Ceramide from sphingomyelin hydrolysis induces neuronal differentiation, whereas de novo ceramide synthesis and sphingomyelin hydrolysis initiate apoptosis after NGF withdrawal in PC12 Cells

Cell Communication and Signaling

Gloria Stoyanova¹  Terri Kagan¹  Richard A. Lockshin²  Zahra Zakeri³ 

[1] Department of Biology, Queens College of the City University of New York, Flushing, NY, USA;Department of Biology, Queens College of the City University of New York, Flushing, NY, USA;St. Johns University, Jamaica, NY, USA;St. Johns University, Jamaica, NY, USA;

关键词: Cell death;    Apoptosis;    Sphingomyelin;    Ceramide;    Nerve growth factor;   

DOI  :  10.1186/s12964-021-00767-2

来源: Springer

【 摘 要 】

BackgroundCeramide, important for both neuronal differentiation and dedifferentiation, resides in several membranes, is synthesized in the endoplasmic reticulum, mitochondrial, and nuclear membranes, and can be further processed into glycosphingolipids or sphingomyelin. Ceramide may also be generated by hydrolysis of sphingomyelin by neutral or acidic sphingomyelinases in lysosomes and other membranes. Here we asked whether the differing functions of ceramide derived from different origins.MethodsWe added NGF to PC12 cells and to TrkA cells. These latter overexpress NGF receptors and are partially activated to differentiate, whereas NGF is required for PC12 cells to differentiate. We differentiated synthesis from hydrolysis by the use of appropriate inhibitors. Ceramide and sphingomyelin were measured by radiolabeling.ResultsWhen NGF is added, the kinetics and amounts of ceramide and sphingomyelin indicate that the ceramide comes primarily from hydrolysis but, when hydrolysis is inhibited, can also come from neosynthesis. When NGF is removed, the ceramide comes from both neosynthesis and hydrolysis.ConclusionWe conclude that the function of ceramide depends heavily on its intracellular location, and that further understanding of its function will depend on resolving its location during changes of cell status.Graphical Abstract9jaz4dWkruTZSXMGGTBHtmVideo Abstract

【 授权许可】

CC BY