Ceramide Enhances Susceptibility of Membrane Phospholipids to Phospholipase A₂ through Modification of Lipid Organization in Platelet Membranes

抄録

The effects of ceramide on agonist-stimulated phospholipase A₂ (PLA₂) activity were studied in platelets. Cell-permeable C₆-ceramide (N-hexanoylsphingosine) exogenously added to platelet suspension enhanced U46619-stimulated arachidonic acid release and lysophosphatidylcholine production. Treatment of platelets with sphingomyelinase also led to an enhancement of the release. The enhanced arachidonic acid release by exogenous ceramide was completely inhibited by methyl arachidonyl fluorophosphonate, a cytosolic PLA₂ inhibitor. However, U46619-stimulated PLA₂ activity was not significantly potentiated by ceramide. These results suggest that enrichment of ceramide in membranes causes modification of intermolecular organization, leading to increased susceptibility of substrate phospholipids to PLA₂.