Tissue-type plasminogen activator induces plasmin-dependent proteolysis of intracellular neuronal nitric oxide synthase

Biology of the Cell
Amandine BaronDenis Vivien

Abstract

Despite its pro-fibrinolytic activity, tPA (tissue plasminogen activator) is a serine protease known to influence a number of physiological and pathological functions in the central nervous system. Accordingly, tPA was reported to mediate some of its functions in the central nervous system through NMDA (N-methyl-D-aspartate) receptors, LRP (low-density lipoprotein receptor-related protein) or annexin II. We provide here both in vitro and in vivo evidence that tPA could mediate proteolysis and subsequent delocalization of neuronal nitric oxide synthase, thereby reducing endogenous neuronal nitric oxide release. We also demonstrate that although this effect is independent of NMDA receptors, LRP signalling and calpain-mediated proteolysis, it is dependent on the ability of tPA to promote the conversion of plasminogen into plasmin. Altogether, these results demonstrate a new function for tPA in the central nervous system, which most likely contributes to its pleiotropic functions.

References

Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·S E TsirkaS Strickland
Oct 16, 1999·Brain Research. Molecular Brain Research·H KawachiM Noda
Nov 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·N W SeedsS P Haffke
Apr 12, 2000·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·R Sattler, M Tymianski
Jul 8, 2003·Molecular Neurobiology·Guy C Brown, Anna Bal-Price
Jul 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·Michael A PackerGrigori Enikolopov
Oct 30, 2004·Scandinavian Journal of Gastroenterology·M B Oleksiewicz
Apr 21, 2005·Thrombosis and Haemostasis·Jerry P Melchor, Sidney Strickland
Aug 17, 2005·Current Drug Targets. CNS and Neurological Disorders·Inês M Araújo, Caetana M Carvalho
Jan 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Laibaik ParkCostantino Iadecola
Jul 24, 2008·Neuroscience Letters·Jeremy Pak Hong ChowMasaharu Noda
Sep 18, 2008·Journal of Neurochemistry·Andre L SamsonRobert L Medcalf
Mar 21, 2009·Nitric Oxide : Biology and Chemistry·Li Zhou, Dong-Ya Zhu
May 22, 2009·Journal of Neurochemistry·Monica AvernaEdon Melloni

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Citations

May 18, 2011·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Meng QiJixin Shi
Nov 15, 2011·Neuropharmacology·Sighild LemarchantMarina Rubio
Jan 8, 2015·Hämostaseologie·R L Medcalf

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