Linked Life Data

7929374

Source:http://linkedlifedata.com/resource/pubmed/id/7929374

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
1994-11-22
pubmed:abstractText
Glutathione (GSH) is one of the most important physiological antioxidants involved in detoxification of hydrogen peroxide and lipid hydroperoxide. Previous studies have shown that cells can maintain and even increase cellular GSH content in response to sublethal oxidative stress. We hypothesized that gamma-glutamylcysteine synthetase (gamma GCS), the rate-limiting enzyme in de novo GSH synthesis, could be induced by oxidative stress. Rat lung epithelial L2 cells were challenged with 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), generates O2.- and H2O2 continuously through redox cycling. Exposure of confluent L2 cells with sublethal doses of DMNQ caused sustained elevation of cellular GSH levels over a 24-h period (to 2.5-fold with 10 microM). DMNQ caused increases in gamma GCS activity (70% at 24 h with 10 microM), the gamma GCS catalytic heavy subunit (gamma GCS-HS) protein level, and gamma GCS-HS mRNA content (approximately 4-fold after 6 h with 10 microM). The elevation of gamma GCS-HS mRNA by DMNQ was eliminated by co-incubation with actinomycin D. Nuclear run-on experiments demonstrated that the transcriptional rate of the gamma GCS-HS gene was increased by 3- or 6-h exposure to 10 microM DMNQ. Our results suggested that the induction of de novo GSH synthesis by naphthoquinone-induced oxidative stress is associated with the transcriptional activation of the gamma GCS-HS gene and the subsequent elevation in gamma GCS activity. Unlike simpler quinones, DMNQ cannot form a GSH conjugate. Thus, the induction of gamma GCS-HS gene transcription does not require formation of an electrophile-glutathione conjugate.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26512-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Quinone-induced oxidative stress elevates glutathione and induces gamma-glutamylcysteine synthetase activity in rat lung epithelial L2 cells.
pubmed:affiliation
Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles 90033.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.