{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:14:20Z","timestamp":1770815660747,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,29]],"date-time":"2018-12-29T00:00:00Z","timestamp":1546041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003381","name":"Minist\u00e9rio da Educa\u00e7\u00e3o e Ci\u00eancia","doi-asserted-by":"publisher","award":["FCT UID\/QUI\/00062\/2013; UID\/AMB\/50017\/2013; LISBOA-01-0145-FEDER-402-022125; BPD\/UI51\/5388\/2017"],"award-info":[{"award-number":["FCT UID\/QUI\/00062\/2013; UID\/AMB\/50017\/2013; LISBOA-01-0145-FEDER-402-022125; BPD\/UI51\/5388\/2017"]}],"id":[{"id":"10.13039\/501100003381","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Nitrated lipids have been detected in vitro and in vivo, usually associated with a protective effect. While nitrated fatty acids have been widely studied, few studies reported the nitration and nitroxidation of the phospholipid classes phosphatidylcholine, and phosphatidylethanolamine. However, no information regarding nitrated and nitroxidized phosphatidylserine can be found in the literature. This work aims to identify and characterize the nitrated and nitroxidized derivatives of 1-palmitoyl-2-oleoyl-sn-3-glycero-phosphoserine (POPS), obtained after incubation with nitronium tetrafluoroborate, by liquid chromatography (LC) coupled to mass spectrometry (MS) and tandem MS (MS\/MS). Several nitrated and nitroxidized products were identified, namely, nitro, nitroso, nitronitroso, and dinitro derivatives, as well as some nitroxidized species such as nitrosohydroxy, nitrohydroxy, and nitrohydroperoxy. The fragmentation pathways identified were structure-dependent and included the loss of HNO and HNO2 for nitroso and nitro derivatives, respectively. Combined losses of PS polar head group plus HNO or HNO2 and carboxylate anions of modified fatty acyl chain were also observed. The nitrated POPS also showed antiradical potential, demonstrated by the ability to scavenge the ABTS\u25cf+ and DPPH\u25cf radicals. Overall, this in vitro model of nitration based on LC-MS\/MS provided additional insights into the nitrated and nitroxidized derivatives of PS and their fragmentation fingerprinting. This information is a valuable tool for targeted analysis of these modified PS in complex biological samples, to further explore the new clues on the antioxidant potential of nitrated POPS.<\/jats:p>","DOI":"10.3390\/molecules24010107","type":"journal-article","created":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T07:22:30Z","timestamp":1546240950000},"page":"107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Profile of Phosphatidylserine Modifications under Nitroxidative Stress Conditions Using a Liquid Chromatography-Mass Spectrometry Based Approach"],"prefix":"10.3390","volume":"24","author":[{"given":"Bruna","family":"Neves","sequence":"first","affiliation":[{"name":"Mass Spectrometry Centre, UI QOPNA, Chemistry Department, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Pedro","family":"Domingues","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Centre, UI QOPNA, Chemistry Department, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Maria Manuel","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Chemistry Department, University of Tr\u00e1s-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal"}]},{"given":"Maria do Ros\u00e1rio","family":"Domingues","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Centre, UI QOPNA, Chemistry Department, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"Biology Department &amp; CESAM &amp; ECOMARE, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"T\u00e2nia","family":"Melo","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Centre, UI QOPNA, Chemistry Department, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1194\/jlr.R700020-JLR200","article-title":"Phosphatidylserine and phosphatidylethanolamine in mammalian cells: Two metabolically related aminophospholipids","volume":"49","author":"Vance","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1126\/science.1152066","article-title":"Membrane Phosphatidylserine Regulates Surface Charge and Protein Localization","volume":"319","author":"Yeung","year":"2008","journal-title":"Science"},{"key":"ref_3","first-page":"543","article-title":"Formation and function of phosphatidylserine and phosphatidylethanolamine in mammalian cells","volume":"1831","author":"Vance","year":"2013","journal-title":"Biochim. Biophys Acta. BBA-Mol. Cell Biol. Lipids"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1146\/annurev.biophys.093008.131234","article-title":"The Distribution and Function of Phosphatidylserine in Cellular Membranes","volume":"39","author":"Leventis","year":"2010","journal-title":"Annu. Rev. Biophys"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18357","DOI":"10.1074\/jbc.M700202200","article-title":"Regulated Externalization of Phosphatidylserine at the Cell Surface: Implications for Apoptosis","volume":"282","author":"Balasubramanian","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1007\/s13361-011-0194-9","article-title":"Structural Characterization of Oxidized Glycerophosphatidylserine: Evidence of Polar Head Oxidation","volume":"22","author":"Maciel","year":"2011","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.abb.2014.02.002","article-title":"Detection of phosphatidylserine with a modified polar head group in human keratinocytes exposed to the radical generator AAPH","volume":"548","author":"Maciel","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.jchromb.2013.04.009","article-title":"Evaluation of oxidation and glyco-oxidation of 1-palmitoyl-2-arachidonoyl-phosphatidylserine by LC\u2013MS\/MS","volume":"929","author":"Maciel","year":"2013","journal-title":"J. Chromatogr. B"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1111\/j.1471-4159.2011.07636.x","article-title":"Tacrine and its analogues impair mitochondrial function and bioenergetics: A lipidomic analysis in rat brain: Effects on non-synaptic brain mitochondria","volume":"120","author":"Melo","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_10","first-page":"119","article-title":"Oxidized Phosphatidylserine: Production and Bioactivities","volume":"57","author":"Matsura","year":"2014","journal-title":"Yonago Acta Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.abb.2012.05.022","article-title":"Evaluation of the capacity of oxidized phosphatidylserines to induce the expression of cytokines in monocytes and dendritic cells","volume":"525","author":"Silva","year":"2012","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5587","DOI":"10.1007\/s00216-015-8766-3","article-title":"Profiling and relative quantification of multiply nitrated and oxidized fatty acids","volume":"407","author":"Milic","year":"2015","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1007\/s00216-018-0912-2","article-title":"Development and application of a UHPLC\u2013MS\/MS metabolomics based comprehensive systemic and tissue-specific screening method for inflammatory, oxidative and nitrosative stress","volume":"410","author":"Schoeman","year":"2018","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s11745-009-3332-4","article-title":"Nitro-fatty Acids Occur in Human Plasma in the Picomolar Range: A Targeted Nitro-lipidomics GC\u2013MS\/MS Study","volume":"44","author":"Tsikas","year":"2009","journal-title":"Lipids"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2622","DOI":"10.1021\/acs.analchem.5b03407","article-title":"Recent Advances on Mass Spectrometry Analysis of Nitrated Phospholipids","volume":"88","author":"Melo","year":"2016","journal-title":"Anal. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.freeradbiomed.2017.02.033","article-title":"Characterization of phospholipid nitroxidation by LC-MS in biomimetic models and in H9c2 Myoblast using a lipidomic approach","volume":"106","author":"Melo","year":"2017","journal-title":"Free Radi.c Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/lipd.12007","article-title":"New Insights into the Anti-Inflammatory and Antioxidant Properties of Nitrated Phospholipids","volume":"53","author":"Melo","year":"2018","journal-title":"Lipids"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.abb.2013.02.012","article-title":"Prospective phospholipid markers for skin sensitization prediction in keratinocytes: A phospholipidomic approach","volume":"533","author":"Santinha","year":"2013","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1667\/RR2297.1","article-title":"Oxidative Lipidomics of \u03b3-Radiation-Induced Lung Injury: Mass Spectrometric Characterization of Cardiolipin and Phosphatidylserine Peroxidation","volume":"175","author":"Tyurina","year":"2011","journal-title":"Radiat. Res."},{"key":"ref_20","first-page":"694","article-title":"Oxidized and nitrated oleic acid in biological systems: Analysis by GC\u2013MS\/MS and LC\u2013MS\/MS, and biological significance","volume":"1811","author":"Tsikas","year":"2011","journal-title":"Biochim. Biophys Acta. BBA-Mol. Cell Biol. Lipids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.bcp.2018.06.014","article-title":"Anti-inflammatory nitro-fatty acids suppress tumor growth by triggering mitochondrial dysfunction and activation of the intrinsic apoptotic pathway in colorectal cancer cells","volume":"155","author":"Brat","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.4049\/jimmunol.1300730","article-title":"The Nitrated Fatty Acid 10-Nitro-Oleate Attenuates Allergic Airway Disease","volume":"191","author":"Reddy","year":"2013","journal-title":"J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1080\/10715762.2016.1225955","article-title":"Nitro-oleic acid ameliorates oxygen and glucose deprivation\/re-oxygenation triggered oxidative stress in renal tubular cells via activation of Nrf2 and suppression of NADPH oxidase","volume":"50","author":"Nie","year":"2016","journal-title":"Free Radic. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1080\/00032719.2012.693558","article-title":"Characterization of nitro arachidonic acid and nitro linoleic acid by mass spectrometry","volume":"45","author":"Chakravartula","year":"2012","journal-title":"Anal. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1073\/pnas.95.5.2175","article-title":"Accelerated reaction of nitric oxide with O2 within the hydrophobic interior of biological membranes","volume":"95","author":"Liu","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1073\/pnas.98.1.355","article-title":"The biological lifetime of nitric oxide: Implications for the perivascular dynamics of NO and O2","volume":"98","author":"Thomas","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1074\/jbc.M106589200","article-title":"Diffusion of Nitric Oxide into Low Density Lipoprotein","volume":"277","author":"Denicola","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1194\/jlr.M200467-JLR200","article-title":"Cholesteryl nitrolinoleate, a nitrated lipid present in human blood plasma and lipoproteins","volume":"44","author":"Lima","year":"2003","journal-title":"J. Lipid Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1074\/mcp.M900375-MCP200","article-title":"A Dual Pressure Linear Ion Trap Orbitrap Instrument with Very High Sequencing Speed","volume":"8","author":"Olsen","year":"2008","journal-title":"Mol. Cell Proteom."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1002\/rcm.8063","article-title":"Comparing the fragmentation reactions of protonated cyclic indolyl \u03b1-amino esters in quadrupole\/orbitrap and quadrupole time-of-flight mass spectrometers","volume":"32","author":"Cao","year":"2018","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.freeradbiomed.2005.04.005","article-title":"Nitrated lipids decompose to nitric oxide and lipid radicals and cause vasorelaxation","volume":"39","author":"Lima","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7517","DOI":"10.1021\/jo801364v","article-title":"Chemistry of Nitrated Lipids: Remarkable Instability of 9-Nitrolinoleic Acid in Neutral Aqueous Medium and a Novel Nitronitrate Ester Product by Concurrent Autoxidation\/Nitric Oxide-Release Pathways","volume":"73","author":"Manini","year":"2008","journal-title":"J. Org. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/10715769409145621","article-title":"Radical Exchange Reactions between Vitamin E, Vitamin C and Phospholipids in Autoxidizing Polyunsaturated Lipids","volume":"20","author":"Lambelet","year":"1994","journal-title":"Free Radic Res"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9690","DOI":"10.1002\/chem.201702041","article-title":"Nitrated Fatty Acids Modulate the Physical Properties of Model Membranes and the Structure of Transmembrane Proteins","volume":"23","author":"Franz","year":"2017","journal-title":"Chem.-Eur. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1007\/s11745-001-0820-7","article-title":"A unique antioxidant activity of phosphatidylserine on iron-induced lipid peroxidation of phospholipid bilayers","volume":"36","author":"Dacaranhe","year":"2001","journal-title":"Lipids"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1016\/0006-291X(91)91929-7","article-title":"Inhibitory effect of phosphatidylserine on iron-dependent lipid peroxidation","volume":"179","author":"Yoshida","year":"1991","journal-title":"Biochem Biophys Res Commun"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0003-2697(70)90343-X","article-title":"Spectrophotometric determination of phosphate esters in the presence and absence of orthophosphate","volume":"36","author":"Bartlett","year":"1970","journal-title":"Anal. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.aca.2005.11.013","article-title":"Automatic method for determination of total antioxidant capacity using 2,2-diphenyl-1-picrylhydrazyl assay","volume":"558","author":"Segundo","year":"2006","journal-title":"Anal. Chim. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.talanta.2012.05.002","article-title":"Rapid assessment of endpoint antioxidant capacity of red wines through microchemical methods using a kinetic matching approach","volume":"97","author":"Barreiros","year":"2012","journal-title":"Talanta"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/1\/107\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:36:36Z","timestamp":1760196996000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/1\/107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,29]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["molecules24010107"],"URL":"https:\/\/doi.org\/10.3390\/molecules24010107","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,29]]}}}