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Apoptosis in hematopoietic cells is associated with an extensive decrease in cellular phosphotyrosine content that
F Lund-Johansen1, T Frey, J A Ledbetter
1Becton Dickinson Immunocytometry Systems, San Jose, California, USA. johansen@dnax.org
Cytometry
|October 1, 1996
Summary
This study reveals that apoptosis in hematopoietic cells involves a significant decrease in cellular phosphotyrosine levels. This tyrosine dephosphorylation is a key event during programmed cell death.
Area of Science:
- Cell Biology
- Biochemistry
- Immunology
Background:
- Apoptosis, or programmed cell death, is crucial for development and tissue homeostasis.
- The role of protein tyrosine phosphorylation in regulating apoptosis is not fully understood.
Purpose of the Study:
- To investigate the association between apoptosis in hematopoietic cells and changes in cellular phosphotyrosine content.
- To explore the potential mechanistic role of tyrosine dephosphorylation in apoptosis.
Main Methods:
- Induction of apoptosis in murine thymocytes, B cells, human leukemia cells, and normal peripheral blood leukocytes.
- Multiparameter flow cytometry to assess phosphotyrosine levels and apoptotic markers (cell shrinkage, DNA fragmentation, membrane integrity loss).
- Treatment with a protein tyrosine phosphatase antagonist (pervanadate) to evaluate its effect on dephosphorylation and apoptosis.
Main Results:
- Apoptosis induction led to a significant decrease in cellular phosphotyrosine levels.
- Tyrosine dephosphorylation preceded loss of membrane integrity and correlated with DNA fragmentation.
- Pervanadate inhibited dephosphorylation and apoptosis in a dose-dependent manner.
Conclusions:
- Extensive tyrosine dephosphorylation is an intrinsic component of the apoptotic process in hematopoietic cells.
- Tyrosine dephosphorylation may play a mechanistic role in apoptosis induced by specific stimuli.