{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T07:04:12Z","timestamp":1765609452697,"version":"build-2065373602"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,10,29]],"date-time":"2010-10-29T00:00:00Z","timestamp":1288310400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011103","name":"Sixth Framework Programme","doi-asserted-by":"publisher","award":["LSHM\u2010CT\u20102004\u2010005033"],"award-info":[{"award-number":["LSHM\u2010CT\u20102004\u2010005033"]}],"id":[{"id":"10.13039\/100011103","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Lipids"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepoxilins are epoxy alcohols synthesized through the 12\u2010lipoxygenase (12\u2010LO) pathway in animal cells. The epidermis is the principal source of hepoxilins in humans. Here we report on the formation of novel hepoxilin regioisomers formed by the 15\u2010LO pathway in human cells. The Hodgkin lymphoma cell line L1236 possesses high 15\u2010lipoxygenase\u20101 (15\u2010LO\u20101) activity and incubation of L1236 cells with arachidonic acid led to the formation of 11(<jats:italic>S<\/jats:italic>)\u2010hydroxy\u201014(<jats:italic>S<\/jats:italic>),15(<jats:italic>S<\/jats:italic>)\u2010epoxy 5(<jats:italic>Z<\/jats:italic>),8(<jats:italic>Z<\/jats:italic>),12(<jats:italic>E<\/jats:italic>) eicosatrienoic acid (14,15\u2010HxA<jats:sub>3<\/jats:sub> 11(<jats:italic>S<\/jats:italic>)) and 13(<jats:italic>R<\/jats:italic>)\u2010hydroxy\u201014(<jats:italic>S<\/jats:italic>),15(<jats:italic>S<\/jats:italic>)\u2010epoxy 5(<jats:italic>Z<\/jats:italic>),8(<jats:italic>Z<\/jats:italic>),11(<jats:italic>Z<\/jats:italic>) eicosatrienoic acid (14,15\u2010HxB<jats:sub>3<\/jats:sub> 13 (<jats:italic>R<\/jats:italic>)). In addition, two hitherto unidentified products were detected and these products were collected and analyzed by positive ion electrospray tandem mass spectrometry. These metabolites were identified as 11(<jats:italic>S<\/jats:italic>),15(<jats:italic>S<\/jats:italic>)\u2010dihydroxy\u201014(<jats:italic>R<\/jats:italic>)\u2010glutathionyl\u20105(<jats:italic>Z<\/jats:italic>),8(<jats:italic>Z<\/jats:italic>),12(<jats:italic>E<\/jats:italic>)\u2010eicosatrienoic acid (14,15\u2010HxA<jats:sub>3<\/jats:sub>\u2010C) and 11(<jats:italic>S<\/jats:italic>),15(<jats:italic>S<\/jats:italic>)\u2010dihydroxy\u201014(<jats:italic>R<\/jats:italic>)\u2010cysteinyl\u2010glycyl\u20105(<jats:italic>Z<\/jats:italic>),8(<jats:italic>Z<\/jats:italic>),12(<jats:italic>E<\/jats:italic>)\u2010eicosatrienoic acid (14,15\u2010HxA<jats:sub>3<\/jats:sub>\u2010D). Incubation of L1236 cells with synthetic 14,15\u2010HxA<jats:sub>3<\/jats:sub> 11(<jats:italic>S<\/jats:italic>) also led to the formation of 14,15\u2010HxA<jats:sub>3<\/jats:sub>\u2010C and 14,15\u2010HxA<jats:sub>3<\/jats:sub>\u2010D. Several soluble glutathione transferases, in particular GST M1\u20101 and GST P1\u20101, were found to catalyze the conversion of 14,15\u2010HxA<jats:sub>3<\/jats:sub> to 14,15\u2010HxA<jats:sub>3<\/jats:sub>\u2010C. L1236 cells produced approximately twice as much eoxins as cysteinyl\u2010containing hepoxilins upon stimulation with arachidonic acid. Human eosinophils, nasal polyps and dendritic cells selectively formed 14,15\u2010HxA<jats:sub>3<\/jats:sub> 11(<jats:italic>S<\/jats:italic>) and 14,15\u2010HxB<jats:sub>3<\/jats:sub> 13(<jats:italic>R<\/jats:italic>) stereoisomers, but not cysteinyl\u2010containing hepoxilins, after stimulation with arachidonic acid. Furthermore, purified recombinant 15\u2010LO\u20101 alone catalyzed the conversion of arachidonic acid to 14,15\u2010HxA<jats:sub>3<\/jats:sub> 11(<jats:italic>S<\/jats:italic>) and 14,15\u2010HxB<jats:sub>3<\/jats:sub> 13(<jats:italic>R<\/jats:italic>), showing that human 15\u2010LO\u20101 possesses intrinsic 14,15\u2010hepoxilin synthase activity.<\/jats:p>","DOI":"10.1007\/s11745-010-3485-1","type":"journal-article","created":{"date-parts":[[2010,11,2]],"date-time":"2010-11-02T20:46:46Z","timestamp":1288730806000},"page":"69-79","source":"Crossref","is-referenced-by-count":16,"title":["Biosynthesis of 14,15\u2010Hepoxilins in Human L1236 Hodgkin Lymphoma Cells and Eosinophils"],"prefix":"10.1002","volume":"46","author":[{"given":"\u00c5sa","family":"Brunnstr\u00f6m","sequence":"first","affiliation":[{"name":"Department of Medicine Karolinska Institutet and Karolinska University Hospital Solna Stockholm 171 76 Sweden"},{"name":"Orexo AB Box 303 Uppsala 75105 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mats","family":"Hamberg","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm 171 77 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J.","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Institute of Mass Spectrometry, School of Medicine Swansea University Singleton Park Swansea SA2 8PP UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bengt","family":"Mannervik","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Organic Chemistry Uppsala University Biomedical Center Uppsala 75123 Sweden"},{"name":"Department of Neurochemistry Stockholms University Stockholm 106 91 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans\u2010Erik","family":"Claesson","sequence":"additional","affiliation":[{"name":"Department of Medicine Karolinska Institutet and Karolinska University Hospital Solna Stockholm 171 76 Sweden"},{"name":"Orexo AB Box 303 Uppsala 75105 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,10,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00168.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(94)90087-6"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307576200"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)32298-1"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(89)91109-1"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(91)90056-N"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3530091"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2007.05909.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1998.00159.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2000.00903.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2007.05910.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20236"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2004.10.007"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.410"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.12.5130"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7827(86)90127-X"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb14249.x"},{"key":"e_1_2_7_19_1","first-page":"95","article-title":"Hepoxilin A3 increases vascular permeability in the rat skin","volume":"4","author":"Laneuville O","year":"1991","journal-title":"Eicosanoids"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(99)00345-7"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400832101"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1992.tb14528.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115110"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2007.06.001"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.14.4633"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)34538-1"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2008.12.003"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2222.2002.01477.x"},{"key":"e_1_2_7_29_1","first-page":"1201","article-title":"15\u2010Lipoxygenase immunoreactivity in normal and in asthmatic airways","volume":"151","author":"Bradding P","year":"1995","journal-title":"Am J Respir Crit Care Med"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/147.4.1024"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0710127105"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2008.06570.x"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.40.28213"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(88)90308-6"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2006.09.007"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.025288"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.1708"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.36.22203"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)81540-9"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-0305(01)00256-2"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.47.30879"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)68802-2"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2003.09.026"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83657-8"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00187-08"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00284a011"}],"container-title":["Lipids"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aocs.onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s11745-010-3485-1","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T08:51:02Z","timestamp":1760950262000},"score":1,"resource":{"primary":{"URL":"https:\/\/aocs.onlinelibrary.wiley.com\/doi\/10.1007\/s11745-010-3485-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,10,29]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,1]]}},"alternative-id":["10.1007\/s11745-010-3485-1"],"URL":"https:\/\/doi.org\/10.1007\/s11745-010-3485-1","archive":["Portico"],"relation":{},"ISSN":["0024-4201","1558-9307"],"issn-type":[{"type":"print","value":"0024-4201"},{"type":"electronic","value":"1558-9307"}],"subject":[],"published":{"date-parts":[[2010,10,29]]}}}