Identification of a human liver cytochrome P-450 homologous to the major isosafrole-inducible cytochrome P-450 in the rat.
The rat 3-methylcholanthrene-inducible family of liver cytochromes P-450 contains two proteins (P-450c and P-450d) that are immunochemically related, possess 68% total sequence homology, and are induced by a number of toxic or carcinogenic compounds. To determine whether equivalent isozymes of hepatic cytochrome P-450 are expressed in humans, as they are in several mammalian species, we performed immunoblot analyses on microsomes prepared from 14 human liver specimens and found that each one contained a 52.5-kDa protein (termed HLd) that reacted with antibodies specific for rat P-450d. In addition, one specimen contained a 54-kDa protein (termed HLc) that reacted with antibodies specific for rat P-450c. HLd was purified through the use of immunoaffinity chromatography and was found to be 56% homologous to rat P-450d and 61% homologous to the equivalent isozyme in the rabbit (P-450 LM4) through their first 18 NH2-terminal amino acids. Finally, levels of immunoreactive HLd varied more than 10-fold among these patients but were unrelated to the patients' drug treatments, smoking habits, or amount of immunoreactive HLp, a human liver cytochrome P-450 related to the glucocorticoid-inducible family of rat cytochromes P-450. We conclude that, in man, there is a cytochrome P-450 family composed of two isozymes (HLc and HLd) that are immunochemically and structurally related to the 3-methylcholanthrene-inducible family observed in several other species.
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis* / Q000096:biosynthesis; D004149:Dioxoles / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D007163:Immunosorbent Techniques; D007527:Isoenzymes / Q000032:analysis* / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D008875:Middle Aged; D051381:Rats; D012451:Safrole / Q000494:pharmacology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; D004149:Dioxoles; D007527:Isoenzymes; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D012451:Safrole; C015959:isosafrole