Linked Life Data

7503769

Source:http://linkedlifedata.com/resource/pubmed/id/7503769

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1996-1-17
pubmed:abstractText
Folates and antifolates are converted to polyglutamates, which are better retained in cells and may also bind more tightly to cellular proteins than the parent compounds. The regulation of the process of polyglutamate formation and breakdown is not fully clarified yet and is being studied by a number of approaches. An early observation concerning the potential regulation of polyglutamate formation was that insulin caused a marked increase in the rate and accumulation of polyglutamates of methotrexate (MTX) in rat hepatoma cells. The present study demonstrated that insulin caused a decrease in the activity of gamma-glutamyl hydrolase (GH), the enzyme that degrades polyglutamates, that was inversely commensurate with the increase in the synthesis of MTX polyglutamates. The effects of insulin on GH activity with regard to concentration, time of onset, and the effect of N6, O2' dibutyryl cAMP and theophylline were consistent with the reduction in GH being responsible for the increase in cellular MTX polyglutamate accumulation. Insulin addition also led to an increase in folate polyglutamates. The insulin effects were also seen with H35D cells, a subline with enhanced glutamyl hydrolase activity as a result of having been made resistant to 5, 10-dideazatetrahydrofolic acid. When H35 cells with insulin were compared with H35D cells lacking insulin, there was an 8-fold increase in GH and a 44-fold decrease in the number of gamma-glutamate residues added to MTX.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1659-63
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Insulin-dependent suppression in glutamyl hydrolase activity and elevated cellular methotrexate polyglutamates.
pubmed:affiliation
Division of Molecular Medicine, Wadsworth Center, New York State Department of Health, Albany, 12201-0509, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.