Activation of hepatic NF-kappa B by phenobarbital in rats

Nuclear factor kappa B (NF-kappa B) 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-kappa B 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-kappa B was determined using electrophoretic mobility shift assays. After 3 days NF-kappa B activity was increased two-fold in rats receiving phenobarbital. NF-kappa B 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-kappa B. These data show that phenobarbital activates hepatic NF-kappa B in rats. (C) 1996 Academic Press.