BDNF regulates BIM expression levels in 3-nitropropionic acid-treated cortical neurons
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-der...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2009-09-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996109001430 |
| _version_ | 1818862572165660672 |
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| author | Sandra Almeida Mário Laço Teresa Cunha-Oliveira Catarina R. Oliveira A. Cristina Rego |
| author_facet | Sandra Almeida Mário Laço Teresa Cunha-Oliveira Catarina R. Oliveira A. Cristina Rego |
| author_sort | Sandra Almeida |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T10:02:00Z |
| format | Article |
| id | doaj.art-4c66dfa3732a49bd9d0b0cb26a97948a |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-19T10:02:00Z |
| publishDate | 2009-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-4c66dfa3732a49bd9d0b0cb26a97948a2022-12-21T20:26:37ZengElsevierNeurobiology of Disease1095-953X2009-09-01353448456BDNF regulates BIM expression levels in 3-nitropropionic acid-treated cortical neuronsSandra Almeida0Mário Laço1Teresa Cunha-Oliveira2Catarina R. Oliveira3A. Cristina Rego4Institute of Biochemistry, Faculty of Medicine, and Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalInstitute of Biochemistry, Faculty of Medicine, and Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalInstitute of Biochemistry, Faculty of Medicine, and Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalInstitute of Biochemistry, Faculty of Medicine, and Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCorresponding author. Fax: +351 239 822776.; Institute of Biochemistry, Faculty of Medicine, and Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal3-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.http://www.sciencedirect.com/science/article/pii/S0969996109001430BDNF3-Nitropropionic acidMitochondriaCell deathNeurotrophinsNeurodegeneration |
| spellingShingle | Sandra Almeida Mário Laço Teresa Cunha-Oliveira Catarina R. Oliveira A. Cristina Rego BDNF regulates BIM expression levels in 3-nitropropionic acid-treated cortical neurons Neurobiology of Disease BDNF 3-Nitropropionic acid Mitochondria Cell death Neurotrophins Neurodegeneration |
| title | BDNF regulates BIM expression levels in 3-nitropropionic acid-treated cortical neurons |
| title_full | BDNF regulates BIM expression levels in 3-nitropropionic acid-treated cortical neurons |
| title_fullStr | BDNF regulates BIM expression levels in 3-nitropropionic acid-treated cortical neurons |
| title_full_unstemmed | BDNF regulates BIM expression levels in 3-nitropropionic acid-treated cortical neurons |
| title_short | BDNF regulates BIM expression levels in 3-nitropropionic acid-treated cortical neurons |
| title_sort | bdnf regulates bim expression levels in 3 nitropropionic acid treated cortical neurons |
| topic | BDNF 3-Nitropropionic acid Mitochondria Cell death Neurotrophins Neurodegeneration |
| url | http://www.sciencedirect.com/science/article/pii/S0969996109001430 |
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