Fibroblast growth factors: structure-activity on dopamine neurons in vitro.
We investigated the effect of neurotrophic factors on dopamine (DA) cells in vitro. At concentrations of nanograms/c.c. basic fibroblast growth factor (bFGF) is a more potent DA-trophic agent than brain derived neurotrophic factor (BDNF) or epidermal growth factor (EGF) in fetal mid brain neurons. In these cells, bFGF produces a greater increase of DA levels and percentage of cells positive for tyrosine hydroxylase (TH+) than BDNF and EGF. Acidic fibroblast growth factor (aFGF) was not tested in fetal DA cells since aFGF requires heparin for its effect and fetal mid brain cultures do not grow well in the presence of a high concentration of heparin. We further investigated the effect of bFGF and aFGF, and two of their analogs, in catecholamine rich human neuroblastoma cells NB69. In these cells aFGF, at concentrations of picograms/c.c., increases DA levels, while its analogs, E118 and super short, have no effect. Acidic FGF also increases norepinephrine levels, the number of TH+ cells, and the percentage of TH+ with respect to the total number of nuclei. Basic fibroblast growth factor (bFGF) produced similar, but less potent effects. Acidic FGF was active only in the presence of heparin; the effect of bFGF was independent of heparin. FGFs are promising drugs for the treatment of PD, though further investigations with these compounds should be performed before their use in clinical trials.
Mena
M A
MA
Departamento de Investigacion, Centro Ramon y Cajal, Fundacion Jimenez Diaz, Madrid, Spain.
Casarejos
M J
MJ
Gimenéz-Gallego
G
G
Garcia de Yebenes
J
J
D000818:Animals; D001921:Brain / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009447:Neuroblastoma / Q000276:immunology; D009474:Neurons / Q000187:drug effects*; D010300:Parkinson Disease; D051381:Rats; D014407:Tumor Cells, Cultured
D016222:Fibroblast Growth Factor 2; D006493:Heparin; D004298:Dopamine