Oxidative stress triggers the amyloidogenic pathway in human vascular smooth muscle cells
Oxidative stress triggers the amyloidogenic pathway in human vascular smooth muscle cells
Citació
- 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
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Resum
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.