Source:http://linkedlifedata.com/resource/pubmed/id/12521994
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
2003-5-6
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| pubmed:abstractText |
Fanconi anemia complementation group C (Fancc)-deficient murine bone marrow progenitors demonstrate increased sensitivity to growth inhibition by interferon gamma (IFNgamma), tumor necrosis factor alpha (TNFalpha), and macrophage inflammatory protein 1alpha (MIP-1alpha). This property has been proposed as a possible pathogenic factor in the marrow failure seen in Fanconi anemia. Supporting our hypothesis that nitric oxide (NO) production might be a common effector in this sensitivity, we found that cytokine-mediated growth inhibition of Fancc(-/-) bone marrow cells was prevented by inhibiting NO synthase activity. Interestingly, Fancc(-/-) hematopoietic cells also exhibited increased growth inhibition on exposure to 2 distinct NO-generating agents, S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and diethylenetriamine nitric oxide adduct (DETA/NO). In keeping with the sensitivity of Fancc(-/-) cells to IFNgamma, inducible nitric oxide synthase (iNOS) levels and nitrite release were both increased following stimulation of Fancc(-/-) macrophages with this cytokine, either alone or in combination with bacterial lipopolysaccharide. Suggesting a plausible mechanism for the increased expression of iNOS, IFNgamma-stimulated Fancc(-/-) macrophages generated higher levels of phospho-Stat1, a positive regulator of inos (nos2) gene expression. These observations, while confined to C57BL/6 Fancc(-/-) hematopoietic cells, raise the possibility that nitric oxide has a role in the pathogenesis of Fanconi anemia.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Fancc protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Fanconi Anemia Complementation...,
http://linkedlifedata.com/resource/pubmed/chemical/Fanconi Anemia Complementation...,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins
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| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0006-4971
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
101
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3877-84
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:12521994-Animals,
pubmed-meshheading:12521994-Bone Marrow Cells,
pubmed-meshheading:12521994-Cell Cycle Proteins,
pubmed-meshheading:12521994-Cell Division,
pubmed-meshheading:12521994-Colony-Forming Units Assay,
pubmed-meshheading:12521994-Cytokines,
pubmed-meshheading:12521994-DNA-Binding Proteins,
pubmed-meshheading:12521994-Fanconi Anemia Complementation Group C Protein,
pubmed-meshheading:12521994-Fanconi Anemia Complementation Group Proteins,
pubmed-meshheading:12521994-Flow Cytometry,
pubmed-meshheading:12521994-Gene Deletion,
pubmed-meshheading:12521994-Hematopoietic Stem Cells,
pubmed-meshheading:12521994-Mice,
pubmed-meshheading:12521994-Mice, Inbred C57BL,
pubmed-meshheading:12521994-Mice, Knockout,
pubmed-meshheading:12521994-Nitric Oxide,
pubmed-meshheading:12521994-Nuclear Proteins,
pubmed-meshheading:12521994-Proteins
|
| pubmed:year |
2003
|
| pubmed:articleTitle |
Increased sensitivity of Fancc-deficient hematopoietic cells to nitric oxide and evidence that this species mediates growth inhibition by cytokines.
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| pubmed:affiliation |
Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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