Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental stroke

CDP-choline has shown neuroprotective effects in cerebral ischemia. In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP-choline and placebo groups, CDP-choline was shown to be more beneficial in some patients, suc...

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Autores: Hurtado Moreno, Olivia, Hernández Jiménez, Macarena, Zarruk, Juan G., Cuartero Desviat, María Isabel, Ballesteros, Iván, Camarero, Guadalupe, Moraga Yébenes, Ana, Pradillo Justo, Jesús Miguel, Moro Sánchez, María Ángeles, Lizasoaín Hernández, Ignacio
Tipo de recurso: artículo
Fecha de publicación:2013
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/96288
Acceso en línea:https://hdl.handle.net/20.500.14352/96288
Access Level:acceso abierto
Palabra clave:615.01/.03
CDP-choline
SIRT1
Citicoline
Neuroprotection
Stroke
Ciencias Biomédicas
32 Ciencias Médicas
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network_acronym_str ES
network_name_str España
repository_id_str
spelling Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental strokeHurtado Moreno, OliviaHernández Jiménez, MacarenaZarruk, Juan G.Cuartero Desviat, María IsabelBallesteros, IvánCamarero, GuadalupeMoraga Yébenes, AnaPradillo Justo, Jesús MiguelMoro Sánchez, María ÁngelesLizasoaín Hernández, Ignacio615.01/.03CDP-cholineSIRT1CiticolineNeuroprotectionStrokeCiencias Biomédicas32 Ciencias MédicasCDP-choline has shown neuroprotective effects in cerebral ischemia. In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP-choline and placebo groups, CDP-choline was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with t-PA. Several mechanisms have been proposed to explain the beneficial actions of CDP-choline. We have now studied the participation of Sirtuin1 (SIRT1) in the neuroprotective actions of CDP-choline. Fischer rats and Sirt1⁻/⁻ mice were subjected to permanent focal ischemia. CDP-choline (0.2 or 2 g/kg), sirtinol (a SIRT1 inhibitor; 10 mg/kg), and resveratrol (a SIRT1 activator; 2.5 mg/kg) were administered intraperitoneally. Brains were removed 24 and 48 h after ischemia for western blot analysis and infarct volume determination. Treatment with CDP-choline increased SIRT1 protein levels in brain concomitantly to neuroprotection. Treatment with sirtinol blocked the reduction in infarct volume caused by CDP-choline, whereas resveratrol elicited a strong synergistic neuroprotective effect with CDP-choline. CDP-choline failed to reduce infarct volume in Sirt1⁻/⁻ mice. Our present results demonstrate a robust effect of CDP-choline like SIRT1 activator by up-regulating its expression. Our findings suggest that therapeutic strategies to activate SIRT1 may be useful in the treatment of stroke. Sirtuin 1 (SIRT1) is implicated in a wide range of cellular functions. Regarding stroke, there is no direct evidence. We have demonstrated that citicoline increases SIRT1 protein levels in brain concomitantly to neuroprotection. Citicoline fails to reduce infarct volume in Sirt1⁻/⁻ mice. Our findings suggest that therapeutic strategies acting on SIRT1 may be useful in the treatment of stroke.WileyUniversidad Complutense de Madrid20132013-05-1320132013-05-13journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/96288reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/962882026-06-02T12:44:21Z
dc.title.none.fl_str_mv Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental stroke
title Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental stroke
spellingShingle Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental stroke
Hurtado Moreno, Olivia
615.01/.03
CDP-choline
SIRT1
Citicoline
Neuroprotection
Stroke
Ciencias Biomédicas
32 Ciencias Médicas
title_short Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental stroke
title_full Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental stroke
title_fullStr Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental stroke
title_full_unstemmed Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental stroke
title_sort Citicoline (CDP-choline) increases Sirtuin1 expression concomitant to neuroprotection in experimental stroke
dc.creator.none.fl_str_mv Hurtado Moreno, Olivia
Hernández Jiménez, Macarena
Zarruk, Juan G.
Cuartero Desviat, María Isabel
Ballesteros, Iván
Camarero, Guadalupe
Moraga Yébenes, Ana
Pradillo Justo, Jesús Miguel
Moro Sánchez, María Ángeles
Lizasoaín Hernández, Ignacio
author Hurtado Moreno, Olivia
author_facet Hurtado Moreno, Olivia
Hernández Jiménez, Macarena
Zarruk, Juan G.
Cuartero Desviat, María Isabel
Ballesteros, Iván
Camarero, Guadalupe
Moraga Yébenes, Ana
Pradillo Justo, Jesús Miguel
Moro Sánchez, María Ángeles
Lizasoaín Hernández, Ignacio
author_role author
author2 Hernández Jiménez, Macarena
Zarruk, Juan G.
Cuartero Desviat, María Isabel
Ballesteros, Iván
Camarero, Guadalupe
Moraga Yébenes, Ana
Pradillo Justo, Jesús Miguel
Moro Sánchez, María Ángeles
Lizasoaín Hernández, Ignacio
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 615.01/.03
CDP-choline
SIRT1
Citicoline
Neuroprotection
Stroke
Ciencias Biomédicas
32 Ciencias Médicas
topic 615.01/.03
CDP-choline
SIRT1
Citicoline
Neuroprotection
Stroke
Ciencias Biomédicas
32 Ciencias Médicas
description CDP-choline has shown neuroprotective effects in cerebral ischemia. In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP-choline and placebo groups, CDP-choline was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with t-PA. Several mechanisms have been proposed to explain the beneficial actions of CDP-choline. We have now studied the participation of Sirtuin1 (SIRT1) in the neuroprotective actions of CDP-choline. Fischer rats and Sirt1⁻/⁻ mice were subjected to permanent focal ischemia. CDP-choline (0.2 or 2 g/kg), sirtinol (a SIRT1 inhibitor; 10 mg/kg), and resveratrol (a SIRT1 activator; 2.5 mg/kg) were administered intraperitoneally. Brains were removed 24 and 48 h after ischemia for western blot analysis and infarct volume determination. Treatment with CDP-choline increased SIRT1 protein levels in brain concomitantly to neuroprotection. Treatment with sirtinol blocked the reduction in infarct volume caused by CDP-choline, whereas resveratrol elicited a strong synergistic neuroprotective effect with CDP-choline. CDP-choline failed to reduce infarct volume in Sirt1⁻/⁻ mice. Our present results demonstrate a robust effect of CDP-choline like SIRT1 activator by up-regulating its expression. Our findings suggest that therapeutic strategies to activate SIRT1 may be useful in the treatment of stroke. Sirtuin 1 (SIRT1) is implicated in a wide range of cellular functions. Regarding stroke, there is no direct evidence. We have demonstrated that citicoline increases SIRT1 protein levels in brain concomitantly to neuroprotection. Citicoline fails to reduce infarct volume in Sirt1⁻/⁻ mice. Our findings suggest that therapeutic strategies acting on SIRT1 may be useful in the treatment of stroke.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-05-13
2013
2013-05-13
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/96288
url https://hdl.handle.net/20.500.14352/96288
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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