Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/27257
DC FieldValueLanguage
dc.contributor.authorFonseca, Ana Catarina R. G.-
dc.contributor.authorFerreiro, Elisabete-
dc.contributor.authorOliveira, Catarina R.-
dc.contributor.authorCardoso, Sandra M.-
dc.contributor.authorPereira, Cláudia F.-
dc.date.accessioned2014-10-14T10:17:08Z-
dc.date.available2014-10-14T10:17:08Z-
dc.date.issued2013-12-
dc.identifier.citationFONSECA, 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. 2191-2203por
dc.identifier.issn0925-4439-
dc.identifier.urihttp://hdl.handle.net/10316/27257-
dc.description.abstractNeurovascular 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.por
dc.language.isoengpor
dc.publisherElsevierpor
dc.rightsopenAccesspor
dc.subjectAlzheimer's diseasepor
dc.subjectAmyloid-beta peptidepor
dc.subjectEndothelial cellspor
dc.subjectEndoplasmic reticulum stresspor
dc.subjectCalcium homeostasispor
dc.subjectApoptosispor
dc.titleActivation of the endoplasmic reticulum stress response by the amyloid-beta 1–40 peptide in brain endothelial cellspor
dc.typearticlepor
degois.publication.firstPage2191por
degois.publication.lastPage2203por
degois.publication.issue12por
degois.publication.titleBiochimica et Biophysica Acta (BBA) - Molecular Basis of Diseasepor
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S092544391300272Xpor
dc.peerreviewedYespor
dc.identifier.doi10.1016/j.bbadis.2013.08.007-
degois.publication.volume1832por
item.fulltextCom Texto completo-
item.grantfulltextopen-
item.languageiso639-1en-
crisitem.author.deptFaculty of Medicine-
crisitem.author.deptFaculty of Medicine-
crisitem.author.deptFaculty of Medicine-
crisitem.author.parentdeptUniversity of Coimbra-
crisitem.author.parentdeptUniversity of Coimbra-
crisitem.author.parentdeptUniversity of Coimbra-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0002-1200-4602-
crisitem.author.orcid0000-0001-6942-4328-
crisitem.author.orcid0000-0002-2199-0555-
crisitem.author.orcid0000-0002-6630-5056-
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais
Files in This Item:
File Description SizeFormat
Activation of the endoplasmic reticulum stress response.pdf745.31 kBAdobe PDFView/Open
Show simple item record

SCOPUSTM   
Citations

68
checked on Feb 18, 2020

WEB OF SCIENCETM
Citations 1

91
checked on Aug 2, 2022

Page view(s) 50

481
checked on Oct 4, 2022

Download(s)

270
checked on Oct 4, 2022

Google ScholarTM

Check

Altmetric

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.