title: c-Jun-dependent sulfiredoxin induction mediates BDNF protection against mitochondrial inhibition in rat cortical neurons.
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.
authors.affiliation: Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Wu
authors.forename: Jiu-Haw
authors.initials: JH
authors.lastname: Yin
authors.forename: Chi-Shin
authors.initials: CS
authors.lastname: Hwang
authors.forename: Shang-Der
authors.initials: SD
authors.lastname: Chen
authors.forename: Ding-Yah
authors.initials: DY
authors.lastname: Yang
authors.forename: Ding-I
authors.initials: DI
authors.lastname: Yang
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004790:Enzyme Induction / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D008928:Mitochondria / Q000201:enzymology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009574:Nitro Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000096:biosynthesis* / Q000502:physiology; D011422:Propionates / Q000037:antagonists & inhibitors / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D050862:Oxidoreductases Acting on Sulfur Group Donors; C542495:Srxn1 protein, rat; D048031:JNK Mitogen-Activated Protein Kinases; C015392:3-nitropropionic acid