Ethanol induces rapid lipid peroxidation and activation of nuclear factor-kappa B in cerebral vascular smooth muscle: relation to alcohol-induced brain injury in rats.
The present study was designed to test the hypothesis that acute administration of alcohol (ethanol) to primary cultured cerebral vascular smooth muscle cells will cause lipid peroxidation, inhibition of IkappaB phosphorylation, and inhibition of nuclear transcription factor-kappa B (NF-kappaB). Ethanol (10, 25, 100 mM) resulted in concentration-dependent rises in malondialdehyde in as little as 30-45 min after exposure to the alcohol, rising to levels 2.5-10x normal after 18-24 h. Using EMSA assays and specific antibodies, ethanol caused three DNA-binding proteins (p50, p65, c-Rel) to rise in nuclear extracts in a concentration-dependent manner. Using a rabbit antibody, IkappaB phosphorylation (and degradation) was stimulated by ethanol (in a concentration-dependent manner) and inhibited by a low concentration of the NF-kappaB inhibitor, pyrrolidine dithiocarbamate. These new biochemical and molecular data indicate that ethanol, even in physiologic concentrations, can elicit rapid lipid peroxidation and activation of NF-kappaB in cerebral vascular muscle cells. The present results when viewed in light of other recently published data suggest that ethanol-induced lipid peroxidation and activation of nuclear transcription factors probably play important roles in alcohol-induced brain-vascular damage, neurobehavioral actions and stroke.
Altura
Burton M
BM
Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA. baltura@netmail.hscbklyn.edu
Gebrewold
Asefa
A
Zhang
Aimin
A
Altura
Bella T
BT
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D002536:Cerebral Arteries / Q000166:cytology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004285:Dogs; D000431:Ethanol / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors
D000975:Antioxidants; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D008054:Lipid Peroxides; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D000431:Ethanol; D008315:Malondialdehyde