Activation of NF-kappaB p65/c-Rel dimer is associated with neuroprotection elicited by mGlu5 receptor agonists against MPP(+) toxicity in SK-N-SH cells.
J Neural Transm (Vienna)
; 115(5): 669-76, 2008 May.
Article
em En
| MEDLINE
| ID: mdl-18094921
ABSTRACT
Nuclear factor-kappaB (NF-kappaB) is a transcriptional regulator of neuron survival eliciting diverse effects according to the specific composition of its active dimer. While p50/p65 mediates neurodegenerative events, c-Rel-containing dimers promote cell survival. Stimulation of metabotropic glutamate receptors type 5 (mGlu5) reduces neuron vulnerability to amyloid-beta through activation of anti-apoptotic, c-Rel-dependent transcription of Bcl-X(L) pathway. We here evaluated the protective activity of mGlu5 agonists in dopaminergic SK-N-SH cells exposed to 1-methyl-4-phenylpyridinium (MPP(+)), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causing parkinsonism in experimental animals. MPP(+) produced a concentration-dependent cell loss. Activation of mGlu5 receptors by CHPG (1 mM) and 3HPG (50 microM) abolished the toxic effect produced by 3 microM MPP(+). The neuroprotection was associated with activation of NF-kappaB p65/c-Rel dimer and reduction of p50/p65. These effects were prevented by the mGlu5 receptor antagonist MPEP (5 microM). It is suggested that mGlu5 receptor agonists through activation of a c-Rel-dependent anti-apoptotic pathway can rescue dopaminergic cell from mitochondrial toxicity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
1-Metil-4-fenilpiridínio
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Regulação da Expressão Gênica
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NF-kappa B
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Agonistas de Aminoácidos Excitatórios
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Proteínas Proto-Oncogênicas c-rel
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Herbicidas
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Neural Transm (Vienna)
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Itália