Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-1-6
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
267
pubmed:geneSymbol
CYP2B1, CYP2B2, CYP2E1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
927-36
pubmed:dateRevised
2007-11-14
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
pubmed:year
1993
pubmed:articleTitle
Enhanced expression of rat hepatic CYP2B1/2B2 and 2E1 by pyridine: differential induction kinetics and molecular basis of expression.
pubmed:affiliation
Institute of Chemical Toxicology, Wayne State University, Detroit, Michigan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.