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. (C) 1995 Academic Press, Inc.