Nerve growth factor induces sphingomyelin accumulation in pheochromocytoma cells

FEBS Letters

Marchesini, Sergio¹  Piccinotti, Alberto¹  Preti, Augusto¹  Benaglia, Giuliana¹  Bresciani, Roberto¹  Presta, Marco²  Zizioli, Daniela¹ 

[1] Unit of Biochemistry, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, Via Valsabbina 19, 25123 Brescia, Italy;Unit of General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, 25123 Brescia, Italy

关键词: Ceramide;    Sphingomyelin;    Nerve growth factor;    Rhodamine;    Cell differentiation;    PC12 cell;   

DOI  :  10.1016/S0014-5793(00)01440-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The pheochromocytoma cells are a well-known model for studying the nerve growth factor (NGF)-induced molecular changes during the differentiation process. The involvement of sphingomyelin (SM) was studied using the fluorescent analogue of ceramide, i.e. N-lissamine rhodaminyl-(12-aminododecanoyl) D-erythro-sphingosine (C12-LRh-Cer). This fluorescent analogue is metabolically active and can be used to follow the biosynthesis of SM in intact cells. NGF induces a 4-fold increase of fluorescent SM content in PC12 cells, when loaded with C12-LRh-Cer. Treatment of PC12 cells with actinomycin D or cycloheximide completely abolishes the NGF-induced elevation of SM. Inhibition of p140^trkA receptor by AG-879 prevents extracellular signal-regulated kinase 1/2 phosphorylation and suppresses the increase of SM. Inhibition of protein kinase C (PKC), protein kinase A (PKA) and phosphatidylinositol 3-kinase does not have any effect on NGF-induced C12-LRh-SM accumulation. On the other hand, activation of PKA or PKC with simultaneous treatment with NGF has a synergistic effect on increase of SM content. The NGF-induced SM increase in PC12 cells is an effect promoted by other differentiating agents like dibutyryl cyclic AMP or fibroblast growth factor-2 but not by a mitogenic agent like epidermal growth factor.

【 授权许可】

Unknown