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Fas antigen-mediated DNA fragmentation and apoptotic morphologic changes are regulated by elevated cytosolic Ca2+
1Department of Physiology, Tokyo Women's Medical College, Japan.
Journal of Immunology (Baltimore, Md. : 1950)
|January 15, 1995
Summary
Fas stimulation triggers rapid calcium (Ca2+) increases in B cells, driving apoptosis. Sustained elevation of cytosolic Ca2+ is crucial for DNA fragmentation and cell death, highlighting calcium
Area of Science:
- Cell Biology
- Immunology
- Biochemistry
Background:
- Fas Ag (antigen) is expressed on human B cell lines.
- Anti-Fas monoclonal antibody (mAb) induces apoptosis in B cells.
- Cytosolic calcium concentration ([Ca2+]i) dynamics are implicated in apoptosis.
Purpose of the Study:
- To investigate the role of cytosolic calcium ([Ca2+]i) rises in Fas-mediated apoptosis.
- To characterize the temporal changes in [Ca2+]i during apoptosis induction.
- To determine the critical calcium levels required for apoptotic events.
Main Methods:
- Continuous single-cell imaging of [Ca2+]i.
- Use of intracellular and extracellular Ca2+ chelators.
- Treatment of FMO human B cells with anti-Fas mAb.
Main Results:
- Four distinct phases of [Ca2+]i elevation were observed post-mAb addition.
- Early [Ca2+]i rises involved Ca2+ entry, while sustained elevation stemmed from intracellular release.
- A sustained [Ca2+]i above 140-150 nM was essential for DNA fragmentation and cell fragmentation, with Ca2+ entry driving later stages.
Conclusions:
- Calcium mobilization is an immediate consequence of Fas stimulation.
- [Ca2+]i elevation is a prerequisite for key apoptotic morphological changes.
- Fas-mediated apoptosis involves a critical, sustained rise in cytosolic calcium.