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Modulation of the nmda receptor function by tissue type plasminogen activator


, : Modulation of the nmda receptor function by tissue type plasminogen activator. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 747 11

Tissue type plasminogen activator (t-PA) is a serine protease characterised by its involvement in the fibrinolytic pathway. t-PA is also express by neurons and astrocytes in the central nervous system. We have showed in primary cultures of cortical neurons that a t-PA treatment enhanced the NMDA-induced neuronal death by cleaving the NR-1 subunit of this receptor. In the present study, we have investigated the molecular mechanism by which t-PA modulates NMDA neurotoxicity. First, to identify the cellular origin of tPA in the CNS, we subjected cortical neurons to 75 mM of KCl. By using zymography assays, we show that neuronal depolarization produces an increase in active t-PA into the extracellular medium, prevented by a pretreatment with either tetanus toxin or BAPTA-AM, an intracellular calcium chelator, suggesting an exocytotic release of t-PA. Next, by using calcium imaging we show that application of t-PA potentiates the NMDA-evoked calcium influx, implicating t-PA in the NMDA-mediated excitotoxicity. Finally, in order to investigate which amino-acids residues are involved in the cleavage of the NR-1 subunit of the NMDA receptor by t-PA, we generated an His-tagged molecular construct of the first extracellular domain of this subunit. By using mass spectrometry following tryptic digestion of our chimeric NR-1 construct, we show that t-PA treatment induces a cleavage of the N-terminus end of NR-1 subunit at position R242. Additional experiments need to be performed in order to further determine what is the participation of t-PA in the modulation of the NMDA receptor-induced reponses.

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Bai, J.; Wang, C.T.en; Richards, D.A.; Jackson, M.B.; Chapman, E.R., 2004: Fusion pore dynamics are regulated by synaptotagmincntdott-SNARE interactions. Exocytosis involves the formation of a fusion pore that connects the lumen of secretory vesicles with the extracellular space. Exocytosis from neurons and neuroendocrine cells is tightly regulated by intracellular (Ca2+) and occurs rapidly, but th...

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Parodi, L.R., 1969: Taxonomic studies on the Gramineae-Paniceae of Argentina and Uruguay. Keys are given for the identification of tribes in the subfamily Panicoideae, of 29 genera in the Paniceae, and for the species in some of these genera. Descriptions are given of the following genera and of their species: Oplismenus, Sacciolepis,...

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Budantsev, A.Iu., 2002: Flow microchamber for the Linnic interference microscope. A flow microchamber for the Linnic microscope was constructed. The volume of the microchamber is 6-10 microliters. The microchamber may be used in two working regimes: (a) under conditions of periodical change of solutions during the analysis of t...

Billa R.F.; Biwole M.S.; Juimo A.G.; Bejanga B.I.; Blackett K., 1991: Gall stone disease in african patients with sickle cell anemia a preliminary report from yaounde cameroon. Cholecystosonography was undertaken in 90 patients with sickle cell disease aged 15 years and over. Gall stones were found in 26 (28.9%) patients. There was no sex difference, but the incidence increased with age from 13.2% at under 20 years to 75...

Butenko, A.T., 1976: Simplified analysis methods of electrocardiograms, rheograms and spirograms. Meditsinskaia Sestra 35(3): 50-50