Depolarization and laminin independently enable bFGF to promote neuronal survival through different second messenger pathways.
This study presents evidence that cellular responsiveness to the neurotrophic factor basic fibroblast growth factor (bFGF) can be achieved by at least two classes of agents using different initial second messenger pathways. Embryonic chick ciliary ganglion neurons plated on polyornithine normally undergo rapid cell death in culture and could not be rescued by addition of bFGF. Similarly, neither exposure to laminin alone nor low levels of depolarization alone was sufficient to promote neuronal survival. In contrast, if ciliary ganglion neurons were exposed to bFGF in the presence of either laminin or low levels of depolarization, nearly all neurons were rescued from cell death. The observed synergistic effect of bFGF and low levels of depolarization required influx of calcium since addition of the L-type calcium channel antagonists PN200-110 completely prevented neuronal survival. The synergistic effect observed between laminin and bFGF was independent of changes in intracellular calcium since PN200-110 failed to block the synergistic effect and because neither addition of bFGF to neurons plated on laminin nor direct addition of laminin caused any significant changes in intracellular calcium. The ability of laminin to enable bFGF to promote neuronal survival could completely be blocked by the addition of antibodies to beta 1-integrin, suggesting a calcium-independent integrin-mediated response. Taken together, these results suggest that both laminin and depolarization can enable bFGF responsiveness by acting through different second messenger pathways.
Schmidt
M F
MF
Department of Anatomy and Neurobiology, Colorado State University, Fort Collins 80523, USA.
Kater
S B
SB
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D005724:Ganglia / Q000166:cytology / Q000502:physiology; D007797:Laminin / Q000494:pharmacology*; D009474:Neurons / Q000502:physiology*; D015290:Second Messenger Systems; D015398:Signal Transduction
D002121:Calcium Channel Blockers; D007797:Laminin; D016222:Fibroblast Growth Factor 2; D002118:Calcium