Source:http://linkedlifedata.com/resource/pubmed/id/12006387
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2002-5-13
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| pubmed:abstractText |
We have previously shown that cytokine stimulation of the expression of vascular cell adhesion molecule-1 (VCAM-1), but not that of intercellular adhesion molecule-1 (ICAM-1), is redox sensitive in endothelial cells. Here, we investigated the role of isoprenylcysteine carboxyl methyltransferase (ICMTase), which methylates isoprenylated CAAX (where C indicates cysteine; A, aliphatic amino acids; and X, almost any other amino acid) proteins, including Rac1, a component of superoxide-generating NAD(P)H oxidase, in the expression of VCAM-1. Pretreatment of endothelial cells with N-acetyl-S-farnesyl-L-cysteine (AFC) or N-acetyl-S-geranylgeranyl-L-cysteine (AGGC), specific inhibitors of ICMTase, inhibited the tumor necrosis factor-alpha (TNF-alpha) stimulation of mRNA expression of VCAM-1 but not that of ICAM-1. Endothelial cells expressed constitutively active ICMTase, as suggested by the presence of methylated Rac1 and the methylation of AFC by the cells. TNF-alpha stimulation of the cells significantly increased the methylation of AFC and Rac1 in endothelial cells. That ICMTase was a component of the redox-sensitive signaling pathway was also suggested by the AFC inhibition of the generation of reactive oxygen species by TNF-alpha. Interestingly, the dominant-negative isoform of Rac1 was not selective but inhibited the TNF-alpha stimulation of the mRNA expression of VCAM-1 and ICAM-1. Thus, ICMTase is a critical component of the redox-sensitive VCAM-1-selective signaling pathway, and it appears to activate a discrete inflammatory signaling pathway, at least in part, through the methylation of Rac1.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Polyomavirus Transforming,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Diterpenes,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/N-acetyl-S-farnesylcysteine,
http://linkedlifedata.com/resource/pubmed/chemical/N-acetyl-S-geranylgeranyl-cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Methyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/protein-S-isoprenylcysteine...,
http://linkedlifedata.com/resource/pubmed/chemical/rac1 GTP-Binding Protein
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
1524-4636
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
1
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| pubmed:volume |
22
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
759-64
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:12006387-Acetylcysteine,
pubmed-meshheading:12006387-Antigens, Polyomavirus Transforming,
pubmed-meshheading:12006387-Aorta,
pubmed-meshheading:12006387-Cell Line, Transformed,
pubmed-meshheading:12006387-Cell Survival,
pubmed-meshheading:12006387-Cysteine,
pubmed-meshheading:12006387-Diterpenes,
pubmed-meshheading:12006387-Endothelium, Vascular,
pubmed-meshheading:12006387-Enzyme Inhibitors,
pubmed-meshheading:12006387-Humans,
pubmed-meshheading:12006387-Hydrogen Peroxide,
pubmed-meshheading:12006387-Intercellular Adhesion Molecule-1,
pubmed-meshheading:12006387-Methylation,
pubmed-meshheading:12006387-Protein Methyltransferases,
pubmed-meshheading:12006387-Tumor Necrosis Factor-alpha,
pubmed-meshheading:12006387-Vascular Cell Adhesion Molecule-1,
pubmed-meshheading:12006387-rac1 GTP-Binding Protein
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| pubmed:year |
2002
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| pubmed:articleTitle |
Role of isoprenylcysteine carboxyl methyltransferase in tumor necrosis factor-alpha stimulation of expression of vascular cell adhesion molecule-1 in endothelial cells.
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| pubmed:affiliation |
Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Ga 30322, USA. mahmad@emory.edu
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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