The liver-specific response to phenobarbital involves a transient increase in phosphorylation of a 34-kda nuclear protein in rat liver and in hepatocytes in culture.
We have examined the influence of phenobarbital, a liver detoxication gene inducer and a potent tumor promoter, on the phosphorylation status of nuclear-enriched proteins in primary rat hepatocyte cultures and in whole livers. Freshly isolated cells were plated on plastic dishes in presence of serum for 4 h and 2 mM phenobarbital was added for various times, following serum withdrawal. A transient increase in phosphorylation of a 34-kda nuclear protein was detected at 6 h. In whole livers, but not in kidneys, a nuclear protein with the same electrophoretic mobility was also transiently over-phosphorylated, following injection of 80 mg/kg phenobarbital, although the peak activity was attained after 30 min only. No immunological relatedness between major histones and the 34-kda protein was found. Our results demonstrate a specific, yet undescribed, transient effect of phenobarbital on the phosphorylation status of a 34-kda nuclei-enriched protein in rat hepatocytes and in rat liver.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001769:Blood; D002478:Cells, Cultured; D003470:Culture Media; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013250:Steroid Hydroxylases / Q000235:genetics
D003470:Culture Media; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D010769:Phosphothreonine; D019000:Phosphotyrosine; D000255:Adenosine Triphosphate; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C025619:steroid 16-beta-hydroxylase; D010634:Phenobarbital