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 |
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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 >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. 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</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1985-06, Vol.82 (12), p.4065-4069</ispartof><rights>1985 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c521t-b2d84fa314564e5dbcd61da1898dddfc9b23b11a6a0fa6e6a8b3283580ee4d643</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/82/12.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26031$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26031$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27923,27924,53790,53792,58016,58249</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=9247578$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/3858864$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koop, Dennis R.</creatorcontrib><creatorcontrib>Crump, Becky L.</creatorcontrib><creatorcontrib>Nordblom, Gerald D.</creatorcontrib><creatorcontrib>Coon, Minor J.</creatorcontrib><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</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><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.</description><subject>Acetone - pharmacology</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Biological and medical sciences</subject><subject>Butanols</subject><subject>Butanols - metabolism</subject><subject>Cellulose nitrate</subject><subject>Cytochrome P-450 Enzyme System - biosynthesis</subject><subject>Cytochrome P-450 Enzyme System - immunology</subject><subject>cytochrome P450</subject><subject>Cytochromes</subject><subject>Enzyme Induction - drug effects</subject><subject>Ethanol</subject><subject>Ethanol - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Hemoproteins</subject><subject>Imidazoles</subject><subject>Imidazoles - pharmacology</subject><subject>Isoenzymes - biosynthesis</subject><subject>Isoenzymes - immunology</subject><subject>Isoniazid - pharmacology</subject><subject>liver</subject><subject>Liver microsomes</subject><subject>Male</subject><subject>Metalloproteins</subject><subject>Microsomes</subject><subject>Microsomes, Liver - enzymology</subject><subject>Oxidation</subject><subject>Proteins</subject><subject>Pyrazoles</subject><subject>Pyrazoles - pharmacology</subject><subject>Rabbits</subject><subject>Trichloroethylene - pharmacology</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1985</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFksFv0zAUxiMEGmNwRkIC-YDgsnR24iQOEoeqFKhUtAmNs-XYTuPJsYvtVGv_P_4vHDVU7AInW-_7fc9-T1-SvERwhmCVX20N8zOSzVA2w7AsHiXnCNYoLXENHyfnEGZVSnCGnybPvL-DENYFgWfJWU4KQkp8nvxa9f1gLO9krzjTYLlTQhouQWsdWBkx8KCsAbYFoZNgrrntrE6v75VQB2U2YLEP0exsL8FNigs4kt9Z06gA1monHfimuLM-6h40e_BprPnYaCNN8B_AMnTMWH0JVr0S7GC1vAS3TvFOW2dl6PZamliacxnseLnZu4liRoCVt0axgxLPkyct016-mM6L5Mfn5e3ia7q-_rJazNcpLzIU0iYTBLcsR7gosSxEw0WJBEOkJkKIltdNljcIsZLBlpWyZKTJM5LHlUmJRYnzi-Tjse92aHopeBzCMU23TvXM7allij5UjOroxu5oXld1XkT_u8nv7M9B-kB75bnUmhlpB0-rEuGyqKv_ggjnhBBYR_DqCI5b9k62p88gSMeE0DEhlGQUZXRMSHS8_nuGEz9FIupvJ535mIjWMcOVP2F1hquiIhF7M2Fj_z_qg3fe_xOg7aB1kPchkq-O5J0P1p3QrIQ5yn8DiLTpyw</recordid><startdate>19850601</startdate><enddate>19850601</enddate><creator>Koop, Dennis R.</creator><creator>Crump, Becky L.</creator><creator>Nordblom, Gerald D.</creator><creator>Coon, Minor J.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19850601</creationdate><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</title><author>Koop, Dennis R. ; Crump, Becky L. ; Nordblom, Gerald D. ; Coon, Minor J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c521t-b2d84fa314564e5dbcd61da1898dddfc9b23b11a6a0fa6e6a8b3283580ee4d643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1985</creationdate><topic>Acetone - pharmacology</topic><topic>Analytical, structural and metabolic biochemistry</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Biological and medical sciences</topic><topic>Butanols</topic><topic>Butanols - metabolism</topic><topic>Cellulose nitrate</topic><topic>Cytochrome P-450 Enzyme System - biosynthesis</topic><topic>Cytochrome P-450 Enzyme System - immunology</topic><topic>cytochrome P450</topic><topic>Cytochromes</topic><topic>Enzyme Induction - drug effects</topic><topic>Ethanol</topic><topic>Ethanol - pharmacology</topic><topic>Fundamental and applied biological sciences. 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 >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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