Synthetic sialyl compounds as well as natural gangliosides induce neuritogenesis in a mouse neuroblastoma cell line (Neuro2a).
Amphipathic compounds containing N-acetylneuraminic acid (sialic acid) [for example, D-N-acetylneuraminyl-(alpha 2-1)-2S,3R,4E-2-N-tetracosanoyl sphingenine, sialyl alkyl glycerol ethers, and sialyl cholesterols] induced neuritogenesis in a neuroblastoma cell line (Neuro2a). The sialic acid in the hydrophilic moiety of the compounds is specifically required for neuritogenesis. The requirement for molecular specificity of the hydrophobic moiety, however, is rather low. Regarding the hydrophobic moiety, no preference for cholesterol, alkyl glycerol ether, or ceramide residues was observed as to their neuritogenic activity. Sialyl compounds with alpha-ketosidic sialyl linkages were more active than the corresponding beta-anomers. These sialyl compounds induced the growth of only one neurite, but a long one, from the cell body. This type of neuritogenes is completely different from that induced by compounds capable of elevating the concentration of intracellular cyclic AMP, which induced the appearance of many neurites from a single cell body. Besides this morphological change, the active sialyl compounds also caused a change in the carbohydrate composition of the cell surface. Sialyl compound treatment drastically increased the concentration of peanut agglutinin binding sites.
Tsuji
S
S
Department of Biochemistry, Faculty of Medicine, University of Tokyo, Japan.
Yamashita
T
T
Tanaka
M
M
Nagai
Y
Y
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure*; D050260:Carbohydrate Metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D002784:Cholesterol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D005312:Fetal Blood; D005732:Gangliosides / Q000494:pharmacology*; D005995:Glyceryl Ethers / Q000494:pharmacology; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000648:ultrastructure*; D012794:Sialic Acids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D005732:Gangliosides; D005995:Glyceryl Ethers; D012794:Sialic Acids; D004247:DNA; D002784:Cholesterol; D000242:Cyclic AMP; D006152:Cyclic GMP