Related Experiment Video

Updated: Jun 22, 2026

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells
05:45

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells

Published on: October 10, 2025

Bax-associated mechanisms underlying the response of embryonic cells to methotrexate

S Savion1, E Shtelman, H Orenstein

  • 1Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel. shoshans@post.tau.ac.il

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|June 16, 2009
PubMed

Insights

Bax protein influences how embryonic cells respond to teratogens like methotrexate. Bax knockout cells showed less sensitivity to methotrexate-induced apoptosis compared to wild-type cells.

Area of Science:

  • Developmental Biology
  • Cell Biology
  • Toxicology

Background:

  • Bax protein regulates apoptosis in various experimental systems.
  • Its role in teratogen-induced apoptosis remains unclear.
  • Understanding Bax's function is crucial for embryonic development and teratogen response.

Purpose of the Study:

  • To investigate the involvement of Bax in the response of mouse embryonic fibroblasts (MEFs) to the teratogen methotrexate (MTX).
  • To compare the effects of MTX on wild-type (WT) and Bax knockout (Bax(-/-)) MEFs.

Main Methods:

  • Utilized Bax WT and Bax(-/-) MEFs exposed to varying doses and durations of MTX.
  • Assessed cell survival, proliferation, cell cycle distribution (Sub-G1, S phase), and nuclear morphology.
  • Quantified the expression of Bax, bcl-2, p65, and IkappaBalpha proteins.

Main Results:

  • MTX induced dose- and time-dependent decreases in cell survival and culture density, more pronounced in WT MEFs.
  • MTX reduced proliferation in WT MEFs but not in Bax(-/-) MEFs, with cell cycle shifts observed.
  • WT MEFs showed increased Bax-positive cells and decreased bcl-2, p65, and IkappaBalpha expression, unlike Bax(-/-) MEFs.

Conclusions:

  • Differential sensitivity of WT and Bax(-/-) MEFs to MTX suggests Bax's involvement in the embryonic cellular response to teratogens.
  • Bax plays a significant role in mediating apoptosis induced by teratogens in embryonic cells.
  • Findings contribute to understanding the mechanisms of teratogenesis and potential therapeutic targets.

More Related Videos

An Alternative Culture Method to Maintain Genomic Hypomethylation of Mouse Embryonic Stem Cells Using MEK Inhibitor PD0325901 and Vitamin C11:53

An Alternative Culture Method to Maintain Genomic Hypomethylation of Mouse Embryonic Stem Cells Using MEK Inhibitor PD0325901 and Vitamin C

Published on: June 1, 2018

A Two-Step Strategy that Combines Epigenetic Modification and Biomechanical Cues to Generate Mammalian Pluripotent Cells08:01

A Two-Step Strategy that Combines Epigenetic Modification and Biomechanical Cues to Generate Mammalian Pluripotent Cells

Published on: August 29, 2020

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Phase II Reactions: Methylation Reactions01:17

Phase II Reactions: Methylation Reactions

Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...