Profiling of phosphoinositide molecular species in human and mouse platelets identifies new species increasing following stimulation

Phosphoinositides are bioactive lipids essential in the regulation of cell signaling as well as cytoskeleton and membrane dynamics. Their metabolism is highly active in blood platelets where they play a critical role during activation, at least through two well identified pathways involving phosphol...

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Bibliographic Details
Published in:Biochimica et biophysica acta. Molecular and cell biology of lipids 2018-09, Vol.1863 (9), p.1121-1131
Main Authors: Mujalli, Abdulrahman, Chicanne, Gaëtan, Bertrand-Michel, Justine, Viars, Fanny, Stephens, Len, Hawkins, Phil, Viaud, Julien, Gaits-Iacovoni, Frédérique, Severin, Sonia, Gratacap, Marie-Pierre, Terrisse, Anne-Dominique, Payrastre, Bernard
Format: Article
Language:English
Subjects:
Animals
Biochemistry, Molecular Biology
Blood Platelets - cytology
Blood Platelets - drug effects
Blood Platelets - metabolism
Carrier Proteins - pharmacology
Cellular Biology
Class I Phosphatidylinositol 3-Kinases - antagonists & inhibitors
Class I Phosphatidylinositol 3-Kinases - deficiency
Class I Phosphatidylinositol 3-Kinases - genetics
Enzyme Inhibitors - pharmacology
Gene Expression
Humans
Life Sciences
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular biology
Molecular Networks
ortho-Aminobenzoates - pharmacology
Peptides - pharmacology
Phosphatidylinositol 4,5-Diphosphate - metabolism
Phosphatidylinositol Phosphates - metabolism
Phosphoinositide 3-kinase
Phosphoinositides
Platelet activation
Platelet Activation - drug effects
Primary Cell Culture
Profiling of molecular species
Protein Subunits - antagonists & inhibitors
Protein Subunits - deficiency
Protein Subunits - genetics
Pyrimidinones - pharmacology
Subcellular Processes
Thrombin - pharmacology
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Summary:Phosphoinositides are bioactive lipids essential in the regulation of cell signaling as well as cytoskeleton and membrane dynamics. Their metabolism is highly active in blood platelets where they play a critical role during activation, at least through two well identified pathways involving phospholipase C and phosphoinositide 3-kinases (PI3K). Here, using a sensitive high-performance liquid chromatography-mass spectrometry method recently developed, we monitored for the first time the profiling of phosphatidylinositol (PI), PIP, PIP2 and PIP3 molecular species (fatty-acyl profiles) in human and mouse platelets during the course of stimulation by thrombin and collagen-related peptide. Furthermore, using class IA PI3K p110α or p110β deficient mouse platelets and a pharmacological inhibitor, we show the crucial role of p110β and the more subtle role of p110α in the production of PIP3 molecular species following stimulation. This comprehensive platelet phosphoinositides profiling provides important resources for future studies and reveals new information on phosphoinositides biology, similarities and differences in mouse and human platelets and unexpected dramatic increase in low-abundance molecular species of PIP2 during stimulation, opening new perspectives in phosphoinositide signaling in platelets. •Comprehensive human and mouse platelet phosphoinositides molecular species profiling using LC/MS analysis.•Changes in the profiling of PI, PIP, PIP2 and PIP3 molecular species during the course of platelets stimulation.•Increase in low-abundance molecular species of PIP and PIP2 during stimulation•Key role of class I PI3Kβ in PIP3 molecular species production following platelet activation.
ISSN:1388-1981
1879-2618
DOI:10.1016/j.bbalip.2018.06.009