Oxidative stress activates the c-Abl/p73 proapoptotic pathway in Niemann-Pick type C neurons

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dc.catalogadoryvc
dc.contributor.authorKlein Posternack, Andrés David
dc.contributor.authorMaldonado Vera, Carola Patricia
dc.contributor.authorVargas Rojas, Lina Marcela
dc.contributor.authorGonzález Bustos, Marcela Paz
dc.contributor.authorRobledo Plaza, Fermín Alberto
dc.contributor.authorPérez de Arce Guzman, Karen Andrea
dc.contributor.authorMuñoz, Francisco J.
dc.contributor.authorHetz, Claudio
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.issued2010
dc.description.abstractNiemann-Pick type C (NPC) is a neurodegenerative disease characterized by the intralysosomal accumulation of cholesterol leading to neuronal apoptosis. We have previously reported the activation of the c-Abl/p73 proapoptotic pathway in the cerebellum of NPC mice; however, upstream signals underlying the engagement of this pathway remain unknown. Here, we investigate the possible role of oxidative stress in the activation of c-Abl/p73 using different in vitro and in vivo NPC models. Our results indicate a close temporal correlation between the appearance of nitrotyrosine (N-Tyr; a post-translational tyrosine modification caused by oxidative stress) and the activation of c-Abl/p73 in NPC models. To test the functional role of oxidative stress in NPC, we have treated NPC neurons with the antioxidant NAC and observed a dramatic decrease of c-Abl/p73 activation and a reduction in the levels of apoptosis in NPC models. In conclusion, our data suggest that oxidative stress is the main upstream stimulus activating the c-Abl/p73 pathway and neuronal apoptosis in NPC neurons.
dc.fuente.origenORCID
dc.identifier.doi10.1016/j.nbd.2010.09.008
dc.identifier.urihttps://doi.org/10.1016/j.nbd.2010.09.008
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/86575
dc.information.autorucFacultad de Ciencias Biológicas;Klein Posternack, Andrés David;S/I;2966
dc.information.autorucFacultad de Ciencias Biológicas;Maldonado Vera, Carola Patricia;S/I;176942
dc.information.autorucFacultad de Ciencias Biológicas;Vargas Rojas, Lina Marcela;S/I;174079
dc.information.autorucFacultad de Ciencias Biológicas;González Bustos, Marcela Paz;S/I;1011022
dc.information.autorucFacultad de Ciencias Biológicas;Robledo Plaza, Fermín Alberto;131967
dc.information.autorucFacultad de Ciencias Biológicas;Pérez de Arce Guzman, Karen Andrea;S/I;18209
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.titleOxidative stress activates the c-Abl/p73 proapoptotic pathway in Niemann-Pick type C neurons
dc.typeartículo
sipa.codpersvinculados72650
sipa.trazabilidadORCID;2024-06-03
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