Relevance of Niemann-Pick type C1 protein expression in controlling plasma cholesterol and biliary lipid secretion in mice

dc.contributor.authorAmigo, L
dc.contributor.authorMendoza, H
dc.contributor.authorCastro, J
dc.contributor.authorQuinones, V
dc.contributor.authorMiquel, JF
dc.contributor.authorZanlungo, S
dc.date.accessioned2024-01-10T12:42:04Z
dc.date.available2024-01-10T12:42:04Z
dc.date.issued2002
dc.description.abstractReceptor-mediated endocytosis is one of the major mechanisms for uptake of lipoprotein cholesterol in the liver. Because Niemann-Pick C1 (NPC1) protein is a key component in the intracellular distribution of cholesterol obtained from lipoproteins by the endocytic pathway, it may play a critical role in controlling plasma lipoprotein cholesterol and its biliary secretion. A murine model of Niemann-Pick type C disease (NPC), the NPC1-deficient [NPC1 (- / -)] mouse, was used to evaluate the relevance of hepatic NPC1 expression in regulating plasma lipoprotein cholesterol profile and biliary lipid secretion under chow and high-cholesterol diets. Total plasma cholesterol concentrations were increased in NPC1 (- / -) mice compared with wild-type mice when both mouse strains were fed chow or high-cholesterol diets. The increased plasma cholesterol levels found in NPC1 (- / -) mice were mostly due to elevated cholesterol content in larger and more heterogeneous HDL particles. On the chow diet, biliary lipid secretion was not impaired by NPC1 deficiency. Furthermore, chow-fed NPC1 (- / -) mice showed a small, but significant, increase in biliary cholesterol secretion. On the high-cholesterol diet, wild-type mice increased biliary cholesterol output, whereas NPC1 (- / -) mice did not. Finally, hepatic NPCI overexpression by adenovirus-mediated gene transfer increased biliary cholesterol secretion by 100% to 150% in both wild-type mice and cholesterol-fed NPC1 (- / -) mice. In conclusion, hepatic NPC1 expression is an important factor for regulating plasma HDL cholesterol levels and biliary cholesterol secretion in mice.
dc.fechaingreso.objetodigital2024-04-25
dc.format.extent10 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1053/jhep.2002.35617
dc.identifier.eissn1527-3350
dc.identifier.issn0270-9139
dc.identifier.pubmedidMEDLINE:12297829
dc.identifier.urihttps://doi.org/10.1053/jhep.2002.35617
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/77478
dc.identifier.wosidWOS:000178301100006
dc.information.autorucMedicina;Miquel J;S/I;72216
dc.information.autorucMedicina;Zanlungo S;S/I;72650
dc.issue.numero4
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final828
dc.pagina.inicio819
dc.publisherWILEY
dc.revistaHEPATOLOGY
dc.rightsacceso restringido
dc.subjectLIPOPROTEIN-CHOLESTEROL
dc.subjectGALLSTONE FORMATION
dc.subjectRECEPTOR
dc.subjectDISEASE
dc.subjectLIVER
dc.subjectMETABOLISM
dc.subjectACCUMULATION
dc.subjectTRANSPORT
dc.subjectEFFLUX
dc.subjectABCA1
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleRelevance of Niemann-Pick type C1 protein expression in controlling plasma cholesterol and biliary lipid secretion in mice
dc.typeartículo
dc.volumen36
sipa.codpersvinculados72216
sipa.codpersvinculados72650
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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