{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:45:44Z","timestamp":1789749944517,"version":"4.0.1"},"reference-count":41,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,9,1]]},"abstract":"<jats:p>Recent evidence suggests that NPC1L1 (Niemann\u2013Pick C1-like 1) is critical for intestinal sterol absorption in mice, yet mechanisms by which NPC1L1 regulates cellular sterol transport are lacking. In the study we used a McArdle-RH7777 rat hepatoma cell line stably expressing NPC1L1 to examine the sterol-specificity and directionality of NPC1L1-mediated sterol transport. As previously described, cholesterol-depletion-driven recycling of NPC1L1 to the cell surface facilitates cellular uptake of non-esterified (free) cholesterol. However, it has no impact on the uptake of esterified cholesterol, indicating free sterol specificity. Interestingly, the endocytic recycling of NPC1L1 was also without effect on \u03b2-sitosterol uptake, indicating that NPC1L1 can differentiate between free sterols of animal and plant origin in hepatoma cells. Furthermore, NPC1L1-driven free cholesterol transport was unidirectional, since cellular cholesterol efflux to apolipoprotein A-I, high-density lipoprotein or serum was unaffected by NPC1L1 expression or localization. Additionally, NPC1L1 facilitates mass non-esterified-cholesterol uptake only when it is located on the cell surface and not when it resides intracellularly. Finally, NPC1L1-dependent cholesterol uptake required adequate intracellular K+, yet did not rely on intracellular Ca2+, the cytoskeleton or signalling downstream of protein kinase A, protein kinase C or pertussis-toxin-sensitive G-protein-coupled receptors. Collectively, these findings support the notion that NPC1L1 can selectively recognize non-esterified cholesterol and promote its unidirectional transport into hepatoma cells.<\/jats:p>","DOI":"10.1042\/bj20070168","type":"journal-article","created":{"date-parts":[[2007,8,14]],"date-time":"2007-08-14T08:40:13Z","timestamp":1187080813000},"page":"273-283","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["NPC1L1 (Niemann\u2013Pick C1-like 1) mediates sterol-specific unidirectional transport of non-esterified cholesterol in McArdle-RH7777 hepatoma cells"],"prefix":"10.1042","volume":"406","author":[{"given":"J.\u00a0Mark","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1040, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence\u00a0L.","family":"Rudel","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1040, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1040, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2007,8,13]]},"reference":[{"key":"2021112213294137800_B1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1006\/geno.2000.6151","article-title":"Evidence for a Niemann\u2013Pick C (NPC) gene family: identification and characterization of NPC1L1","volume":"65","author":"Davies","year":"2000","journal-title":"Genomics"},{"key":"2021112213294137800_B2","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1126\/science.1093131","article-title":"Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption","volume":"303","author":"Altmann","year":"2004","journal-title":"Science"},{"key":"2021112213294137800_B3","doi-asserted-by":"crossref","first-page":"12710","DOI":"10.1074\/jbc.M409110200","article-title":"Inactivation of NPC1L1 causes multiple lipid transport defects and protects against diet-induced hypercholesterolemia","volume":"280","author":"Davies","year":"2005","journal-title":"J. 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