The Mechanism of Cyanohydroxybutene Induced Glutathione Elevation: The Role of Gamma-Glutamylcysteine Synthetase

Cyanohydroxybutene (CHB; 200 mg/kg po) causes a 2- and 7-fold elevation in glutathione (GSH) in liver and pancreas, respectively. The mechanism of elevation is currently unknown. In an attempt to identify the mechanism of this GSH induction, the effect of CHB on hepatic and pancreatic γ-glutamylcysteine synthetase (GCS) activity, formation in vitro of a glutathione-S-transferase (GST) catalyzed adduct, the effect of CHB on hepatic and pancreatic cysteine equivalents (cysteine, cystine, and cysteinylglycine), and the acute effect of CHB on expression of the hepatic mRNA for γ-glutamylcysteine synthetase (GCS) were investigated. The results of these studies suggest that the mechanism of CHB-mediated induction of GSH involves an increase in GCS mRNA producing an increase in GCS enzyme and thereby increasing GSH synthesis. This mechanism and the subsequent GSH elevation may have possible therapeutic and prophylactic implications.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Veterinary Medical Science

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2014

Author dc:creator

• Davis, Myrtle A.

Contributors dc:contributor

• Jeffery, E.,

• Health Sciences, Toxicology
• Biology, Veterinary Science

Identifier

(UMI)AAI9305502

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/72554