出版社：American Society for Biochemistry and Molecular Biology
摘要：To investigate the role of sphingomyelin (SM) in the regulationof inflammatory reactions, we studied its effect on the activityand fatty acid specificity of group X secretory phospholipaseA2 (sPLA2X). Compared with other phospholipases, recombinantsPLA2X released more arachidonate from HDL. Pretreatment ofHDL with sphingomyelinase (SMase) C activated the sPLA2X activity,but the release of arachidonate was stimulated less than thatof linoleate. In liposomes containing synthetic phosphatidylcholines(PCs), sPLA2X showed no clear selectivity among the varioussn-2 unsaturated fatty acids. However, when SM was incorporatedinto liposomes at 30 mol%, the enzyme exhibited strong preferencefor arachidonate, although its overall activity was inhibited.Degradation of liposomal SM by SMase C resulted in sPLA2X activationand loss of its arachidonate preference. Incorporation of ceramideinto HDL or PC liposomes activated the enzyme activity, therelease of arachidonate being stimulated more than that of linoleate.SM-deficient cells released more arachidonate than normal cellsin response to exogenous sPLA2X. SMase pretreatment of normalcells stimulated the release of arachidonate by the exogenoussPLA2X. These results show that SM not only inhibits sPLA2Xactivity but also contributes to its selectivity for arachidonate,whereas ceramide stimulates the hydrolysis of arachidonate-containingPCs.Supplementary key words sphingomyelin • ceramide • fatty acid specificity • inflammation
Abbreviations: PC, phosphatidylcholine; SM, sphingomyelin; SMase, sphingomyelinase; sPLA2, secretory phospholipase A2
