C-Jun-dependent sulfiredoxin induction mediates BDNF protection against mitochondrial inhibition in rat cortical neurons

Chia Lin Wu, Jiu Haw Yin, Chi Shin Hwang, Shang Der Chen, Ding Yah Yang, Ding I. Yang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

31 Scopus citations

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 → ERK1/2-Pi → c-Jun → sulfiredoxin → 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.

Original languageEnglish
Pages (from-to)450-462
Number of pages13
JournalNeurobiology of Disease
Volume46
Issue number2
DOIs
StatePublished - 05 2012

Keywords

  • Akt
  • ERK1/2
  • JNK
  • Neuroprotection
  • PI3-K
  • Primary cortical neurons
  • SiRNA

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