{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:17:40Z","timestamp":1788434260694,"version":"build-2803163510"},"reference-count":32,"publisher":"American Chemical Society (ACS)","issue":"17","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23H05481"],"award-info":[{"award-number":["JP23H05481"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K17449"],"award-info":[{"award-number":["JP23K17449"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The oxidative modification of low-density lipoprotein (LDL) is involved in the generation of lipid peroxidation-derived electrophilic aldehydes, which covalently react with apolipoprotein B-100 to form various adducts. Although the oxidative modification of LDL is critical in the pathogenesis of atherosclerosis, the structural properties of adducts in oxidized LDL (oxLDL) remain unclear. Thus, we aimed to characterize oxLDL using the adductome approach, a comprehensive mass spectrometry-based analysis designed to detect specific product ions from positively ionized oxidized phosphatidylcholine (oxPC) adducts. The amounts of several adducts, including four major oxPC-lysine (oxPC-Lys) adducts, prominently increased when LDL was oxidized with Cu2+. Analysis of the synthetic adduct candidates through mass spectrometry revealed two oxPC-Lys Schiff base adducts and two novel oxPC-Lys amide-type adducts as the major lysine adducts in oxLDL. The oxPC-Lys Schiff base adducts could be transformed into stable amide-type adducts during LDL oxidation. The amounts of oxPC-Lys adducts were significantly higher in the sera of hyperlipidemic mice than in the sera of control mice. The recognition of oxPC-Lys adducts by macrophages suggested that these adducts were involved in the phagocytosis of oxLDL by macrophages. These findings provide insights into the structural properties of lipoproteins modified under oxidative stress and their biological implications. Moreover, this study is the first to identify and quantify oxPC-Lys amide-type adducts in vitro and in vivo.<\/jats:p>","DOI":"10.1021\/acs.biochem.6c00425","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:01:58Z","timestamp":1786626118000},"page":"2689-2698","source":"Crossref","is-referenced-by-count":0,"title":["Adductome-Based Identification of Novel Oxidized Phospholipid-Lysine\nAdducts Formed in Low-Density Lipoprotein"],"prefix":"10.1021","volume":"65","author":[{"given":"Fumie","family":"Nakashima","sequence":"first","affiliation":[{"name":"Nagoya University , , ,","place":["Nagoya, Japan, 464\u22128601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuto","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Nagoya University , , ,","place":["Nagoya, Japan, 464\u22128601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuo","family":"Aoyama","sequence":"additional","affiliation":[{"name":"Nagoya University , , ,","place":["Nagoya, Japan, 464\u22128601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Hirade","sequence":"additional","affiliation":[{"name":"Nagoya University , , ,","place":["Nagoya, Japan, 464\u22128601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Sei","sequence":"additional","affiliation":[{"name":"Nagoya University , , ,","place":["Nagoya, Japan, 464\u22128601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Hattori","sequence":"additional","affiliation":[{"name":"Nagoya University , , ,","place":["Nagoya, Japan, 464\u22128601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Gifu University Hospital , , ,","place":["Gifu, Japan, 501\u22121194"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Nagoya University Hospital , , ,","place":["Nagoya, Japan, 466\u22128560"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2100-8477","authenticated-orcid":true,"given":"Ken-Ichi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Kyushu University , , ,","place":["Fukuoka, Japan, 812\u22128582"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Uchida","sequence":"additional","affiliation":[{"name":"The University of Tokyo , , ,","place":["Tokyo, Japan, 113\u22128657"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3194-607X","authenticated-orcid":true,"given":"Takahiro","family":"Shibata","sequence":"additional","affiliation":[{"name":"Nagoya University , , ,","place":["Nagoya, Japan, 464\u22128601"]},{"name":"Nagoya University , , ,","place":["Nagoya, Japan, 464\u22128601"]},{"name":"Nagoya University , , ,","place":["Nagoya, Japan, 464\u22128601"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"2026090306413039700_cit1","first-page":"927","article-title":"Atherosclerosis: Process, Indicators, Risk Factors and New Hopes","author":"Rafieian-Kopaei","year":"2014","journal-title":"I. J. Prev. Med."},{"issue":"14","key":"2026090306413039700_cit2","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1056\/NEJM198904063201407","article-title":"Beyond\nCholesterol. Modifications of Low-Density Lipoprotein That Increase\nIts Atherogenicity","volume":"320","author":"Steinberg","year":"1989","journal-title":"N. Engl. J. Med."},{"key":"2026090306413039700_cit3","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/978-1-4615-1957-7_5","article-title":"Role of Oxidized\nLDL and Antioxidants in Atherosclerosis","volume":"369","author":"Steinberg","year":"1995","journal-title":"Adv.\nExp. Med. Biol."},{"key":"2026090306413039700_cit4","doi-asserted-by":"publisher","first-page":"20963","DOI":"10.1074\/jbc.272.34.20963","article-title":"Low Density\nLipoprotein Oxidation and Its Pathobiological Significance","volume":"272","author":"Steinberg","year":"1997","journal-title":"J. Biol. Chem."},{"issue":"6","key":"2026090306413039700_cit5","doi-asserted-by":"publisher","first-page":"5747","DOI":"10.3390\/ijms24065747","article-title":"The Oxidized Lipoproteins In Vivo: Its Diversity and Behavior in\nthe Human Circulation","volume":"24","author":"Itabe","year":"2023","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"2026090306413039700_cit6","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/0891-5849(91)90192-6","article-title":"Chemistry\nand Biochemistry of 4-Hydroxynonenal,\nMalonaldehyde and Related Aldehydes","volume":"11","author":"Esterbauer","year":"1991","journal-title":"Free Rad.\nBiol. Med."},{"key":"2026090306413039700_cit7","doi-asserted-by":"publisher","first-page":"109956","DOI":"10.1016\/j.abb.2024.109956","article-title":"Oxidized Phospholipid-Protein Adducts:\nThe Future Targets\nof Interest","volume":"754","author":"Ferreira","year":"2024","journal-title":"Arch. Biochem. Biophys."},{"issue":"12","key":"2026090306413039700_cit8","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1016\/S0891-5849(00)00333-6","article-title":"Immunological Responses to Oxidized\nLDL","volume":"28","author":"Ho\u0308rkko\u0308","year":"2000","journal-title":"Free Rad. Biol. Med."},{"issue":"3","key":"2026090306413039700_cit9","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/s41569-023-00937-4","article-title":"Oxidized Phospholipids\nin Cardiovascular Disease","volume":"21","author":"Tsimikas","year":"2024","journal-title":"Nat. Rev. Cardiol."},{"key":"2026090306413039700_cit10","doi-asserted-by":"publisher","first-page":"4569","DOI":"10.1016\/S0021-9258(18)53430-X","article-title":"Molecular Flypaper,\nHost Defense, and Atherosclerosis.\nStructure, Binding Properties, and Functions of Macrophage Scavenger\nReceptors","volume":"268","author":"Krieger","year":"1993","journal-title":"J. Biol. 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Lipid Res."},{"issue":"2","key":"2026090306413039700_cit14","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/s00216-017-0764-1","article-title":"Evaluation\nof Oxidized Phospholipids Analysis by LC-MS\/MS","volume":"410","author":"Khoury","year":"2018","journal-title":"Anal. Bioanal. Chem."},{"issue":"2","key":"2026090306413039700_cit15","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1021\/tx00014a001","article-title":"Biochemical\nStructural and Functional Properties of Oxidized Low-Density Lipoprotein","volume":"3","author":"Esterbauer","year":"1990","journal-title":"Chem. Res. Toxicol."},{"issue":"2","key":"2026090306413039700_cit16","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1194\/jlr.M400311-JLR200","article-title":"Identification\nand Analysis of Products Formed from Phospholipids in the Free Radical\nOxidation of Human Low Density Lipoproteins","volume":"46","author":"Milne","year":"2005","journal-title":"J. Lipid Res."},{"issue":"6","key":"2026090306413039700_cit17","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1021\/tx800080x","article-title":"Protein N-Acylation:\nH2O2-Mediated Covalent Modification of Protein\nby Lipid\nPeroxidation-Derived Saturated Aldehydes","volume":"21","author":"Ishino","year":"2008","journal-title":"Chem.\nRes. Toxicol."},{"issue":"41","key":"2026090306413039700_cit18","doi-asserted-by":"publisher","first-page":"38517","DOI":"10.1074\/jbc.M205924200","article-title":"A Novel\nFamily of Atherogenic Oxidized Phospholipids Promotes Macrophage Foam\nCell Formation via the Scavenger Receptor CD36 and Is Enriched in\nAtherosclerotic Lesions","volume":"277","author":"Podrez","year":"2002","journal-title":"J. Biol. 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Biol."},{"issue":"1","key":"2026090306413039700_cit22","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1182\/blood.V99.1.199","article-title":"Oxidized Phospholipids\nStimulate Tissue Factor Expression in Human Endothelial Cells via\nActivation of ERK\/EGR-1 and Ca++\/NFAT","volume":"99","author":"Bochkov","year":"2002","journal-title":"Blood"},{"key":"2026090306413039700_cit23","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.freeradbiomed.2011.10.481","article-title":"Physiological Effects of Oxidized\nPhospholipids and Their Cellular Signaling Mechanisms in Inflammation","volume":"52","author":"Greig","year":"2012","journal-title":"Free Radic Biol. Med."},{"issue":"10","key":"2026090306413039700_cit24","doi-asserted-by":"publisher","first-page":"4237","DOI":"10.1021\/pr8001222","article-title":"Identification of\nProteins Adducted by Lipid Peroxidation Products in Plasma and Modifications\nof Apolipoprotein A1 with a Novel Biotinylated Phospholipid Probe","volume":"7","author":"Szapacs","year":"2008","journal-title":"J. Proteome Res."},{"issue":"3","key":"2026090306413039700_cit25","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1194\/jlr.M700264-JLR200","article-title":"Protein Targets\nof Oxidized Phospholipids in Endothelial Cells","volume":"49","author":"Gugiu","year":"2008","journal-title":"J. Lipid Res."},{"issue":"9","key":"2026090306413039700_cit26","doi-asserted-by":"publisher","first-page":"4621","DOI":"10.1021\/ac400131f","article-title":"Use of Narrow Mass-Window,\nHigh-Resolution\nExtracted Product Ion Chromatograms for the Sensitive and Selective\nIdentification of Protein Modifications","volume":"85","author":"Spickett","year":"2013","journal-title":"Anal.\nChem."},{"issue":"2","key":"2026090306413039700_cit27","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.bbrc.2013.07.073","article-title":"Design of\na Novel LOX-1 Receptor Antagonist Mimicking the Natural Substrate","volume":"438","author":"Falconi","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"14","key":"2026090306413039700_cit28","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1161\/HC3901.096665","article-title":"Prevention\nand Treatment of Coronary Heart Disease: Who Benefits?","volume":"104","author":"LaRosa","year":"2001","journal-title":"Circulation"},{"issue":"2","key":"2026090306413039700_cit29","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1097\/MED.0b013e328329135a","article-title":"Approach to the Diagnosis\nand Management of Lipoprotein Disorders","volume":"16","author":"Alwaili","year":"2009","journal-title":"Curr.\nOpin. Endocrinol., Diabetes Obes"},{"issue":"6","key":"2026090306413039700_cit30","doi-asserted-by":"publisher","first-page":"579","DOI":"10.2174\/1566524023362177","article-title":"Oxidation\nof Low-Density Lipoprotein\nin Atherosclerosis from Basic Biochemistry to Clinical Studies","volume":"2","author":"Albertini","year":"2002","journal-title":"Curr. Mol. Med."},{"key":"2026090306413039700_cit31","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1146\/annurev.immunol.23.021704.115816","article-title":"Macrophage Receptors and Immune Recognition","volume":"23","author":"Taylor","year":"2005","journal-title":"Annu. Rev. Immunol."},{"issue":"11","key":"2026090306413039700_cit32","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1038\/nm1102-1235","article-title":"The Macrophage Foam\nCell as a Target for Therapeutic\nIntervention","volume":"8","author":"Li","year":"2002","journal-title":"Nat. Med."}],"container-title":["Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.biochem.6c00425","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/bichaw\/article-pdf\/65\/17\/2689\/66523242\/acs.biochem.6c00425.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/bichaw\/article-pdf\/65\/17\/2689\/66523242\/acs.biochem.6c00425.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:41:40Z","timestamp":1788432100000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/bichaw\/article\/65\/17\/2689\/5254170\/Adductome-Based-Identification-of-Novel-Oxidized"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":32,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,8,13]]},"published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.biochem.6c00425","relation":{},"ISSN":["0006-2960","1520-4995"],"issn-type":[{"value":"0006-2960","type":"print"},{"value":"1520-4995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]}}}