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Apoptosis induced by atRA in MEPM cells is mediated through activation of caspase and RAR

Zengli Yu1, Jing Han, Jiuxiang Lin

  • 1School of Stomatology, Peking University Health Science Center, Beijing, China.

Toxicological Sciences : an Official Journal of the Society of Toxicology
|November 18, 2005
PubMed

Insights

All-trans retinoic acid (atRA) triggers apoptosis in mouse embryonic palate mesenchymal cells (MEPM) via caspase-9 and caspase-3 activation. This cell death pathway is dependent on retinoic acid receptors (RARs).

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • All-trans retinoic acid (atRA) is known to inhibit growth and induce apoptosis in mouse embryonic palate mesenchymal cells (MEPM).
  • The precise molecular mechanisms and signaling pathways underlying atRA-induced apoptosis require further elucidation.

Purpose of the Study:

  • To investigate the molecular mechanisms of atRA-induced apoptosis in MEPM cells.
  • To identify the specific caspase activation and receptor pathways involved in atRA-mediated cell death.

Main Methods:

  • Assessing apoptosis via DNA fragmentation and sub-G1 fraction analysis.
  • Utilizing specific caspase inhibitors (broad, caspase-9, caspase-3, caspase-8) to block atRA effects.
  • Quantifying mRNA expression of retinoic acid receptors (RARs) using RT-qPCR.
  • Employing a pan RAR antagonist (BMS493) to determine receptor dependency.

Main Results:

  • atRA-induced apoptosis involves the activation of caspase-9 and caspase-3, but not caspase-8.
  • Caspase inhibitors targeting caspase-9 and caspase-3, but not caspase-8, effectively blocked atRA-induced DNA fragmentation and sub-G1 accumulation.
  • atRA dose-dependently increased mRNA expression of RAR-beta and RAR-gamma, with a slight increase in RAR-alpha at high concentrations.
  • The pan RAR antagonist BMS493 completely inhibited atRA-induced DNA fragmentation, sub-G1 fraction, and caspase-3 activation.

Conclusions:

  • atRA induces apoptosis in MEPM cells through a caspase-dependent pathway involving caspase-9 and caspase-3.
  • This apoptotic process is mediated by the retinoic acid receptor (RAR) signaling pathway.
  • The findings highlight the critical role of RARs in mediating the cellular effects of atRA on apoptosis.

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