Linked Life Data

8301591

Source:http://linkedlifedata.com/resource/pubmed/id/8301591

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-3-10
pubmed:abstractText
The down regulation of constitutive hepatic microsomal cytochromes P-450 (P450) by interferons has been well described in experimental animals and humans, however the down regulation of induced forms of P450 has not been documented clearly. Differential down regulation of constitutive and induced P450 could alter the proportions of P450 enzymes and, hence, the relative bioactivation/detoxification of xenobiotics. We investigated the effects of polyinosinic acid-polycytidylic acid, a potent stimulator of interferon alpha/beta production on CYP1A and CYP2E induction in the rat. Polyinosinic acid-polycytidylic acid down regulated the constitutive and pyridine-induced expression of CYP2E1 and the pyridine- and beta-naphthoflavone-induced expression of CYP1A1 as demonstrated by metabolic activity and immunoblot analyses. Depression of CYP2E1 and CYP1A1 protein expression by polyinosinic acid-polycytidylic acid was accompanied by a corresponding decrease in mRNA encoding these proteins. Induction of CYP1A2 mRNA also was depressed. Therefore, interferon alpha/beta down regulated induction of members of the CYP1A and CYP2E subfamilies at a pretranslational level independent of the mechanism of induction. Induction of the CYP1A and CYP2E subfamilies did not confer resistance to down regulation by interferon, although the magnitude of down regulation by interferon appeared to be influenced by the magnitude of P450 induction. The potential significance of down regulation of induced P450 in the clearance of certain therapeutic agents and in xenobiotic bioactivation and detoxification is discussed.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
268
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
487-94
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Regulation of cytochrome P-4501A and cytochrome P-4502E induction in the rat during the production of interferon alpha/beta.
pubmed:affiliation
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't