Linked Life Data

9804903

Source:http://linkedlifedata.com/resource/pubmed/id/9804903

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1998-12-9
pubmed:abstractText
The relationship between l-cystine transport and intracellular glutathione (GSH) levels was investigated in cultured pancreatic AR42J acinar and betaTC3 islet cells exposed to diethylmaleate, an electrophilic agent known to activate cellular antioxidant responses. Cystine transport was mediated predominantly by the Na+-independent anionic amino acid transport system x-c, with influx inhibited potently by glutamate and homocysteate but unaffected by cationic or neutral amino acids. Saturable cystine transport was 10-fold higher in AR42J (531 pmol (mg protein)-1 min-1) than in betaTC3 (49 pmol (mg protein)-1 min-1) cells, and GSH levels were higher in AR42J cells. Treatment with 2-mercaptoethanol increased GSH levels in betaTC3 cells from 7.5 to 36 nmol (mg protein)-1, whilst the GSH content in AR42J cells (64 nmol (mg protein)-1) was not altered significantly. Incubation of AR42J or betaTC3 cells with homocysteate (2.5 mM, 0-48 h), a competitive inhibitor of cystine transport via system x-c, reduced intracellular GSH levels and resulted in a time-dependent (6-24 h) induction of system x-c transport activity. Treatment of AR42J cells with diethylmaleate (100 microM, 0-48 h) resulted in a time- (5-10 h) and protein synthesis-dependent induction of cystine transport, with intracellular GSH levels initially decreasing and then increasing 2-fold above control levels after 24 h. Diethylmaleate also depressed GSH levels in betaTC3 cells, but cystine transport was not elevated significantly. In both AR42J and betaTC3 cells, inhibition of gamma-glutamyl cysteine synthetase by buthionine sulphoximine (100 microM, 24 h) reduced GSH levels but had no effect on cystine transport. The present findings establish that induction of system x-c leads to changes in GSH levels in pancreatic AR42J acinar and betaTC3 islet cells, with changes in the intracellular redox state stimulating transporter expression. Induction of activity of system x-c, together with adaptive increases in GSH synthesis in response to oxidative stress, may contribute to cellular antioxidant defences in pancreatic disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Amino Acid Transport Systems, Basic, http://linkedlifedata.com/resource/pubmed/chemical/Amino Acid Transport Systems..., http://linkedlifedata.com/resource/pubmed/chemical/Buthionine Sulfoximine, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cystine, http://linkedlifedata.com/resource/pubmed/chemical/Glutathione, http://linkedlifedata.com/resource/pubmed/chemical/Homocysteine, http://linkedlifedata.com/resource/pubmed/chemical/Maleates, http://linkedlifedata.com/resource/pubmed/chemical/Mercaptoethanol, http://linkedlifedata.com/resource/pubmed/chemical/Slc3a1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Slc3a1 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/diethyl maleate, http://linkedlifedata.com/resource/pubmed/chemical/homocysteic acid
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
1414
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
85-94
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Induction of cystine transport via system x-c and maintenance of intracellular glutathione levels in pancreatic acinar and islet cell lines.
pubmed:affiliation
Division of Physiology, School of Biomedical Sciences, King's College London, Campden Hill Road, London W8 7AH, UK.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't