{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:08:09Z","timestamp":1786118889516,"version":"build-2736575974"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":11322,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1984,9]]},"abstract":"\n \n \n Low density lipoprotein (LDL) processing was investigated in a human hepatoma-derived cell line, Hep G2. Hep G2 cells bound, internalized and degraded LDL via a saturable, high affinity (Kd \u2014 2 \u00b1 10\n \u22128<\/jats:sup>\n M<\/jats:italic>\n ) pathway similar to that present in other mammalian cells. Although 80% of the uptake and degradation of\n 125<\/jats:sup>\n I-LDL was inhibited by 40-fold excess native LDL, the same concentration of methylated LDL, which cannot bind to LDL receptors, had virtually no effect on processing. When added at low concentrations, the lysosomotropic agent, chloroquine, inhibited degradation (I\n 50<\/jats:sub>\n \u2014 15 \u03bc\n M<\/jats:italic>\n ) without affecting the rate of lipoprotein internalization. Receptor activity was decreased 60% by preincubation of the cells in medium containing a source of cholesterol (LDL or unesterified cholesterol) and increased 1.7-fold by preincubation with compactin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. The Hep G2 cell line may prove a useful system both for the further study of hepatic lipoprotein metabolism and for the evaluation of new antihypercholesterolemic agents.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/hep.1840040518","type":"journal-article","created":{"date-parts":[[2008,8,22]],"date-time":"2008-08-22T09:06:35Z","timestamp":1219395995000},"page":"897-901","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":21,"title":["Regulation of Low Density Lipoprotein Receptor Function in a Human Hepatoma Cell Line"],"prefix":"10.1097","volume":"4","author":[{"given":"Alan M.","family":"Leichtner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monty","family":"Krieger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan L.","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1002\/hep.1840040518-BIB1","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1172\/JCI106949","article-title":"The metabolism of low density lipoprotein in familial type II hyperlipoproteinemia","volume":"51","author":"Langer","year":"1972","journal-title":"J Clin Invest"},{"key":"10.1002\/hep.1840040518-BIB2","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1172\/JCI109490","article-title":"Metabolic studies in familial hypercholesterolemia: evidence for a gene-dosage effect in vivo","volume":"64","author":"Bilheimer","year":"1979","journal-title":"J Clin Invest"},{"key":"10.1002\/hep.1840040518-BIB3","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1126\/science.174194","article-title":"Receptor-mediated control of cholesterol metabolism","volume":"191","author":"Brown","year":"1976","journal-title":"Science"},{"key":"10.1002\/hep.1840040518-BIB4","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1146\/annurev.bi.46.070177.004341","article-title":"The low density lipoprotein pathway and its relation to atherosclerosis","volume":"46","author":"Goldstein","year":"1977","journal-title":"Ann Rev Biochem"},{"key":"10.1002\/hep.1840040518-BIB5","doi-asserted-by":"crossref","first-page":"7994","DOI":"10.1016\/S0021-9258(18)34287-X","article-title":"Receptor-dependent and receptor-independent degradation of low density lipoprotein in normal rabbits and in receptor-deficiency mutant rabbits","volume":"257","author":"Pittman","year":"1982","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840040518-BIB6","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1056\/NEJM198308043090507","article-title":"Defective lipoprotein receptors and atherosclerosis: lessons from an animal counterpart of familial hypercholesterolemia","volume":"309","author":"Goldstein","year":"1983","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840040518-BIB7","doi-asserted-by":"crossref","first-page":"3340","DOI":"10.1016\/S0021-9258(19)69612-2","article-title":"Receptor-mediated catabolism of homologous low density lipoprotein in cultured pig hepatocytes","volume":"256","author":"Pangburn","year":"1981","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840040518-BIB8","doi-asserted-by":"crossref","first-page":"5675","DOI":"10.1021\/bi00265a044","article-title":"High-affinity uptake and degradation of apolipoprotein E free high-density lipoprotein and low-density lipoprotein in cultured porcine hepatocytes","volume":"21","author":"Bachorik","year":"1982","journal-title":"Biochem"},{"key":"10.1002\/hep.1840040518-BIB9","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/S0021-9258(19)42998-0","article-title":"Regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured human fibroblast: comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia","volume":"249","author":"Brown","year":"1974","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840040518-BIB10","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0092-8674(76)90258-0","article-title":"Release of low density lipoprotein from its cell surface receptor by sulfated glycosaminoglycans","volume":"7","author":"Goldstein","year":"1976","journal-title":"Cell"},{"key":"10.1002\/hep.1840040518-BIB11","doi-asserted-by":"crossref","first-page":"9053","DOI":"10.1016\/S0021-9258(17)34284-9","article-title":"Role of the lysine residues of plasma lipoproteins in high affinity binding to cell surface receptors","volume":"253","author":"Weisgraber","year":"1978","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840040518-BIB12","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0021-9258(17)38120-6","article-title":"Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase","volume":"253","author":"Brown","year":"1978","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840040518-BIB13","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/0022-2836(81)90447-2","article-title":"Isolation of Chinese hamster cell mutants defective in receptor-mediated endocytosis of low density lipoprotein","volume":"150","author":"Krieger","year":"1981","journal-title":"J Molec Biol"},{"key":"10.1002\/hep.1840040518-BIB14","doi-asserted-by":"crossref","first-page":"11249","DOI":"10.1016\/S0021-9258(17)44410-3","article-title":"Biosynthesis of the human asialoglycoprotein receptor","volume":"258","author":"Schwartz","year":"1983","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840040518-BIB15","doi-asserted-by":"crossref","first-page":"5153","DOI":"10.1016\/S0021-9258(19)42341-7","article-title":"Binding and degradation of low-density lipoproteins by cultured fibroblasts: comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia","volume":"249","author":"Goldstein","year":"1974","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840040518-BIB16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/0005-2744(73)90373-2","article-title":"Specificite de l\u030c iodotryosine desiodase des microsomes thyroidiens et hepatiques","volume":"293","author":"Dumas","year":"1973","journal-title":"Biochim Biophys Acta"},{"key":"10.1002\/hep.1840040518-BIB17","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840040518-BIB18","doi-asserted-by":"crossref","first-page":"7854","DOI":"10.1016\/S0021-9258(19)40894-6","article-title":"Inhibition of the proteolytic degradation of low density lipoprotein in human fibroblasts by chloroquine, concanavalin A and Triton WR 1339","volume":"250","author":"Goldstein","year":"1975","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840040518-BIB19","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/0092-8674(83)90423-3","article-title":"Complementation of mutations in the LDL pathway of receptor-mediated endocytosis by cocultivation of LDL receptor-defective hamster cell mutants","volume":"33","author":"Krieger","year":"1983","journal-title":"Cell"},{"key":"10.1002\/hep.1840040518-BIB20","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0022-2275(20)42221-7","article-title":"Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth","volume":"21","author":"Brown","year":"1980","journal-title":"J Lipid Res"},{"key":"10.1002\/hep.1840040518-BIB21","doi-asserted-by":"crossref","first-page":"7084","DOI":"10.1021\/bi00528a006","article-title":"Characterization of the major apolipoproteins secreted by two human hepatoma lines","volume":"20","author":"Zannis","year":"1981","journal-title":"Biochemistry"},{"key":"10.1002\/hep.1840040518-BIB22","doi-asserted-by":"crossref","first-page":"8878","DOI":"10.1016\/S0021-9258(19)52477-2","article-title":"Characterization of asialoglycoprotein receptor in a continuous hepatoma line","volume":"256","author":"Schwartz","year":"1981","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840040518-BIB23","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0092-8674(75)90182-8","article-title":"Regulation of the activity of the low density lipoprotein receptor in human fibroblasts","volume":"6","author":"Brown","year":"1975","journal-title":"Cell"},{"key":"10.1002\/hep.1840040518-BIB24","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1073\/pnas.78.4.2268","article-title":"Deficiency of low density lipoprotein receptors in liver and adrenal gland of the WHHL rabbit, an animal model of familial hypercholesterolemia","volume":"78","author":"Kita","year":"1981","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1002\/hep.1840040518-BIB25","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1016\/0006-291X(77)90593-9","article-title":"Specific, saturable, and high affinity binding of 125I-low density lipoprotein to glass beads","volume":"74","author":"Dana","year":"1977","journal-title":"Biochem Biophys Res Comm"},{"key":"10.1002\/hep.1840040518-BIB26","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1042\/bj2140951","article-title":"The metabolism in vitro of human low-density lipoprotein by the human hepatoma cell line Hep G2","volume":"214","author":"Havekes","year":"1983","journal-title":"Biochem J"},{"key":"10.1002\/hep.1840040518-BIB27","doi-asserted-by":"crossref","first-page":"5646","DOI":"10.1016\/S0021-9258(19)69254-9","article-title":"Lipoprotein binding to canine hepatic membranes: metabolically distinct apo-E and apo-B, E receptors","volume":"256","author":"Hui","year":"1981","journal-title":"J Biol Chem"},{"key":"10.1002\/hep.1840040518-BIB28","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1056\/NEJM198108273050902","article-title":"Effects of an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase on serum lipoproteins and ubiquinone-10 levels in patients with familial hypercholesterolemia","volume":"305","author":"Mabuchi","year":"1981","journal-title":"N Engl J Med"},{"key":"10.1002\/hep.1840040518-BIB29","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1056\/NEJM198303173081101","article-title":"Reduction of serum cholesterol in heterozygous patients with familial hypercholesterolemia: additive effects of compactin and cholestyramine","volume":"308","author":"Mabuchi","year":"1983","journal-title":"N Engl J Med"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.1840040518","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ovid.com\/01515467-198409000-00018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T17:14:24Z","timestamp":1786036464000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/01515467-198409000-00018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1984,9]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1984]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.1840040518","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[1984,9]]}}}