PMID- 19428112
OWN - NLM
STAT- MEDLINE
DCOM- 20091027
LR  - 20151119
IS  - 1872-9711 (Electronic)
IS  - 0161-813X (Linking)
VI  - 30
IP  - 4
DP  - 2009 Jul
TI  - Protective effects of brain-derived neurotrophic factor against neurotoxicity of 
      3-nitropropionic acid in rat cortical neurons.
PG  - 718-26
LID - 10.1016/j.neuro.2009.03.008 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) deficiency has been implicated in 
      pathogenesis of Huntington's disease (HD). 3-Nitropropionic acid (3-NP), an 
      irreversible mitochondrial complex II inhibitor, has been commonly used as a 
      pharmacological model recapitulating HD phenotypes in rodents and nonhuman 
      primates. Herein we test whether BDNF may exert neuroprotective effects against 
      mitochondrial dysfunction caused by 3-NP in primary culture of fetal rat cortical 
      neurons. Preconditioning of neuronal cells with BDNF (100 ng/ml for 8h) 
      attenuated 3-NP toxicity (2.5 mM for additional 24h) based on Hoechst and 
      propidium iodide (PI) staining. BDNF effects can be inhibited by the nitric oxide 
      synthase (NOS) inhibitor L-nitroarginine methylester (L-NAME, 100 microM), the 
      cGMP-dependent protein kinase (PKG) inhibitor KT5823 (2 microM), the thioredoxin 
      reductase inhibitor 1-chloro-2,4-dinitrobenzene (DNCB, 5 microM), and a 
      membrane-permeable Bcl-2 inhibitor (12.5 microM). 8-Br-cGMP is a cGMP analogue 
      capable of activating PKG independent of NO. Exogenous application of 8-Br-cGMP 
      (3-30 microM) and purified thioredoxin (3-5 microM) partially mimicked BDNF 
      effects in conferring 3-NP resistance to cortical cells. These results, together 
      with our previous report showing NO donor S-nitrosoglutathione (GSNO)-mediated 
      neuroprotective effects against 3-NP toxicity, suggest that BDNF may protect 
      neurons from mitochondrial dysfunction at least partly via activation of the 
      signaling cascades involving NOS/NO, PKG, thioredoxin and Bcl-2.
FAU - Wu, Chia-Lin
AU  - Wu CL
AD  - Institute of Brain Science and Brain Research Center, National Yang-Ming 
      University, Taipei 112, Taiwan.
FAU - Hwang, Chi-Shin
AU  - Hwang CS
FAU - Yang, Ding-I
AU  - Yang DI
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090408
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Convulsants)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nitro Compounds)
RN  - 0 (Propionates)
RN  - QY4L0FOX0D (3-nitropropionic acid)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cerebral Cortex/*cytology
MH  - Convulsants/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Embryo, Mammalian
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nerve Tissue Proteins/metabolism
MH  - Neurons/*drug effects
MH  - Neuroprotective Agents/*pharmacology
MH  - Nitro Compounds/*toxicity
MH  - Propionates/*toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - Time Factors
EDAT- 2009/05/12 09:00
MHDA- 2009/10/29 06:00
CRDT- 2009/05/12 09:00
PHST- 2008/04/24 00:00 [received]
PHST- 2009/02/14 00:00 [revised]
PHST- 2009/03/26 00:00 [accepted]
PHST- 2009/05/12 09:00 [entrez]
PHST- 2009/05/12 09:00 [pubmed]
PHST- 2009/10/29 06:00 [medline]
AID - S0161-813X(09)00079-5 [pii]
AID - 10.1016/j.neuro.2009.03.008 [doi]
PST - ppublish
SO  - Neurotoxicology. 2009 Jul;30(4):718-26. doi: 10.1016/j.neuro.2009.03.008. Epub 
      2009 Apr 8.