PMID- 19555760 OWN - NLM STAT- MEDLINE DCOM- 20091203 LR - 20161125 IS - 1095-953X (Electronic) IS - 0969-9961 (Linking) VI - 35 IP - 3 DP - 2009 Sep TI - BDNF regulates BIM expression levels in 3-nitropropionic acid-treated cortical neurons. PG - 448-56 LID - 10.1016/j.nbd.2009.06.006 [doi] AB - 3-Nitropropionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase that has been used to explore the primary mechanisms of cell death associated with mitochondrial dysfunction and neurodegeneration in Huntington's disease. In this study we investigated the ability of brain-derived neurotrophic factor (BDNF) to suppress mitochondrial-dependent cell death induced by 3-NP in primary cortical neurons. This neurotrophin prevented 3-NP-induced release of cytochrome c and Smac/Diablo, caspase-3-like activity and nuclear condensation/fragmentation. Furthermore, it greatly increased phosphorylation of Akt and MAPK, suggesting the involvement of these signalling pathways in BDNF neuroprotection. Interestingly, BDNF decreased the levels of the pro-apoptotic protein Bim in mitochondrial and total cell lysates through the activation of the MEK1/2 pathway. This effect was due to an increase in the degradation rates of Bim. Our data support an important role for BDNF, in protecting cortical neurons against apoptotic cell death caused by inhibition of mitochondrial complex II. FAU - Almeida, Sandra AU - Almeida S AD - Institute of Biochemistry, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra 3004-504, Portugal. FAU - Laco, Mario AU - Laco M FAU - Cunha-Oliveira, Teresa AU - Cunha-Oliveira T 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 - 20090623 PL - United States TA - Neurobiol Dis JT - Neurobiology of disease JID - 9500169 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Bcl-2-Like Protein 11) RN - 0 (Bcl2l11 protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carrier Proteins) RN - 0 (Central Nervous System Agents) RN - 0 (Chromatin) RN - 0 (DIABLO protein, rat) RN - 0 (Membrane Proteins) RN - 0 (Mitochondrial Proteins) RN - 0 (Nitro Compounds) RN - 0 (Propionates) RN - 0 (Proto-Oncogene Proteins) RN - 9007-43-6 (Cytochromes c) RN - EC 1.3.99.1 (Succinate Dehydrogenase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.4.22.- (Casp3 protein, rat) RN - EC 3.4.22.- (Caspase 3) RN - QY4L0FOX0D (3-nitropropionic acid) SB - IM MH - Animals MH - Apoptosis/drug effects/*physiology MH - Apoptosis Regulatory Proteins/*metabolism MH - Bcl-2-Like Protein 11 MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Carrier Proteins/metabolism MH - Caspase 3/metabolism MH - Cells, Cultured MH - Central Nervous System Agents/toxicity MH - Cerebral Cortex/drug effects/*physiology MH - Chromatin/drug effects/metabolism MH - Cytochromes c/metabolism MH - MAP Kinase Signaling System/physiology MH - Membrane Proteins/*metabolism MH - Mitochondria/drug effects/physiology MH - Mitochondrial Proteins/metabolism MH - Neurons/drug effects/*physiology MH - Nitro Compounds/toxicity MH - Phosphorylation MH - Propionates/toxicity MH - Proto-Oncogene Proteins/*metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - Rats, Wistar MH - Succinate Dehydrogenase/antagonists & inhibitors EDAT- 2009/06/27 09:00 MHDA- 2009/12/16 06:00 CRDT- 2009/06/27 09:00 PHST- 2009/01/15 00:00 [received] PHST- 2009/06/03 00:00 [revised] PHST- 2009/06/11 00:00 [accepted] PHST- 2009/06/27 09:00 [entrez] PHST- 2009/06/27 09:00 [pubmed] PHST- 2009/12/16 06:00 [medline] AID - S0969-9961(09)00143-0 [pii] AID - 10.1016/j.nbd.2009.06.006 [doi] PST - ppublish SO - Neurobiol Dis. 2009 Sep;35(3):448-56. doi: 10.1016/j.nbd.2009.06.006. Epub 2009 Jun 23.