Possible role of lipid peroxidation in the induction of NF-kappa B and AP-1 in RFL-6 cells by crocidolite asbestos: evidence following protection by vitamin E.
Asbestos fibers cause persistent induction of the oxidative stress sensitive transcription factors nuclear factor kappa-B (NF-kappa B) and activator protein-1 (AP-1) in mammalian cells. These transcription factors play an important role in the regulation of cellular activity. Lipid peroxidation, mediated by reactive oxygen species, is thought to be a possible mechanism in the pathogenicity of asbestos fibers. These studies were designed to determine if crocidolite asbestos-induced lipid peroxidation plays a role in the mechanism of formation of NF-kappa B and AP-1. Treatment of a rat lung fibroblast cell line (RFL-6) with crocidolite asbestos in the presence and absence of the membrane antioxidant vitamin E decreased the levels of crocidolite-induced AP-1 and NF-kappa B to background levels. Preincubation of RFL-6 cells with 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism, prior to exposure to crocidolite, abrogated crocidolite-induced NF-kappa B DNA-binding activity to background levels. Coincubation with indomethacin, a cyclooxygenase inhibitor, had no effect on NF-kappa B DNA-binding activity induced by crocidolite. However, nordihydroguaiaretic acid, a lipoxygenase inhibitor, decreased levels of NF-kappa B to background levels. This would suggest that lipoxygenase metabolites of arachidonic acid, produced following lipid peroxidation, are involved in the cellular signalling events to NF-kappa B transcription factor induction by asbestos.
Faux
S P
SP
Institute of Occupational Health, University of Birmingham, Edgbaston, United Kingdom. spf7@leicester.ac.uk
Howden
P J
PJ
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D017638:Asbestos, Crocidolite / Q000633:toxicity*; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D002460:Cell Line; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D016328:NF-kappa B / Q000096:biosynthesis*; D051381:Rats; D018808:Transcription Factor AP-1 / Q000096:biosynthesis*; D014810:Vitamin E / Q000494:pharmacology*
D002273:Carcinogens; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D017638:Asbestos, Crocidolite; D014810:Vitamin E; D016718:Arachidonic Acid; D004247:DNA