHATIC HYDROCARBONS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
MAMMALS
MATERIALS
ORGANIC ACIDS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PEPTIDES
PIGMENTS
POLYPEPTIDES
PORPHYRINS
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESPONSE MODIFYING FACTORS
RODENTS
THIOLS
VERTEBRATES