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Thapsigargin-induced apoptosis involves Cabin1-MEF2-mediated induction of Nur77

W Liu1, H D Youn, J O Liu

  • 1Center for Cancer Research, Departments of Biology and Chemistry, Massachusetts Institute of Technology, Cambridge 02139, USA.

European Journal of Immunology
|June 1, 2001
PubMed

Insights

Thapsigargin induces apoptosis in T cells by increasing cytosolic calcium. This process involves the orphan steroid receptor Nur77, calcineurin, and MEF2 activation, mirroring pathways in T cell receptor-mediated apoptosis.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Thapsigargin (TG) inhibits endoplasmic reticulum Ca(2+)-ATPase, increasing cytosolic Ca(2+).
  • TG induces apoptosis in various cell types, including T lymphocytes.
  • The precise molecular mechanisms of TG-induced apoptosis in T cells require further elucidation.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying Thapsigargin (TG)-induced apoptosis in T cell hybridomas.
  • To identify key signaling pathways involved in TG-mediated T cell apoptosis.

Main Methods:

  • Exposure of T cell hybridomas to Thapsigargin (TG).
  • Analysis of Nur77 gene expression.
  • Assessment of cyclosporin A sensitivity.
  • Investigation of Cabin1 overexpression effects.
  • Evaluation of MEF2 transcription factor activity.

Main Results:

  • Thapsigargin (TG) exposure rapidly induces orphan steroid receptor Nur77 expression.
  • TG-induced Nur77 expression and apoptosis are sensitive to cyclosporin A, indicating calcineurin pathway involvement.
  • Overexpression of Cabin1 inhibits TG-induced Nur77 expression, suggesting MEF2 pathway activation is necessary.

Conclusions:

  • TG-induced Nur77 expression and apoptosis in T cell hybridomas are mediated by the calcineurin and Cabin1-MEF2 signaling pathways.
  • These pathways are similar to those involved in T cell receptor-mediated thymocyte apoptosis.

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