4-Hydroxy-2-nonenal is a powerful endogenous inhibitor of endothelial response.
There is increasing evidence that lipid peroxidation is involved in many of the pathophysiologies associated with cardiovascular diseases, such as atherosclerosis and the long-term complications of diabetes. Among the products which originate from the peroxidation of cellular membrane lipids, 4-hydroxy-2-nonenal (HNE) is believed to be largely responsible for the cytopathological effects observed during oxidative stress in vivo. Here we found that HNE dramatically inhibited the expression of adhesion molecules induced by inflammatory stimuli in human aortic endothelial cells. The inhibition was found to be accompanied by a significant reduction of NF-kappaB activation followed by nuclear localization. This and the observation that the HNE treatment of the cells resulted in a rapid reduction of intracellular glutathione levels suggest that redox regulation of NF-kappaB may be involved in the modulation of the endothelial response by reactive aldehydes.
Minekura
H
H
Sankyo Research Laboratories, Sankyo Co., LtD., Shinagawa, Tokyo, 140-8710, Japan.
Kumagai
T
T
Kawamoto
Y
Y
Nara
F
F
Uchida
K
K
D000447:Aldehydes / Q000378:metabolism* / Q000633:toxicity; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000447:Aldehydes; D018932:Chemokine CCL2; D019040:E-Selectin; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D005978:Glutathione; C027576:4-hydroxy-2-nonenal