Age and albumin D site-binding protein control tissue plasminogen activator levels: neurotoxic impact
Identifieur interne : 001132 ( Main/Exploration ); précédent : 001131; suivant : 001133Age and albumin D site-binding protein control tissue plasminogen activator levels: neurotoxic impact
Auteurs : Benoit D. Roussel [France] ; Richard Macrez [France] ; Amandine Jullienne [France] ; Véronique Agin [France] ; Eric Maubert [France] ; Luce Dauphinot [France] ; Marie-Claude Potier [France] ; Laurent Plawinski [France] ; Hervé Castel [France] ; Yannick Hommet [France] ; Josep Munuera [Espagne] ; Joan Montaner [Espagne] ; Manuel Yepes [États-Unis] ; Carine Ali [France] ; Denis Vivien [France]Source :
- Brain [ 0006-8950 ] ; 2009-08.
Abstract
Recombinant tissue-type plasminogen activator (tPA) is the fibrinolytic drug of choice to treat stroke patients. However, a growing body of evidence indicates that besides its beneficial thrombolytic role, tPA can also have a deleterious effect on the ischaemic brain. Although ageing influences stroke incidence, complications and outcome, age-dependent relationships between endogenous tPA and stroke injuries have not been investigated yet. Here, we report that ageing is associated with a selective lowering of brain tPA expression in the murine brain. Moreover, our results show that albumin D site-binding protein (DBP) as a key age-associated regulator of the neuronal transcription of tPA. Additionally, inhibition of DBP-mediated tPA expression confers in vitro neuroprotection. Accordingly, reduced levels of tPA in old mice are associated with smaller excitotoxic/ischaemic injuries and protection of the permeability of the neurovascular unit during cerebral ischaemia. Likewise, we provide neuroradiological evidence indicating the existence of an inverse relationship between age and the volume of the ischaemic lesion in patients with acute ischaemic stroke. Together, these results indicate that the relationship among DBP, tPA and ageing play an important role in the outcome of cerebral ischaemia.
Url:
DOI: 10.1093/brain/awp162
Affiliations:
- Espagne, France, États-Unis
- Basse-Normandie, Catalogne, Géorgie (États-Unis), Région Normandie
- Paris
- Université de Caen Basse-Normandie
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Université de Caen Basse-Normandie, Caen, F-14074</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Basse-Normandie</region></placeName><orgName type="university">Université de Caen Basse-Normandie</orgName></affiliation></author><author><name sortKey="Castel, Herve" sort="Castel, Herve" uniqKey="Castel H" first="Hervé" last="Castel">Hervé Castel</name><affiliation wicri:level="4"><country xml:lang="fr">France</country><wicri:regionArea>1 INSERM U919 ‘serine proteases and pathophysiology of the neurovascular unit’, UMR-CNRS 6232 CINAPS, Cyceron, Caen, F-14074 France; Université de Caen Basse-Normandie, Caen, F-14074</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Basse-Normandie</region></placeName><orgName type="university">Université de Caen Basse-Normandie</orgName></affiliation></author><author><name sortKey="Hommet, Yannick" sort="Hommet, Yannick" uniqKey="Hommet Y" first="Yannick" last="Hommet">Yannick Hommet</name><affiliation wicri:level="4"><country xml:lang="fr">France</country><wicri:regionArea>1 INSERM U919 ‘serine proteases and pathophysiology of the neurovascular unit’, UMR-CNRS 6232 CINAPS, Cyceron, Caen, F-14074 France; Université de Caen Basse-Normandie, Caen, F-14074</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Basse-Normandie</region></placeName><orgName type="university">Université de Caen Basse-Normandie</orgName></affiliation></author><author><name sortKey="Munuera, Josep" sort="Munuera, Josep" uniqKey="Munuera J" first="Josep" last="Munuera">Josep Munuera</name><affiliation wicri:level="2"><country xml:lang="fr">Espagne</country><wicri:regionArea>3 Neuroimaging Unit, Department of Neuroradiology, Hospital Vall d’Hebron, Universitat Autonoma de Barcelona, 08035 Barcelona</wicri:regionArea><placeName><region nuts="2" type="communauté">Catalogne</region></placeName></affiliation></author><author><name sortKey="Montaner, Joan" sort="Montaner, Joan" uniqKey="Montaner J" first="Joan" last="Montaner">Joan Montaner</name><affiliation wicri:level="2"><country xml:lang="fr">Espagne</country><wicri:regionArea>4 Neurovascular Research Laboratory, Stroke Unit, Department of Neurology, Hospital Vall d’Hebron, Universitat Autonoma de Barcelona, 08035 Barcelona</wicri:regionArea><placeName><region nuts="2" type="communauté">Catalogne</region></placeName></affiliation></author><author><name sortKey="Yepes, Manuel" sort="Yepes, Manuel" uniqKey="Yepes M" first="Manuel" last="Yepes">Manuel Yepes</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>5 Department of Neurology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA30322</wicri:regionArea><placeName><region type="state">Géorgie (États-Unis)</region></placeName></affiliation></author><author><name sortKey="Ali, Carine" sort="Ali, Carine" uniqKey="Ali C" first="Carine" last="Ali">Carine Ali</name><affiliation wicri:level="4"><country xml:lang="fr">France</country><wicri:regionArea>1 INSERM U919 ‘serine proteases and pathophysiology of the neurovascular unit’, UMR-CNRS 6232 CINAPS, Cyceron, Caen, F-14074 France; Université de Caen Basse-Normandie, Caen, F-14074</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Basse-Normandie</region></placeName><orgName type="university">Université de Caen Basse-Normandie</orgName></affiliation><affiliation wicri:level="1"><country wicri:rule="url">France</country></affiliation></author><author><name sortKey="Vivien, Denis" sort="Vivien, Denis" uniqKey="Vivien D" first="Denis" last="Vivien">Denis Vivien</name><affiliation wicri:level="4"><country xml:lang="fr">France</country><wicri:regionArea>1 INSERM U919 ‘serine proteases and pathophysiology of the neurovascular unit’, UMR-CNRS 6232 CINAPS, Cyceron, Caen, F-14074 France; Université de Caen Basse-Normandie, Caen, F-14074</wicri:regionArea><placeName><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Basse-Normandie</region></placeName><orgName type="university">Université de Caen Basse-Normandie</orgName></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain</title><idno type="ISSN">0006-8950</idno><idno type="eISSN">1460-2156</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2009-08">2009-08</date><biblScope unit="volume">132</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="2219">2219</biblScope><biblScope unit="page" to="2230">2230</biblScope></imprint><idno type="ISSN">0006-8950</idno></series><idno type="istex">BD4E2C9443B938FC3AECA5239FEA6837A5B171A4</idno><idno type="DOI">10.1093/brain/awp162</idno><idno type="ArticleID">awp162</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Recombinant tissue-type plasminogen activator (tPA) is the fibrinolytic drug of choice to treat stroke patients. However, a growing body of evidence indicates that besides its beneficial thrombolytic role, tPA can also have a deleterious effect on the ischaemic brain. Although ageing influences stroke incidence, complications and outcome, age-dependent relationships between endogenous tPA and stroke injuries have not been investigated yet. Here, we report that ageing is associated with a selective lowering of brain tPA expression in the murine brain. Moreover, our results show that albumin D site-binding protein (DBP) as a key age-associated regulator of the neuronal transcription of tPA. Additionally, inhibition of DBP-mediated tPA expression confers in vitro neuroprotection. Accordingly, reduced levels of tPA in old mice are associated with smaller excitotoxic/ischaemic injuries and protection of the permeability of the neurovascular unit during cerebral ischaemia. Likewise, we provide neuroradiological evidence indicating the existence of an inverse relationship between age and the volume of the ischaemic lesion in patients with acute ischaemic stroke. Together, these results indicate that the relationship among DBP, tPA and ageing play an important role in the outcome of cerebral ischaemia.</div></front></TEI><affiliations><list><country><li>Espagne</li><li>France</li><li>États-Unis</li></country><region><li>Basse-Normandie</li><li>Catalogne</li><li>Géorgie (États-Unis)</li><li>Région Normandie</li></region><settlement><li>Paris</li></settlement><orgName><li>Université de Caen Basse-Normandie</li></orgName></list><tree><country name="France"><region name="Région Normandie"><name sortKey="Roussel, Benoit D" sort="Roussel, Benoit D" uniqKey="Roussel B" first="Benoit D." last="Roussel">Benoit D. Roussel</name></region><name sortKey="Agin, Veronique" sort="Agin, Veronique" uniqKey="Agin V" first="Véronique" last="Agin">Véronique Agin</name><name sortKey="Ali, Carine" sort="Ali, Carine" uniqKey="Ali C" first="Carine" last="Ali">Carine Ali</name><name sortKey="Ali, Carine" sort="Ali, Carine" uniqKey="Ali C" first="Carine" last="Ali">Carine Ali</name><name sortKey="Castel, Herve" sort="Castel, Herve" uniqKey="Castel H" first="Hervé" last="Castel">Hervé Castel</name><name sortKey="Dauphinot, Luce" sort="Dauphinot, Luce" uniqKey="Dauphinot L" first="Luce" last="Dauphinot">Luce Dauphinot</name><name sortKey="Hommet, Yannick" sort="Hommet, Yannick" uniqKey="Hommet Y" first="Yannick" last="Hommet">Yannick Hommet</name><name sortKey="Jullienne, Amandine" sort="Jullienne, Amandine" uniqKey="Jullienne A" first="Amandine" last="Jullienne">Amandine Jullienne</name><name sortKey="Macrez, Richard" sort="Macrez, Richard" uniqKey="Macrez R" first="Richard" last="Macrez">Richard Macrez</name><name sortKey="Maubert, Eric" sort="Maubert, Eric" uniqKey="Maubert E" first="Eric" last="Maubert">Eric Maubert</name><name sortKey="Plawinski, Laurent" sort="Plawinski, Laurent" uniqKey="Plawinski L" first="Laurent" last="Plawinski">Laurent Plawinski</name><name sortKey="Potier, Marie Claude" sort="Potier, Marie Claude" uniqKey="Potier M" first="Marie-Claude" last="Potier">Marie-Claude Potier</name><name sortKey="Vivien, Denis" sort="Vivien, Denis" uniqKey="Vivien D" first="Denis" last="Vivien">Denis Vivien</name></country><country name="Espagne"><region name="Catalogne"><name sortKey="Munuera, Josep" sort="Munuera, Josep" uniqKey="Munuera J" first="Josep" last="Munuera">Josep Munuera</name></region><name sortKey="Montaner, Joan" sort="Montaner, Joan" uniqKey="Montaner J" first="Joan" last="Montaner">Joan Montaner</name></country><country name="États-Unis"><region name="Géorgie (États-Unis)"><name sortKey="Yepes, Manuel" sort="Yepes, Manuel" uniqKey="Yepes M" first="Manuel" last="Yepes">Manuel Yepes</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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