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Activation of NF-kappaB is involved in 6-hydroxydopamine-but not MPP+ -induced dopaminergic neuronal cell death: its potential role as a survival determinant.
Park, Seong H; Choi, Won-Seok; Yoon, So-Young; Ahn, Young Soo; Oh, Young J.
Afiliação
  • Park SH; Department of Biology, Yonsei University College of Science, Seoul 120-749, Republic of Korea.
Biochem Biophys Res Commun ; 322(3): 727-33, 2004 Sep 24.
Article em En | MEDLINE | ID: mdl-15336524
The nuclear factor-kappaB (NF-kappaB) family plays an important role in the control of the apoptotic response. Its activation has been demonstrated in both neurons and glial cells in many neurological disorders. In the present study, we specifically examined whether and to what extent NF-kappaB activation is involved in culture models of Parkinson's disease following exposure of MN9D dopaminergic neuronal cells to 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-4-phenylpyridinium ion (MPP(+)). Both analysis by immunocytochemistry and of immunoblots revealed that NF-kappaB-p65 was translocated into the nuclei following 6-OHDA but not MPP(+)-treatment. A time-dependent activation of NF-kappaB induced by 6-OHDA but not MPP(+) was also demonstrated by an electrophoretic mobility shift assay. A competition assay indicated that not only NF-kappaB-p65 but also -p50 is involved in 6-OHDA-induced NF-kappaB activity. Co-treatment with an antioxidant, N-acetyl-l-cysteine, blocked 6-OHDA-induced activation of NF-kappaB signaling. In the presence of an NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), 6-OHDA-induced cell death was accelerated while PDTC did not affect MPP(+)-induced cell death. Our data may point to a drug-specific activation of NF-kappaB as a survival determinant for dopaminergic neurons.
Assuntos
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Base de dados: MEDLINE Assunto principal: Dopamina / 1-Metil-4-fenilpiridínio / NF-kappa B / Oxidopamina / Neurônios Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2004 Tipo de documento: Article
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Base de dados: MEDLINE Assunto principal: Dopamina / 1-Metil-4-fenilpiridínio / NF-kappa B / Oxidopamina / Neurônios Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2004 Tipo de documento: Article