Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.16/563
Título: Activation of ERK1/2 MAP kinases in familial amyloidotic polyneuropathy
Barbas-Amaral, J.
Data: Abr-2006
Editora: Wiley-Blackwell
Resumo: J Neurochem. 2006 Apr;97(1):151-61. Epub 2006 Mar 3. Activation of ERK1/2 MAP kinases in familial amyloidotic polyneuropathy. Monteiro FA, Sousa MM, Cardoso I, do Amaral JB, Guimarães A, Saraiva MJ. Molecular Neurobiology, Instituto de Biologia Celular e Molecular, ICBAS, University of Porto, and Estomatology, Maxillofacial Surgery, Hospital Geral de Santo António, Portugal. Abstract Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by the extracellular deposition of transthyretin (TTR), especially in the PNS. Given the invasiveness of nerve biopsy, salivary glands (SG) from FAP patients were used previously in microarray analysis; mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) was down-regulated in FAP. Results were validated by RT-PCR and immunohistochemistry both in SG and in nerve biopsies of different stages of disease progression. MKP-3 was also down-regulated in FAP SG biopsies. Given the relationship between MKPs and MAPKs, the latter were investigated. Only extracellular signal-regulated kinases 1/2 (ERK1/2) displayed increased activation in FAP SG and nerves. ERK1/2 kinase (MEK1/2) activation was also up-regulated in FAP nerves. In addition, an FAP transgenic mouse model revealed increased ERK1/2 activation in peripheral nerve affected with TTR deposition when compared to control animals. Cultured rat Schwannoma cell line treatment with TTR aggregates stimulated ERK1/2 activation, which was partially mediated by the receptor for advanced glycation end-products (RAGE). Moreover, caspase-3 activation triggered by TTR aggregates was abrogated by U0126, a MEK1/2 inhibitor, indicating that ERK1/2 activation is essential for TTR aggregates-induced cytotoxicity. Taken together, these data suggest that abnormally sustained activation of ERK in FAP may represent an early signaling cascade leading to neurodegeneration. PMID: 16515552 [PubMed - indexed for MEDLINE]
Peer review: yes
URI: http://hdl.handle.net/10400.16/563
ISSN: 0022-3042
Versão do Editor: http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2006.03716.x/pdf
Aparece nas colecções:SECMF - Artigos publicados em revistas indexadas na Medline

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