title: TrkB is involved in the mechanism by which BDNF accelerates the glutamate-induced death of rat neuroblastoma B35 cells.
abstract: OBJECTIVE
  Brain-derived neurotrophic factor (BDNF) binds to its high-affinity binding receptor, tropomyosin-related kinase (Trk) B, and can induce neuronal differentiation and survival. BDNF also accelerates neuronal cell death in a glutamate-induced model; however, it has been unknown whether the mechanism involves TrkB. In the current study, to determine the role of TrkB in neuronal cell death, we investigated TrkB involvement in BDNF acceleration of glutamate-induced neuronal death.
  
  
  METHODS
  A TrkB-stable transformant of rat neuroblastoma B35 (B35(TrkB)) cells was utilized to investigate whether TrkB is involved in BDNF acceleration of neuronal death. The cell viability of the B35(TrkB) cells was compared to that of mock vector-transgened B35 (B35(mock)) cells after treatment with/without BDNF and glutamate.
  
  
  RESULTS
  In both B35(TrkB) and B35(mock) cells, glutamate treatment decreased the cell viability. BDNF treatment further accelerated the decrease in the viability of B35(TrkB) cells, but not that in the viability of B35(mock) cells. At glutamate concentrations that did not significantly decrease cell viability, BDNF increased the cell viability of B35(TrkB), but not that of B35(mock). A mitogen-activated protein kinase (MAPK) inhibitor, U0126, suppressed BDNF's accelerating effect on cell death. Although B35 parental cells endogenously express other neurotrophin receptors such as TrkA, nerve growth factor β (a ligand of TrkA and p75(NTR)) could not influence the viability of B35(TrkB) or B35(mock) cells.
  
  
  CONCLUSIONS
  These results indicate that TrkB is an intermediator for the trophic and toxicity-exacerbating effects of BDNF against cell viabilities at non-cytotoxic and cytotoxic glutamate concentrations, respectively.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Maki
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Arishima
authors.forename: Masako
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Motoharu
authors.initials: M
authors.lastname: Sakaue
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002070:Butadienes / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000378:metabolism; D009447:Neuroblastoma / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D018698:Glutamic Acid; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D020813:Receptor, trkB; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: BDNF,; Glutamate,; NGFβ,; Neuronal cell death,; TrkB,; p75NTR