PMID- 30243728
OWN - NLM
STAT- MEDLINE
DCOM- 20190528
LR  - 20190528
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 505
IP  - 1
DP  - 2018 Oct 20
TI  - The signaling pathways underlying BDNF-induced Nrf2 hippocampal nuclear 
      translocation involve ROS, RyR-Mediated Ca(2+) signals, ERK and PI3K.
PG  - 201-207
LID - S0006-291X(18)32005-9 [pii]
LID - 10.1016/j.bbrc.2018.09.080 [doi]
AB  - The neurotrophin Brain-Derived Neurotrophic Factor (BDNF) induces complex 
      neuronal signaling cascades that are critical for the cellular changes underlying 
      synaptic plasticity. These pathways include activation of Ca(2+) entry via 
      N-methyl-D-aspartate receptors and sequential activation of nitric oxide synthase 
      and NADPH oxidase, which via generation of reactive nitrogen/oxygen species 
      stimulate Ca(2+)-induced Ca(2+) release mediated by Ryanodine Receptor (RyR) 
      channels. These sequential events underlie BDNF-induced spine remodeling and 
      type-2 RyR up-regulation. In addition, BDNF induces the nuclear translocation of 
      the transcription factor Nrf2, a master regulator of antioxidant protein 
      expression that protects cells against the oxidative damage caused by injury and 
      inflammation. To investigate the possible BDNF-induced signaling cascades that 
      mediate Nrf2 nuclear translocation in primary hippocampal cultures, we tested 
      here whether reactive oxygen species, RyR-mediated Ca(2+) release, ERK or PI3K 
      contribute to this response. We found that pre-incubation of cultures with 
      inhibitory ryanodine to suppress RyR-mediated Ca(2+) release, with the reducing 
      agent N-acetylcysteine or with inhibitors of ERK or PI3K activity, prevented the 
      nuclear translocation of Nrf2 induced by incubation for 6 h with BFNF. Based on 
      these combined results, we propose that the key role played by BDNF as an inducer 
      of neuronal antioxidant responses, characterized by BDNF-induced Nfr2 nuclear 
      translocation, entails crosstalk between reactive oxygen species and RyR-mediated 
      Ca(2+) release, and the participation of ERK and PI3K activities.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Bruna, Barbara
AU  - Bruna B
AD  - Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile.
FAU - Lobos, Pedro
AU  - Lobos P
AD  - Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile.
FAU - Herrera-Molina, Rodrigo
AU  - Herrera-Molina R
AD  - Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany; Centro Integrativo 
      de Biologia y Quimica Aplicada, Universidad Bernardo O'Higgins, Santiago, Chile.
FAU - Hidalgo, Cecilia
AU  - Hidalgo C
AD  - Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile; Institute of Biomedical Sciences, Faculty of Medicine, 
      Universidad de Chile, Santiago, Chile; Department of Neurosciences, Faculty of 
      Medicine, Universidad de Chile, Santiago, Chile; Center for Molecular Studies of 
      the Cell, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
FAU - Paula-Lima, Andrea
AU  - Paula-Lima A
AD  - Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile; Institute for Research in Dental Sciences, Faculty of Dentistry, 
      Universidad de Chile, Santiago, Chile.
FAU - Adasme, Tatiana
AU  - Adasme T
AD  - Biomedical Neuroscience Institute, Faculty of Medicine, Universidad de Chile, 
      Santiago, Chile; Centro Integrativo de Biologia y Quimica Aplicada, Universidad 
      Bernardo O'Higgins, Santiago, Chile. Electronic address: tatiana.adasme@ubo.cl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180919
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, rat)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Ryanodine Receptor Calcium Release Channel)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Calcium Signaling/drug effects
MH  - Cells, Cultured
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Free Radical Scavengers/pharmacology
MH  - Hippocampus/cytology/embryology
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Neurons/drug effects/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/*metabolism
MH  - Ryanodine Receptor Calcium Release Channel/*metabolism
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Antioxidant signaling
OT  - Calcium signaling
OT  - Neuronal redox state
OT  - Synaptic plasticity
OT  - Transcription factor
EDAT- 2018/09/24 06:00
MHDA- 2019/05/29 06:00
CRDT- 2018/09/24 06:00
PHST- 2018/08/15 00:00 [received]
PHST- 2018/09/12 00:00 [accepted]
PHST- 2018/09/24 06:00 [pubmed]
PHST- 2019/05/29 06:00 [medline]
PHST- 2018/09/24 06:00 [entrez]
AID - S0006-291X(18)32005-9 [pii]
AID - 10.1016/j.bbrc.2018.09.080 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2018 Oct 20;505(1):201-207. doi: 
      10.1016/j.bbrc.2018.09.080. Epub 2018 Sep 19.