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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2010-11-16
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pubmed:abstractText |
Niemann-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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1095-953X
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
209-18
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pubmed:meshHeading |
pubmed-meshheading:20883783-Animals,
pubmed-meshheading:20883783-Apoptosis,
pubmed-meshheading:20883783-DNA-Binding Proteins,
pubmed-meshheading:20883783-Disease Models, Animal,
pubmed-meshheading:20883783-Down-Regulation,
pubmed-meshheading:20883783-Mice,
pubmed-meshheading:20883783-Mice, Inbred BALB C,
pubmed-meshheading:20883783-Neurons,
pubmed-meshheading:20883783-Niemann-Pick Disease, Type C,
pubmed-meshheading:20883783-Nuclear Proteins,
pubmed-meshheading:20883783-Oxidative Stress,
pubmed-meshheading:20883783-Proto-Oncogene Proteins c-abl,
pubmed-meshheading:20883783-Rats,
pubmed-meshheading:20883783-Rats, Sprague-Dawley,
pubmed-meshheading:20883783-Tumor Suppressor Proteins,
pubmed-meshheading:20883783-Up-Regulation
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pubmed:year |
2011
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pubmed:articleTitle |
Oxidative stress activates the c-Abl/p73 proapoptotic pathway in Niemann-Pick type C neurons.
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pubmed:affiliation |
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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