{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T12:07:33Z","timestamp":1761394053793},"reference-count":66,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ATVB"],"published-print":{"date-parts":[[1999,4]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014The concept that hepatic cholesteryl ester (CE) mass and the rate of cholesterol esterification regulate hepatocyte assembly and secretion of apoB-containing lipoproteins remains controversial. The present study was carried out in HepG2 cells to correlate the rate of cholesterol esterification and CE mass with apoB secretion by CI-1011, an acyl CoA:cholesterol acyltransferase (ACAT) inhibitor that is known to decrease apoB secretion, in vivo, in miniature pigs. HepG2 cells were incubated with CI-1011 (10 nmol\/L, 1 \u03bcmol\/L, and 10 \u03bcmol\/L) for 24 hours. ApoB secretion into media was decreased by 25%, 27%, and 43%, respectively (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.0012). CI-1011 (10 \u03bcmol\/L) inhibited HepG2 cell ACAT activity by 79% (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.002) and cellular CE mass by 32% (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.05). In contrast, another ACAT inhibitor, DuP 128 (10 \u03bcmol\/L), decreased cellular ACAT activity and CE mass by 85% (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.002) and 42% (\n            <jats:italic>P<\/jats:italic>\n            =0.01), respectively, but had no effect on apoB secretion into media. To characterize the reduction in apoB secretion by CI-1011, pulse-chase experiments were performed and analyzed by multicompartmental modelling using SAAM II. CI-1011 did not affect the synthesis of apoB or albumin. However, apoB secretion into the media was decreased by 42% (\n            <jats:italic>P<\/jats:italic>\n            =0.019). Intracellular apoB degradation increased proportionately (\n            <jats:italic>P<\/jats:italic>\n            =0.019). The secretion of albumin and cellular reuptake of labeled lipoproteins were unchanged. CI-1011 and DuP 128 did not affect apoB mRNA concentrations. These results show that CI-1011 decreases apoB secretion by a mechanism that involves an enhanced intracellular degradation of apoB. This study demonstrates that ACAT inhibitors can exert differential effects on apoB secretion from HepG2 cells that do not reflect their efficacy in inhibiting cholesterol esterification.\n          <\/jats:p>","DOI":"10.1161\/01.atv.19.4.939","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T19:44:19Z","timestamp":1308339859000},"page":"939-949","source":"Crossref","is-referenced-by-count":40,"title":["ApoB100 Secretion From HepG2 Cells is Decreased by the ACAT Inhibitor CI-1011"],"prefix":"10.1161","volume":"19","author":[{"given":"Lisa J.","family":"Wilcox","sequence":"first","affiliation":[{"name":"From the Departments of Medicine and Biochemistry and The John P. Robarts Research Institute, University of Western Ontario, London, Ontario, Canada (L.J.W., M.W.H.); the University of Washington, Seattle, WA (P.H.R.B.); and Parke-Davis Pharmaceutical Research, Warner Lambert Co, Ann Arbor, MI (R.S.N.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. Hugh R.","family":"Barrett","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Biochemistry and The John P. Robarts Research Institute, University of Western Ontario, London, Ontario, Canada (L.J.W., M.W.H.); the University of Washington, Seattle, WA (P.H.R.B.); and Parke-Davis Pharmaceutical Research, Warner Lambert Co, Ann Arbor, MI (R.S.N.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger S.","family":"Newton","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Biochemistry and The John P. Robarts Research Institute, University of Western Ontario, London, Ontario, Canada (L.J.W., M.W.H.); the University of Washington, Seattle, WA (P.H.R.B.); and Parke-Davis Pharmaceutical Research, Warner Lambert Co, Ann Arbor, MI (R.S.N.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murray W.","family":"Huff","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Biochemistry and The John P. Robarts Research Institute, University of Western Ontario, London, Ontario, Canada (L.J.W., M.W.H.); the University of Washington, Seattle, WA (P.H.R.B.); and Parke-Davis Pharmaceutical Research, Warner Lambert Co, Ann Arbor, MI (R.S.N.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"crossref","first-page":"25621","DOI":"10.1016\/S0021-9258(18)35646-1","volume":"267","year":"1992","journal-title":"J Biol Chem"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108229"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3513311"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"22967","DOI":"10.1016\/S0021-9258(19)49411-8","volume":"268","year":"1993","journal-title":"J Biol Chem"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"24169","DOI":"10.1016\/S0021-9258(19)51064-X","volume":"269","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"7160","DOI":"10.1016\/S0021-9258(19)50552-X","volume":"267","year":"1992","journal-title":"J Biol Chem"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/S0022-2275(20)39963-6","volume":"35","year":"1994","journal-title":"J Lipid Res"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/S0022-2275(20)38287-0","volume":"30","year":"1989","journal-title":"J Lipid Res"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"26920","DOI":"10.1016\/S0021-9258(19)74198-2","volume":"268","year":"1993","journal-title":"J Biol Chem"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/atv91.13.5.8485114"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0022-2275(20)40744-8","volume":"34","year":"1993","journal-title":"J Lipid Res"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"5080","DOI":"10.1016\/S0021-9258(19)67758-6","volume":"266","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(93)90172-6"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"12375","DOI":"10.1016\/S0021-9258(17)32726-6","volume":"269","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.16.10.1229"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"2998","DOI":"10.1016\/S0021-9258(18)69166-5","volume":"263","year":"1988","journal-title":"J Biol Chem"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0022-2275(20)37630-6","volume":"37","year":"1996","journal-title":"J Lipid Res"},{"key":"e_1_3_2_18_2","doi-asserted-by":"crossref","first-page":"12713","DOI":"10.1016\/S0021-9258(18)31446-7","volume":"268","year":"1993","journal-title":"J Biol Chem"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1016\/S0022-2275(20)42269-2","volume":"31","year":"1990","journal-title":"J Lipid Res"},{"key":"e_1_3_2_20_2","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1016\/S0022-2275(20)41088-0","volume":"36","year":"1995","journal-title":"J Lipid Res"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(92)90201-6"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0022-2275(20)39751-0","volume":"36","year":"1995","journal-title":"J Lipid Res"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/atv91.14.9.8068612"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(92)90206-P"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.17.11.2589"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(90)90053-Z"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(90)92151-O"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm960674d"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2760(98)00059-9"},{"key":"e_1_3_2_30_2","unstructured":"Krause BR Pape ME Rea T Bousley R Stanfield R Kieft K Anderson MK Lee H Homan R. CI-1011: a novel cholesterol-lowering compound in both chow-fed and cholesterol-fed rodent and nonrodent species. XII International Symposium on Drugs Affecting Lipid Metabolism . 1995;136. Abstract."},{"key":"e_1_3_2_31_2","unstructured":"Auerbach B Bousley R Stanfield R Bisgaier CL Homan R Krause BR. Modulation of apoB kinetics and lipoprotein cholesterol in the casein-fed rabbit by CI-1011: in vivo evidence for liver ACAT inhibition. XII International Symposium on Drugs Affecting Lipid Metabolism . 1995;135. Abstract."},{"key":"e_1_3_2_32_2","unstructured":"Lee HT Picard JA Sliskovic DR Roth BD Hamelehle KL Bousley R Krause BR Stanfield R. CI-1011: A potent lipid regulating agent. XII International Symposium on Drugs Affecting Lipid Metabolism . 1995;101. Abstract."},{"key":"e_1_3_2_33_2","unstructured":"Burnett JR Wilcox LJ Telford DE Kleinstiver SJ Barrett PHR Newton RS Huff MW. Hepatic apolipoprotein B secretion in vivo is decreased by the ACAT inhibitor CI-1011 in miniature pigs. Circulation . 1997;S96:I-544. Abstract."},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","first-page":"10743","DOI":"10.1016\/S0021-9258(19)50081-3","volume":"267","year":"1992","journal-title":"J Biol Chem"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(78)90586-9"},{"key":"e_1_3_2_36_2","first-page":"39","volume":"26","year":"1993","journal-title":"Biochemistry"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/S0022-2275(20)33868-2","volume":"39","year":"1998","journal-title":"J Lipid Res"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)64849-5"},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/S0022-2275(20)34265-6","volume":"26","year":"1985","journal-title":"J Lipid Res"},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/S0022-2275(20)37908-6","volume":"24","year":"1983","journal-title":"J Lipid 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