Modulating GSH synthesis using glutamate cysteine ligase transgenic and gene-targeted mice.
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.
Botta
Dianne
D
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle 98195, USA.
White
Collin C
CC
Vliet-Gregg
Portia
P
Mohar
Isaac
I
Shi
Shengli
S
McGrath
Monica B
MB
McConnachie
Lisa A
LA
Kavanagh
Terrance J
TJ
D000082:Acetaminophen; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004195:Disease Models, Animal; D018390:Gene Targeting; D005838:Genotype; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008107:Liver Diseases / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype
D000975:Antioxidants; D000082:Acetaminophen; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione