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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1994-1-6
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pubmed:abstractText |
Expression of the cytochrome P450 (CYP) 2B subfamily in rat and rabbit hepatic tissues after pyridine (PY) treatment has been examined, and the molecular basis for enhanced 2B1/2B2 expression has been determined. P450 expression was monitored using metabolic activity, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses, and the identity of the proteins was confirmed through N-terminus microsequence analysis. PY caused a dose-dependent elevation of hepatic CYP2B1/B2B levels in rats, which ranged from 4- to 22-fold over the dosing regimen of 100 to 400 mg PY/kg/day, for 3 days, respectively. PY at low dose failed to induce CYP2B in rabbit hepatic tissue, suggesting a species-dependent response in 2B expression. Anti-2B1 IgG addition to PY-induced microsomes inhibited benzphetamine N-demethylase activity by only approximately 15%, in sharp contrast to the approximately 73% inhibition observed for phenobarbital-induced microsomes, suggesting the induction of other form(s) of P450 having benzphetamine N-demethylase activity. Northern blot analysis revealed that PY treatment increased 2B1 and 2B2 poly(A)+ RNA levels approximately 69- and approximately 34-fold, respectively, whereas the 2E1 poly(A)+ RNA levels failed to increase. The results of this study show that PY induces CYP2B1/2B2 and that induction is species-dependent and kinetically distinguishable from 2E1 induction. Moreover, 2B1/2B2 induction occurs as a result of elevated mRNA levels associated with either transcriptional activation or mRNA stabilization, and it differs from the mechanism of hepatic 2E1 induction by PY.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP2B1,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP2E1,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidoreductases, N-Demethylating,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/pyridine
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
267
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pubmed:geneSymbol |
CYP2B1,
CYP2B2,
CYP2E1
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
927-36
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8246169-Animals,
pubmed-meshheading:8246169-Base Sequence,
pubmed-meshheading:8246169-Cytochrome P-450 CYP2B1,
pubmed-meshheading:8246169-Cytochrome P-450 CYP2E1,
pubmed-meshheading:8246169-Cytochrome P-450 Enzyme System,
pubmed-meshheading:8246169-Dose-Response Relationship, Drug,
pubmed-meshheading:8246169-Enzyme Induction,
pubmed-meshheading:8246169-Gene Expression,
pubmed-meshheading:8246169-Kinetics,
pubmed-meshheading:8246169-Liver,
pubmed-meshheading:8246169-Male,
pubmed-meshheading:8246169-Molecular Sequence Data,
pubmed-meshheading:8246169-Oxidoreductases,
pubmed-meshheading:8246169-Oxidoreductases, N-Demethylating,
pubmed-meshheading:8246169-Pyridines,
pubmed-meshheading:8246169-RNA, Messenger,
pubmed-meshheading:8246169-Rabbits,
pubmed-meshheading:8246169-Rats,
pubmed-meshheading:8246169-Rats, Sprague-Dawley,
pubmed-meshheading:8246169-Species Specificity
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pubmed:year |
1993
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pubmed:articleTitle |
Enhanced expression of rat hepatic CYP2B1/2B2 and 2E1 by pyridine: differential induction kinetics and molecular basis of expression.
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pubmed:affiliation |
Institute of Chemical Toxicology, Wayne State University, Detroit, Michigan.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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