Source:http://linkedlifedata.com/resource/pubmed/id/18025230
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
2007-11-20
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| pubmed:abstractText |
Heme oxygenase-1 (HO-1; encoded by the Hmox1 gene) catalyzes the degradation of free heme into biliverdin, via a reaction that releases iron (Fe) and carbon monoxide. We report that HO-1 down-regulates the proinflammatory phenotype associated with endothelial cell (EC) activation by reducing intracellular nonprotein-bound Fe (labile Fe). EC isolated from Hmox1(-/-) mice have higher levels of intracellular labile Fe and reactive oxygen species (ROS) as compared with EC isolated from Hmox1(+/+) mice. Basal and TNF-induced expression of VCAM-1, ICAM-1, and E-selectin were increased in Hmox1(-/-) vs Hmox1(+/+) EC, an effect reversed by Fe chelation using deferoxamine mesylate (DFO). Fe chelation inhibits TNF-driven transcription of Vcam-1, Icam-1, and E-selectin, as assessed using luciferase reporter assays. This effect is associated with inhibition of the transcription factor NF-kappaB via a mechanism that is not associated with the inhibition of IkappaBalpha phosphorylation/degradation or NF-kappaB (i.e., RelA) nuclear translocation, although it affects very modestly NF-kappaB binding to DNA kappaB consensus sequences in the Vcam-1 and E-selectin promoters. HO-1 inhibits NF-kappaB (i.e., RelA) phosphorylation at Ser(276), a phosphoacceptor that is critical to sustain TNF-driven NF-kappaB activity in EC. This effect was mimicked by Fe chelation as well as by antioxidants (N-acetylcysteine). In conclusion, we demonstrate a novel mechanism via which HO-1 down-modulates the proinflammatory phenotype of activated EC, i.e., the inhibition of RelA phosphorylation at Ser(276).
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Ferric Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase-1,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
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| pubmed:volume |
179
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
7840-51
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| pubmed:meshHeading |
pubmed-meshheading:18025230-Animals,
pubmed-meshheading:18025230-Cell Adhesion Molecules,
pubmed-meshheading:18025230-Cells, Cultured,
pubmed-meshheading:18025230-Down-Regulation,
pubmed-meshheading:18025230-Endothelial Cells,
pubmed-meshheading:18025230-Ferric Compounds,
pubmed-meshheading:18025230-Gene Expression Regulation,
pubmed-meshheading:18025230-Heme Oxygenase-1,
pubmed-meshheading:18025230-Inflammation,
pubmed-meshheading:18025230-Mice,
pubmed-meshheading:18025230-Mice, Inbred BALB C,
pubmed-meshheading:18025230-Mice, Knockout,
pubmed-meshheading:18025230-NF-kappa B,
pubmed-meshheading:18025230-Phosphorylation,
pubmed-meshheading:18025230-Serine,
pubmed-meshheading:18025230-Transcription, Genetic,
pubmed-meshheading:18025230-Transcription Factor RelA,
pubmed-meshheading:18025230-Vascular Cell Adhesion Molecule-1
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| pubmed:year |
2007
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| pubmed:articleTitle |
Heme oxygenase-1 inhibits the expression of adhesion molecules associated with endothelial cell activation via inhibition of NF-kappaB RelA phosphorylation at serine 276.
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| pubmed:affiliation |
Instituto Gulbenkian de Ciência, Apartado 14, Oeiras, Portugal.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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