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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2004-7-12
pubmed:abstractText
The concentration of glutathione (GSH), the most abundant intracellular nonprotein thiol and important antioxidant, declines with age and in some age-related diseases. The underlying mechanism, however, is not clear. The previous studies from our laboratory showed that the age-dependent decline in GSH content in Fisher 344 rats was associated with a downregulation of glutamate cysteine ligase (GCL), the rate-limiting enzyme in de novo GSH synthesis. Our recent studies further indicated that the activity and mRNA content of glutathione synthase (GS), which catalyzes the second reaction in de novo GSH synthesis, were also decreased with age in some tissues. No age-associated change was observed in glutathione reductase or gamma-glutamyl transpeptidase activities. Also, although GSH content declined with age in both male and female mice, male mice experienced more dramatic age-associated decline in many tissues/organs than female mice. Furthermore, we found that GSH content was significantly decreased in the red blood cells from male Alzheimer disease patients, which was associated with decreases in GCL and GS activities. Finally, we showed that estrogen increased GSH content, GS and GR activities, and GCL gene expression in the liver of both male and female mice. Taken together, our results suggest that (1) GCL plays a critical role in maintaining GSH homeostasis under both physiological and pathological conditions; (2) decreased GSH content may be involved in AD pathology in humans; and (3) estrogen increases GSH content in mice by multiple mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:volume
1019
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
346-9
pubmed:dateRevised
2005-11-16
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Glutathione metabolism during aging and in Alzheimer disease.
pubmed:affiliation
Department of Immunology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-0022, USA.
pubmed:publicationType
Journal Article, Review