Role of sphingomyelin and ceramide in the regulation of the activity and fatty acid specificity of group V secretory phospholipase A2.
We previously showed that group V secretory phospholipase A(2) (sPLA(2)V) is inhibited by sphingomyelin (SM), but activated by ceramide. Here, we investigated the effect of sphingolipid structure on the activity and acyl specificity of sPLA(2)V. Degradation of HDL SM to ceramide, but not to ceramide phosphate, stimulated the activity by 6-fold, with the release of all unsaturated fatty acids being affected equally. Ceramide-enrichment of HDL similarly stimulated the release of unsaturated fatty acids. Incorporation of SM into phosphatidylcholine (PC) liposomes preferentially inhibited the hydrolysis of 16:0-20:4 PC. Conversely, SMase C treatment or ceramide incorporation resulted in preferential stimulation of hydrolysis of 16:0-20:4 PC. The presence of a long chain acyl group in ceramide was essential for the activation, and long chain diacylglycerols were also effective. However, ceramide phosphate was inhibitory. These studies show that SM and ceramide in the membranes and lipoproteins not only regulate the activity of phospholipases, but also the release of arachidonate, the precursor of eicosanoids.
Singh
Dev K
DK
Department of Medicine, Section of Diabetes and Metabolism, University of Illinois at Chicago, 1819 West Polk, M/C 797, Chicago, IL 60612, USA.
Gesquiere
Laurence R
LR
Subbaiah
Papasani V
PV
D002518:Ceramides / Q000737:chemistry*; D004789:Enzyme Activation; D004795:Enzyme Stability; D005227:Fatty Acids / Q000737:chemistry*; D054505:Group V Phospholipases A2; D010741:Phospholipases A / Q000737:chemistry*; D054467:Phospholipases A2; D013109:Sphingomyelins / Q000737:chemistry*
D002518:Ceramides; D005227:Fatty Acids; D013109:Sphingomyelins; D010741:Phospholipases A; D054505:Group V Phospholipases A2; D054467:Phospholipases A2