Title: [13] N-Acetylation of sphingosine by platelet-activating factor: Sphingosine transacetylase
Abstract: Most mammalian cells appear to have a signaling system through the sphingomyelin pathway. Sphingomyelin is hydrolyzed by sphingomyelinase (SMase) to generate ceramides. Ceramides are important lipid second messengers involved in mediating a variety of cell functions, including cell cycle arrest, cell differentiation, and apoptosis, C2-ceramide (N-acetyl-sphingosine) has been used extensively by many investigators as an unnatural, cell-permeable analog of ceramides. However, cumulative evidence indicates that C2-ceramide can mimic many, but not all, of the effects of ceramides that were produced during signaling through the sphingomyelin pathway. For instance, SMase treatment antagonized the mitogenic effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, whereas C2-ceramide had no effect. This chapter discusses a CoA-independent platelet-activating factor (PAF): sphingosine transacetylase (TAs) in the membrane fraction of HL-60 cells that can transfer the acetate group from PAF to sphingosine, forming N-acetylsphingosine (C2-ceramide). In addition, TAs activity can be induced by nerve growth factor and lysophosphatidic acid. C2-ceramide in micromolar concentrations was detected in HL-60 cells, which is the concentration range where C2-ceramide exerts most of its biological effects. Taken together, these data suggest the possibility that some of the observed physiological effects by several factors, such as cytokines and environmental stresses through sphingomyelin signaling, may be accounted for by the action of C2-ceramide and that C2-ceramide should be considered a naturally occurring lipid mediator. This chapter describes assay procedures and properties of PAF: sphingosine transacetylase, the only enzyme known so far to be responsible for the synthesis of C2-ceramide in mammalian systems.
Publication Year: 2000
Publication Date: 2000-01-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 1
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