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Oxidative Medicine and Cellular Longevity
Volume 2011, Article ID 391659, 8 pages
http://dx.doi.org/10.1155/2011/391659
Research Article

Chopper Is Prodeath Regardless of the Effect of p75ICD on Sensitivity to Oxidative Stress

1Department of Pediatrics, Golisano Children's Hospital at URMC, University of Rochester Medical Center, Rochester, NY 14642, USA
2Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA
3The Center for Neural Development and Disease, University of Rochester Medical Center, Rochester, NY 14642, USA
4Departments of Neurobiology & Anatomy, University of Rochester Medical Center, Rochester, NY 14642, USA

Received 16 May 2011; Revised 21 June 2011; Accepted 23 June 2011

Academic Editor: Oren Tirosh

Copyright © 2011 Alliya Qazi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. The intracellular domain (ICD) of the neurotrophin receptor, p75NTR, exhibits variably pro- and antiapoptotic activity and has been implicated in neurodegenerative and neurodestructive disease. The molecular determinants of these cellular effects are not completely understood. The “Chopper” domain of p75ICD has been shown to be proapoptotic in in vitro systems in which p75ICD is proapoptotic. The effects of Chopper in systems in which p75ICD is antiapoptotic and, therefore, whether or not Chopper accounts for the variability of the cellular effects of p75ICD are not known. We therefore examined the effects of deletion of Chopper on the effects of p75ICD on in vitro cell culture systems in which p75ICD is pro- or antiapoptotic, respectively. Results. In HN33.11 murine neuroblastoma-hippocampal neuron hybrid cells, p75ICD is antiapoptotic. In NIH 3T3 cells, p75ICD is proapoptotic. In both cell lines deletion of the Chopper domain from p75ICD decreases the incidence of apoptosis resulting from oxidative stress. Thus, irrespective of the nature of the effects of p75ICD on the cell, its Chopper domain is proapoptotic. Conclusions. Expression of p75ICD can enhance or attenuate oxidative induction of apoptosis. Variability of the effects of p75ICD is not related to variability of the effects of its Chopper domain.