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2-Chlorohexadecanal and 2-chlorohexadecanoic acid induce COX-2 expression in human coronary artery endothelial cells.

Abstract
2-Chlorohexadecanal (2-ClHDA), a 16-carbon chain chlorinated fatty aldehyde that is produced by reactive chlorinating species attack of plasmalogens, is elevated in atherosclerotic plaques, infarcted myocardium, and activated leukocytes. We tested the hypothesis that 2-ClHDA and its metabolites, 2-chlorohexadecanoic acid (2-ClHA) and 2-chlorohexadecanol (2-ClHOH), induce COX-2 expression in human coronary artery endothelial cells (HCAEC). COX-2 protein expression increased in response to 2-ClHDA treatments at 8 and 20 h. 2-ClHA also increased COX-2 expression following an 8 h treatment. Quantitative PCR showed that 2-ClHDA treatment increased COX-2 mRNA over 8 h, while 2-ClHA treatment led to a modest increase by 1 h and those levels remained constant over 8 h. 2-ClHDA led to a significant increase in 6-keto-PGF(1alpha) release (a measure of PGI(2) release) by HCAEC. These data suggest that 2-ClHDA and its metabolite 2-ClHA, which are produced during leukocyte activation, may alter vascular endothelial cell function by upregulation of COX-2 expression.
AuthorsMaria C Messner, Carolyn J Albert, David A Ford
JournalLipids (Lipids) Vol. 43 Issue 7 Pg. 581-8 (Jul 2008) ISSN: 0024-4201 [Print] United States
PMID18493808 (Publication Type: Journal Article)
Chemical References
  • 2-chlorohexadecanal
  • 2-chlorohexadecanoic acid
  • Aldehydes
  • I-kappa B Proteins
  • Palmitic Acids
  • Tumor Necrosis Factor-alpha
  • Palmitic Acid
  • 6-Ketoprostaglandin F1 alpha
  • Cyclooxygenase 2
Topics
  • 6-Ketoprostaglandin F1 alpha (metabolism)
  • Aldehydes (pharmacology)
  • Blotting, Western
  • Cells, Cultured
  • Coronary Vessels (cytology, drug effects)
  • Cyclooxygenase 2 (genetics, metabolism)
  • Endothelial Cells (drug effects, enzymology)
  • Gene Expression Regulation (drug effects)
  • Humans
  • I-kappa B Proteins (metabolism)
  • Palmitic Acid (pharmacology)
  • Palmitic Acids (pharmacology)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction (drug effects)
  • Tumor Necrosis Factor-alpha (pharmacology)

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