{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:32:00Z","timestamp":1790937120621,"version":"4.1.0"},"reference-count":91,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,5,10]],"date-time":"2018-05-10T00:00:00Z","timestamp":1525910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["228143"],"award-info":[{"award-number":["228143"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Exposure to diesel exhaust particles (DEPs) affects endothelial function and may contribute to the development of atherosclerosis and vasomotor dysfunction. As intracellular calcium concentration [Ca2+]i is considered important in myoendothelial signalling, we explored the effects of extractable organic matter from DEPs (DEP-EOM) on [Ca2+]i and membrane microstructure in endothelial cells. DEP-EOM of increasing polarity was obtained by pressurized sequential extraction of DEPs with n-hexane (n-Hex-EOM), dichloromethane (DCM-EOM), methanol, and water. Chemical analysis revealed that the majority of organic matter was extracted by the n-Hex- and DCM-EOM, with polycyclic aromatic hydrocarbons primarily occurring in n-Hex-EOM. The concentration of calcium was measured in human microvascular endothelial cells (HMEC-1) using micro-spectrofluorometry. The lipophilic n-Hex-EOM and DCM-EOM, but not the more polar methanol- and water-soluble extracts, induced rapid [Ca2+]i increases in HMEC-1. n-Hex-EOM triggered [Ca2+]i increase from intracellular stores, followed by extracellular calcium influx consistent with store operated calcium entry (SOCE). By contrast, the less lipophilic DCM-EOM triggered [Ca2+]i increase via extracellular influx alone, resembling receptor operated calcium entry (ROCE). Both extracts increased [Ca2+]i via aryl hydrocarbon receptor (AhR) non-genomic signalling, verified by pharmacological inhibition and RNA-interference. Moreover, DCM-EOM appeared to induce an AhR-dependent reduction in the global plasma membrane order, as visualized by confocal fluorescence microscopy. DCM-EOM-triggered [Ca2+]i increase and membrane alterations were attenuated by the membrane stabilizing lipid cholesterol. In conclusion, lipophilic constituents of DEPs extracted by n-hexane and DCM seem to induce rapid AhR-dependent [Ca2+]i increase in HMEC-1 endothelial cells, possibly involving both ROCE and SOCE-mediated mechanisms. The semi-lipophilic fraction extracted by DCM also caused an AhR-dependent reduction in global membrane order, which appeared to be connected to the [Ca2+]i increase.<\/jats:p>","DOI":"10.3390\/ijms19051429","type":"journal-article","created":{"date-parts":[[2018,5,11]],"date-time":"2018-05-11T03:42:48Z","timestamp":1526010168000},"page":"1429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Lipophilic Chemicals from Diesel Exhaust Particles Trigger Calcium Response in Human Endothelial Cells via Aryl Hydrocarbon Receptor Non-Genomic Signalling"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8023-1148","authenticated-orcid":false,"given":"Bendik C.","family":"Brinchmann","sequence":"first","affiliation":[{"name":"Department of Air Pollution and Noise, Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, N-0403 Oslo, Norway"},{"name":"Division of Laboratory Medicine, Faculty of Medicine, University of Oslo, N-0315 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Le Ferrec","sequence":"additional","affiliation":[{"name":"Inserm, EHESP, Irset (Institut de Recherche en Sant\u00e9, Environnement et Travail), Univ. Rennes, UMR_S 1085, F-35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Normand","family":"Podechard","sequence":"additional","affiliation":[{"name":"Inserm, EHESP, Irset (Institut de Recherche en Sant\u00e9, Environnement et Travail), Univ. Rennes, UMR_S 1085, F-35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Lagadic-Gossmann","sequence":"additional","affiliation":[{"name":"Inserm, EHESP, Irset (Institut de Recherche en Sant\u00e9, Environnement et Travail), Univ. Rennes, UMR_S 1085, F-35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji F.","family":"Shoji","sequence":"additional","affiliation":[{"name":"Inserm, EHESP, Irset (Institut de Recherche en Sant\u00e9, Environnement et Travail), Univ. Rennes, UMR_S 1085, F-35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1070-5990","authenticated-orcid":false,"given":"Aubin","family":"Penna","sequence":"additional","affiliation":[{"name":"Inserm, EHESP, Irset (Institut de Recherche en Sant\u00e9, Environnement et Travail), Univ. Rennes, UMR_S 1085, F-35000 Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Kukowski","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of North Dakota, Grand Forks, ND 58202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2318-5883","authenticated-orcid":false,"given":"Alena","family":"Kub\u00e1tov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of North Dakota, Grand Forks, ND 58202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rn A.","family":"Holme","sequence":"additional","affiliation":[{"name":"Department of Air Pollution and Noise, Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, N-0403 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"\u00d8vrevik","sequence":"additional","affiliation":[{"name":"Department of Air Pollution and Noise, Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, N-0403 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1161\/CIR.0b013e3181dbece1","article-title":"Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association","volume":"121","author":"Brook","year":"2010","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1016\/j.jacc.2012.08.974","article-title":"Chronic air pollution exposure and endothelial dysfunction: What you can\u2019t see-can harm you","volume":"60","author":"Brook","year":"2012","journal-title":"J. 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