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See 1 citation in Cell Metab 2016:

Cell Metab. 2016 May 10;23(5):930-44. doi: 10.1016/j.cmet.2016.04.001. Epub 2016 Apr 28.

Mapping the Human Platelet Lipidome Reveals Cytosolic Phospholipase A2 as a Regulator of Mitochondrial Bioenergetics during Activation.

Author information

1
Institute of Infection and Immunity and Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
2
School of Computer Science and Informatics, Cardiff University, Cardiff CF14 4XN, UK.
3
Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045, USA.
4
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
5
Institute of Infection and Immunity and Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK. Electronic address: o-donnellvb@cardiff.ac.uk.

Abstract

Human platelets acutely increase mitochondrial energy generation following stimulation. Herein, a lipidomic circuit was uncovered whereby the substrates for this are exclusively provided by cPLA2, including multiple fatty acids and oxidized species that support energy generation via β-oxidation. This indicates that acute lipid membrane remodeling is required to support energetic demands during platelet activation. Phospholipase activity is linked to energy metabolism, revealing cPLA2 as a central regulator of both lipidomics and energy flux. Using a lipidomic approach (LipidArrays), we also estimated the total number of lipids in resting, thrombin-activated, and aspirinized platelets. Significant diversity between genetically unrelated individuals and a wealth of species was revealed. Resting platelets demonstrated ∼5,600 unique species, with only ∼50% being putatively identified. Thrombin elevated ∼900 lipids >2-fold with 86% newly appearing and 45% inhibited by aspirin supplementation, indicating COX-1 is required for major activation-dependent lipidomic fluxes. Many lipids were structurally identified. With ∼50% of the lipids being absent from databases, a major opportunity for mining lipids relevant to human health and disease is presented.

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