Fas activation increases neural progenitor cell survival
Julia C Knight1, Eugene L Scharf, Yang Mao-Draayer
1Neuroscience Graduate Program, University of Vermont, Burlington, Vermont, USA.
Journal of Neuroscience Research
|October 16, 2009
Summary
Adult neural progenitor cells (NPCs) resist Fas ligand-induced death. Fas activation promotes NPC survival by reducing apoptosis via Birc3 up-regulation, revealing a novel neuroprotective pathway.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Adult neural progenitor cells (NPCs) are researched for neurodegenerative disease therapies.
- The role of Fas signaling in NPC survival is largely unknown.
- Fas is a death receptor superfamily member with known immune system functions.
Purpose of the Study:
- To investigate the effects of Fas signaling on adult murine NPC survival in vitro.
- To determine the mechanisms underlying Fas-mediated effects on NPCs.
Main Methods:
- Cultured murine adult NPCs were treated with recombinant Fas ligand (FasL).
- Cell viability, apoptosis, and proliferation were assessed.
- Expression levels of apoptosis-related proteins, including Birc3 and FLIP, were analyzed.
Main Results:
- FasL treatment did not induce apoptosis in NPCs; instead, it increased cell viability.
- FasL mediated neuroprotection by reducing apoptosis, not by increasing proliferation.
- The antiapoptotic effect was linked to the up-regulation of Birc3 (an inhibitor of apoptosis protein).
- Altered caspase activation or FLIP up-regulation were not responsible for the observed effect.
Conclusions:
- Murine adult NPCs are resistant to FasL-induced cell death.
- Fas activation enhances NPC survival by decreasing apoptosis through Birc3 up-regulation.
- This study identifies a novel pathway regulating NPC survival.
