{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T02:02:58Z","timestamp":1768701778865,"version":"3.49.0"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T00:00:00Z","timestamp":1563926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS PI13\/00364 and FIS PI16\/00471"],"award-info":[{"award-number":["FIS PI13\/00364 and FIS PI16\/00471"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CIBERDEM CB07\/08\/0016"],"award-info":[{"award-number":["CIBERDEM CB07\/08\/0016"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008666","name":"Fundaci\u00f3 la Marat\u00f3 de TV3","doi-asserted-by":"publisher","award":["158\/U\/2017"],"award-info":[{"award-number":["158\/U\/2017"]}],"id":[{"id":"10.13039\/100008666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2017-SGR-1149"],"award-info":[{"award-number":["2017-SGR-1149"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Electronegative low-density lipoprotein (LDL(\u2212)) is a minor LDL subfraction that is present in blood with inflammatory and apoptotic effects. We aimed to evaluate the role of sphingolipids ceramide (Cer), sphingosine (Sph), and sphingosine-1-phosphate (S1P) in the LDL(\u2212)-induced effect on monocytes. Total LDL was subfractioned into native LDL and LDL(\u2212) by anion-exchange chromatography and their sphingolipid content evaluated by mass spectrometry. LDL subfractions were incubated with monocytes in the presence or absence of enzyme inhibitors: chlorpromazine (CPZ), d-erythro-2-(N-myristoyl amino)-1-phenyl-1-propanol (MAPP), and N,N-dimethylsphingosine (DMS), which inhibit Cer, Sph, and S1P generation, respectively. After incubation, we evaluated cytokine release by enzyme-linked immunosorbent assay (ELISA) and apoptosis by flow cytometry. LDL(\u2212) had an increased content in Cer and Sph compared to LDL(+). LDL(\u2212)-induced cytokine release from cultured monocytes was inhibited by CPZ and MAPP, whereas DMS had no effect. LDL(\u2212) promoted monocyte apoptosis, which was inhibited by CPZ, but increased with the addition of DMS. LDL enriched with Sph increased cytokine release in monocytes, and when enriched with Cer, reproduced both the apoptotic and inflammatory effects of LDL(\u2212). These observations indicate that Cer content contributes to the inflammatory and apoptotic effects of LDL(\u2212) on monocytes, whereas Sph plays a more important role in LDL(\u2212)-induced inflammation, and S1P counteracts apoptosis.<\/jats:p>","DOI":"10.3390\/biom9080300","type":"journal-article","created":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T05:37:41Z","timestamp":1564033061000},"page":"300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The Role of Distinctive Sphingolipids in the Inflammatory and Apoptotic Effects of Electronegative LDL on Monocytes"],"prefix":"10.3390","volume":"9","author":[{"given":"N\u00faria","family":"Puig","sequence":"first","affiliation":[{"name":"Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain. C\/Sant Quinti 77-79, 08041 Barcelona, Spain"},{"name":"Department of Biochemistry and Molecular Biology, Faculty of Medicine, Building M, Universitat Aut\u00f2noma de Barcelona (UAB), Cerdanyola del Vall\u00e8s, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Montserrat","family":"Estruch","sequence":"additional","affiliation":[{"name":"Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain. C\/Sant Quinti 77-79, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Jin","sequence":"additional","affiliation":[{"name":"Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain. C\/Sant Quinti 77-79, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0224-591X","authenticated-orcid":false,"given":"Jose Luis","family":"Sanchez-Quesada","sequence":"additional","affiliation":[{"name":"Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain. C\/Sant Quinti 77-79, 08041 Barcelona, Spain"},{"name":"CIBER of Diabetes and Metabolic Diseases (CIBERDEM), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Benitez","sequence":"additional","affiliation":[{"name":"Cardiovascular Biochemistry, Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain. C\/Sant Quinti 77-79, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/nature13475","article-title":"Sphingolipid metabolites in inflammatory disease","volume":"510","author":"Maceyka","year":"2014","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1161\/ATVBAHA.116.305675","article-title":"Sphingolipids contribute to human atherosclerotic plaque inflammation","volume":"36","author":"Edsfeldt","year":"2016","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.bbalip.2008.06.002","article-title":"Ceramidases: Regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate","volume":"1781","author":"Mao","year":"2008","journal-title":"Biochim. 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