Ceramide enhances susceptibility of membrane phospholipids to phospholipase A2 through modification of lipid organization in platelet membranes.
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.
Hashizume
T
T
Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Japan.
Kitatani
K
K
Kageura
T
T
Hayama
M
M
Akiba
S
S
Sato
T
T
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001095:Arachidonic Acids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002518:Ceramides / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000096:biosynthesis; D063065:Organophosphonates / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D011817:Rabbits; D015398:Signal Transduction; D013928:Thromboxane A2 / Q000031:analogs & derivatives
D001095:Arachidonic Acids; D002518:Ceramides; D004791:Enzyme Inhibitors; D008244:Lysophosphatidylcholines; D063065:Organophosphonates; D010743:Phospholipids; C104810:methyl arachidonylfluorophosphonate; D016718:Arachidonic Acid; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D010741:Phospholipases A; D054467:Phospholipases A2