Further characterization of the polycyclic aromatic hydrocarbon binding properties of the 4S protein.
A 4-S protein which specifically binds [3H]benzo(a)pyrene and other polycyclic aromatic hydrocarbons has been investigated in the rat using a hydroxylapatite assay and sucrose gradient analysis. Although there was significant interanimal variation, the specific polycyclic aromatic hydrocarbon binding activity appeared to be highest in 4-week-old male rats and declined with age. The specific [3H]benzo(a)pyrene binding activity was induced after pretreatment with either phenobarbital or isosafrole as evidenced by a 72 and 61% increase, respectively, over untreated controls. No apparent increase in specific binding activity was observed after pretreatment of animals with 3-methylcholanthrene. Pretreatment with either phenobarbital or isosafrole also resulted in the appearance of a small, nonspecific, benzo(a)pyrene binding peak at the 8- to 9-S region in the sucrose density gradients. This 8-S peak was not seen in untreated control animals and represented low affinity, high capacity binding sites. In contrast to the 8-S protein, the 4-S binding protein had low affinity for polychlorinated aromatic compounds such as tetrachlorodibenzodioxin and tetrachlorodibenzofuran. The addition of a 200-fold excess of tetrachlorodibenzofuran to incubations did not displace [3H]benzo(a)pyrene from the 4-S protein. The addition of sodium molybdate to isolation buffers, known to stabilize certain hormone receptors, did not alter the sedimentation coefficient or the specific binding activity of the 4-S protein. These experiments indicate that the 4-S protein does not appear to be a subunit of the 8-S protein. We conclude that in the rat the 4-S protein is distinct from the 8-S protein and the 4-S species may regulate the polycyclic aromatic hydrocarbon-induced expression of aryl hydrocarbon hydroxylase activity.
D000367:Age Factors; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism; D001572:Benzofurans / Q000378:metabolism; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004790:Enzyme Induction; D005260:Female; D008099:Liver / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D008982:Molybdenum / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000378:metabolism*; D051381:Rats; D012451:Safrole / Q000494:pharmacology
D001572:Benzofurans; D002352:Carrier Proteins; D046911:Macromolecular Substances; D011083:Polycyclic Compounds; D001564:Benzo(a)pyrene; D008982:Molybdenum; C024687:sodium molybdate(VI); D012451:Safrole; C015959:isosafrole; C014211:2,3,7,8-tetrachlorodibenzofuran; D010634:Phenobarbital