title: Brain-derived neurotrophic factor accelerates nitric oxide donor-induced apoptosis of cultured cortical neurons.
abstract: Brain-derived neurotrophic factor (BDNF) is known to have important functions in neuronal survival, differentiation, and plasticity. In addition to its role as a survival-promoting factor, BDNF reportedly can enhance neuronal cell death in some cases, for example, the death caused by excitotoxicity or glucose deprivation. The cellular mechanism of the death-enhancing effect of BDNF remains unknown, in contrast to that of its survival-promoting effect. In this work, we found that BDNF markedly accelerated the nitric oxide (NO) donor-induced death of cultured embryonic cortical neurons. BDNF increased the number of cells with nuclear condensation and DNA fragmentation 24 h after treatment with the NO donor, but it did not change the number of those cells 36 h after the treatment. The BDNF-accelerated death of cortical neurons was inhibited by the addition of actinomycin D or cycloheximide. These results suggest that BDNF can accelerate apoptotic cell death elicited by NO donor. TrkB-IgG and K252a blocked the BDNF-induced acceleration of the death, indicating that the death-accelerating effect by BDNF is mediated by TrkB. In addition, the BDNF-accelerated apoptosis was inhibited by the addition of SB202190 and SB203580, specific inhibitors of p38 mitogen-activated protein kinase (MAPK), and U0126, a specific inhibitor of MAPK/ERK kinase 1, indicating that the activation of both p38 MAPK and ERK is involved in the signaling cascade of the BDNF-accelerated, NO donor-induced apoptosis.
authors.affiliation: Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: T
authors.initials: T
authors.lastname: Ikeuchi
authors.forename: H
authors.initials: H
authors.lastname: Hatanaka
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002070:Butadienes / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D003513:Cycloheximide / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004357:Drug Synergism; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D026121:Indole Alkaloids; D007700:Kinetics; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002070:Butadienes; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007074:Immunoglobulin G; D026121:Indole Alkaloids; D020030:Nitric Oxide Donors; D009570:Nitriles; D011725:Pyridines; C113580:U 0126; D009599:Nitroprusside; D003609:Dactinomycin; C049985:staurosporine aglycone; D003513:Cycloheximide; D020813:Receptor, trkB; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole