Significance of gangliosides in neuronal differentiation of neuroblastoma cells and neurite growth in tissue culture.
Addition of DL-threo-1-phenyl-2-decanolylamine-3-morpholino-1-propanol HCl (PDMP; 7-24 microM) or Fumonisin B1 (FB1; 30-50 microM) to SH-SY5Ytrk-A human neuroblastoma cells results within 4 days in a 40% decrease of the ganglioside content and in a reduction of nerve-growth-factor (NGF)-induced outgrowth of neuritic processes. NGF-induced enhancement of GAP-43 expression was not affected. However, unlike controls, immunostained GAP-43 appeared concentrated in defined areas of cell perikarya and mostly absent from cell processes. Presence of 20-microM exogenous GM1 for 4 days in NGF and PDMP containing cell cultures led to an increase of cell-associated GM1(15-fold), GM2 (10-fold), GM3 (15 fold), GD1a (4-fold), GD2, GD1b, and GT1b (all 3-fold), and partially reversed the PDMP (and FB1) effects on neurite growth and GAP-43 distribution. In a newly developed neuronal tissue culture system, PDMP and FB1 led to a comparable dose-dependent inhibition of neurite outgrowth from embryonic chicken spinal cord explants, which had been embedded into a fibrin matrix. In this system, addition of GM1 led to a further inhibition of neurite growth, probably due to an interaction with growth-promoting components present in the surrounding fibrin matrix.
Institute of Zoology, University of Hohenheim-Stuttgart, Germany. roesnerh@uni-hohenheim.de
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D000818:Animals; D002264:Carboxylic Acids / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002642:Chick Embryo; D004791:Enzyme Inhibitors / Q000494:pharmacology; D037341:Fumonisins; D005677:G(M1) Ganglioside / Q000494:pharmacology; D019922:GAP-43 Protein / Q000032:analysis / Q000096:biosynthesis; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D009183:Mycotoxins / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D014407:Tumor Cells, Cultured
D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D037341:Fumonisins; D019922:GAP-43 Protein; D005732:Gangliosides; D009025:Morpholines; D009183:Mycotoxins; D009414:Nerve Growth Factors; D005677:G(M1) Ganglioside; C056933:fumonisin B1; C033110:RV 538