BDNF regulates BIM expression levels in 3-nitropropionic acid-treated cortical neurons

Autor: Sandra Aparecida de Almeida, Teresa Cunha-Oliveira, A. Cristina Rego, Catarina R. Oliveira, Mário N. Laço
Jazyk: angličtina
Rok vydání: 2009
Předmět:
MAPK/ERK pathway
Apoptosis
Mitochondrion
0302 clinical medicine
Neurotrophic factors
Phosphorylation
Cells
Cultured
Cerebral Cortex
Neurons
0303 health sciences
Bcl-2-Like Protein 11
3-Nitropropionic acid
Caspase 3
Neurodegeneration
Cytochromes c
Nitro Compounds
Chromatin
Mitochondria
Succinate Dehydrogenase
Neurology
Neurotrophin
Cell death
medicine.medical_specialty
Programmed cell death
MAP Kinase Signaling System
Biology
Neuroprotection
Neurotrophins
lcsh:RC321-571
Mitochondrial Proteins
03 medical and health sciences
Proto-Oncogene Proteins
Internal medicine
medicine
Animals
Rats
Wistar
Protein kinase B
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
030304 developmental biology
Brain-Derived Neurotrophic Factor
Membrane Proteins
medicine.disease
Rats
Endocrinology
BDNF
biology.protein
Propionates
Apoptosis Regulatory Proteins
Carrier Proteins
Proto-Oncogene Proteins c-akt
030217 neurology & neurosurgery
Central Nervous System Agents
Zdroj: Neurobiology of Disease, Vol 35, Iss 3, Pp 448-456 (2009)
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Popis: 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.
Databáze: OpenAIRE
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