Necdin and TrkA contribute to modulation by p75NTR of resistance to oxidant stress.
The neurotrophin receptor p75NTR provides protection from oxidant stress induced by 6-hydroxydopamine (6-OHDA) and resultant cell death. In the absence of p75NTR, TrkA is upregulated and its signaling pathway effectors are increasingly activated. Necdin, a MAGE protein and known interactor of p75NTR and TrkA, is a potential mediator of this phenomenon. Decreased expression of necdin protein in p75NTR-deficient PC12 cells decreased TrkA expression and increased PC12 cell resistance to 6-OHDA. Inhibition of JNK phosphorylation by SP600125 also resulted in increased resistance to 6-OHDA, suggesting that TrkA signaling underlies the susceptibility of these cells to oxidant stress.
Ingraham
Christopher A
CA
Department of Pediatrics, University of Rochester Medical Center, Rochester, NY 14642, USA.
Schor
Nina F
NF
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism*; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051023:BH3 Interacting Domain Death Agonist Protein; C494828:Bax protein, rat; C494816:Bid protein, rat; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D051028:bcl-2-Associated X Protein; C069766:necdin; C068313:Ngfr protein, rat; D016627:Oxidopamine; D020917:Receptor, trkA; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4; C505410:Casp3 protein, rat; D053148:Caspase 3