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Brain‐Derived Neurotrophic Factor Accelerates Nitric Oxide Donor‐Induced Apoptosis of Cultured Cortical Neurons
Author(s) -
Ishikawa Yasuyuki,
Ikeuchi Toshihiko,
Hatanaka Hiroshi
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0750494.x
Subject(s) - tropomyosin receptor kinase b , brain derived neurotrophic factor , neurotrophic factors , programmed cell death , mapk/erk pathway , microbiology and biotechnology , apoptosis , biology , p38 mitogen activated protein kinases , neurotrophin , nerve growth factor , protein kinase a , kinase , chemistry , biochemistry , receptor
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.