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Thapsigargin-induced apoptosis involves Cabin1-MEF2-mediated induction of Nur77
1Center for Cancer Research, Departments of Biology and Chemistry, Massachusetts Institute of Technology, Cambridge 02139, USA.
European Journal of Immunology
|June 1, 2001
Summary
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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