Trk receptors need neutral sphingomyelinase activity to promote cell viability

FEBS Lett. 2014 Jan 3;588(1):167-74. doi: 10.1016/j.febslet.2013.11.032. Epub 2013 Dec 5.

Abstract

Neurotrophins are a group of secreted polypeptides, which comprises Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). Each neurotrophin can bind specifically to a tyrosine kinase Trk receptor (TrkA, TrkB or TrkC), while all of the neurotrophins can bind, with similar affinity, to the p75 neurotrophin receptor (p75(NTR)). Experiments on cell viability promotion by BDNF in granule neurons or by NGF in PC12 cells show that neurotrophin-exerted cell viability is neutral sphingomyelinase (nSMase)-dependent, since GW4869 or siRNA knockdown abrogates the protective effects, as well as neurotrophin-induced Akt phosphorylation. Finally, the assessment of nSMase activity promotion drives to the conclusion that neurotrophins can promote cell viability through Trk receptors in a manner depending on basal nSMase but not through SMase activity enhancement.

Keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; BDNF; Brain-Derived Neurotrophic Factor; CGN; Cer; Ceramide; Granule neuron; MTT; NGF; NT; Nerve Growth Factor; Neurotrophin; PC12; Phosphorylation; SM; SphK; Sphingomyelinase; ceramide; cultured granule neurons; nSMase; neurotrophins; neutral sphingomyelinase; sphingomyelin; sphingosine kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Benzylidene Compounds / pharmacology
  • Blotting, Western
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cerebellum / cytology
  • Microscopy, Fluorescence
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Nerve Growth Factor / pharmacology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • PC12 Cells
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • Rats
  • Receptor, trkA / metabolism*
  • Receptor, trkB / metabolism*
  • Receptor, trkC / metabolism*
  • Sphingomyelin Phosphodiesterase / antagonists & inhibitors
  • Sphingomyelin Phosphodiesterase / genetics
  • Sphingomyelin Phosphodiesterase / metabolism*

Substances

  • Aniline Compounds
  • Benzylidene Compounds
  • Brain-Derived Neurotrophic Factor
  • GW 4869
  • Nerve Growth Factor
  • Receptor, trkA
  • Receptor, trkB
  • Receptor, trkC
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Sphingomyelin Phosphodiesterase