NGF induces apoptosis in a human neuroblastoma cell line expressing the neurotrophin receptor p75NTR.
Nerve growth factor (NGF) has been demonstrated to support survival and differentiation of neuronal cells. Recently, a role of NGF in neuronal apoptosis has been suggested. NGF binds to tropomyosin receptor kinase A (TrkA) and to 75-kDa NGF receptor (p75NTR). TrkA is responsible for differentiation and survival, but p75NTR, a member of the death receptor family, seems to mediate the apoptotic effect of NGF. Here we demonstrate that NGF-but not neurotrophin-3 (NT-3) or brain-derived neurotrophic factor (BDNF)-induced apoptosis in p75NTR-expressing human neuroblastoma SK-N-MC cells. BDNF prevented NGF-induced apoptosis. NGF-induced apoptosis was accompanied by the release of NFkappaB p65 and the activation of stress-activated protein kinase/c-jun amino terminal kinase. Because p75NTR and NGF are upregulated in Alzheimer's disease, NGF/p75NTR might be involved in neuronal cell death related to the disease.
Kuner
P
P
F. Hoffmann-LaRoche Ltd., Pharma Division, Preclinical Research, Basel, Switzerland.
Hertel
C
C
D000544:Alzheimer Disease / Q000209:etiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002518:Ceramides / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020933:Neurotrophin 3; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D051996:Transcription Factor RelA; D014407:Tumor Cells, Cultured
D019208:Brain-Derived Neurotrophic Factor; D002518:Ceramides; D016328:NF-kappa B; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D011518:Proto-Oncogene Proteins; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; D051996:Transcription Factor RelA; D005047:Etoposide; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D013108:Sphingomyelin Phosphodiesterase