Reorganization of platelet membrane sphingomyelins by adenosine diphosphate and ticagrelor

• Published in: Chemistry and physics of lipids 2018-11, Vol.216, p.25-29
• Main Authors: Haghighi, Fatemeh, Rabani, Vahideh, Pais-De-Barros, Jean-Paul, Davani, Siamak
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - chemistry; Cell Membrane - chemistry; Cholesterol; Detergent-resistant membrane; Endocrinology and metabolism; Human health and pathology; Life Sciences; P2Y12 receptor; Sphingomyelins - analysis; Ticagrelor - chemistry; Triton X-100
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2018.09.008

•We found 16 species of sphingomyelins in detergent-resistant membrane of platelet membrane.•Sphingomyelin d18:1/16:0 was the predominant species of sphingomyelins in platelet membrane.•ADP and ticagrelor induce reorganization in the distribution and changes in the concentration of sphingomyelins species. Platelets are major targets for the treatment of thrombo-embolic disorders. Their plasma membrane contains specialized microdomains enriched in sphingomyelins and free cholesterol including membrane receptors. P2Y12 receptors need to be situated in these domains to be able to conduct activation signaling by adenosine diphosphate (ADP). We studied the impact of ticagrelor, a P2Y12 antagonist, and ADP on the composition and distribution of sphingomyelins in detergent-resistant membrane (DRM) of platelet membranes. Platelets were obtained from healthy donors. DRMs of platelet membranes were isolated in 4 experimental groups: control; ADP, with platelets stimulated by 20 μM ADP and 5 mM CaCl2; ticagrelor, with platelets incubated by ticagrelor 4 μM methanol dissolved; and ticagrelor + ADP, with incubation by ticagrelor followed by stimulation by ADP as above. After mass spectrometry analysis, we found 16 species of sphingomyelins in platelet membrane DRMs. We also found that treatment with ticagrelor and stimulation by ADP could induce changes in the composition, distribution and concentration of sphingomyelins in membranes of platelets. In all groups, the predominant species of sphingomyelins in platelet membrane was d18:1/16:0. Taken together, our results show that stimulation by ADP or inhibition by ticagrelor changed the level and composition of sphingomyelins in platelet membranes. These changes might be considered as reorganization or new recruitment of certain types of sphingomyelins through the membrane.