Title: Modulating GSH synthesis using glutamate cysteine ligase transgenic and gene-targeted mice.
Authors: Botta, Dianne; White, Collin C; Vliet-Gregg, Portia; Mohar, Isaac; Shi, Shengli; McGrath, Monica B; McConnachie, Lisa A; Kavanagh, Terrance J
Published In Drug Metab Rev, (2008)
Abstract: Glutathione (GSH) is an important antioxidant and cofactor for glutathione S-transferase conjugation. GSH synthesis is catalyzed by glutamate cysteine ligase (GCL), composed of catalytic (GCLC) and modifier (GCLM) subunits. Transgenic mice that conditionally over express GCL subunits are protected from acetaminophen induced liver injury. Gclm null mice exhibit low GSH levels and enhanced sensitivity to acetaminophen. When Gclm expression and GCL activity are restored in Gclm conditional transgenic X Gclm null mice, they become resistant to APAP-induced liver damage. These animal models are a valuable resource for investigating the role of GSH synthesis in modulating oxidative damage and drug-induced hepatotoxicity.
PubMed ID: 18642143
MeSH Terms: Acetaminophen; Animals; Antioxidants/metabolism*; Disease Models, Animal; Gene Targeting*; Genotype; Glutamate-Cysteine Ligase/genetics; Glutamate-Cysteine Ligase/metabolism*; Glutathione/metabolism*; Liver Diseases/enzymology; Liver Diseases/genetics; Liver Diseases/prevention & control; Liver/enzymology*; Mice; Mice, Knockout; Mice, Transgenic; Phenotype