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Involvement of NF-kappaB in the response of embryonic cells to methotrexate

Masha Brengauz-Breitmann1, Elena Friedman, Shoshana Savion

  • 1Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.

Reproductive Toxicology (Elmsford, N.Y.)
|February 18, 2006
PubMed

Insights

The p65 subunit of Nuclear Factor-kappaB (NF-kappaB) plays a key role in how embryonic cells respond to the anti-cancer drug methotrexate (MTX). Mouse embryonic fibroblasts lacking p65 were more sensitive to MTX-induced cell death.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Toxicology

Background:

  • Nuclear Factor-kappaB (NF-kappaB) is implicated in apoptosis regulation, but its precise role remains unclear.
  • Understanding teratogen-induced cell death mechanisms is crucial for developmental toxicology.

Purpose of the Study:

  • To investigate the role of the NF-kappaB p65 subunit in mouse embryonic fibroblasts (MEFs) exposed to methotrexate (MTX).
  • To elucidate the involvement of p65 in MTX-induced cellular responses, including cell death and cell cycle regulation.

Main Methods:

  • Utilized p65 knockout (p65(-/-)) MEFs and wild-type (WT) MEFs.
  • Assessed cell survival, cell cycle progression, proliferation, and apoptosis/necrosis rates.
  • Analyzed the intracellular localization of p65, IkappaBalpha, and Bax.

Main Results:

  • p65(-/-) MEFs exhibited increased susceptibility to MTX compared to WT MEFs.
  • Profound alterations in cell survival, cell cycle, proliferation, and cell death were observed in p65(-/-) cells.
  • Distinct intracellular localization patterns of p65, IkappaBalpha, and Bax were detected in response to MTX.

Conclusions:

  • The p65 subunit of NF-kappaB is significantly involved in the response of embryonic cells to MTX.
  • p65 plays a protective or regulatory role in mitigating MTX-induced cellular damage in MEFs.

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