Linked Life Data

15385644

Source:http://linkedlifedata.com/resource/pubmed/id/15385644

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-9-23
pubmed:abstractText
Exposure of the human breast epithelial cell line MCF10A to > or = 1 microg/ml cycloheximide (CHX)-induced accumulations of CYP1A1 mRNA 6-fold greater than that achieved with only 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Cotreatment with CHX and TCDD caused superinduction of CYP1A1 with accumulations of CYP1A1 mRNA 30-fold greater than that achieved with only TCDD. Similar results were obtained with the protein translation inhibitors anisomycin (ANS) and puromycin (PUR). Intra- and interinhibitor comparisons of dose/concentration response curves demonstrated the absence of a quantitative relationship between [3H]leucine incorporation and CYP1A1 induction/superinduction. The inducing/superinducing activities of CHX were suppressed by coincubation with the aryl hydrocarbon receptor (AhR) antagonists alpha-naphthoflavone and 3'-methoxy-4'-nitroflavone (PD168641). Electrophoretic mobility shift assays demonstrated that nuclear extracts from CHX-treated and CHX + TCDD cotreated cultures formed approximately 58 and approximately 340% of the AhR/DNA complexes obtained with TCDD-treated cultures, respectively. In contrast, rat liver extracts did not form AhR/DNA complexes after in vitro transformation with CHX. AhR turnover in TCDD-treated hepatoma 1c1c7 cultures was suppressed by cotreatment with CHX. In contrast, CHX or ANS treatment of MCF10A cultures induced AhR loss and enhanced AhR loss in cultures cotreated with TCDD. Cotreatment with N-benzoyloxycarbonyl-(Z)-Leu-Leu-leucinal (MG132) but not leptomycin B suppressed AhR loss. Hence, in MCF10A cells, CHX is not an AhR agonist but can superinduce CYP1A1 via an AhR-dependent mechanism; CYP1A1 superinduction by translation inhibitors is neither quantitatively related to effects on protein synthesis nor due to a generalized prevention of AhR proteolysis, and proteasome-mediated degradation of the activated AhR can occur in the nucleus.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Anisomycin, http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide, http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP1A1, http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP1A2, http://linkedlifedata.com/resource/pubmed/chemical/DNA, http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acids, Unsaturated, http://linkedlifedata.com/resource/pubmed/chemical/Leucine, http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins, http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex, http://linkedlifedata.com/resource/pubmed/chemical/Puromycin, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Aryl Hydrocarbon, http://linkedlifedata.com/resource/pubmed/chemical/Tetrachlorodibenzodioxin, http://linkedlifedata.com/resource/pubmed/chemical/Tritium, http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylleucyl-leucyl-leuci..., http://linkedlifedata.com/resource/pubmed/chemical/leptomycin B
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
936-47
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Superinduction of CYP1A1 in MCF10A cultures by cycloheximide, anisomycin, and puromycin: a process independent of effects on protein translation and unrelated to suppression of aryl hydrocarbon receptor proteolysis by the proteasome.
pubmed:affiliation
Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48201, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.