Metabolic fate of exogenous sphingosine in neuroblastoma neuro2A cells. Dose-dependence and biological effects.
The possible relationship between metabolism and biological effects of sphingosine was investigated in Neuro2a cells. [C3-3H]-sphingosine, administered at different doses (80 pmol-80 nmol/mg cell protein). Amounts up to hundredfold were rapidly taken up and metabolized, the intracellular content of sphingosine being processed within 2 h. At low doses, [3H]-sphingosine represented a minor portion of the cellular radiolabel, and N-acylated metabolites, particularly ceramide, prevailed over degradation products. Neuro2a cell differentiation took place in conjunction with ceramide increase. At increasing exogenous sphingosine/cell ratio, the acylation process became saturated while sphingosine degradation increased proportionally. From this point on [3H]-sphingosine accumulated and cell toxicity occurred. In conclusion, in Neuro2a cells the biological effects exerted by exogenous sphingosine are strictly connected to the exogenous sphingosine/cell ratio and to the capacity of the cell to metabolize sphingosine.
Department of Medical Chemistry and Biochemistry, University of Milan, Italy.
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Riboni
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Bassi
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Caminiti
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Prinetti
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Viani
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Tettamanti
D000818:Animals; D001692:Biological Transport; D002518:Ceramides / Q000378:metabolism; D006017:Glycolipids / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D011865:Radioisotope Dilution Technique; D013109:Sphingomyelins / Q000378:metabolism; D013110:Sphingosine / Q000378:metabolism*; D014316:Tritium; D014407:Tumor Cells, Cultured
D002518:Ceramides; D006017:Glycolipids; D013109:Sphingomyelins; D014316:Tritium; D013110:Sphingosine