Linked Life Data

9210482

Source:http://linkedlifedata.com/resource/pubmed/id/9210482

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-8-4
pubmed:abstractText
Expression of P-glycoprotein, a plasma-membrane glycoprotein involved in multidrug resistance and encoded by mdr genes, was investigated in cultured rat liver cells acutely exposed to doxorubicin. This anticancer drug was shown to increase mdr mRNA levels in a dose-dependent manner in both rat liver epithelial (RLE) cells and primary rat hepatocytes. This induction of mdr transcripts was detected as early as a 4-h exposure to doxorubicin used at 0.5 microg/ml. It occurred through increased expression of the mdr1 gene as assessed by northern blot analysis using rat mdr-gene-specific probes. In addition, RLE cells exposed to doxorubicin displayed an overexpression of a 140-kDa P-glycoprotein as demonstrated by western blotting. Moreover, doxorubicin-treated RLE cells displayed enhanced cellular efflux of the P-glycoprotein substrate rhodamine 123 that was inhibited by the P-glycoprotein blocker verapamil, thus providing evidence that doxorubicin-induced P-glycoprotein was functional in liver cells. Doxorubicin-mediated mdr mRNA induction was found to be fully inhibited by actinomycin D, thus indicating its dependence on RNA synthesis; it was demonstrated to be not associated with alteration of protein synthesis, suggesting it differed from the known mdr mRNA overexpression occurring in response to cycloheximide. In contrast to P-glycoprotein, other liver detoxification pathways such as cytochromes P-450 1A were not induced by doxorubicin treatment. These data indicate that doxorubicin can act as a potent acute inducer of functional P-glycoprotein in rat liver cells and therefore may modulate both chemosensitivity of hepatic cells and P-glycoprotein-mediated biliary secretion of xenobiotics.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
246
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
186-92
pubmed:dateRevised
2007-7-23
pubmed:meshHeading
pubmed-meshheading:9210482-ATP-Binding Cassette Transporters, pubmed-meshheading:9210482-Animals, pubmed-meshheading:9210482-Antibiotics, Antineoplastic, pubmed-meshheading:9210482-Blotting, Northern, pubmed-meshheading:9210482-Blotting, Western, pubmed-meshheading:9210482-Cell Line, pubmed-meshheading:9210482-Cell Survival, pubmed-meshheading:9210482-Cells, Cultured, pubmed-meshheading:9210482-Cycloheximide, pubmed-meshheading:9210482-Cytochrome P-450 CYP1A1, pubmed-meshheading:9210482-Cytochrome P-450 CYP1A2, pubmed-meshheading:9210482-Dactinomycin, pubmed-meshheading:9210482-Doxorubicin, pubmed-meshheading:9210482-Drug Resistance, Multiple, pubmed-meshheading:9210482-Genes, MDR, pubmed-meshheading:9210482-Liver, pubmed-meshheading:9210482-P-Glycoprotein, pubmed-meshheading:9210482-P-Glycoproteins, pubmed-meshheading:9210482-RNA, Messenger, pubmed-meshheading:9210482-Rats, pubmed-meshheading:9210482-Rats, Sprague-Dawley, pubmed-meshheading:9210482-Up-Regulation
pubmed:year
1997
pubmed:articleTitle
Up-regulation of P-glycoprotein expression in rat liver cells by acute doxorubicin treatment.
pubmed:affiliation
Unité Détoxication et Réparation Tissulaire, U456 de l'INSERM, Faculté de Pharmacie, Rennes, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't