PMID- 12358795
OWN - NLM
STAT- MEDLINE
DCOM- 20021018
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 82
IP  - 4
DP  - 2002 Aug
TI  - The role of NADPH oxidase, neuronal nitric oxide synthase and poly(ADP ribose) 
      polymerase in oxidative neuronal death induced in cortical cultures by 
      brain-derived neurotrophic factor and neurotrophin-4/5.
PG  - 894-902
AB  - Certain neurotrophins promote or induce oxidative neuronal death in cortical 
      cultures. However, the effector mechanisms mediating this phenomenon have not 
      been delineated. In this study, we investigated the possibility that NADPH 
      oxidase and nitric oxide synthase (NOS) function as such effectors. Western blot 
      analysis showed that treatment with brain-derived neurotrophic factor (BDNF) and 
      neurotrophin (NT)-4/5 increased the levels of NADPH oxidase subunits. Moreover, 
      neurotrophin treatment resulted in membrane translocation of p67phox, a 
      characteristic feature of NADPH oxidase activation. Administration of the 
      specific NADPH oxidase inhibitor, 4-(2-aminoethyl)benzenesulfonylfluoride 
      (AEBSF), attenuated increases in oxygen free radicals thereby suggesting that 
      NADPH oxidase contributes to the oxidative stress induced by neurotrophins. 
      Furthermore, neuronal death induced by BDNF or NT-4/5 was significantly 
      attenuated by AEBSF. Treatment with BDNF has previously been shown to induce 
      neuronal NOS (nNOS). Our data indicated that inhibitors of nNOS attenuated 
      neuronal death induced by BDNF or NT-4/5, consistent with an active role of nNOS 
      in the mediation of neurotrophin neurotoxicity. As in other models of oxidative 
      cell death, BDNF-induced neuronal death was accompanied by poly(ADP ribose) 
      polymerase (PARP) activation. AEBSF or N-nitro-l-arginine (NNA) reduced 
      BDNF-mediated PARP activation. PARP and poly(ADP ribose) glycohydrolase (PARG) 
      are actively involved in mediating neurotrophin neurotoxicity since inhibitors of 
      PARP and PARG significantly reduced levels of cell death. These results suggest 
      that NADPH oxidase and nNOS contribute to increased oxidative stress, subsequent 
      activation of PARP/PARG, and neuronal death induced by prolonged neurotrophin 
      exposure.
FAU - Hwang, Jung-Jin
AU  - Hwang JJ
AD  - National Creative Research Initiative Center for the Study of CNS Zinc, 
      University of Ulsan College of Medicine, Seoul, Korea.
FAU - Choi, So-Young
AU  - Choi SY
FAU - Koh, Jae-Young
AU  - Koh JY
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Phosphoproteins)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 0 (Protein Subunits)
RN  - 0 (neutrophil cytosol factor 67K)
RN  - 145172-44-7 (neurotrophin 5)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 1.14.13.39 (Nos1 protein, mouse)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 3.2.1.- (Glycoside Hydrolases)
RN  - EC 3.2.1.143 (poly ADP-ribose glycohydrolase)
RN  - P658DCA9XD (neurotrophin 4)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/physiology
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Enzyme Inhibitors/pharmacology
MH  - Glycoside Hydrolases/antagonists & inhibitors
MH  - Mice
MH  - NADPH Oxidases/antagonists & inhibitors/*metabolism
MH  - Nerve Growth Factors/*pharmacology
MH  - Neurons/cytology/*drug effects/metabolism
MH  - Nitric Oxide Synthase/antagonists & inhibitors/*metabolism
MH  - Nitric Oxide Synthase Type I
MH  - Oxidation-Reduction
MH  - Phosphoproteins/metabolism
MH  - Poly(ADP-ribose) Polymerase Inhibitors
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - Protein Subunits
MH  - Protein Transport/drug effects
EDAT- 2002/10/03 04:00
MHDA- 2002/10/19 04:00
CRDT- 2002/10/03 04:00
PHST- 2002/10/03 04:00 [pubmed]
PHST- 2002/10/19 04:00 [medline]
PHST- 2002/10/03 04:00 [entrez]
AID - 1040 [pii]
AID - 10.1046/j.1471-4159.2002.01040.x [doi]
PST - ppublish
SO  - J Neurochem. 2002 Aug;82(4):894-902. doi: 10.1046/j.1471-4159.2002.01040.x.