Linoleic acid activates nuclear transcription factor-kappa B (NF-kappa B) and induces NF-kappa B-dependent transcription in cultured endothelial cells.
High dietary intakes of unsaturated fats may be atherogenic by disrupting normal functions of the vascular endothelium, due in part to the ability of linoleic acid (18:2n-6) to contribute to an increase in cellular oxidative stress and related injurious events. Exposing endothelial cells to 90 micromol linoleic acid/L for 6 h resulted in a significant increase in lipid hydroperoxides that coincided wih an increase in intracellular calcium concentrations. Treatment with this fatty acid caused an initial decrease in glutathione concentrations, which was followed by an increase at later time points. Most importantly, a significant activation of the oxidative stress-sensitive nuclear transcription factor-kappa B (NF-kappa B) was achieved after a 6-h exposure to 18:2n-6, which is the time point at which maximal depletion of cellular glutathione was observed. The fatty acid-mediated NF-kappa B activation was accompanied by induction of NF-kappa B-dependent transcription, as measured by chloramphenicol acetyltransferase (CAT) assay of an NF-kappa B-responsive promoter construct. Pretreatment of endothelial cells with vitamin E and N-acetyl cysteine inhibited the fatty acid-induced activation of NF-kappa B and formation of lipid hydroperoxides. These data suggest that oxidative stress-induced cellular changes are critical early events in fatty acid-mediated endothelial cell dysfunction.
Hennig
B
B
Department of Nutrition and Food Science, University of Kentucky, Lexington, USA.
Toborek
M
M
Joshi-Barve
S
S
Barger
S W
SW
Barve
S
S
Mattson
M P
MP
McClain
C J
CJ
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D011651:Pulmonary Artery; D013552:Swine; D014158:Transcription, Genetic / Q000187:drug effects*
D008041:Linoleic Acids; D016328:NF-kappa B; D019787:Linoleic Acid; D005978:Glutathione; D002118:Calcium