Oxidative stress triggers the amyloidogenic pathway in human vascular smooth muscle cells
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- dc.contributor.author Coma Camprodón, Mireia
- dc.contributor.author Guix Ràfols, Francesc Xavier
- dc.contributor.author Ill-Raga, Gerard, 1982-
- dc.contributor.author Uribesalgo Micàs, Iris
- dc.contributor.author Alameda Quitllet, Francisco
- dc.contributor.author Valverde, M. A. (Miguel Ángel), 1963-
- dc.contributor.author Muñoz López, Francisco José, 1964-
- dc.date.accessioned 2024-06-20T14:57:26Z
- dc.date.available 2024-06-20T14:57:26Z
- dc.date.issued 2008
- dc.description.abstract 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.
- dc.format.mimetype application/pdf
- dc.identifier.citation Coma M, Guix FX, Ill-Raga G, Uribesalgo I, Alameda F, Valverde MA, et al. Oxidative stress triggers the amyloidogenic pathway in human vascular smooth muscle cells. Neurobiol Aging. 2008 Jul;29(7):969-80. DOI: 10.1016/j.neurobiolaging.2007.01.009
- dc.identifier.doi http://dx.doi.org/10.1016/j.neurobiolaging.2007.01.009
- dc.identifier.issn 0197-4580
- dc.identifier.uri http://hdl.handle.net/10230/60550
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.ispartof Neurobiol Aging. 2008 Jul;29(7):969-80
- dc.rights © Elsevier http://dx.doi.org/10.1016/j.neurobiolaging.2007.01.009
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.subject.keyword Alzheimer’s disease
- dc.subject.keyword Amyloid ß-peptide
- dc.subject.keyword BACE1
- dc.subject.keyword Vascular smooth muscle cells
- dc.subject.keyword Oxidative stress
- dc.subject.keyword c-JNK
- dc.subject.keyword p38 MAPK
- dc.title Oxidative stress triggers the amyloidogenic pathway in human vascular smooth muscle cells
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/acceptedVersion