Effect of BACE1-inhibited astrocytes on endothelial cells in a glutamate toxic environment
ABSTRACT: After cerebral ischemia or during several central nervous system (CNS) pathologies, exacerbated high glutamate concentration are released into the cerebral parenchyma producing a toxic environment that damages the components of the neurovascular unit (NVU) including the endothelial cells;...
- Autores:
-
Pineda López, Lina Gisela
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2020
- Institución:
- Universidad de Antioquia
- Repositorio:
- Repositorio UdeA
- Idioma:
- eng
- OAI Identifier:
- oai:bibliotecadigital.udea.edu.co:10495/17671
- Acceso en línea:
- http://hdl.handle.net/10495/17671
- Palabra clave:
- Glutamic acid
Amyloid precursor protein secretases
Endothelial cells
Astrocytes
http://id.nlm.nih.gov/mesh/D053829
http://id.nlm.nih.gov/mesh/D001253
http://id.nlm.nih.gov/mesh/D018698
http://id.nlm.nih.gov/mesh/D042783
- Rights
- embargoedAccess
- License
- Atribución-NoComercial-SinDerivadas 2.5 Colombia (CC BY-NC-ND 2.5 CO)
id |
UDEA2_cb987c7693efd0a4021cb8d84fa4b980 |
---|---|
oai_identifier_str |
oai:bibliotecadigital.udea.edu.co:10495/17671 |
network_acronym_str |
UDEA2 |
network_name_str |
Repositorio UdeA |
repository_id_str |
|
dc.title.spa.fl_str_mv |
Effect of BACE1-inhibited astrocytes on endothelial cells in a glutamate toxic environment |
title |
Effect of BACE1-inhibited astrocytes on endothelial cells in a glutamate toxic environment |
spellingShingle |
Effect of BACE1-inhibited astrocytes on endothelial cells in a glutamate toxic environment Glutamic acid Amyloid precursor protein secretases Endothelial cells Astrocytes http://id.nlm.nih.gov/mesh/D053829 http://id.nlm.nih.gov/mesh/D001253 http://id.nlm.nih.gov/mesh/D018698 http://id.nlm.nih.gov/mesh/D042783 |
title_short |
Effect of BACE1-inhibited astrocytes on endothelial cells in a glutamate toxic environment |
title_full |
Effect of BACE1-inhibited astrocytes on endothelial cells in a glutamate toxic environment |
title_fullStr |
Effect of BACE1-inhibited astrocytes on endothelial cells in a glutamate toxic environment |
title_full_unstemmed |
Effect of BACE1-inhibited astrocytes on endothelial cells in a glutamate toxic environment |
title_sort |
Effect of BACE1-inhibited astrocytes on endothelial cells in a glutamate toxic environment |
dc.creator.fl_str_mv |
Pineda López, Lina Gisela |
dc.contributor.advisor.none.fl_str_mv |
Cardona Gómez, Gloria Patricia Posada Duque, Rafael Andrés |
dc.contributor.author.none.fl_str_mv |
Pineda López, Lina Gisela |
dc.subject.mesh.none.fl_str_mv |
Glutamic acid Amyloid precursor protein secretases Endothelial cells Astrocytes |
topic |
Glutamic acid Amyloid precursor protein secretases Endothelial cells Astrocytes http://id.nlm.nih.gov/mesh/D053829 http://id.nlm.nih.gov/mesh/D001253 http://id.nlm.nih.gov/mesh/D018698 http://id.nlm.nih.gov/mesh/D042783 |
dc.subject.lcshuri.none.fl_str_mv |
http://id.nlm.nih.gov/mesh/D053829 |
dc.subject.meshuri.none.fl_str_mv |
http://id.nlm.nih.gov/mesh/D001253 http://id.nlm.nih.gov/mesh/D018698 http://id.nlm.nih.gov/mesh/D042783 |
description |
ABSTRACT: After cerebral ischemia or during several central nervous system (CNS) pathologies, exacerbated high glutamate concentration are released into the cerebral parenchyma producing a toxic environment that damages the components of the neurovascular unit (NVU) including the endothelial cells; which affects the function and structure of the blood-brain barrier. Astrocytes, glial cells that are closely related to the endothelium, change their gene expression profile in the face of toxicity and, depending of such profile, can be either protective or damage mediators. The enzyme BACE-1, involved in amyloidosis and vascular deterioration, increases its expression after an ischemic event even in astrocytes. Given the above, our aim was to determine the effect of BACE-1-inhibited astrocytes on endothelial cells integrity in a glutamate toxic environment by observing the effect of BACE-1 inhibition in endothelial cells and astrocytes cultures and endothelium-astrocyte co-cultures, through cytotoxicity and immunofluorescence assays. The results obtained suggest BACE1 inhibition protects endothelial cells integrity by reversing structural and inflammatory damage, also reverses astrocytic reactivity causing structural changes in cytoskeleton and cell inflammation. Furthermore, BACE1-inhibited astrocytes protect endothelial cells integrity regulating the Zonula occludens-1 distribution and decreasing inflammatory processes caused by glutamate toxicity. In summary, these results suggest inhibition of BACE1 under a glutamate toxicity has a protective effect on endothelium and astrocytes and their interactions. |
publishDate |
2020 |
dc.date.accessioned.none.fl_str_mv |
2020-12-07T17:58:45Z |
dc.date.available.none.fl_str_mv |
2020-12-07T17:58:45Z |
dc.date.issued.none.fl_str_mv |
2020 |
dc.type.spa.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_b1a7d7d4d402bcce |
dc.type.hasversion.spa.fl_str_mv |
info:eu-repo/semantics/draft |
dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.redcol.spa.fl_str_mv |
https://purl.org/redcol/resource_type/ART |
dc.type.local.spa.fl_str_mv |
Artículo de investigación |
format |
http://purl.org/coar/resource_type/c_2df8fbb1 |
status_str |
draft |
dc.identifier.uri.none.fl_str_mv |
http://hdl.handle.net/10495/17671 |
url |
http://hdl.handle.net/10495/17671 |
dc.language.iso.spa.fl_str_mv |
eng |
language |
eng |
dc.rights.*.fl_str_mv |
Atribución-NoComercial-SinDerivadas 2.5 Colombia (CC BY-NC-ND 2.5 CO) |
dc.rights.spa.fl_str_mv |
info:eu-repo/semantics/embargoedAccess |
dc.rights.uri.*.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/2.5/co/ |
dc.rights.accessrights.spa.fl_str_mv |
http://purl.org/coar/access_right/c_f1cf |
dc.rights.creativecommons.spa.fl_str_mv |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
rights_invalid_str_mv |
Atribución-NoComercial-SinDerivadas 2.5 Colombia (CC BY-NC-ND 2.5 CO) http://creativecommons.org/licenses/by-nc-nd/2.5/co/ http://purl.org/coar/access_right/c_f1cf https://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
embargoedAccess |
dc.format.extent.spa.fl_str_mv |
22 |
dc.format.mimetype.spa.fl_str_mv |
application/pdf |
dc.publisher.group.spa.fl_str_mv |
Grupo de Neurociencias de Antioquia |
dc.publisher.place.spa.fl_str_mv |
Medellín, Colombia |
institution |
Universidad de Antioquia |
bitstream.url.fl_str_mv |
http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/12/license.txt http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/1/PinedaLina_2020_InhibitionBACE1Astrocytes.pdf http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/4/PinedaLina_InhibitionBACE1Figura1.pdf http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/5/PinedaLina_InhibitionBACE1Figura2.pdf http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/6/PinedaLina_InhibitionBACE1Figura3.pdf http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/7/PinedaLina_InhibitionBACE1Figura4.pdf http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/8/PinedaLina_InhibitionBACE1Figura5.pdf http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/9/PinedaLina_InhibitionBACE1Figura6.pdf http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/10/PinedaLina_InhibitionBACE1Figura7.pdf http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/11/license_rdf |
bitstream.checksum.fl_str_mv |
8a4605be74aa9ea9d79846c1fba20a33 dbd7ccdeff399962dcc81ec769368ab3 f01b9b879c6b04bcca17b803052267b2 0728fd1f08a5d35e88c5713b2865e664 024169d72ea3e5b366f2013e3b30408c c98ff7eb73684ecd1ef7c6d007fcc57a eefbf2c8eb56eaabb2a119e0494025d7 93e8c2b53a61516ea8767e6f5ed51440 aa441403a001e49260febe223218f603 b88b088d9957e670ce3b3fbe2eedbc13 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositorio Institucional Universidad de Antioquia |
repository.mail.fl_str_mv |
andres.perez@udea.edu.co |
_version_ |
1812173150065000448 |
spelling |
Cardona Gómez, Gloria PatriciaPosada Duque, Rafael AndrésPineda López, Lina Gisela2020-12-07T17:58:45Z2020-12-07T17:58:45Z2020http://hdl.handle.net/10495/17671ABSTRACT: After cerebral ischemia or during several central nervous system (CNS) pathologies, exacerbated high glutamate concentration are released into the cerebral parenchyma producing a toxic environment that damages the components of the neurovascular unit (NVU) including the endothelial cells; which affects the function and structure of the blood-brain barrier. Astrocytes, glial cells that are closely related to the endothelium, change their gene expression profile in the face of toxicity and, depending of such profile, can be either protective or damage mediators. The enzyme BACE-1, involved in amyloidosis and vascular deterioration, increases its expression after an ischemic event even in astrocytes. Given the above, our aim was to determine the effect of BACE-1-inhibited astrocytes on endothelial cells integrity in a glutamate toxic environment by observing the effect of BACE-1 inhibition in endothelial cells and astrocytes cultures and endothelium-astrocyte co-cultures, through cytotoxicity and immunofluorescence assays. The results obtained suggest BACE1 inhibition protects endothelial cells integrity by reversing structural and inflammatory damage, also reverses astrocytic reactivity causing structural changes in cytoskeleton and cell inflammation. Furthermore, BACE1-inhibited astrocytes protect endothelial cells integrity regulating the Zonula occludens-1 distribution and decreasing inflammatory processes caused by glutamate toxicity. In summary, these results suggest inhibition of BACE1 under a glutamate toxicity has a protective effect on endothelium and astrocytes and their interactions.22application/pdfenginfo:eu-repo/semantics/draftinfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARTArtículo de investigaciónhttp://purl.org/coar/version/c_b1a7d7d4d402bcceAtribución-NoComercial-SinDerivadas 2.5 Colombia (CC BY-NC-ND 2.5 CO)info:eu-repo/semantics/embargoedAccesshttp://creativecommons.org/licenses/by-nc-nd/2.5/co/http://purl.org/coar/access_right/c_f1cfhttps://creativecommons.org/licenses/by-nc-nd/4.0/Glutamic acidAmyloid precursor protein secretasesEndothelial cellsAstrocyteshttp://id.nlm.nih.gov/mesh/D053829http://id.nlm.nih.gov/mesh/D001253http://id.nlm.nih.gov/mesh/D018698http://id.nlm.nih.gov/mesh/D042783Effect of BACE1-inhibited astrocytes on endothelial cells in a glutamate toxic environmentGrupo de Neurociencias de AntioquiaMedellín, ColombiaBiólogaPregradoFacultad de Ciencias Exactas y Naturales. Carrera de BiologíaUniversidad de AntioquiaLICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/12/license.txt8a4605be74aa9ea9d79846c1fba20a33MD512ORIGINALPinedaLina_2020_InhibitionBACE1Astrocytes.pdfPinedaLina_2020_InhibitionBACE1Astrocytes.pdfArtículo de investigaciónapplication/pdf586131http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/1/PinedaLina_2020_InhibitionBACE1Astrocytes.pdfdbd7ccdeff399962dcc81ec769368ab3MD51PinedaLina_InhibitionBACE1Figura1.pdfPinedaLina_InhibitionBACE1Figura1.pdfAnexosapplication/pdf257721http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/4/PinedaLina_InhibitionBACE1Figura1.pdff01b9b879c6b04bcca17b803052267b2MD54PinedaLina_InhibitionBACE1Figura2.pdfPinedaLina_InhibitionBACE1Figura2.pdfAnexosapplication/pdf264725http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/5/PinedaLina_InhibitionBACE1Figura2.pdf0728fd1f08a5d35e88c5713b2865e664MD55PinedaLina_InhibitionBACE1Figura3.pdfPinedaLina_InhibitionBACE1Figura3.pdfAnexosapplication/pdf213097http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/6/PinedaLina_InhibitionBACE1Figura3.pdf024169d72ea3e5b366f2013e3b30408cMD56PinedaLina_InhibitionBACE1Figura4.pdfPinedaLina_InhibitionBACE1Figura4.pdfAnexosapplication/pdf252923http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/7/PinedaLina_InhibitionBACE1Figura4.pdfc98ff7eb73684ecd1ef7c6d007fcc57aMD57PinedaLina_InhibitionBACE1Figura5.pdfPinedaLina_InhibitionBACE1Figura5.pdfAnexosapplication/pdf181566http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/8/PinedaLina_InhibitionBACE1Figura5.pdfeefbf2c8eb56eaabb2a119e0494025d7MD58PinedaLina_InhibitionBACE1Figura6.pdfPinedaLina_InhibitionBACE1Figura6.pdfAnexosapplication/pdf212053http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/9/PinedaLina_InhibitionBACE1Figura6.pdf93e8c2b53a61516ea8767e6f5ed51440MD59PinedaLina_InhibitionBACE1Figura7.pdfPinedaLina_InhibitionBACE1Figura7.pdfAnexosapplication/pdf158438http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/10/PinedaLina_InhibitionBACE1Figura7.pdfaa441403a001e49260febe223218f603MD510CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8823http://bibliotecadigital.udea.edu.co/bitstream/10495/17671/11/license_rdfb88b088d9957e670ce3b3fbe2eedbc13MD51110495/17671oai:bibliotecadigital.udea.edu.co:10495/176712021-06-14 09:41:22.577Repositorio Institucional Universidad de Antioquiaandres.perez@udea.edu.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 |