title: Chopper is prodeath regardless of the effect of p75ICD on sensitivity to oxidative stress.
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.
authors: Department of Pediatrics, Golisano Children's Hospital at URMC, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors: Alliya
authors: A
authors: Qazi
authors: Marc W
authors: MW
authors: Halterman
authors: Zhiping
authors: Z
authors: Mi
authors: Tong
authors: T
authors: Zhang
authors: Nina F
authors: NF
authors: Schor
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D005434:Flow Cytometry; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D041681:NIH 3T3 Cells; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D016627:Oxidopamine / Q000494:pharmacology; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D016627:Oxidopamine; D006861:Hydrogen Peroxide