c-Jun-dependent sulfiredoxin induction mediates BDNF protection against mitochondrial inhibition in rat cortical neurons.
Neurobiol Dis
; 46(2): 450-62, 2012 May.
Article
in En
| MEDLINE
| ID: mdl-22402332
ABSTRACT
In current study, we tested the hypothesis that c-Jun-dependent sulfiredoxin expression mediates protective effects of brain-derived neurotrophic factor (BDNF) against neurotoxicity induced by 3-nitropropionic acid (3-NP), a mitochondrial complex II inhibitor, in primary rat cortical cultures. We found that BDNF-dependent c-Jun expression and nuclear translocation required prior phosphorylation of extracellular signal-regulated kinase (ERK)1/2, but not Akt. BDNF also transiently activated the expression of sulfiredoxin, an ATP-dependent antioxidant enzyme, at both mRNA and protein levels. Furthermore, both c-Jun siRNA and ERK1/2 inhibitor PD98059 suppressed BDNF-induced sulfiredoxin expression. Finally, PD98059, c-Jun siRNA, and sulfiredoxin siRNA all abrogated BDNF-mediated 3-NP resistance. Together, these results established a signaling cascade of "BDNF â ERK1/2-Pi â c-Jun â sulfiredoxin â 3-NP resistance". We therefore conclude that c-Jun-induced sulfiredoxin mediates the BDNF-dependent neuroprotective effects against 3-NP toxicity in primary rat cortical neurons, at least in part.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain-Derived Neurotrophic Factor
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JNK Mitogen-Activated Protein Kinases
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Oxidoreductases Acting on Sulfur Group Donors
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Mitochondria
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Neural Inhibition
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Neurons
Limits:
Animals
Language:
En
Journal:
Neurobiol Dis
Journal subject:
NEUROLOGIA
Year:
2012
Document type:
Article
Affiliation country: