Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/27257
Title: Activation of the endoplasmic reticulum stress response by the amyloid-beta 1–40 peptide in brain endothelial cells
Authors: Fonseca, Ana Catarina R. G. 
Ferreiro, Elisabete 
Oliveira, Catarina R. 
Cardoso, Sandra M. 
Pereira, Cláudia F. 
Keywords: Alzheimer's disease; Amyloid-beta peptide; Endothelial cells; Endoplasmic reticulum stress; Calcium homeostasis; Apoptosis
Issue Date: Dec-2013
Publisher: Elsevier
Citation: FONSECA, Ana Catarina R. G. [et.al] - Activation of the endoplasmic reticulum stress response by the amyloid-beta 1–40 peptide in brain endothelial cells. "Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease". ISSN 0925-4439. Vol. 1832 Nº. 12 (2013) p. 2191-2203
Serial title, monograph or event: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Volume: 1832
Issue: 12
Abstract: Neurovascular dysfunction arising from endothelial cell damage is an early pathogenic event that contributes to the neurodegenerative process occurring in Alzheimer's disease (AD). Since the mechanisms underlying endothelial dysfunction are not fully elucidated, this study was aimed to explore the hypothesis that brain endothelial cell death is induced upon the sustained activation of the endoplasmic reticulum (ER) stress response by amyloid-beta (Aβ) peptide, which deposits in the cerebral vessels in many AD patients and transgenic mice. Incubation of rat brain endothelial cells (RBE4 cell line) with Aβ1–40 increased the levels of several markers of ER stress-induced unfolded protein response (UPR), in a time-dependent manner, and affected the Ca2 + homeostasis due to the release of Ca2 + from this intracellular store. Finally, Aβ1–40 was shown to activate both mitochondria-dependent and -independent apoptotic cell death pathways. Enhanced release of cytochrome c from mitochondria and activation of the downstream caspase-9 were observed in cells treated with Aβ1–40 concomitantly with caspase-12 activation. Furthermore, Aβ1–40 activated the apoptosis effectors' caspase-3 and promoted the translocation of apoptosis-inducing factor (AIF) to the nucleus demonstrating the involvement of caspase-dependent and -independent mechanisms during Aβ-induced endothelial cell death. In conclusion, our data demonstrate that ER stress plays a significant role in Aβ1–40-induced apoptotic cell death in brain endothelial cells suggesting that ER stress-targeted therapeutic strategies might be useful in AD to counteract vascular defects and ultimately neurodegeneration.
URI: http://hdl.handle.net/10316/27257
ISSN: 0925-4439
DOI: 10.1016/j.bbadis.2013.08.007
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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