title: Targeted lipidomics - advances in profiling lysophosphocholine and platelet-activating factor second messengers.
abstract: Glycerophosphocholines are the major building blocks of biological membranes. They are also precursors of low-molecular-weight second messengers with mass to charge ratios of 450-600. These messengers include lysophosphatidylcholines (LPCs) and lyso-platelet activating factors (PAFs) that may be further processed into PAFs. Often considered as a single species, LPCs, PAFs and lyso-PAFs are, in fact, families of glycerophosphocholine-derived lipids distinguished by the linkage of their sn-1 carbon chains to the phosphoglyceride backbone (ester or ether), their sn-1 carbon chain length and degree of unsaturation, and the identity of their sn-2 constituents (a hydroxyl or acetyl group). Each LPC and PAF species exhibits a different affinity for its cognate G-protein-coupled receptors, and each species elicits receptor-independent actions that play critical signalling roles. Targeted mass spectrometry-based lipidomic approaches are enabling the molecular identification and quantification of these low-abundance second messengers. Variations between datasets map the temporal landscape of second messengers available for signalling, and provide snapshots of the state of structural membrane compositional remodelling at the time of extraction. Here, we review a number of advances in lipidomic methodologies used to identify LPCs, lyso-PAFs and PAFs, and highlight how these targeted approaches are providing valuable insight into the roles played by the cellular lipidome in cell function and disease susceptibility.
authors.affiliation: Ottawa Institute of Systems Biology, University of Ottawa, Ontario, Canada; Neural Regeneration Laboratory, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ontario, Canada.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Xu
authors.forename: Nicolas
authors.initials: N
authors.lastname: Valenzuela
authors.forename: Stephen
authors.initials: S
authors.lastname: Fai
authors.forename: Daniel
authors.initials: D
authors.lastname: Figeys
authors.forename: Steffany A L
authors.initials: SA
authors.lastname: Bennett
mesh_terms: D006801:Humans; D050356:Lipid Metabolism; D008244:Lysophosphatidylcholines / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D015290:Second Messenger Systems
chemical_list: D008244:Lysophosphatidylcholines; D008563:Membrane Lipids; C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor
keywords: alzheimer disease; lipid second messenger; lipidomics; liquid chromatography; lysophosphatidylcholine; mass spectrometry; neurodegeneration; neurolipidomics; phospholipase; platelet activating factor