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Molecular Pharmacology

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Abstract

Identification of a human liver cytochrome P-450 homologous to the major isosafrole-inducible cytochrome P-450 in the rat.

S A Wrighton, C Campanile, P E Thomas, S L Maines, P B Watkins, G Parker, G Mendez-Picon, M Haniu, J E Shively and W Levin
Molecular Pharmacology April 1986, 29 (4) 405-410;
S A Wrighton
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C Campanile
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P E Thomas
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S L Maines
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P B Watkins
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G Parker
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G Mendez-Picon
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M Haniu
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J E Shively
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W Levin
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Abstract

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.

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Molecular Pharmacology
Vol. 29, Issue 4
1 Apr 1986
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Abstract

Identification of a human liver cytochrome P-450 homologous to the major isosafrole-inducible cytochrome P-450 in the rat.

S A Wrighton, C Campanile, P E Thomas, S L Maines, P B Watkins, G Parker, G Mendez-Picon, M Haniu, J E Shively and W Levin
Molecular Pharmacology April 1, 1986, 29 (4) 405-410;

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Abstract

Identification of a human liver cytochrome P-450 homologous to the major isosafrole-inducible cytochrome P-450 in the rat.

S A Wrighton, C Campanile, P E Thomas, S L Maines, P B Watkins, G Parker, G Mendez-Picon, M Haniu, J E Shively and W Levin
Molecular Pharmacology April 1, 1986, 29 (4) 405-410;
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