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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1996-4-25
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pubmed:abstractText |
Inflammatory mediators stimulate arginine-derived nitric oxide (NO) production in a variety of cells. The purpose of this study was to determine if the inflammatory mediators, endotoxin (LPS) and interferon gamma (IFN), stimulate arginine transport and nitric oxide production in a murine breast cancer cell line. We also investigated the effect of the nitric oxide synthase (NOS) inhibitors, omega-nitro-L-arginine methyl ester (LNAME) and aminoguanidine (AG), as well as the effect of varying the concentration of L-arginine in the cellular media, on arginine transport and NO production in these tumors cells. Confluent EMT-6 murine breast cancer cells were incubated with LPS (10 microgram/ml) and IFN (50 units/ml) in the presence or absence of the NOS inhibitors, L-NAME (2 mM) or AG (1 mM), and arginine transport (using L-[3H]arginine) and NO production (the stable end-product nitrite was assayed using the Greiss reagent) were measured at various time points. In addition, the effect of varying the concentration of L-arginine (0, 10, 100, 1000, 10,000 mM) in the cellular media on stimulated L-arginine transport and nitrite accumulation was assessed. Incubation of EMT-6 with LPS and IFN stimulated arginine transport approximately 70% over control levels at 12 hr and transport returned to basal levels at 24 hr. LPS/IFN-stimulated EMT-6 cells produced 25 microM nitrite at 24 hr and reached a plateau of 55 microM nitrite at 48 hr. The NO synthase inhibitors, L-NAME and AG, failed to inhibit basal and stimulated levels of arginine transport, but significantly inhibited nitrite accumulation, which was restored by 10 mM L-arginine. Finally, L-arginine was necessary in the media for nitrite accumulation by LPS/IFN-stimulated cells, with maximal accumulation at 1 mM L-arginine. In summary, LPS/IFN stimulate arginine transport and NO production in the EMT-6 breast cancer cell line. L-NAME and AG do not inhibit basal or stimulated arginine transport in this tumor cell line and extracellular L-arginine is required for NO synthesis in these cells. LPS/IFN stimulation of arginine transport may represent an adaptive response to provide increased substrate for enhanced tumor cell NO production.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Inflammation Mediators,
http://linkedlifedata.com/resource/pubmed/chemical/Interferons,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/NG-Nitroarginine Methyl Ester,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-4804
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
60
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
284-8
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:8598655-Animals,
pubmed-meshheading:8598655-Arginine,
pubmed-meshheading:8598655-Biological Transport,
pubmed-meshheading:8598655-Dose-Response Relationship, Drug,
pubmed-meshheading:8598655-Inflammation Mediators,
pubmed-meshheading:8598655-Interferons,
pubmed-meshheading:8598655-Lipopolysaccharides,
pubmed-meshheading:8598655-Mammary Neoplasms, Animal,
pubmed-meshheading:8598655-Mice,
pubmed-meshheading:8598655-NG-Nitroarginine Methyl Ester,
pubmed-meshheading:8598655-Nitric Oxide,
pubmed-meshheading:8598655-Tumor Cells, Cultured
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pubmed:year |
1996
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pubmed:articleTitle |
Inflammatory mediators stimulate arginine transport and arginine-derived nitric oxide production in a murine breast cancer cell line.
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pubmed:affiliation |
Department of Surgery, University of Florida College of Medicine, Gainesville, 32610-00286, USA.
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pubmed:publicationType |
Journal Article
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