PMID- 19422804 OWN - NLM STAT- MEDLINE DCOM- 20090622 LR - 20151119 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 385 IP - 1 DP - 2009 Jul 17 TI - Sonic hedgehog mediates BDNF-induced neuroprotection against mitochondrial inhibitor 3-nitropropionic acid. PG - 112-7 LID - 10.1016/j.bbrc.2009.04.145 [doi] AB - 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. FAU - Wu, Chia-Lin AU - Wu CL AD - Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei 11221, Taiwan. FAU - Chen, Shang-Der AU - Chen SD FAU - Hwang, Chi-Shin AU - Hwang CS FAU - Yang, Ding-I AU - Yang DI LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090505 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Hedgehog Proteins) RN - 0 (Neuroprotective Agents) RN - 0 (Neurotoxins) RN - 0 (Nitro Compounds) RN - 0 (Propionates) RN - 0 (RNA, Messenger) RN - QY4L0FOX0D (3-nitropropionic acid) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cells, Cultured MH - Cerebral Cortex/cytology/drug effects/metabolism MH - *Cytoprotection MH - Hedgehog Proteins/*biosynthesis/genetics/pharmacology MH - Mitochondria/drug effects MH - Neuroprotective Agents/*pharmacology MH - Neurotoxins/antagonists & inhibitors/toxicity MH - Nitro Compounds/antagonists & inhibitors/toxicity MH - Propionates/antagonists & inhibitors/toxicity MH - RNA, Messenger/biosynthesis MH - Rats MH - Rats, Sprague-Dawley EDAT- 2009/05/09 09:00 MHDA- 2009/06/23 09:00 CRDT- 2009/05/09 09:00 PHST- 2009/04/18 00:00 [received] PHST- 2009/04/29 00:00 [accepted] PHST- 2009/05/09 09:00 [entrez] PHST- 2009/05/09 09:00 [pubmed] PHST- 2009/06/23 09:00 [medline] AID - S0006-291X(09)00853-5 [pii] AID - 10.1016/j.bbrc.2009.04.145 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2009 Jul 17;385(1):112-7. doi: 10.1016/j.bbrc.2009.04.145. Epub 2009 May 5.