Activation of hepatic NF-kappaB by phenobarbital in rats.
Nuclear factor kappaB (NF-kappaB) is an important stress-induced transcription factor in many cell types. In this study we examined if the hepatic tumor promoting agent phenobarbital could activate NF-kappaB in the liver. Rats were fed 0.05% phenobarbital in the diet for 3, 6, or 10 days. Benzyloxyresorufin dealkylase activity was greatly increased in rats receiving phenobarbital. The DNA binding activity of NF-kappaB was determined using electrophoretic mobility shift assays. After 3 days, NF-kappaB activity was increased two-fold in rats receiving phenobarbital. NF-kappaB activity continued to increase at 6 and 10 days in rats fed phenobarbital, with a four-fold increase seen at day 10. Cold competition and antibody supershift experiments showed the DNA binding activity to be specific for NF-kappaB. These data show that phenobarbital activates hepatic NF-kappaB in rats.
Li
Y
Y
Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky, 40506, USA. nfshpg@ukcc.uky.edu
Leung
L K
LK
Spear
B T
BT
Glauert
H P
HP
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016328:NF-kappa B; D010634:Phenobarbital