title: Necdin and neurotrophin receptors: interactors of relevance for neuronal resistance to oxidant stress.
abstract: Necdin is a protein known to interact with the neurotrophin receptors, neurotrophic tyrosine kinase receptor type 1 (TrkA) and 75 kD low-affinity neurotrophin receptor (p75NTR). TrkA and p75NTR play roles in development and disease of the nervous system and chemoresistance of nervous system tumors. Necdin deletion is associated with Prader-Willi syndrome. The present studies demonstrate that the effects of necdin on the susceptibility of neuroblastoma cells to oxidant stress are dependent on the ratio of p75NTR to TrkA in the cell. In low p75NTR:TrkA ratio cells, necdin down-regulation decreases sensitivity to oxidant stress and expression of and signaling through TrkA. In high p75NTR:TrkA cells, necdin down-regulation is without effect. The effects of necdin deletion on the developing nervous system may depend on the relative expression of p75NTR and TrkA in the cells of particular regions of the nervous system.
authors.affiliation: Department of Pediatrics, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ingraham
authors.forename: Larissa
authors.initials: L
authors.lastname: Wertalik
authors.forename: Nina F
authors.initials: NF
authors.lastname: Schor
mesh_terms: D018663:Adrenergic Agents / Q000378:metabolism; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D016627:Oxidopamine / Q000378:metabolism; D016716:PC12 Cells; D011218:Prader-Willi Syndrome / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018663:Adrenergic Agents; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D020800:Receptor, Nerve Growth Factor; C069766:necdin; D016627:Oxidopamine; D020917:Receptor, trkA