1. Academic Validation
  2. Reorganization of platelet membrane sphingomyelins by adenosine diphosphate and ticagrelor

Reorganization of platelet membrane sphingomyelins by adenosine diphosphate and ticagrelor

  • Chem Phys Lipids. 2018 Nov:216:25-29. doi: 10.1016/j.chemphyslip.2018.09.008.
Fatemeh Haghighi 1 Vahideh Rabani 1 Jean-Paul Pais-De-Barros 2 Siamak Davani 3
Affiliations

Affiliations

  • 1 UBFC, University of Burgundy Franche-Comte, 25000, Besancon, France; EA 3920, University of Franche-Comté, 25000, Besancon, France.
  • 2 UBFC, University of Burgundy Franche-Comte, 25000, Besancon, France; Plateforme de Lipidomique, INSERM ULR 1231, University of Burgundy Franche-Comte, 21000 Dijon, France.
  • 3 UBFC, University of Burgundy Franche-Comte, 25000, Besancon, France; EA 3920, University of Franche-Comté, 25000, Besancon, France; Pharmacology & Toxicology Laboratory, University Hospital Besancon, 25000 Besancon, France. Electronic address: siamak.davani@univ-fcomte.fr.
Abstract

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.

Keywords

Cholesterol; Detergent-resistant membrane; P2Y12 receptor; Triton X-100.

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