Investigation of the ability of several naturally occurring and synthetic polyanions to bind to and potentiate the biological activity of acidic fibroblast growth factor.
The ability of several animal, plant, and bacterial derived polyanions (PAs) as well as synthetic PAs to compete with heparin for the binding of acidic fibroblast growth factor (aFGF) was correlated with their ability to potentiate the mitogenic and neurotrophic actions of this factor. Dextran sulphate, kappa-carrageenan, pentosan sulphate, polyanethole sulfonate, heparin, and fucoidin competed for the heparin binding site on aFGF at relatively low concentrations (< 50 micrograms/ml). lambda-carrageenan, iota-carrageenan, and polyvinyl sulphate exhibited lower affinity for aFGF, whereas hyaluronic acid, dermatan sulphate, chondroitin-6-sulphate, chondroitin-4-sulphate, and uncharged dextran displayed very low or no demonstrable affinity. Potentiation of the mitogenic action of aFGF for Balb/c 3T3 fibroblasts tended to be in general agreement with the aFGF binding affinity of the PAs. However, polyanethole sulfonate, the carrageenans, polyvinyl sulphate, fucoidin, and pentosan sulphate exerted a mitogenic action on the 3T3 cells that was independent of, and in addition to, the ability of these GAGs to potentiate the action of aFGF. The ability to potentiate the neurotrophic action of aFGF for E8 chick ciliary neurons was a general property of those PA with low or no activity in the mitogen assay. Thus hyaluronic acid, dermatan sulphate, chondroitin-4-sulphate, chondroitin-6-sulphate, and even unchanged dextran all potentiated aFGF induced neuronal survival. The differential effects of these PA in potentiating the biological activities of aFGF are discussed in relation to their ability to compete for the heparin-binding site of aFGF.
Belford
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Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra ACT.
Hendry
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Parish
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D016475:3T3 Cells; D000818:Animals; D001667:Binding, Competitive; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism* / Q000494:pharmacology*; D006493:Heparin / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D000071228:Polyelectrolytes; D011108:Polymers / Q000378:metabolism* / Q000494:pharmacology*; D012685:Sepharose / Q000378:metabolism
D016220:Fibroblast Growth Factor 1; D006493:Heparin; D008934:Mitogens; D009414:Nerve Growth Factors; D000071228:Polyelectrolytes; D011108:Polymers; D012685:Sepharose