PMID- 26208700
OWN - NLM
STAT- MEDLINE
DCOM- 20180115
LR  - 20220624
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 53
IP  - 6
DP  - 2016 Aug
TI  - Nuclear Factor-kappaB-Dependent Sestrin2 Induction Mediates the Antioxidant 
      Effects of BDNF Against Mitochondrial Inhibition in Rat Cortical Neurons.
PG  - 4126-4142
LID - 10.1007/s12035-015-9357-1 [doi]
AB  - Brain-derived neurotrophic factor (BDNF), in addition to its neurotrophic action, 
      also possesses antioxidant activities. However, the underlying mechanisms remain 
      to be fully defined. Sestrin2 is a stress-responsive gene implicated in the 
      cellular defense against oxidative stress. Currently, the potential functions of 
      sestrin2 in nervous system, in particular its correlation with neurotrophic 
      factors, have not been well established. In this study, we hypothesized that BDNF 
      may enhance sestrin2 expression to confer neuronal resistance against oxidative 
      stress induced by 3-nitropropionic acid (3-NP), an irreversible mitochondrial 
      complex II inhibitor, and characterized the molecular mechanisms underlying BDNF 
      induction of sestrin2 in primary rat cortical cultures. We found that 
      BDNF-mediated sestrin2 expression in cortical neurons required formation of 
      nitric oxide (NO) with subsequent production of 3',5'-cyclic guanosine 
      monophosphate (cGMP) and activation of cGMP-dependent protein kinase (PKG). BDNF 
      induced localization of nuclear factor-kappaB (NF-kappaB) subunits p65 and p50 into 
      neuronal nuclei that required PKG activities. Interestingly, BDNF exposure led to 
      formation of a protein complex containing at least PKG-1 and p65/p50, which bound 
      to sestrin2 promoter with resultant upregulation of its protein products. 
      Finally, BDNF preconditioning mitigated production of reactive oxygen species 
      (ROS) as a result of 3-NP exposure; this antioxidative effect of BDNF was 
      dependent upon PKG activity, NF-kappaB, and sestrin2. Taken together, our results 
      indicated that BDNF enhances sestrin2 expression to confer neuronal resistance 
      against oxidative stress induced by 3-NP through attenuation of ROS formation; 
      furthermore, BDNF induction of sestrin2 requires activation of a pathway 
      involving NO/PKG/NF-kappaB.
FAU - Wu, Chia-Lin
AU  - Wu CL
AD  - Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, 
      Taipei, Taiwan.
AD  - Institute of Brain Science and Brain Research Center, National Yang-Ming 
      University, Taipei, Taiwan.
FAU - Chen, Shang-Der
AU  - Chen SD
AD  - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung 
      University College of Medicine, Kaohsiung, Taiwan.
AD  - Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung 
      Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 
      Taiwan.
FAU - Yin, Jiu-Haw
AU  - Yin JH
AD  - Department of Neurology, Cheng Hsin General Hospital, Taipei, Taiwan.
AD  - Department of Neurology, Tri-Service General Hospital, National Defense Medical 
      Center, Taipei, Taiwan.
FAU - Hwang, Chi-Shin
AU  - Hwang CS
AD  - Department of Neurology, Taipei City Hospital, Taipei, Taiwan.
AD  - Department of Medicine, National Yang-Ming University, Taipei, Taiwan.
FAU - Yang, Ding-I
AU  - Yang DI
AD  - Institute of Brain Science and Brain Research Center, National Yang-Ming 
      University, Taipei, Taiwan. diyang@ym.edu.tw.
AD  - Institute of Brain Science, National Yang-Ming University, Number 155, Section 2, 
      Linong Street, Beitou District, Taipei, 11221, Taiwan. diyang@ym.edu.tw.
LA  - eng
PT  - Journal Article
DEP - 20150726
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Antioxidants)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitro Compounds)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Propionates)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sesn2 protein, rat)
RN  - 0 (Transcription Factors)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
RN  - H2D2X058MU (Cyclic GMP)
RN  - QY4L0FOX0D (3-nitropropionic acid)
SB  - IM
MH  - Animals
MH  - Antioxidants/*physiology
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Nucleus/drug effects/metabolism
MH  - Cerebral Cortex/*cytology
MH  - Cyclic GMP/metabolism
MH  - Cyclic GMP-Dependent Protein Kinases/metabolism
MH  - Mitochondria/drug effects/*metabolism
MH  - NF-kappa B/*metabolism
MH  - Neurons/drug effects/*metabolism
MH  - Neuroprotection/drug effects
MH  - Nitric Oxide/metabolism
MH  - Nitro Compounds
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Propionates
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Transcription Factors/metabolism
OTO - NOTNLM
OT  - 3-Nitropropionic acid
OT  - Free radicals
OT  - Nitric oxide
OT  - Reactive oxygen species
OT  - Soluble guanylate cyclase
OT  - cGMP-dependent protein kinase
EDAT- 2015/07/26 06:00
MHDA- 2018/01/16 06:00
CRDT- 2015/07/26 06:00
PHST- 2015/04/15 00:00 [received]
PHST- 2015/07/13 00:00 [accepted]
PHST- 2015/07/26 06:00 [entrez]
PHST- 2015/07/26 06:00 [pubmed]
PHST- 2018/01/16 06:00 [medline]
AID - 10.1007/s12035-015-9357-1 [pii]
AID - 10.1007/s12035-015-9357-1 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2016 Aug;53(6):4126-4142. doi: 10.1007/s12035-015-9357-1. Epub 
      2015 Jul 26.