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FGF induces a switch in death receptor pathways in neuronal cells
E M Eves1, C Skoczylas, K Yoshida
1Ben May Institute for Cancer Research, Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.
Summary
Basic fibroblast growth factor (FGF2) influences neuronal development. FGF2 suppresses the Fas death pathway but activates a TNFalpha pathway, explaining its varied effects on neuronal survival and highlighting the need for multiple trophic signals.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Basic fibroblast growth factor (FGF2) plays crucial roles in neuronal development and maintenance.
- FGF2 impacts neuronal processes like survival, differentiation, and migration.
Purpose of the Study:
- To investigate how FGF2 regulates the tumor necrosis factor (TNF) superfamily of death receptors and ligands in neuronal cells.
- To elucidate the mechanisms underlying FGF2's pro-apoptotic and anti-apoptotic effects.
Main Methods:
- Utilized a conditionally immortalized rat hippocampal cell line (H19-7) and primary hippocampal cultures.
- Analyzed apoptosis pathways, including Fas-dependent and TNFalpha-dependent mechanisms, in response to FGF2 treatment.
- Examined the expression of TNF receptors (TNFR1, TNFR2) and their role in TNFalpha-induced apoptosis.
Main Results:
- FGF2 treatment induced apoptosis via a Fas-independent mechanism in H19-7 cells.
- FGF2 suppressed the Fas death pathway while simultaneously activating a TNFalpha death pathway.
- Expression of TNFR1 or TNFR2 sensitized cells to TNFalpha, mimicking FGF2's effects.
Conclusions:
- FGF2 differentially regulates TNF superfamily death receptors and ligands, impacting neuronal apoptosis.
- The dual action of FGF2 on Fas and TNFalpha pathways provides insight into its complex trophic effects.
- These findings suggest that multiple trophic inputs are essential for specific neuronal survival.