| MeSH term | MeSH ID | Detail |
|---|---|---|
| Arteriosclerosis | D001161 | 86 associated lipids |
| Carcinoma, Hepatocellular | D006528 | 140 associated lipids |
| Niemann-Pick Diseases | D009542 | 25 associated lipids |
| Atherosclerosis | D050197 | 85 associated lipids |
Total
4
25-Hydroxycholesterol
25-Hydroxycholesterol is a lipid of Sterol Lipids (ST) class. 25-hydroxycholesterol is associated with abnormalities such as Hereditary Diseases, Atherosclerosis, Fatty Liver, Infection and Exanthema. The involved functions are known as Binding (Molecular Function), cholesterol binding, sterol binding, oxysterol binding and Regulation. 25-hydroxycholesterol often locates in Membrane, Golgi membrane, Cellular Membrane, Cytoplasmic matrix and Golgi Apparatus. The associated genes with 25-Hydroxycholesterol are PTPN7 gene, OSBP gene, N-glycylalanine, SCAP gene and TSPO gene. The related lipids are 25-hydroxycholesterol, Sterols, Hydroxycholesterols, 27-hydroxycholesterol and Steroids. The related experimental models are Knock-out.
Cross Reference
Introduction
To understand associated biological information of 25-Hydroxycholesterol, we collected biological information of abnormalities, associated pathways, cellular/molecular locations, biological functions, related genes/proteins, lipids and common seen animal/experimental models with organized paragraphs from literatures.
What diseases are associated with 25-Hydroxycholesterol?
25-Hydroxycholesterol is suspected in Atherosclerosis, Keratoconjunctivitis Sicca, Hypercholesterolemia, Fatty Streak, Arterial, Hypochondroplasia (disorder), Infection and other diseases in descending order of the highest number of associated sentences.
Related references are mostly published in these journals:
| Disease | Cross reference | Weighted score | Related literature |
|---|
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Possible diseases from mapped MeSH terms on references
We collected disease MeSH terms mapped to the references associated with 25-Hydroxycholesterol
PubChem Associated disorders and diseases
What pathways are associated with 25-Hydroxycholesterol
There are no associated biomedical information in the current reference collection.
PubChem Biomolecular Interactions and Pathways
Link to PubChem Biomolecular Interactions and PathwaysWhat cellular locations are associated with 25-Hydroxycholesterol?
Visualization in cellular structure
Associated locations are in red color. Not associated locations are in black.
Related references are published most in these journals:
| Location | Cross reference | Weighted score | Related literatures |
|---|
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What functions are associated with 25-Hydroxycholesterol?
Related references are published most in these journals:
| Function | Cross reference | Weighted score | Related literatures |
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What lipids are associated with 25-Hydroxycholesterol?
Related references are published most in these journals:
| Lipid concept | Cross reference | Weighted score | Related literatures |
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What genes are associated with 25-Hydroxycholesterol?
Related references are published most in these journals:
| Gene | Cross reference | Weighted score | Related literatures |
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What common seen animal models are associated with 25-Hydroxycholesterol?
Knock-out
Knock-out are used in the study 'Marked accumulation of 27-hydroxycholesterol in SPG5 patients with hereditary spastic paresis.' (Schüle R et al., 2010) and Knock-out are used in the study 'SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth.' (Porstmann T et al., 2008).
Related references are published most in these journals:
| Model | Cross reference | Weighted score | Related literatures |
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NCBI Entrez Crosslinks
All references with 25-Hydroxycholesterol
Download all related citations| Authors | Title | Published | Journal | PubMed Link |
|---|---|---|---|---|
| Sparrow SM et al. | U18666A inhibits intracellular cholesterol transport and neurotransmitter release in human neuroblastoma cells. | 1999 | Neurochem. Res. | pmid:9973239 |
| Ayala-Torres S et al. | Apoptosis induced by oxysterol in CEM cells is associated with negative regulation of c-myc. | 1999 | Exp. Cell Res. | pmid:9882528 |
| Du EZ et al. | Translocation-arrested apolipoprotein B evades proteasome degradation via a sterol-sensitive block in ubiquitin conjugation. | 1999 | J. Biol. Chem. | pmid:9880570 |
| Lagace TA et al. | Chinese hamster ovary cells overexpressing the oxysterol binding protein (OSBP) display enhanced synthesis of sphingomyelin in response to 25-hydroxycholesterol. | 1999 | J. Lipid Res. | pmid:9869656 |
| Holleran AL et al. | Effect of tamoxifen on cholesterol synthesis in HepG2 cells and cultured rat hepatocytes. | 1998 | Metab. Clin. Exp. | pmid:9867082 |
| Moog C et al. | Oxysterols, but not cholesterol, inhibit human immunodeficiency virus replication in vitro. | 1998 | Antivir. Chem. Chemother. | pmid:9865387 |
| Storey MK et al. | Cholesterol regulates oxysterol binding protein (OSBP) phosphorylation and Golgi localization in Chinese hamster ovary cells: correlation with stimulation of sphingomyelin synthesis by 25-hydroxycholesterol. | 1998 | Biochem. J. | pmid:9806908 |
| Christenson LK et al. | Oxysterol regulation of steroidogenic acute regulatory protein gene expression. Structural specificity and transcriptional and posttranscriptional actions. | 1998 | J. Biol. Chem. | pmid:9804848 |
| Nohturfft A et al. | Sterols regulate processing of carbohydrate chains of wild-type SREBP cleavage-activating protein (SCAP), but not sterol-resistant mutants Y298C or D443N. | 1998 | Proc. Natl. Acad. Sci. U.S.A. | pmid:9789003 |
| Kato H et al. | Macrophage inhibition of lymphocyte and tumor cell growth is mediated by 25-hydroxycholesterol in the cell membrane. | 1998 | Int. Arch. Allergy Immunol. | pmid:9751851 |
| Chang JY et al. | Cholesterol oxides induce programmed cell death in microglial cells. | 1998 | Biochem. Biophys. Res. Commun. | pmid:9731219 |
| Thewke DP et al. | Oleate potentiates oxysterol inhibition of transcription from sterol regulatory element-1-regulated promoters and maturation of sterol regulatory element-binding proteins. | 1998 | J. Biol. Chem. | pmid:9694903 |
| Fu Q et al. | Control of cholesterol biosynthesis in Schwann cells. | 1998 | J. Neurochem. | pmid:9681444 |
| Stengel D et al. | Inhibition of LPL expression in human monocyte-derived macrophages is dependent on LDL oxidation state: a key role for lysophosphatidylcholine. | 1998 | Arterioscler. Thromb. Vasc. Biol. | pmid:9672079 |
| Dushkin M et al. | Effects of oxysterols upon macrophage and lymphocyte functions in vitro. | 1998 | Prostaglandins Other Lipid Mediat. | pmid:9644113 |
| Rosenfeld JM and Osborne TF | HLH106, a Drosophila sterol regulatory element-binding protein in a natural cholesterol auxotroph. | 1998 | J. Biol. Chem. | pmid:9632664 |
| Bucci C et al. | Free fatty acids modulate LDL receptor activity in BHK-21 cells. | 1998 | Atherosclerosis | pmid:9622276 |
| Mellon SH and Bair SR | 25-Hydroxycholesterol is not a ligand for the orphan nuclear receptor steroidogenic factor-1 (SF-1). | 1998 | Endocrinology | pmid:9607816 |
| Grøndahl C et al. | Meiosis-activating sterol promotes resumption of meiosis in mouse oocytes cultured in vitro in contrast to related oxysterols. | 1998 | Biol. Reprod. | pmid:9603267 |
| Chang JY and Liu LZ | Neurotoxicity of cholesterol oxides on cultured cerebellar granule cells. | 1998 | Neurochem. Int. | pmid:9596554 |
| Lin HS et al. | Synthesis of 4 alpha-(2-propenyl)-5,6-secocholestan-3 alpha-ol, a novel B-ring seco analog of the hypocholesterolemic agent 4 alpha-(2-propenyl)-5 alpha-cholestan-3 alpha-ol. | 1998 | Steroids | pmid:9589554 |
| Chang JY et al. | Neurotoxicity of 25-OH-cholesterol on sympathetic neurons. | 1998 | Brain Res. Bull. | pmid:9566506 |
| Kaur M et al. | Receptor-Ck-dependent regulation of genes involved in the cell cycle. | 1998 | Mol. Cell. Biochem. | pmid:9562250 |
| Halvorsen B et al. | Effect of a coffee lipid (cafestol) on cholesterol metabolism in human skin fibroblasts. | 1998 | J. Lipid Res. | pmid:9555953 |
| Ellsworth JL and Starr JR | Inhibition of acyl coenzyme A:cholesterol acyltransferase blocks esterification but not uptake of cholesterol in Caco-2 cells. | 1998 | Metab. Clin. Exp. | pmid:9500571 |
| Norlin M and Wikvall K | Biochemical characterization of the 7alpha-hydroxylase activities towards 27-hydroxycholesterol and dehydroepiandrosterone in pig liver microsomes. | 1998 | Biochim. Biophys. Acta | pmid:9487148 |
| Ridgway ND et al. | Inhibition of phosphorylation of the oxysterol binding protein by brefeldin A. | 1998 | Biochim. Biophys. Acta | pmid:9487139 |
| Musatov MI et al. | [Effect of oxidized cholesterol derivatives on lymphokine stimulated differentiation of macrophages and primary allogenic mixed human lymphocyte culture]. | 1997 | Biull Eksp Biol Med | pmid:9483320 |
| Chang JY et al. | Neurotoxicity of 25-OH-cholesterol on NGF-differentiated PC12 cells. | 1998 | Neurochem. Res. | pmid:9482261 |
| Bertherat J | The nuclear receptor SF-1 (steroidogenic factor-1) is no longer an orphan. | 1998 | Eur. J. Endocrinol. | pmid:9461312 |
| Tatidis L et al. | Decreased feedback regulation of low density lipoprotein receptor activity by sterols in leukemic cells from patients with acute myelogenous leukemia. | 1997 | J. Lipid Res. | pmid:9458267 |
| Carsia RV and McIlroy PJ | Dietary protein restriction stress in the domestic turkey (Meleagris gallopavo) induces hypofunction and remodeling of adrenal steroidogenic tissue. | 1998 | Gen. Comp. Endocrinol. | pmid:9446731 |
| Nilsson J et al. | Lipoprotein-like phospholipid particles inhibit the smooth muscle cell cytotoxicity of lysophosphatidylcholine and platelet-activating factor. | 1998 | Arterioscler. Thromb. Vasc. Biol. | pmid:9445250 |
| Suresh S et al. | Cellular cholesterol storage in the Niemann-Pick disease type C mouse is associated with increased expression and defective processing of apolipoprotein D. | 1998 | J. Neurochem. | pmid:9422368 |
| Miura S et al. | Cholesterol-mediated changes of neutral cholesterol esterase activity in macrophages. Mechanism for mobilization of cholesteryl esters in lipid droplets by HDL. | 1997 | Arterioscler. Thromb. Vasc. Biol. | pmid:9409290 |
| Duan H et al. | Degradation of macrophage ApoE in a nonlysosomal compartment. Regulation by sterols. | 1997 | J. Biol. Chem. | pmid:9388269 |
| Ares MP et al. | Ca2+ channel blockers verapamil and nifedipine inhibit apoptosis induced by 25-hydroxycholesterol in human aortic smooth muscle cells. | 1997 | J. Lipid Res. | pmid:9374127 |
| Chang JY et al. | Establishment of two morphologically distinct PC12 cell lines resistant to 25-OH-cholesterol toxicity. | 1997 | Biochem. Biophys. Res. Commun. | pmid:9344846 |
| Lagace TA et al. | Altered regulation of cholesterol and cholesteryl ester synthesis in Chinese-hamster ovary cells overexpressing the oxysterol-binding protein is dependent on the pleckstrin homology domain. | 1997 | Biochem. J. | pmid:9337870 |
| Johnson BH et al. | Glucocorticoid/oxysterol-induced DNA lysis in human leukemic cells. | 1997 | J. Steroid Biochem. Mol. Biol. | pmid:9328208 |
| Chang JY and Liu LZ | 25-Hydroxycholesterol causes death but does not prevent nerve growth factor-induced neurite outgrowth in PC12 cells. | 1997 | Neurochem. Int. | pmid:9308000 |
| Ayala-Torres S et al. | Characteristics of 25-hydroxycholesterol-induced apoptosis in the human leukemic cell line CEM. | 1997 | Exp. Cell Res. | pmid:9281350 |
| Phelan KD and Mahler HR | Acute exposure to 25-hydroxy-cholesterol selectively reduces GABAb and not GABAa receptor-mediated synaptic inhibition. | 1997 | Biochem. Biophys. Res. Commun. | pmid:9266831 |
| Zhang J et al. | 7alpha-Hydroxylation and 3-dehydrogenation abolish the ability of 25-hydroxycholesterol and 27-hydroxycholesterol to induce apoptosis in thymocytes. | 1997 | Eur. J. Biochem. | pmid:9249018 |
| Harada K et al. | Bcl-2 protein inhibits oxysterol-induced apoptosis through suppressing CPP32-mediated pathway. | 1997 | FEBS Lett. | pmid:9247143 |
| McCourt MP et al. | X-ray crystal structure of cytotoxic oxidized cholesterols: 7-ketocholesterol and 25-hydroxycholesterol. | 1997 | J. Lipid Res. | pmid:9186918 |
| Vanderhyden BC | Oocyte-secreted factors regulate granulosa cell steroidogenesis. | 1996 | Zygote | pmid:9153773 |
| Lala DS et al. | Activation of the orphan nuclear receptor steroidogenic factor 1 by oxysterols. | 1997 | Proc. Natl. Acad. Sci. U.S.A. | pmid:9144161 |
| Wohlfeil ER and Campbell WB | 25-Hydroxycholesterol enhances eicosanoid production in cultured bovine coronary artery endothelial cells by increasing prostaglandin G/H synthase-2. | 1997 | Biochim. Biophys. Acta | pmid:9084508 |
| Liu Y et al. | Macrophages isolated from human atherosclerotic plaques produce IL-8, and oxysterols may have a regulatory function for IL-8 production. | 1997 | Arterioscler. Thromb. Vasc. Biol. | pmid:9081687 |
| Zhang J et al. | Metabolism of 27-, 25- and 24-hydroxycholesterol in rat glial cells and neurons. | 1997 | Biochem. J. | pmid:9078259 |
| Zhang J et al. | Studies on the relationships between 7 alpha-hydroxylation and the ability of 25- and 27-hydroxycholesterol to suppress the activity of HMG-CoA reductase. | 1997 | Biochim. Biophys. Acta | pmid:9059514 |
| Baum CL et al. | Sterol carrier protein-2 overexpression enhances sterol cycling and inhibits cholesterol ester synthesis and high density lipoprotein cholesterol secretion. | 1997 | J. Biol. Chem. | pmid:9045674 |
| Bowling N et al. | LY295427, a novel hypocholesterolemic agent, enhances [3H]25-hydroxycholesterol binding to liver cytosolic proteins. | 1996 | J. Lipid Res. | pmid:9017510 |
| Peffley DM and Gayen AK | Inhibition of squalene synthase but not squalene cyclase prevents mevalonate-mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase synthesis at a posttranscriptional level. | 1997 | Arch. Biochem. Biophys. | pmid:9016820 |
| Warren JT and Gilbert LI | Metabolism in vitro of cholesterol and 25-hydroxycholesterol by the larval prothoracic glands of Manduca sexta. | 1996 Sep-Oct | Insect Biochem. Mol. Biol. | pmid:9014337 |
| Lehmann JM et al. | Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. | 1997 | J. Biol. Chem. | pmid:9013544 |
| Chiloeches A et al. | Effect of mevalonate availability on the association of G-protein alpha-subunits with the plasma membrane in GH4C1 cells. | 1997 | FEBS Lett. | pmid:9003808 |
| Babischkin JS et al. | Estrogen stimulation of P450 cholesterol side-chain cleavage activity in cultures of human placental syncytiotrophoblasts. | 1997 | Biol. Reprod. | pmid:9002660 |
| Spicer LJ et al. | Insulin-like growth factor I enhancement of steroidogenesis by bovine granulosa cells and thecal cells: dependence on de novo cholesterol synthesis. | 1996 | J. Endocrinol. | pmid:8994382 |
| Bhuvaneswaran C et al. | Activation of acyl-CoA: cholesterol acyltransferase in rat liver microsomes by 25-hydroxycholesterol. | 1997 | Biochem. Pharmacol. | pmid:8960060 |
| Nohturfft A et al. | Recurrent G-to-A substitution in a single codon of SREBP cleavage-activating protein causes sterol resistance in three mutant Chinese hamster ovary cell lines. | 1996 | Proc. Natl. Acad. Sci. U.S.A. | pmid:8942999 |
| Pak YK | Serum response element-like sequences of the human low density lipoprotein receptor promoter: possible regulation sites for sterol-independent transcriptional activation. | 1996 | Biochem. Mol. Biol. Int. | pmid:8932516 |
| Liza M et al. | Application of 2-hydroxypropyl-beta-cyclodextrin in the assay of acyl-CoA:cholesterol acyltransferase and neutral and acid cholesterol ester hydrolases. | 1996 | Lipids | pmid:8900462 |
| Morel DW et al. | Comparison of the intracellular metabolism and trafficking of 25-hydroxycholesterol and cholesterol in macrophages. | 1996 | J. Lipid Res. | pmid:8895069 |
| Taniguchi S et al. | Dehydroepiandrosterone markedly inhibits the accumulation of cholesteryl ester in mouse macrophage J774-1 cells. | 1996 | Atherosclerosis | pmid:8879442 |
| Nishio E and Watanabe Y | Oxysterols induced apoptosis in cultured smooth muscle cells through CPP32 protease activation and bcl-2 protein downregulation. | 1996 | Biochem. Biophys. Res. Commun. | pmid:8831713 |
| Verhagen JC et al. | Physical effects of biologically formed cholesterol oxidation products on lipid membranes investigated with fluorescence depolarization spectroscopy and electron spin resonance. | 1996 | J. Lipid Res. | pmid:8827521 |
| Lin CY and Morel DW | Esterification of oxysterols in human serum: effects on distribution and cellular uptake. | 1996 | J. Lipid Res. | pmid:8820112 |
| Musanti R et al. | Inhibition of acyl-CoA: cholesterol acyltransferase decreases apolipoprotein B-100-containing lipoprotein secretion from HepG2 cells. | 1996 | J. Lipid Res. | pmid:8820097 |
| McGee TP et al. | Degradation of 3-hydroxy-3-methylglutaryl-CoA reductase in endoplasmic reticulum membranes is accelerated as a result of increased susceptibility to proteolysis. | 1996 | J. Biol. Chem. | pmid:8810339 |
| Jepson CA et al. | Down-regulation of hormone-sensitive lipase in sterol ester-laden J774.2 macrophages. | 1996 | Biochem. J. | pmid:8761468 |
| Chen H et al. | Depletion and repopulation of Leydig cells in the testes of aging brown Norway rats. | 1996 | Endocrinology | pmid:8754773 |
| Richardson MA et al. | Human liposarcoma cell line, SW872, secretes cholesteryl ester transfer protein in response to cholesterol. | 1996 | J. Lipid Res. | pmid:8725167 |
| Graham A et al. | Cholesterol esterification is not essential for secretion of lipoprotein components by HepG2 cells. | 1996 | Biochim. Biophys. Acta | pmid:8695654 |
| Monier S et al. | Oligomerization of VIP21-caveolin in vitro is stabilized by long chain fatty acylation or cholesterol. | 1996 | FEBS Lett. | pmid:8690074 |
| Berkhout TA et al. | The novel cholesterol-lowering drug SR-12813 inhibits cholesterol synthesis via an increased degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. | 1996 | J. Biol. Chem. | pmid:8662919 |
| Graham A et al. | Impaired mobilisation of cholesterol from stored cholesteryl esters in human (THP-1) macrophages. | 1996 | Atherosclerosis | pmid:8645354 |
| Palladini G et al. | Modifications of vimentin filament architecture and vimentin-nuclear interactions by cholesterol oxides in 73/73 endothelial cells. | 1996 | Exp. Cell Res. | pmid:8635498 |
| Palladini G et al. | Disruption of actin microfilament organization by cholesterol oxides in 73/73 endothelial cells. | 1996 | Exp. Cell Res. | pmid:8635497 |
| Carlberg M and Larsson O | Stimulatory effect of PDGF on HMG-CoA reductase activity and N-linked glycosylation contributes to increased expression of IGF-1 receptors in human fibroblasts. | 1996 | Exp. Cell Res. | pmid:8635486 |
| Aupeix K et al. | Oyxsterols induce membrane procoagulant activity in monocytic THP-1 cells. | 1996 | Biochem. J. | pmid:8615754 |
| Cerda SR et al. | Regulation of cholesterol synthesis in four colonic adenocarcinoma cell lines. | 1995 | Lipids | pmid:8614298 |
| Kawabe Y et al. | Regulation of fatty acid synthase expression by cholesterol in human cultured cells. | 1996 | Biochem. Biophys. Res. Commun. | pmid:8605019 |
| Doris PA et al. | Ouabain production by cultured adrenal cells. | 1996 | Endocrinology | pmid:8593799 |
| Deng J et al. | Lysosomal degradation and sorting of apolipoprotein E in macrophages. | 1995 | J. Lipid Res. | pmid:8576639 |
| Ranheim T et al. | Effect of a coffee lipid (cafestol) on regulation of lipid metabolism in CaCo-2 cells. | 1995 | J. Lipid Res. | pmid:8576635 |
| Hultén LM et al. | Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-derived macrophages. | 1996 | J. Clin. Invest. | pmid:8567968 |
| Kocarek TA et al. | Regulation of phenobarbital-inducible cytochrome P450 2B1/2 mRNA by lovastatin and oxysterols in primary cultures of adult rat hepatocytes. | 1993 | Toxicol. Appl. Pharmacol. | pmid:8511800 |
| Tuckey RC and Cameron KJ | Catalytic properties of cytochrome P-450scc purified from the human placenta: comparison to bovine cytochrome P-450scc. | 1993 | Biochim. Biophys. Acta | pmid:8490050 |
| Carlberg M and Larsson O | Role of N-linked glycosylation in cell-cycle progression and initiation of DNA synthesis in tumor-transformed human fibroblasts. | 1993 Jan-Feb | Anticancer Res. | pmid:8476209 |
| Kraemer R et al. | Induction of basic fibroblast growth factor mRNA and protein synthesis in smooth muscle cells by cholesteryl ester enrichment and 25-hydroxycholesterol. | 1993 | J. Biol. Chem. | pmid:8463321 |
| Lund E et al. | 24-, 25- and 27-hydroxylation of cholesterol by a purified preparation of 27-hydroxylase from pig liver. | 1993 | Biochim. Biophys. Acta | pmid:8443234 |
| Furukawa S and Hirano T | Rapid stimulation of apolipoprotein B secretion by oleate is not associated with cholesteryl ester biosynthesis in HepG2 cells. | 1993 | Biochim. Biophys. Acta | pmid:8399324 |
| Pinkerton FD et al. | Differing effects of three oxysterols on low density lipoprotein metabolism in HepG2 cells. | 1993 | Biochem. Biophys. Res. Commun. | pmid:8391799 |
| Parker RA et al. | Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. | 1993 | J. Biol. Chem. | pmid:8388388 |
| Stephan ZF and Yurachek EC | Rapid fluorometric assay of LDL receptor activity by DiI-labeled LDL. | 1993 | J. Lipid Res. | pmid:8381454 |
| Larsson O and Blegen H | Regulatory role of mevalonate in the growth of normal and neoplastic human mammary epithelial cells. | 1993 Jul-Aug | Anticancer Res. | pmid:8352528 |
| Dahl NK et al. | Abnormal regulation of low density lipoprotein-sensitive events in a cholesterol transport mutant. | 1993 | J. Biol. Chem. | pmid:8349588 |
| Ellsworth JL et al. | Ketoconazole and 25-hydroxycholesterol produce reciprocal changes in the rate of transcription of the human LDL receptor gene. | 1994 | Biochim. Biophys. Acta | pmid:8305487 |