Linked Life Data

11135617

Source:http://linkedlifedata.com/resource/pubmed/id/11135617

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pubmed-article:11135617pubmed:abstractTextTissue-plasminogen activator (t-PA) is now available for the treatment of thrombo-embolic stroke but adverse effects have been reported in some patients, particularly hemorrhaging. In contrast, the results of animal studies have indicated that t-PA could increase neuronal damage after focal cerebral ischemia. Here we report for the first time that t-PA potentiates signaling mediated by glutamatergic receptors by modifying the properties of the N-methyl-D-aspartate (NMDA) receptor. When depolarized, cortical neurons release bio-active t-PA that interacts with and cleaves the NR1 subunit of the NMDA receptor. Moreover, the treatment with recombinant t-PA leads to a 37% increase in NMDA-stimulated fura-2 fluorescence, which may reflect an increased NMDA-receptor function. These results were confirmed in vivo by the intrastriatal injection of recombinant-PA, which potentiated the excitotoxic lesions induced by NMDA. These data provide insight into the regulation of NMDA-receptor-mediated signaling and could initiate therapeutic strategies to improve the efficacy of t-PA treatment in man.lld:pubmed
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pubmed-article:11135617pubmed:articleTitleThe proteolytic activity of tissue-plasminogen activator enhances NMDA receptor-mediated signaling.lld:pubmed
pubmed-article:11135617pubmed:affiliationUniversité de CAEN, UMR CNRS 6551, and CEA-Université LRA10V, UPRES EA 2609, Bd H. Becquerel, Cyeron BP 5229, F-14074 CAEN Cedex, France.lld:pubmed
pubmed-article:11135617pubmed:publicationTypeJournal Articlelld:pubmed
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