Immunochemical evidence for induction of the alcohol-oxidizing cytochrome P-450 of rabbit liver microsomes by diverse agents: Ethanol, imidazole, trichloroethylene, acetone, pyrazole, and isoniazid

Dennis Koop, B. L. Crump, G. D. Nordblom, M. J. Coon

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256 Citations (Scopus)

Abstract

Isozyme 3a of rabbit liver microsomal cytochrome P-450, also termed P-450(ALC), was previously isolated in this laboratory from animals administered ethanol or imidazole, and the purified cytochrome was shown to function in the reconstituted system as an oxygenase in catalyzing the oxidation of ethanol and other alcohols. Although liver microsomes from animals treated in various ways exhibit increased alcohol-oxidizing activity, evidence was not available as to whether this was due to enzyme induction or to other factors influencing the activity. Immunochemical quantitation of P-450 isozyme 3a has now been achieved by use of purified antibody to this cytochrome in NaDodSO4/PAGE/blotting and dot-blotting techniques. The specific content of isozyme 3a in liver microsomes was found to be increased from 2- to >4-fold by administration of the following agents, in increasing order of effectiveness as inducers: isoniazid, trichloroethylene, pyrazole, ethanol, imidazole, and acetone. Isozyme 3a represents about 5% of the total P-450 in control animals and is increased to as high as 27% by acetone treatment. Isozyme 3a-dependent butanol-oxidation activity, determined by the inhibitory effect of antibody on the various microsomal preparations, was found to increase proportionally with increased content of this cytochrome.

Original languageEnglish (US)
Pages (from-to)4065-4069
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume82
Issue number12
StatePublished - 1985
Externally publishedYes

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Trichloroethylene
Isoniazid
Liver Microsomes
Acetone
Cytochrome P-450 Enzyme System
Isoenzymes
Ethanol
Alcohols
Rabbits
Cytochromes
Oxygenases
Butanols
Enzyme Induction
Antibodies
Laboratory Animals
imidazole
pyrazole
Liver

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

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title = "Immunochemical evidence for induction of the alcohol-oxidizing cytochrome P-450 of rabbit liver microsomes by diverse agents: Ethanol, imidazole, trichloroethylene, acetone, pyrazole, and isoniazid",
abstract = "Isozyme 3a of rabbit liver microsomal cytochrome P-450, also termed P-450(ALC), was previously isolated in this laboratory from animals administered ethanol or imidazole, and the purified cytochrome was shown to function in the reconstituted system as an oxygenase in catalyzing the oxidation of ethanol and other alcohols. Although liver microsomes from animals treated in various ways exhibit increased alcohol-oxidizing activity, evidence was not available as to whether this was due to enzyme induction or to other factors influencing the activity. Immunochemical quantitation of P-450 isozyme 3a has now been achieved by use of purified antibody to this cytochrome in NaDodSO4/PAGE/blotting and dot-blotting techniques. The specific content of isozyme 3a in liver microsomes was found to be increased from 2- to >4-fold by administration of the following agents, in increasing order of effectiveness as inducers: isoniazid, trichloroethylene, pyrazole, ethanol, imidazole, and acetone. Isozyme 3a represents about 5{\%} of the total P-450 in control animals and is increased to as high as 27{\%} by acetone treatment. Isozyme 3a-dependent butanol-oxidation activity, determined by the inhibitory effect of antibody on the various microsomal preparations, was found to increase proportionally with increased content of this cytochrome.",
author = "Dennis Koop and Crump, {B. L.} and Nordblom, {G. D.} and Coon, {M. J.}",
year = "1985",
language = "English (US)",
volume = "82",
pages = "4065--4069",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
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TY - JOUR

T1 - Immunochemical evidence for induction of the alcohol-oxidizing cytochrome P-450 of rabbit liver microsomes by diverse agents

T2 - Ethanol, imidazole, trichloroethylene, acetone, pyrazole, and isoniazid

AU - Koop, Dennis

AU - Crump, B. L.

AU - Nordblom, G. D.

AU - Coon, M. J.

PY - 1985

Y1 - 1985

N2 - Isozyme 3a of rabbit liver microsomal cytochrome P-450, also termed P-450(ALC), was previously isolated in this laboratory from animals administered ethanol or imidazole, and the purified cytochrome was shown to function in the reconstituted system as an oxygenase in catalyzing the oxidation of ethanol and other alcohols. Although liver microsomes from animals treated in various ways exhibit increased alcohol-oxidizing activity, evidence was not available as to whether this was due to enzyme induction or to other factors influencing the activity. Immunochemical quantitation of P-450 isozyme 3a has now been achieved by use of purified antibody to this cytochrome in NaDodSO4/PAGE/blotting and dot-blotting techniques. The specific content of isozyme 3a in liver microsomes was found to be increased from 2- to >4-fold by administration of the following agents, in increasing order of effectiveness as inducers: isoniazid, trichloroethylene, pyrazole, ethanol, imidazole, and acetone. Isozyme 3a represents about 5% of the total P-450 in control animals and is increased to as high as 27% by acetone treatment. Isozyme 3a-dependent butanol-oxidation activity, determined by the inhibitory effect of antibody on the various microsomal preparations, was found to increase proportionally with increased content of this cytochrome.

AB - Isozyme 3a of rabbit liver microsomal cytochrome P-450, also termed P-450(ALC), was previously isolated in this laboratory from animals administered ethanol or imidazole, and the purified cytochrome was shown to function in the reconstituted system as an oxygenase in catalyzing the oxidation of ethanol and other alcohols. Although liver microsomes from animals treated in various ways exhibit increased alcohol-oxidizing activity, evidence was not available as to whether this was due to enzyme induction or to other factors influencing the activity. Immunochemical quantitation of P-450 isozyme 3a has now been achieved by use of purified antibody to this cytochrome in NaDodSO4/PAGE/blotting and dot-blotting techniques. The specific content of isozyme 3a in liver microsomes was found to be increased from 2- to >4-fold by administration of the following agents, in increasing order of effectiveness as inducers: isoniazid, trichloroethylene, pyrazole, ethanol, imidazole, and acetone. Isozyme 3a represents about 5% of the total P-450 in control animals and is increased to as high as 27% by acetone treatment. Isozyme 3a-dependent butanol-oxidation activity, determined by the inhibitory effect of antibody on the various microsomal preparations, was found to increase proportionally with increased content of this cytochrome.

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