Activation of the Integrated Stress Response and ER Stress Protect from Fluorizoline-Induced Apoptosis in HEK293T and U2OS Cell Lines

The prohibitin (PHB)-binding compound fluorizoline as well as PHB-downregulation activate the integrated stress response (ISR) in HEK293T and U2OS human cell lines. This activation is denoted by phosphorylation of eIF2 alpha and increases in ATF4, ATF3, and CHOP protein levels. The blockage of the a...

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Autores: Saura-Esteller, José, Sánchez Vera, Ismael, Núñez-Vázquez, Sonia, Cosialls Castel, Ana Mª, Gama-Perez, Pau, Bhosale, Gauri, Mendive Tapia, Lorena, Lavilla Grífols, Rodolfo, Pons i Irazazábal, Gabriel, Garcia Roves, Pablo M., Duchen, Michael R., Iglesias i Serret, Daniel, Gil i Santano, Joan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/178630
Acceso en línea:https://hdl.handle.net/2445/178630
Access Level:acceso abierto
Palabra clave:Apoptosi
Càncer
Apoptosis
Cancer
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spelling Activation of the Integrated Stress Response and ER Stress Protect from Fluorizoline-Induced Apoptosis in HEK293T and U2OS Cell LinesSaura-Esteller, JoséSánchez Vera, IsmaelNúñez-Vázquez, SoniaCosialls Castel, Ana MªGama-Perez, PauBhosale, GauriMendive Tapia, LorenaLavilla Grífols, RodolfoPons i Irazazábal, GabrielGarcia Roves, Pablo M.Duchen, Michael R.Iglesias i Serret, DanielGil i Santano, JoanApoptosiCàncerApoptosisCancerThe prohibitin (PHB)-binding compound fluorizoline as well as PHB-downregulation activate the integrated stress response (ISR) in HEK293T and U2OS human cell lines. This activation is denoted by phosphorylation of eIF2 alpha and increases in ATF4, ATF3, and CHOP protein levels. The blockage of the activation of the ISR by overexpression of GRP78, as well as an increase in IRE1 activity, indicate the presence of ER stress after fluorizoline treatment. The inhibition of the ER stress response in HEK293T and U2OS led to increased sensitivity to fluorizoline-induced apoptosis, indicating a pro-survival role of this pathway after fluorizoline treatment in these cell lines. Fluorizoline induced an increase in calcium concentration in the cytosol and the mitochondria. Finally, two different calcium chelators reduced fluorizoline-induced apoptosis in U2OS cells. Thus, we have found that fluorizoline causes increased ER stress and activation of the integrated stress response, which in HEK293T and U2OS cells are protective against fluorizoline-induced apoptosis.MDPI2021202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion20 p.application/pdfhttps://hdl.handle.net/2445/178630Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/ijms22116117International Journal of Molecular Sciences, 2021, vol. 22https://doi.org/10.3390/ijms22116117cc by (c) Saura-Esteller et al., 2021http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1786302026-05-29T05:05:01Z
dc.title.none.fl_str_mv Activation of the Integrated Stress Response and ER Stress Protect from Fluorizoline-Induced Apoptosis in HEK293T and U2OS Cell Lines
title Activation of the Integrated Stress Response and ER Stress Protect from Fluorizoline-Induced Apoptosis in HEK293T and U2OS Cell Lines
spellingShingle Activation of the Integrated Stress Response and ER Stress Protect from Fluorizoline-Induced Apoptosis in HEK293T and U2OS Cell Lines
Saura-Esteller, José
Apoptosi
Càncer
Apoptosis
Cancer
title_short Activation of the Integrated Stress Response and ER Stress Protect from Fluorizoline-Induced Apoptosis in HEK293T and U2OS Cell Lines
title_full Activation of the Integrated Stress Response and ER Stress Protect from Fluorizoline-Induced Apoptosis in HEK293T and U2OS Cell Lines
title_fullStr Activation of the Integrated Stress Response and ER Stress Protect from Fluorizoline-Induced Apoptosis in HEK293T and U2OS Cell Lines
title_full_unstemmed Activation of the Integrated Stress Response and ER Stress Protect from Fluorizoline-Induced Apoptosis in HEK293T and U2OS Cell Lines
title_sort Activation of the Integrated Stress Response and ER Stress Protect from Fluorizoline-Induced Apoptosis in HEK293T and U2OS Cell Lines
dc.creator.none.fl_str_mv Saura-Esteller, José
Sánchez Vera, Ismael
Núñez-Vázquez, Sonia
Cosialls Castel, Ana Mª
Gama-Perez, Pau
Bhosale, Gauri
Mendive Tapia, Lorena
Lavilla Grífols, Rodolfo
Pons i Irazazábal, Gabriel
Garcia Roves, Pablo M.
Duchen, Michael R.
Iglesias i Serret, Daniel
Gil i Santano, Joan
author Saura-Esteller, José
author_facet Saura-Esteller, José
Sánchez Vera, Ismael
Núñez-Vázquez, Sonia
Cosialls Castel, Ana Mª
Gama-Perez, Pau
Bhosale, Gauri
Mendive Tapia, Lorena
Lavilla Grífols, Rodolfo
Pons i Irazazábal, Gabriel
Garcia Roves, Pablo M.
Duchen, Michael R.
Iglesias i Serret, Daniel
Gil i Santano, Joan
author_role author
author2 Sánchez Vera, Ismael
Núñez-Vázquez, Sonia
Cosialls Castel, Ana Mª
Gama-Perez, Pau
Bhosale, Gauri
Mendive Tapia, Lorena
Lavilla Grífols, Rodolfo
Pons i Irazazábal, Gabriel
Garcia Roves, Pablo M.
Duchen, Michael R.
Iglesias i Serret, Daniel
Gil i Santano, Joan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Apoptosi
Càncer
Apoptosis
Cancer
topic Apoptosi
Càncer
Apoptosis
Cancer
description The prohibitin (PHB)-binding compound fluorizoline as well as PHB-downregulation activate the integrated stress response (ISR) in HEK293T and U2OS human cell lines. This activation is denoted by phosphorylation of eIF2 alpha and increases in ATF4, ATF3, and CHOP protein levels. The blockage of the activation of the ISR by overexpression of GRP78, as well as an increase in IRE1 activity, indicate the presence of ER stress after fluorizoline treatment. The inhibition of the ER stress response in HEK293T and U2OS led to increased sensitivity to fluorizoline-induced apoptosis, indicating a pro-survival role of this pathway after fluorizoline treatment in these cell lines. Fluorizoline induced an increase in calcium concentration in the cytosol and the mitochondria. Finally, two different calcium chelators reduced fluorizoline-induced apoptosis in U2OS cells. Thus, we have found that fluorizoline causes increased ER stress and activation of the integrated stress response, which in HEK293T and U2OS cells are protective against fluorizoline-induced apoptosis.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/178630
url https://hdl.handle.net/2445/178630
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/ijms22116117
International Journal of Molecular Sciences, 2021, vol. 22
https://doi.org/10.3390/ijms22116117
dc.rights.none.fl_str_mv cc by (c) Saura-Esteller et al., 2021
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Saura-Esteller et al., 2021
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 20 p.
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.811543

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