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

Isozyme 3a of rabbit liver microsomal cytochrome P-450, also termed P-450ALC, 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 ethano...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 1985-06, Vol.82 (12), p.4065-4069
Hauptverfasser: Koop, Dennis R., Crump, Becky L., Nordblom, Gerald D., Coon, Minor J.
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container_issue 12
container_start_page 4065
container_title Proceedings of the National Academy of Sciences - PNAS
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creator Koop, Dennis R.
Crump, Becky L.
Nordblom, Gerald D.
Coon, Minor J.
description Isozyme 3a of rabbit liver microsomal cytochrome P-450, also termed P-450ALC, 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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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 &gt;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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.82.12.4065</identifier><identifier>PMID: 3858864</identifier><identifier>CODEN: PNASA6</identifier><language>eng</language><publisher>Washington, DC: National Academy of Sciences of the United States of America</publisher><subject>Acetone - pharmacology ; Analytical, structural and metabolic biochemistry ; Animals ; Antibodies ; Biological and medical sciences ; Butanols ; Butanols - metabolism ; Cellulose nitrate ; Cytochrome P-450 Enzyme System - biosynthesis ; Cytochrome P-450 Enzyme System - immunology ; cytochrome P450 ; Cytochromes ; Enzyme Induction - drug effects ; Ethanol ; Ethanol - pharmacology ; Fundamental and applied biological sciences. 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Psychology</topic><topic>Hemoproteins</topic><topic>Imidazoles</topic><topic>Imidazoles - pharmacology</topic><topic>Isoenzymes - biosynthesis</topic><topic>Isoenzymes - immunology</topic><topic>Isoniazid - pharmacology</topic><topic>liver</topic><topic>Liver microsomes</topic><topic>Male</topic><topic>Metalloproteins</topic><topic>Microsomes</topic><topic>Microsomes, Liver - enzymology</topic><topic>Oxidation</topic><topic>Proteins</topic><topic>Pyrazoles</topic><topic>Pyrazoles - pharmacology</topic><topic>Rabbits</topic><topic>Trichloroethylene - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Koop, Dennis R.</creatorcontrib><creatorcontrib>Crump, Becky L.</creatorcontrib><creatorcontrib>Nordblom, Gerald D.</creatorcontrib><creatorcontrib>Coon, Minor J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koop, Dennis R.</au><au>Crump, Becky L.</au><au>Nordblom, Gerald D.</au><au>Coon, Minor J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1985-06-01</date><risdate>1985</risdate><volume>82</volume><issue>12</issue><spage>4065</spage><epage>4069</epage><pages>4065-4069</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><coden>PNASA6</coden><abstract>Isozyme 3a of rabbit liver microsomal cytochrome P-450, also termed P-450ALC, 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 &gt;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.</abstract><cop>Washington, DC</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>3858864</pmid><doi>10.1073/pnas.82.12.4065</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
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subjects Acetone - pharmacology
Analytical, structural and metabolic biochemistry
Animals
Antibodies
Biological and medical sciences
Butanols
Butanols - metabolism
Cellulose nitrate
Cytochrome P-450 Enzyme System - biosynthesis
Cytochrome P-450 Enzyme System - immunology
cytochrome P450
Cytochromes
Enzyme Induction - drug effects
Ethanol
Ethanol - pharmacology
Fundamental and applied biological sciences. Psychology
Hemoproteins
Imidazoles
Imidazoles - pharmacology
Isoenzymes - biosynthesis
Isoenzymes - immunology
Isoniazid - pharmacology
liver
Liver microsomes
Male
Metalloproteins
Microsomes
Microsomes, Liver - enzymology
Oxidation
Proteins
Pyrazoles
Pyrazoles - pharmacology
Rabbits
Trichloroethylene - pharmacology
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
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