Lysosomal vitamin E accumulation in Niemann-Pick type C disease

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dc.catalogadoryvc
dc.contributor.authorYévenes, Luz Fernanda
dc.contributor.authorKlein Posternack, Andrés David
dc.contributor.authorCastro, Juan Francisco
dc.contributor.authorMarín Marín, Tamara Alejandra
dc.contributor.authorLeal Reyes, Nancy Valeria
dc.contributor.authorLeighton Puga, Federico
dc.contributor.authorÁlvarez, Alejandra R.
dc.contributor.authorZanlungo Matsuhiro, Silvana
dc.date.accessioned2024-06-06T19:19:45Z
dc.date.available2024-06-06T19:19:45Z
dc.date.issued2011
dc.description.abstractNiemann-Pick C disease (NPC) is a neuro-visceral lysosomal storage disorder mainly caused by genetic defects in the NPC1 gene. As a result of loss of NPC1 function large quantities of free cholesterol and other lipids accumulate within late endosomes and lysosomes. In NPC livers and brains, the buildup of lipids correlates with oxidative damage; however the molecular mechanisms that trigger it remain unknown. Here we study potential alterations in vitamin E (α-tocopherol, α-TOH), the most potent endogenous antioxidant, in liver tissue and neurons from NPC1 mice. We found increased levels of α-TOH in NPC cells. We observed accumulation and entrapment of α-TOH in NPC neurons, mainly in the late endocytic pathway. Accordingly, α-TOH levels were increased in cerebellum of NPC1 mice. Also, we found decreased mRNA levels of the α-TOH transporter, α-Tocopherol Transfer Protein (α-TTP), in the cerebellum of NPC1 mice. Finally, by subcellular fractionation studies we detected a significant increase in the hepatic α-TOH content in purified lysosomes from NPC1 mice. In conclusion, these results suggest that NPC cells cannot transport vitamin E correctly leading to α-TOH buildup in the endosomal/lysosomal system. This may result in a decreased bioavailability and impaired antioxidant function of vitamin E in NPC, contributing to the disease pathogenesis.
dc.fuente.origenORCID
dc.identifier.doi10.1016/j.bbadis.2011.11.009
dc.identifier.urihttps://doi.org/10.1016/j.bbadis.2011.11.009
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/86574
dc.identifier.wosidWOS:000299986600006
dc.information.autorucFacultad de Ciencias Biológicas;Yévenes, Luz Fernanda;S/I;142390
dc.information.autorucFacultad de Ciencias Biológicas;Klein Posternack, Andrés David;S/I;2966
dc.information.autorucEscuela de Medicina;Marín Marín, Tamara Alejandra;S/I;249923
dc.information.autorucFacultad de Ciencias Biológicas;Leal Reyes, Nancy Valeria;S/I;10604
dc.information.autorucFacultad de Ciencias Biológicas;Leighton Puga, Federico;S/I;98261
dc.information.autorucEscuela de Medicina; Zanlungo Matsuhiro, Silvana; 0000-0001-8383-9829; 72650
dc.language.isoen
dc.nota.accesocontenido parcial
dc.rightsacceso restringido
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleLysosomal vitamin E accumulation in Niemann-Pick type C disease
dc.typeartículo
sipa.codpersvinculados72650
sipa.trazabilidadORCID;2024-06-03
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