Linked Life Data

8630083

Source:http://linkedlifedata.com/resource/pubmed/id/8630083

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1996-6-24
pubmed:abstractText
Expression of P-glycoprotein (P-gp), a plasma membrane glycoprotein involved in multidrug resistance and encoded by mdr genes, was investigated in nonparenchymal rat liver epithelial (RLE) cells in response to acute exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs). High levels of mdr mRNAs were evidenced by Northern blotting in two independent RLE cell lines after treatment by either 3-methylcholanthrene (MC) or benzo-(a)pyrene. MC-mediated mdr mRNA induction was demonstrated to be dose-dependent; it occurred through enhanced expression of the mdr 1 gene, as indicated by reverse transcriptase-polymerase chain reaction analysis using rat mdr gene-specific primers and paralleled an induction of a 140 kDa P-gp as demonstrated by Western blotting. In addition, MC-induced P-gp appeared to be fully functional because RLE cells exposed to MC displayed enhanced cellular efflux of rhodamine 123, a known P-gp substrate, compared to their untreated counterparts. Analysis of time-course induction revealed that mdr mRNA levels were maximally increased when RLE cells were treated for 48 to 96 hr and returned to low levels after the PAH was removed. In contrast to P-gp, both cytochrome P-450 1A1 and cytochrome P-450 1A2 were not detected after exposure to MC, thus indicating that these liver detoxification pathways are not coordinately regulated with P-gp in RLE cells. In addition, MC-mediated P-gp regulation was not associated with major cellular disturbances such as alteration of protein synthesis and, thereby, differed from the known mdr mRNA induction occurring in response to cycloheximide. Moreover, cotreatment with MC and cycloheximide led to a superinduction of mdr mRNAs, thus suggesting that the effects of the two xenobiotics were, at least partly, additive. In contrast to MC and benzo(a)pyrene, 2,3,7,8-tetrachlorodibenzo-p-dioxin and benzo(e)pyrene were unable to increase P-gp expression. These results indicate that some PAHs can act as potent inducers of P-gp in RLE cells and may be interpreted as an adaptive reaction of these cells in lowering cellular accumulation of toxic drugs, including carcinogens transported by P-gp and, therefore, conferring protection on these compounds.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1427-36
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8630083-Animals, pubmed-meshheading:8630083-Base Sequence, pubmed-meshheading:8630083-Blotting, Northern, pubmed-meshheading:8630083-Carcinogens, pubmed-meshheading:8630083-Cells, Cultured, pubmed-meshheading:8630083-Cytochrome P-450 CYP1A1, pubmed-meshheading:8630083-Cytochrome P-450 Enzyme System, pubmed-meshheading:8630083-Drug Resistance, Multiple, pubmed-meshheading:8630083-Gene Expression, pubmed-meshheading:8630083-Liver, pubmed-meshheading:8630083-Methylcholanthrene, pubmed-meshheading:8630083-Molecular Sequence Data, pubmed-meshheading:8630083-Oxidoreductases, pubmed-meshheading:8630083-P-Glycoprotein, pubmed-meshheading:8630083-Polymerase Chain Reaction, pubmed-meshheading:8630083-RNA, Messenger, pubmed-meshheading:8630083-Rats, pubmed-meshheading:8630083-Rats, Inbred F344, pubmed-meshheading:8630083-Rats, Sprague-Dawley
pubmed:year
1996
pubmed:articleTitle
P-glycoprotein induction in rat liver epithelial cells in response to acute 3-methylcholanthrene treatment.
pubmed:affiliation
INSERM U 49, Unité de Recherches Hépatologiques, Hôpital de Pontchaillou, Rennes, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't