FGF induces a switch in death receptor pathways in neuronal cells.

E M Eves, C Skoczylas, K Yoshida, E S Alnemri, M R Rosner
Author Information
  1. E M Eves: Ben May Institute for Cancer Research, Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.

Abstract

Basic fibroblast growth factor (FGF2) has many roles in neuronal development and maintenance including effects on mitogenesis, survival, fate determination, differentiation, and migration. Using a conditionally immortalized rat hippocampal cell line, H19-7, and primary hippocampal cultures, we now demonstrate that FGF2 treatment differentially regulates members of the tumor necrosis factor (TNF) superfamily of death domain receptors and their ligands. H19-7 cells transferred from serum to defined (N2) medium undergo apoptosis by a Fas-dependent mechanism similar to primary neurons. In contrast, H19-7 cells treated with FGF undergo apoptosis by a Fas-independent mechanism. FGF suppresses the Fas death pathway but also induces apoptosis by activation of a TNFalpha death pathway in both H19-7 and hippocampal progenitor cells. Expression of the TNF receptor 1 (TNFR1) or TNFR2 in H19-7 cells is sufficient to sensitize the cells to TNFalpha, similar to the effects of FGF. Because TNFalpha can be either proapoptotic or antiapoptotic, these results provide an explanation for the divergent trophic effects of FGF2 treatment and the observation that multiple trophic inputs are required for the survival of specific neurons.

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Grants

  1. NS33858/NINDS NIH HHS

MeSH Term

Animals
Antigens, CD
Apoptosis
CASP8 and FADD-Like Apoptosis Regulating Protein
Carrier Proteins
Caspase Inhibitors
Caspases
Cell Survival
Cells, Cultured
Dose-Response Relationship, Drug
Fas Ligand Protein
Fibroblast Growth Factor 2
Hippocampus
Intracellular Signaling Peptides and Proteins
Membrane Glycoproteins
Neurons
RNA, Messenger
Rats
Receptors, Tumor Necrosis Factor
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Signal Transduction
Transfection
Tumor Necrosis Factor-alpha
fas Receptor

Chemicals

Antigens, CD
CASP8 and FADD-Like Apoptosis Regulating Protein
Carrier Proteins
Caspase Inhibitors
Fas Ligand Protein
Faslg protein, rat
Intracellular Signaling Peptides and Proteins
Membrane Glycoproteins
RNA, Messenger
Receptors, Tumor Necrosis Factor
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Tumor Necrosis Factor-alpha
fas Receptor
Fibroblast Growth Factor 2
Caspases

Word Cloud

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