Sphingoid bioregulators in the differentiation of cells of neural origin.
The involvement of ceramide in the differentiation of two neuroblastoma cell lines, Neuro2a and SH-SY5Y, and cerebellar granule cells in primary culture was investigated. The following results were obtained: (a) the cellular content of ceramide markedly increased with induced differentiation of Neuro2a cells (inducers: RA, FCS deprivation), SH-SY5Y cells (inducers: RA, PMA), and spontaneous differentiation of cerebellar granule cells; (b) all the investigated cells in the differentiated form displayed a higher ability to produce ceramide from exogenously administered [3H]Sph-SM and expressed a higher content of neutral sphingomyelinase and, in the case of cerebellar granule cells, also of acidic sphingomyelinase; (c) inhibition of ceramide biosynthesis by Fumonisin B1 blocked the process of differentiation in Neuro2a and cerebellar granule cells; and (d) treatments capable of enhancing ceramide level (administration of sphingosine or C2-Ceramide) induced differentiation in both Neuro2a and SH-SY5Y cells. The data obtained support the notion that ceramide plays a general biomodulatory role in neural cell differentiation.
Tettamanti
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G
Department of Medical Chemistry and Biochemistry, University of Milan, Italy. tetta-man@imiucca.csi.unimi.it
Prinetti
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A
Bassi
R
R
Viani
P
P
Giussani
P
P
Riboni
L
L
D000818:Animals; D002454:Cell Differentiation; D002518:Ceramides / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002518:Ceramides; D013108:Sphingomyelin Phosphodiesterase