Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2000-12-7
pubmed:abstractText
The controlled step in de novo glutathione (GSH) synthesis is catalyzed by gamma-glutamylcysteine synthetase (gamma-GCS), a dimeric enzyme consisting of a heavy catalytic subunit (gamma-GCS-HS) and a light regulatory subunit (gamma-GCS-LS). We have previously reported that exposure to cadmium (Cd) induces pulmonary gamma-GCS-HS mRNA and protein, and that these alterations are accompanied by increases in GSH synthesis and its steady-state level. The current study was designed to test the hypothesis that Cd exposure also up-regulates the expression of the regulatory gamma-GCS subunit. By using northern blotting, we have demonstrated that a single Cd aerosol exposure of adult male Lewis rats results in time- and dose-dependent increases in pulmonary levels of gamma-GCS-LS mRNA. Transcripts of gamma-GCS-LS in rat lung are maximally elevated (8-fold) 2 h following Cd inhalation exposure and remain significantly higher than air controls at 24 h. This response is highly correlated with Cd dose, ranging from 0.9 to 5 mg Cd per m(3), and with lung Cd burden. We also observed Cd-induced up-regulation of gamma-GCS-LS mRNA expression in alveolar epithelial cells exposed to Cd in vitro, either acutely or after repeated passaging in Cd-containing medium. The magnitude of the gamma-GCS regulatory subunit induction observed in Cd-treated cells was approximately five times greater than the induction of the catalytic subunit. These modifications in the expression of gamma-GCS subunits may offer protection from Cd toxicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0300-483X
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
151
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
45-54
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Cadmium-induced elevations in the gene expression of the regulatory subunit of gamma-glutamylcysteine synthetase in rat lung and alveolar epithelial cells.
pubmed:affiliation
Biochemistry Department, College of Medicine, University of Vermont, Room C-440, Given Medical Building, 05405-0068, Burlington, VT, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.