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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2000-9-25
pubmed:abstractText
Dithiocarbamates are a well-defined family of antioxidants that may have therapeutic uses such as in treatment of inflammation and atherosclerosis. A critical event in the pathogenesis of atherosclerosis is the infiltration of inflammatory cells into the vessel wall. Vascular cell adhesion molecule-1 (VCAM-1) plays a pivotal role in this process by mediating leukocyte binding to endothelial cells. VCAM-1 expression is stimulated by oxidized polyunsaturated fatty acids such as 13-hydroperoxy-octadecadienoic acid (13-HPODE), and this lipid hydroperoxide has been proposed to be a second messenger for induction of VCAM-1 gene expression. Pyrrolidine dithiocarbamate (PDTC) markedly represses cytokine-induced VCAM-1 gene expression in cultured human endothelial cells; however, its effects on the oxidative second messenger pathway are unknown. Using a lipoxygenase (LO) inhibition assay in tandem with a colorimetric assay for lipid peroxides, we determined that PDTC does not inhibit the enzymatic oxidation of linoleic acid to 13-HPODE by LO, but directly interacts with and chemically reduces 13-HPODE. We hypothesize that dithiocarbamates may intercept the oxidative second-messenger-induced expression of VCAM-1 and other redox-regulated genes important in inflammation and atherosclerosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0891-5849
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1532-7
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Dithiocarbamates: effects on lipid hydroperoxides and vascular inflammatory gene expression.
pubmed:affiliation
AtheroGenics, Inc., Alpharetta, GA, USA.pksomers@home.com
pubmed:publicationType
Journal Article