{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:45:38Z","timestamp":1791978338713,"version":"4.4.0"},"reference-count":64,"publisher":"American Physiological Society","issue":"5","funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["R01 GM041935"],"award-info":[{"award-number":["R01 GM041935"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["NIH R35 GM122576"],"award-info":[{"award-number":["NIH R35 GM122576"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["NIH T32 GM086330"],"award-info":[{"award-number":["NIH T32 GM086330"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007083","name":"Orion Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007083","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003125","name":"Suomen Kulttuurirahasto (Finnish Cultural Foundation)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003125","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2018,5,1]]},"abstract":"<jats:p> The heteromeric steroid transporter organic solute transporter \u03b1\/\u03b2 (OST\u03b1\/\u03b2, SLC51A\/B) was discovered over a decade ago, but its physiological significance in the liver remains uncertain. A major challenge has been the lack of suitable models expressing OST\u03b1\/\u03b2. Based on observations first reported here that hepatic OST\u03b1\/\u03b2 is upregulated in nonalcoholic steatohepatitis, the aim of this research was to develop an in vitro model to evaluate OST\u03b1\/\u03b2 function and interaction with drugs and bile acids. OST\u03b1\/\u03b2 expression in human liver tissue was analyzed by quantitative RT-PCR, Western blotting, and immunofluorescence. Radiolabeled compounds were used to determine OST\u03b1\/\u03b2-mediated transport in the established in vitro model. The effect of bile acids and drugs, including those associated with cholestatic drug-induced liver injury, on OST\u03b1\/\u03b2-mediated transport was evaluated. Expression of OST\u03b1\/\u03b2 was elevated in the liver of patients with nonalcoholic steatohepatitis and primary biliary cholangitis, whereas hepatocyte expression of OST\u03b1\/\u03b2 was low in control liver tissue. Studies in the novel cell-based system showed rapid and linear OST\u03b1\/\u03b2-mediated transport for all tested compounds: dehydroepiandrosterone sulfate, digoxin, estrone sulfate, and taurocholate. The interaction study with 26 compounds revealed novel OST\u03b1\/\u03b2 inhibitors: a biomarker for cholestasis, glycochenodeoxycholic acid; the major metabolite of troglitazone, troglitazone sulfate; and a macrocyclic antibiotic, fidaxomicin. Additionally, some drugs (e.g., digoxin) consistently stimulated taurocholate uptake in OST\u03b1\/\u03b2-overexpressing cells. Our findings demonstrate that OST\u03b1\/\u03b2 is an important transporter in liver disease and imply a role for this transporter in bile acid-bile acid and drug-bile acid interactions, as well as cholestatic drug-induced liver injury. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY The organic solute transporter OST\u03b1\/\u03b2 is highly expressed in hepatocytes of liver tissue obtained from patients with nonalcoholic steatohepatitis and primary biliary cholangitis. OST\u03b1\/\u03b2 substrates exhibit rapid, linear, and concentration-driven transport in an OST\u03b1\/\u03b2-overexpressing cell line. Drugs associated with hepatotoxicity modulate OST\u03b1\/\u03b2-mediated taurocholate transport. These data suggest that hepatic OST\u03b1\/\u03b2 plays an essential role in patients with cholestasis and may have important clinical implications for bile acid and drug disposition. <\/jats:p>","DOI":"10.1152\/ajpgi.00310.2017","type":"journal-article","created":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T12:00:45Z","timestamp":1518091245000},"page":"G597-G609","source":"Crossref","is-referenced-by-count":47,"title":["Organic solute transporter OST\u03b1\/\u03b2 is overexpressed in nonalcoholic steatohepatitis and modulated by drugs associated with liver injury"],"prefix":"10.1152","volume":"314","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9955-5043","authenticated-orcid":false,"given":"Melina M.","family":"Malinen","sequence":"first","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izna","family":"Ali","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Bezen\u00e7on","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Beaudoin","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1945-4929","authenticated-orcid":false,"given":"Kim L. R.","family":"Brouwer","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S1665-2681(19)31170-6","volume":"14","author":"Aguilar-Olivos NE","year":"2015","journal-title":"Ann Hepatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.028654"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2017.02.011"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20961"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90319.2008"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28323"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00539.2005"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.114.062703"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2016.03.002"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120055"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.03.006"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2016.02.015"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.02.021"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412752200"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.040758"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-016-4121-6"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1055\/s-2004-861552"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1042\/bj2840341"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.11.004"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06920.x"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-015-3776-8"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00479.2005"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153959"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(01)00460-7"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.2.C328"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X12461294"},{"key":"B27","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/S0016-5085(19)33226-3","volume":"63","author":"Greim H","year":"1972","journal-title":"Gastroenterology"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.026450"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1124\/mol.105.019547"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.041012"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1089\/aivt.2016.0023"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-011-0564-9"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1021\/jm300212s"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.663"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.113.054304"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2013.01.022"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.156653"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.112.045666"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20070716"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfu151"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.03.020"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1021\/mp4000822"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfq269"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kft176"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25497"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.58.6.1196"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-006-9163-6"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.07.033"},{"key":"B49","first-page":"1460","volume":"81","author":"Pasqualini JR","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22771"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12558"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M301106200"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.DMPK-11-SH-080"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2017.04.053"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13092"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12168"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.161099898"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158269"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00138.2013"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.221564"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/934594"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1021\/mp900163d"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00490.2005"}],"container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpgi.00310.2017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,21]],"date-time":"2019-09-21T14:38:55Z","timestamp":1569076735000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.00310.2017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,1]]},"references-count":64,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5,1]]}},"alternative-id":["10.1152\/ajpgi.00310.2017"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.00310.2017","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,1]]}}}