Linked Life Data

7913422

Source:http://linkedlifedata.com/resource/pubmed/id/7913422

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1994-8-17
pubmed:abstractText
The concentration of glutathione (GSH) and the expressions of gamma-glutamylcysteine synthetase and gamma-glutamyltranspeptidase (GGT) were assessed in rat embryo fibroblasts (REF) displaying various stages of X-ray-induced transformation. A secondary culture of REF cells was irradiated, and a normal-immortalized cell line (X-REF-23) was isolated. Chronic exposure of X-REF-23 cells to 12-O-tetradecanoyl-phorbol-13-acetate (TPA) yielded cells (X-REF-23-TP) capable of benign tumor formation in nude mice. These cells exhibited GSH concentrations and gamma-glutamylcysteine synthetase heavy subunit mRNA levels that were approximately 50% less than those measured in X-REF-23 cells. Neither X-REF-23 nor X-REF-23-TP cells exhibited detectable GGT mRNA or activity. Administration of 3 Gy of X-rays followed by chronic TPA treatment yielded cells (X-REF-23-TPX) capable of malignant tumor formation in nude mice. These cells expressed GGT mRNA and Concanavalin-A minus GGT activity. One TPX clone (X-REF-23-TPX.1) was chosen for further characterization. Northern blotting of X-REF-23-TPX.1 cells indicated that gamma-glutamylcysteine synthetase heavy subunit mRNA levels were similar to those of X-REF-TP cells. X-REF-23-TPX.1 cells contained nearly the same amount of GSH as X-REF-23 cells. However, the ability of diethylmaleate (DEM) to deplete GSH was diminished in X-REF-23-TPX.1 cells compared with X-REF-23 cells. Furthermore, exposure of X-REF-23-TPX.1 cells to DEM stimulated GSH resynthesis such that the GSH concentration exceeded control values during exposure. The resynthesis of GSH during a DEM exposure was found to be dependent upon the expression of GGT, as demonstrated by inhibition with AT-125. These experiments indicate that ionizing radiation can lead to elevated constitutive expression of GGT in transformed REF cells and that expression of GGT activity was responsible for the increased rate of GSH repletion observed in X-REF-23-TPX.1 cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1301-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Genes regulating glutathione concentrations in X-ray-transformed rat embryo fibroblasts: changes in gamma-glutamylcysteine synthetase and gamma-glutamyltranspeptidase expression.
pubmed:affiliation
Vanderbilt Center for Radiation Oncology, Vanderbilt University School of Medicine, Nashville, TN 37232.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.