Genetically altered mice to evaluate glutathione homeostasis in health and disease.
The tripeptide glutathione (GSH) is part of an integrated antioxidant system that protects cells and tissues from oxidative damage. Oxidative stress can result from exposure to excessive amounts of endogenous and exogenous electrophiles. Until recently, animal and cell model systems used to investigate the role of GSH in disease processes had employed chemical agents that deplete cellular GSH by inhibiting GSH synthesis or by reacting chemically with GSH. Such models have proven useful, but questions concerning nonspecific effects of such chemicals remain. Recently, our laboratories and others have developed mouse models with genetic deficiencies in enzymes of the GSH biosynthetic pathway. This review focuses on the regulation of GSH homeostasis and, specifically, the new GSH-deficient mouse models that have been developed. These models will improve our understanding of the role of GSH in animal and human diseases.
Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, 123 East Shields Street, P.O. Box 670056, Cincinnati, OH 45267-0056, USA. daltontp@ucmail.uc.edu
Timothy P
TP
Dalton
Ying
Y
Chen
Scott N
SN
Schneider
Daniel W
DW
Nebert
Howard G
HG
Shertzer
D000818:Animals; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism*; D005978:Glutathione / Q000235:genetics / Q000378:metabolism*; D005981:Glutathione Synthase / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D005723:gamma-Glutamyltransferase / Q000235:genetics / Q000378:metabolism
D005723:gamma-Glutamyltransferase; D005721:Glutamate-Cysteine Ligase; D005981:Glutathione Synthase; D005978:Glutathione