Oxidized low density lipoprotein induces activation of the transcription factor NF kappa B in fibroblasts, endothelial and smooth muscle cells.
The effect of cupric ions or endothelial cell-oxidized LDL on the transcription factor NF kappa B activation was investigated by electrophoretic mobility shift assay. Oxidized LDL induced NF kappa B activation in fibroblasts, endothelial and smooth muscle cells. The extent of NF kappa B activation was proportional to the degree of LDL oxidation, as assessed by the lipid peroxidation product and the conjugated diene level. A similar activation was observed with the lipid extract of copper-oxidized LDL, which indicates that lipid peroxidation products are involved in the activation mechanism. Furthermore, alpha-tocopherol, a lipophilic free radical scavenger, partially inhibited the stimulatory effect of Cu(2+)-oxidized LDL. Since NF kappa B is considered as an oxidative stress-responsive transcription factor, our study supports the evidence that the stress induced by oxidized LDL causes NF kappa B activation in different cell types, and that this effect can be ascribed to the lipid peroxidation products.
Maziere
C
C
Laboratoire de Biochimie, Faculté de Médecine Saint-Antoine, Paris, France.
Auclair
M
M
Djavaheri-Mergny
M
M
Packer
L
L
Maziere
J C
JC
D000818:Animals; D002460:Cell Line; D003300:Copper; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D014810:Vitamin E / Q000494:pharmacology
D008077:Lipoproteins, LDL; D016328:NF-kappa B; C099252:oxidized low density lipoprotein; D014810:Vitamin E; D003300:Copper