Stimulation of endogenous ganglioside metabolism by neurotrophic growth factors in cultured retinal Müller glia.
Neurotrophic factors such as basic fibroblast and epidermal factor (bFGF and EGF respectively) are known to influence many differentiative processes, but their effects on an important group of glycosylated signalling molecules involved in neural differentiation, the gangliosides, are unknown. To study this possibility, we analyzed the effects of exogenously added bFGF and EGF upon the amount and type of endogenous gangliosides extracted from purified cultures of retinal Müller glial cells. A single addition of 500 pM bFGF or EGF for 48 h to such cultures led to significant increases in total ganglioside levels of 30-40%. Analysis of the distribution of specific ganglioside species within control and growth factor treated cells revealed that the precursor form GM3 formed 50-60% of the total ganglioside pool in all cases, the remainder being composed principally of GD1a (20%) with no detectable tri-sialogangliosides. Growth factor treatment for 48 h led to increases mainly in GM3, whereas longer exposure (96 h) of confluent glial cultures to growth factors additionally stimulated synthesis of GT1b. Furthermore, growth factor-induced ganglioside increases were dose-dependent, reaching maximal stimulation at 500 pM for bFGF. Incorporation of radiolabelled [3H]-glucosamine into glial cultures showed that ganglioside synthesis was stimulated 2-fold by the growth factors. To our knowledge these data constitute the first demonstration of neurotrophic factor stimulation of ganglioside levels in cells of central nervous system origin. Such complex interactions between peptide growth factors and gangliosides, if occurring in vivo, could have important consequences for retinal cell behaviour.
Hicks
D
D
INSERM CJF 92/02, Clinique Ophtalmologique, Centre Hospitalier et Universitaire de Strasbourg, France.
Guerold
B
B
Dreyfus
H
H
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005679:G(M3) Ganglioside / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D050356:Lipid Metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013268:Stimulation, Chemical
D005679:G(M3) Ganglioside; D005732:Gangliosides; D016222:Fibroblast Growth Factor 2; C016481:trisialoganglioside GT1; D004815:Epidermal Growth Factor