NGF induces apoptosis in a human neuroblastoma cell line expressing the neurotrophin receptor p75NTR

J Neurosci Res. 1998 Nov 15;54(4):465-74. doi: 10.1002/(SICI)1097-4547(19981115)54:4<465::AID-JNR4>3.0.CO;2-T.

Abstract

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.

MeSH terms

  • Alzheimer Disease / etiology
  • Animals
  • Apoptosis / drug effects*
  • Blotting, Western
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Ceramides / pharmacology
  • DNA Fragmentation / drug effects
  • Etoposide / pharmacology
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases*
  • NF-kappa B / metabolism
  • Nerve Growth Factors / pharmacology*
  • Neuroblastoma
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurotrophin 3
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Rats
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, Nerve Growth Factor
  • Receptor, trkA
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism*
  • Recombinant Proteins / pharmacology
  • Sphingomyelin Phosphodiesterase / metabolism
  • Transcription Factor RelA
  • Tumor Cells, Cultured

Substances

  • Brain-Derived Neurotrophic Factor
  • Ceramides
  • NF-kappa B
  • Nerve Growth Factors
  • Neurotrophin 3
  • Proto-Oncogene Proteins
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor
  • Recombinant Proteins
  • Transcription Factor RelA
  • Etoposide
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Sphingomyelin Phosphodiesterase