PMID- 12460985
OWN - NLM
STAT- MEDLINE
DCOM- 20030123
LR  - 20181113
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 159
IP  - 5
DP  - 2002 Dec 9
TI  - Brain-derived neurotrophic factor can act as a pronecrotic factor through 
      transcriptional and translational activation of NADPH oxidase.
PG  - 821-31
AB  - Several lines of evidence suggest that neurotrophins (NTs) potentiate or cause 
      neuronal injury under various pathological conditions. Since NTs enhance survival 
      and differentiation of cultured neurons in serum or defined media containing 
      antioxidants, we set out experiments to delineate the patterns and underlying 
      mechanisms of brain-derived neurotrophic factor (BDNF)-induced neuronal injury in 
      mixed cortical cell cultures containing glia and neurons in serum-free media 
      without antioxidants, where the three major routes of neuronal cell death, 
      oxidative stress, excitotoxicity, and apoptosis, have been extensively studied. 
      Rat cortical cell cultures, after prolonged exposure to NTs, underwent widespread 
      neuronal necrosis. BDNF-induced neuronal necrosis was accompanied by reactive 
      oxygen species (ROS) production and was dependent on the macromolecular 
      synthesis. cDNA microarray analysis revealed that BDNF increased the expression 
      of cytochrome b558, the plasma membrane-spanning subunit of NADPH oxidase. The 
      expression and activation of NADPH oxidase were increased after exposure to BDNF. 
      The selective inhibitors of NADPH oxidase prevented BDNF-induced ROS production 
      and neuronal death without blocking antiapoptosis action of BDNF. The present 
      study suggests that BDNF-induced expression and activation of NADPH oxidase cause 
      oxidative neuronal necrosis and that the neurotrophic effects of NTs can be 
      maximized under blockade of the pronecrotic action.
FAU - Kim, Sun H
AU  - Kim SH
AD  - Department of Pharmacology, Center for the Interventional Therapy of Stroke and 
      Alzheimer's Disease, School of Medicine, Ajou University, Suwon, Kyungkido, South 
      Korea.
FAU - Won, Seok J
AU  - Won SJ
FAU - Sohn, Seonghyang
AU  - Sohn S
FAU - Kwon, Hyuk J
AU  - Kwon HJ
FAU - Lee, Jee Y
AU  - Lee JY
FAU - Park, Jong H
AU  - Park JH
FAU - Gwag, Byoung J
AU  - Gwag BJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20021202
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cytochrome b Group)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 9064-78-2 (cytochrome b558)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology/physiology
MH  - Cell Death/drug effects
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology/drug effects/*enzymology
MH  - Coculture Techniques
MH  - Corpus Striatum/cytology
MH  - Cytochrome b Group/metabolism
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - *Gene Expression Regulation, Enzymologic
MH  - Male
MH  - NADPH Oxidases/chemistry/*genetics/metabolism
MH  - *Necrosis
MH  - Neuroglia/cytology
MH  - Neurons/*enzymology/metabolism/ultrastructure
MH  - Oxidative Stress/drug effects
MH  - Protein Biosynthesis
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Transcription, Genetic
PMC - PMC2173377
EDAT- 2002/12/04 04:00
MHDA- 2003/01/24 04:00
PMCR- 2003/06/09
CRDT- 2002/12/04 04:00
PHST- 2002/12/04 04:00 [pubmed]
PHST- 2003/01/24 04:00 [medline]
PHST- 2002/12/04 04:00 [entrez]
PHST- 2003/06/09 00:00 [pmc-release]
AID - jcb.200112131 [pii]
AID - 200112131 [pii]
AID - 10.1083/jcb.200112131 [doi]
PST - ppublish
SO  - J Cell Biol. 2002 Dec 9;159(5):821-31. doi: 10.1083/jcb.200112131. Epub 2002 Dec 
      2.