Sonic hedgehog mediates BDNF-induced neuroprotection against mitochondrial inhibitor 3-nitropropionic acid.
Sonic hedgehog (SHH), a morphogen critical for embryogenesis, has also been shown to be neuroprotective. We have recently reported that pretreatment of rat cortical neurons for 8 h with brain-derived neurotrophic factor (BDNF; 100 ng/ml) affords protection against neurotoxicity of 3-nitropropionic acid (3-NP; 2.5 mM for 24 h), a mitochondrial complex II inhibitor. However, whether SHH is involved in BDNF-mediated neuroprotection remains unknown. Herein we tested whether BDNF induces SHH expression and if so, whether BDNF induction of SHH contributes to the observed neuroprotective effects. We found BDNF (100 ng/ml) increased SHH expression at both mRNA and protein levels. BDNF protection against 3-NP was abolished by cyclopamine (CPM; 5 microM), the SHH pathway inhibitor. Preconditioning of cortical neurons with N-terminal fragment of SHH (SHH-N; 0.1-1 ng/ml) was sufficient to confer resistance. These results indicate that BDNF induces SHH expression, which contributes to neuroprotection against 3-NP toxicity in rat cortical neurons.
Wu
Chia-Lin
CL
Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei 11221, Taiwan.
Chen
Shang-Der
SD
Hwang
Chi-Shin
CS
Yang
Ding-I
DI
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection; D053823:Hedgehog Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D009574:Nitro Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity; D011422:Propionates / Q000037:antagonists & inhibitors / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor; D053823:Hedgehog Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D012333:RNA, Messenger; C015392:3-nitropropionic acid