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The role of cysteine in the regulation of blood glutathione-protein mixed disulfides in rats treated with diamide.
Toxicol Appl Pharmacol. 1998 Jan; 148(1):56-64.TA

Abstract

The kinetics of GSH, GSSG, and thiol-protein mixed disulfides (RS-SP) of GSH (GS-SP) and cysteine (CYS-SP) were studied in rat blood and liver in the time range 0-120 min after treatment with 100 and 200 mg/kg i.p. of diamide. Total consumption (10 min) and regeneration (120 min) of blood GSH, matched by parallel increases and decreases in RS-SP, were observed. GSSG did not change appreciably. No dose-effect relationship was obtained with either treatment. On the contrary, in vitro treatment of blood with 0.75 mM diamide provoked the same trends of GSH and RS-SP as in vivo (e.g., reversible modifications), whereas treatment with 1.5 mM caused drops and rises in GSH and RS-SP, respectively, without any subsequent return to control values. The presence of a hematic factor responsible for RS-SP regulation is hypothesized in the in vivo experiment. Successive experiments involving in vitro pretreatment with 2 mM diamide and treatment with 0.5 mM of various thiols indicated that cysteine (CYS), but not GSH or N-acetylcysteine, rapidly restored erythrocyte GSH and RS-SP to their basal levels. No evident sign of hemolysis was observed in these experiments. These results indicate that CYS is a diffusible thiol important for RS-SP regulation. Analysis of whole blood of rats treated with 100 mg/kg i.p. diamide and the presence of two reversible peaks (about 10 times the corresponding control level) of CYS-SP and free CYS confirmed the plausible role of CYS in maintaining the reversibility of the process. Preliminary results in liver of rats treated with 100 mg/kg diamide indicated that CYS may act by metabolic cooperation between organs. We suggest that CYS may have a role in the regulation of the intracellular redox state of rat erythrocytes during oxidative stress.

Authors+Show Affiliations

Department of Environmental Biology, University of Siena, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9465264

Citation

Di Simplicio, P, et al. "The Role of Cysteine in the Regulation of Blood Glutathione-protein Mixed Disulfides in Rats Treated With Diamide." Toxicology and Applied Pharmacology, vol. 148, no. 1, 1998, pp. 56-64.
Di Simplicio P, Giannerini F, Giustarini D, et al. The role of cysteine in the regulation of blood glutathione-protein mixed disulfides in rats treated with diamide. Toxicol Appl Pharmacol. 1998;148(1):56-64.
Di Simplicio, P., Giannerini, F., Giustarini, D., Lusini, L., & Rossi, R. (1998). The role of cysteine in the regulation of blood glutathione-protein mixed disulfides in rats treated with diamide. Toxicology and Applied Pharmacology, 148(1), 56-64.
Di Simplicio P, et al. The Role of Cysteine in the Regulation of Blood Glutathione-protein Mixed Disulfides in Rats Treated With Diamide. Toxicol Appl Pharmacol. 1998;148(1):56-64. PubMed PMID: 9465264.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of cysteine in the regulation of blood glutathione-protein mixed disulfides in rats treated with diamide. AU - Di Simplicio,P, AU - Giannerini,F, AU - Giustarini,D, AU - Lusini,L, AU - Rossi,R, PY - 1998/2/18/pubmed PY - 1998/2/18/medline PY - 1998/2/18/entrez SP - 56 EP - 64 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 148 IS - 1 N2 - The kinetics of GSH, GSSG, and thiol-protein mixed disulfides (RS-SP) of GSH (GS-SP) and cysteine (CYS-SP) were studied in rat blood and liver in the time range 0-120 min after treatment with 100 and 200 mg/kg i.p. of diamide. Total consumption (10 min) and regeneration (120 min) of blood GSH, matched by parallel increases and decreases in RS-SP, were observed. GSSG did not change appreciably. No dose-effect relationship was obtained with either treatment. On the contrary, in vitro treatment of blood with 0.75 mM diamide provoked the same trends of GSH and RS-SP as in vivo (e.g., reversible modifications), whereas treatment with 1.5 mM caused drops and rises in GSH and RS-SP, respectively, without any subsequent return to control values. The presence of a hematic factor responsible for RS-SP regulation is hypothesized in the in vivo experiment. Successive experiments involving in vitro pretreatment with 2 mM diamide and treatment with 0.5 mM of various thiols indicated that cysteine (CYS), but not GSH or N-acetylcysteine, rapidly restored erythrocyte GSH and RS-SP to their basal levels. No evident sign of hemolysis was observed in these experiments. These results indicate that CYS is a diffusible thiol important for RS-SP regulation. Analysis of whole blood of rats treated with 100 mg/kg i.p. diamide and the presence of two reversible peaks (about 10 times the corresponding control level) of CYS-SP and free CYS confirmed the plausible role of CYS in maintaining the reversibility of the process. Preliminary results in liver of rats treated with 100 mg/kg diamide indicated that CYS may act by metabolic cooperation between organs. We suggest that CYS may have a role in the regulation of the intracellular redox state of rat erythrocytes during oxidative stress. SN - 0041-008X UR - https://www.unboundmedicine.com/medline/citation/9465264/The_role_of_cysteine_in_the_regulation_of_blood_glutathione_protein_mixed_disulfides_in_rats_treated_with_diamide_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(97)98305-8 DB - PRIME DP - Unbound Medicine ER -