JPET xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Madhu, C.
Right arrow Articles by Klaassen, C. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Madhu, C.
Right arrow Articles by Klaassen, C. D.

Identification of the mixed disulfide of glutathione and cysteinylglycine in bile: dependence on gamma-glutamyl transferase and responsiveness to oxidative stress

C Madhu, Z Gregus, CC Cheng and CD Klaassen

Environmental Health and Occupational Medicine Center, University of Kansas Medical Center, Kansas City.

Biliary excretion of glutathione disulfide (GSSG) is used as an index of oxidative stress. Analysis of endogenous thiols and disulfides in rat bile by reverse phase high performance liquid chromatography with electrochemical detection revealed an unknown disulfide which eluted immediately after GSSG. This disulfide was tentatively identified as the mixed disulfide of glutathione (GSH) and cysteinylglycine (Cys- Gly), based on its coelution on a reverse phase column with the synthetic GS-Cys-Gly. GS-Cys-Gly was also detected in bile of other species. On analyzing species differences in biliary excretion of GSH- related thiols and disulfides, it was concluded that biliary excretion of GS-Cys-Gly was related to the excretion of both GSSG and Cys-Gly, which is formed from GSH by gamma-glutamyltransferase (gamma-GT)- catalyzed hydrolysis. Species with low hepatic gamma-GT (i.e., hamsters and mice) excreted little Cys-Gly in bile. These animals excreted negligible amounts of GS-Cys-Gly even when biliary excretion of GSSG was markedly increased by paraquat-induced oxidative stress. Rats and guinea pigs, which have high hepatic gamma-GT activities, excreted large amounts of both Cys-Gly and GS-Cys-Gly. Treatment of rats with acivicin, an inhibitor of gamma-GT, decreased the biliary excretion of both Cys-Gly and GS-Cys-Gly. Paraquat treatment of rats resulted in an increase in GSSG excretion with concomitant increase of GS-Cys-Gly excretion. Rabbits, which also have high hepatic gamma-GT activity, excreted little GS-Cys-Gly into bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 262, Issue 3, pp. 896-900, 09/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. G. Knickelbein, T. Seres, G. Lam, R. B. Johnston Jr., and J. B. Warshaw
Characterization of multiple cysteine and cystine transporters in rat alveolar type II cells
Am J Physiol Lung Cell Mol Physiol, December 1, 1997; 273(6): L1147 - L1155.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1992 by the American Society for Pharmacology and Experimental Therapeutics.