Exogenous gangliosides stimulate breakdown of neuro-2A phosphoinositides in a manner unrelated to neurite outgrowth.
Gangliosides administered exogenously are well-known effectors of differentiation in many neuroblastoma lines and primary neuronal cultures. Previous studies suggested the phosphoinositide signaling mechanism could be a contributing factor. We have found that treatment of Neuro-2A cells with bovine brain ganglioside mixture (BBG) causes breakdown of phosphoinositides, as measured by increased levels of inositol phosphates. The effect was optimal at 60 min and required a minimal BBG concentration of 25 microM. However, addition of neomycin, which blocked phosphoinositide breakdown, had no observable effect on ganglioside-stimulated neurite outgrowth. A similar result was obtained with psi-tectorigenin, which also inhibited phosphoinositide hydrolysis. When cells were treated with maitotoxin, an agent that promotes phosphoinositide breakdown, there was no enhancement of neurite outgrowth. These findings indicate that although exogenous gangliosides elevate inositol phosphate formation over a prolonged period in neuro-2A cells, this reaction is not integral to the differentiation of these cells. The possibility of secondary effects influencing neurite type and structure cannot be excluded.
Vaswani
K K
KK
Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461.
Wu
G S
GS
Ledeen
R W
RW
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000502:physiology*; D001923:Brain Chemistry; D002417:Cattle; D002454:Cell Differentiation; D002460:Cell Line; D005732:Gangliosides / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology; D007700:Kinetics; D008387:Marine Toxins / Q000494:pharmacology; D009355:Neomycin / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D035964:Oxocins; D010716:Phosphatidylinositols / Q000378:metabolism*; D000095702:Polyether Toxins
D000255:Adenosine Triphosphate; D005732:Gangliosides; D007295:Inositol Phosphates; D007529:Isoflavones; D008387:Marine Toxins; D009355:Neomycin; D035964:Oxocins; D010716:Phosphatidylinositols; C055439:psi-tectorigenin; C020394:maitotoxin; D000095702:Polyether Toxins