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http://purl.uniprot.org/citations/16524875http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16524875http://www.w3.org/2000/01/rdf-schema#comment"Both apolipoprotein E (apoE) and 24(S)-hydroxycholesterol are involved in the pathogenesis of Alzheimer disease (AD). It has been hypothesized that apoE affects AD development via isoform-specific effects on lipid trafficking between astrocytes and neurons. However, the regulation of the cholesterol supply of neurons via apoE-containing high density lipoproteins remains to be clarified. We show for the first time that the brain-specific metabolite of cholesterol produced by neurons, i.e. 24(S)-hydroxycholesterol, induces apoE transcription, protein synthesis, and secretion in a dose- and time-dependent manner in cells of astrocytic but not of neuronal origin. Moreover, 24(S)-hydroxycholesterol primes astrocytoma, but not neuroblastoma cells, to mediate cholesterol efflux to apoE. Similar results were obtained using the synthetic liver X receptor (LXR) agonist GW683965A, suggesting involvement of an LXR-controlled signaling pathway. A 10-20-fold higher basal LXRalpha and -beta expression level in astrocytoma compared with neuroblastoma cells may underlie these differential effects. Furthermore, apoE-mediated cholesterol efflux from astrocytoma cells may be controlled by the ATP binding cassette transporters ABCA1 and ABCG1, since their expression was also up-regulated by both compounds. In contrast, ABCG4 seems not to be involved, because its expression was induced only in neuronal cells. The expression of sterol regulatory element-binding protein (SREBP-2), low density lipoprotein receptor, 3-hydroxy-3-methylglutaryl-CoA reductase, and SREBP-1c was transiently up-regulated by GW683965A in astrocytes but down-regulated by 24(S)-hydroxycholesterol, suggesting that cholesterol efflux and synthesis are regulated independently. In conclusion, evidence is provided that 24(S)-hydroxycholesterol induces apoE-mediated efflux of cholesterol in astrocytes via an LXR-controlled pathway, which may be relevant for chronic and acute neurological diseases."xsd:string
http://purl.uniprot.org/citations/16524875http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m601019200"xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/author"Wellington C.L."xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/author"Groen A.K."xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/author"Kuipers F."xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/author"Mulder M."xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/author"Jansen P.J."xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/author"Bakker A.H."xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/author"Ramaekers F.C."xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/author"Hirsch-Reinshagen V."xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/author"Bloks V.W."xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/author"de Vente J."xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/author"Abildayeva K."xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/pages"12799-12808"xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/title"24(S)-hydroxycholesterol participates in a liver X receptor-controlled pathway in astrocytes that regulates apolipoprotein E-mediated cholesterol efflux."xsd:string
http://purl.uniprot.org/citations/16524875http://purl.uniprot.org/core/volume"281"xsd:string
http://purl.uniprot.org/citations/16524875http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/16524875
http://purl.uniprot.org/citations/16524875http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/16524875
http://purl.uniprot.org/uniprot/#_A0A0S2Z3B1-mappedCitation-16524875http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16524875
http://purl.uniprot.org/uniprot/#_A0A0S2Z3V0-mappedCitation-16524875http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16524875
http://purl.uniprot.org/uniprot/#_A6J8R5-mappedCitation-16524875http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16524875
http://purl.uniprot.org/uniprot/#_A6J8R8-mappedCitation-16524875http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16524875