PMID- 19779956 OWN - NLM STAT- MEDLINE DCOM- 20100623 LR - 20211020 IS - 1476-3524 (Electronic) IS - 1029-8428 (Linking) VI - 17 IP - 4 DP - 2010 May TI - Dysregulation of CREB activation and histone acetylation in 3-nitropropionic acid-treated cortical neurons: prevention by BDNF and NGF. PG - 399-405 LID - 10.1007/s12640-009-9116-z [doi] AB - 3-Nitropropionic acid (3-NP), an inhibitor of mitochondrial complex II, leads to metabolic impairment and neurodegeneration. In this study, we investigated the roles of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the dysregulation of transcription factors and histone modifying enzymes induced by 3-NP in primary cortical neurons. BDNF prevented the 3-NP-induced decrease in cAMP response-element binding protein (CREB) phosphorylation and CREB-binding protein levels. Both NGF and BDNF counteracted the increase in the levels of histone H3 and H4 acetylations and reduced histone deacetylase (HDAC) activity induced by 3-NP. BDNF further led to hyperphosphorylation of HDAC2. Our results support an important role for neurotrophins, particularly BDNF, in preventing detrimental changes in transcription factors and histone acetylation states in cortical neurons that have been subjected to selective mitochondrial inhibition. FAU - Almeida, Sandra AU - Almeida S AD - Center for Neuroscience and Cell Biology, Faculty of Medicine, Institute of Biochemistry, University of Coimbra, 3004-504 Coimbra, Portugal. FAU - Cunha-Oliveira, Teresa AU - Cunha-Oliveira T FAU - Laco, Mario AU - Laco M FAU - Oliveira, Catarina R AU - Oliveira CR FAU - Rego, A Cristina AU - Rego AC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090925 PL - United States TA - Neurotox Res JT - Neurotoxicity research JID - 100929017 RN - 0 (Anilides) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Convulsants) RN - 0 (Histones) RN - 0 (Nitro Compounds) RN - 0 (Oligopeptides) RN - 0 (Propionates) RN - 0 (acetyl-aspartyl-glutamyl-valyl-aspartic acid p-nitroanilide) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 2.3.1.48 (CREB-Binding Protein) RN - EC 2.3.1.48 (Histone Acetyltransferases) RN - EC 3.4.22.- (Caspases) RN - EC 3.5.1.98 (Hdac2 protein, rat) RN - EC 3.5.1.98 (Histone Deacetylase 2) RN - QY4L0FOX0D (3-nitropropionic acid) SB - IM MH - Acetylation/drug effects MH - Analysis of Variance MH - Anilides/pharmacology MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - CREB-Binding Protein/*metabolism MH - Caspases/metabolism MH - Cells, Cultured MH - Cerebral Cortex/cytology MH - Convulsants/*toxicity MH - Dose-Response Relationship, Drug MH - Enzyme Activation/drug effects MH - Histone Acetyltransferases/metabolism MH - Histone Deacetylase 2/metabolism MH - Histones/metabolism MH - Nerve Growth Factor/*pharmacology MH - Neurons/*drug effects MH - Nitro Compounds/*toxicity MH - Oligopeptides/pharmacology MH - Propionates/*toxicity MH - Rats MH - Rats, Wistar EDAT- 2009/09/26 06:00 MHDA- 2010/06/24 06:00 CRDT- 2009/09/26 06:00 PHST- 2008/12/12 00:00 [received] PHST- 2009/09/08 00:00 [accepted] PHST- 2009/08/28 00:00 [revised] PHST- 2009/09/26 06:00 [entrez] PHST- 2009/09/26 06:00 [pubmed] PHST- 2010/06/24 06:00 [medline] AID - 10.1007/s12640-009-9116-z [doi] PST - ppublish SO - Neurotox Res. 2010 May;17(4):399-405. doi: 10.1007/s12640-009-9116-z. Epub 2009 Sep 25.