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...
| Autores: | , , , , , , , , , |
|---|---|
| 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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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/ |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Wiley |
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Wiley |
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reponame:Docta Complutense instname:Universidad Complutense de Madrid (UCM) |
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Universidad Complutense de Madrid (UCM) |
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Docta Complutense |
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Docta Complutense |
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1869405650557075456 |
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15.301629 |