Thrombin-activated human platelets acutely generate oxidized docosahexaenoic-acid-containing phospholipids via 12-lipoxygenase

The Biochemical Journal
Lloyd MorganValerie B O'Donnell

Abstract

Arachidonate-containing oxidized phospholipids are acutely generated by 12-LOX (12-lipoxygenase) in agonist-activated platelets. In the present study, formation of structurally related lipids by oxidation of DHA (docosahexaenoic acid)-containing phospholipids is demonstrated using lipidomic approaches. Precursor scanning reverse-phase LC (liquid chromatography)-MS/MS (tandem MS) identified a new family of lipids that comprise phospholipid-esterified HDOHE (hydroxydocosahexaenoic acid). Two diacyl and two plasmalogen PEs (phosphatidylethanolamines) containing predominantly the 14-HDOHE positional isomer (18:0p/14-HDOHE-PE, 18:0a/14-HDOHE-PE, 16:0a/14-HDOHE-PE and 16:0p/14-HDOHE-PE) were structurally characterized using MS/MS and by comparison with biogenic standards. An involvement of 12-LOX was indicated as purified recombinant human 12-LOX also generated the 14-HDOHE isomer from DHA. Pharmacological studies using inhibitors and recombinant platelet 12-LOX indicate that they form via esterification of newly formed non-esterified HDOHE. HDOHE-PEs formed at significant rates (2-4 ng/4×10(7) cells) within 2-180 min of thrombin stimulation, and their formation was blocked by calcium chelation. In summary, a new family of oxidized p...Continue Reading

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Citations

Mar 21, 2013·Current Atherosclerosis Reports·Maceler Aldrovandi, Valerie B O'Donnell
Sep 21, 2011·Chemical Reviews·Francisco J SchopferBruce A Freeman
Dec 4, 2010·Nature Protocols·Alwena H MorganValerie B O'Donnell
Sep 18, 2012·Journal of Lipid Research·Kenneth N IkeiMichael Holinstat
Apr 4, 2014·Cancer Metastasis Reviews·David G MenterKenneth V Honn
Sep 2, 2014·Prostaglandins & Other Lipid Mediators·Simona ZariniMiguel A Gijón
Mar 8, 2016·Molecular Aspects of Medicine·Christina MauerhoferValery N Bochkov
Jul 3, 2013·Analytical Biochemistry·Weiqiang LuJin Huang
Mar 29, 2013·Platelets·Ann-Charlotte B Svensson HolmEva G Lindström
Dec 28, 2011·Biochimica Et Biophysica Acta·Victoria J Hammond, Valerie B O'Donnell
Aug 8, 2014·Blood·Jennifer YeungMichael Holinstat
Mar 10, 2017·IUBMB Life·Sebastian Doll, Marcus Conrad
Mar 1, 2017·Journal of Lipid Research·Valerie B O'Donnell, Robert C Murphy
Sep 7, 2017·Journal of Lipid Research·Ryohei AoyagiMakoto Arita
Mar 29, 2014·Circulation Research·Valerie B O'DonnellSteve P Watson
Aug 5, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Reheman AdiliMichael Holinstat
Jan 1, 2019·Mass Spectrometry Reviews·Simone ColomboM Rosário Domingues
Dec 24, 2019·Journal of Thrombosis and Haemostasis : JTH·Madhumita Chatterjee
Apr 19, 2017·British Journal of Haematology·Maria Elisa Mancuso, Elena Santagostino
Nov 19, 2019·Oxidative Medicine and Cellular Longevity·Lian-Jiu SuZhi-Yong Peng
May 11, 2017·Cellular and Molecular Life Sciences : CMLS·Annalisa ContursiPaola Patrignani
Dec 29, 2017·Journal of Mass Spectrometry : JMS·Simone ColomboM Rosário Domingues
Apr 24, 2018·The Journal of Clinical Investigation·Valerie B O'DonnellMichael Jo Wakelam
Dec 18, 2020·Frontiers in Endocrinology·Ali A HajeyahValerie B O'Donnell
Oct 8, 2020·Molecular Aspects of Medicine·Ji NieXiawei Wei
Aug 28, 2018·Chemical Reviews·Saba ParvezYimon Aye
Aug 13, 2011·Biochimica Et Biophysica Acta·Valerie B O'Donnell

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