Oxidative stress triggers the amyloidogenic pathway in human vascular smooth muscle cells.
Neurobiol Aging
; 29(7): 969-80, 2008 Jul.
Article
em En
| MEDLINE
| ID: mdl-17306421
Cerebral amyloid angiopathy, associated to most cases of Alzheimer's disease (AD), is characterized by the deposition of amyloid ss-peptide (Ass) in brain vessels, although the origin of the vascular amyloid deposits is still controversial: neuronal versus vascular. In the present work, we demonstrate that primary cultures of human cerebral vascular smooth muscle cells (HC-VSMCs) have all the secretases involved in amyloid ss-protein precursor (APP) cleavage and produce Ass(1-40) and Ass(1-42). Oxidative stress, a key factor in the etiology and pathophysiology of AD, up-regulates ss-site APP cleaving enzyme 1 (BACE1) expression, as well as Ass(1-40) and Ass(1-42) secretion in HC-VSMCs. This process is mediated by c-Jun N-terminal Kinase and p38 MAPK signaling and appears restricted to BACE1 regulation as no changes in the other secretases were observed. In conclusion, oxidative stress-mediated up-regulation of the amyloidogenic pathway in human cerebral vascular smooth muscle cells may contribute to the overall cerebrovascular amyloid angiopathy observed in AD patients.
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Bases de dados:
MEDLINE
Assunto principal:
Encéfalo
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Transdução de Sinais
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Precursor de Proteína beta-Amiloide
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Estresse Oxidativo
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Miócitos de Músculo Liso
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Músculo Liso Vascular
Limite:
Humans
Idioma:
En
Revista:
Neurobiol Aging
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Espanha