RGD Reference Report - Oxidative stress activates the c-Abl/p73 proapoptotic pathway in Niemann-Pick type C neurons. - Rat Genome Database

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

Authors: Klein, A  Maldonado, C  Vargas, LM  Gonzalez, M  Robledo, F  Perez de Arce, K  Munoz, FJ  Hetz, C  Alvarez, AR  Zanlungo, S 
Citation: Klein A, etal., Neurobiol Dis. 2011 Jan;41(1):209-18. doi: 10.1016/j.nbd.2010.09.008. Epub 2010 Sep 29.
RGD ID: 8693571
Pubmed: PMID:20883783   (View Abstract at PubMed)
DOI: DOI:10.1016/j.nbd.2010.09.008   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ABL1HumanNiemann-Pick disease  ISOAbl1 (Mus musculus)protein:increased expression:cerebellum:RGD 
Abl1MouseNiemann-Pick disease  IEP protein:increased expression:cerebellum:RGD 
Abl1RatNiemann-Pick disease  ISOAbl1 (Mus musculus)protein:increased expression:cerebellum:RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Abl1Ratcellular response to oxidative stress  IEP protein:increased expression:cerebellum:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abl1  (ABL proto-oncogene 1, non-receptor tyrosine kinase)

Genes (Mus musculus)
Abl1  (c-abl oncogene 1, non-receptor tyrosine kinase)

Genes (Homo sapiens)
ABL1  (ABL proto-oncogene 1, non-receptor tyrosine kinase)


Additional Information