Document Detail


Involvement of NF-kappaB in the response of embryonic cells to methotrexate.
MedLine Citation:
PMID:  16483740     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The involvement of NF-kappaB in the regulation of the apoptotic process was demonstrated previously, however, its exact role has not been established yet. In order to unravel mechanisms underlying teratogen-induced cell death, we tried in our present study to assess the involvement of the p65 subunit of NF-kappaB in the response of mouse embryonic fibroblasts (MEFs) to the anti-cancer drug methotrexate (MTX), using p65 knockout MEFs (p65(-/-)). Indeed, this cell line was found to be more susceptible to the exposure to MTX, demonstrated by more profound changes in cell survival, cell cycle, proliferation and the percentage of apoptotic or necrotic cells, as compared to wild type (WT) MEFs. Also, a different pattern of intracellular localization of p65 in WT cells as well as IkappaBalpha and Bax in both cell lines was detected in response to MTX. Altogether, our results implicate the p65 subunit of NF-kappaB to play an important role in the response of embryonic cells to MTX.
Authors:
Masha Brengauz-Breitmann; Elena Friedman; Shoshana Savion; Arkady Torchinsky; Amos Fein; Vladimir Toder
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-02-17
Journal Detail:
Title:  Reproductive toxicology (Elmsford, N.Y.)     Volume:  22     ISSN:  0890-6238     ISO Abbreviation:  Reprod. Toxicol.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-15     Completed Date:  2006-11-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8803591     Medline TA:  Reprod Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  469-78     Citation Subset:  IM    
Affiliation:
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antimetabolites, Antineoplastic / toxicity*
Apoptosis / drug effects
Apoptosis Regulatory Proteins / metabolism
Blotting, Western
Cell Cycle / drug effects
Cell Line
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Embryo, Mammalian
Fibroblasts / drug effects*,  metabolism
I-kappa B Proteins / metabolism
In Situ Nick-End Labeling
Methotrexate / toxicity*
Mice
Mice, Knockout
Microscopy, Confocal
NF-kappa B / metabolism*
Transcription Factor RelA / metabolism
bcl-2-Associated X Protein / metabolism
Chemical
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/Apoptosis Regulatory Proteins; 0/Bax protein, mouse; 0/I-kappa B Proteins; 0/NF-kappa B; 0/Rela protein, mouse; 0/Transcription Factor RelA; 0/bcl-2-Associated X Protein; 139874-52-5/NF-kappaB inhibitor alpha; 59-05-2/Methotrexate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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