title: Tissue-type plasminogen activator induces plasmin-dependent proteolysis of intracellular neuronal nitric oxide synthase.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Altogether, these results demonstrate a new function for tPA in the central nervous system, which most likely contributes to its pleiotropic functions.
authors.affiliation: INSERM U919, Serine Proteases and Pathophysiology of the Neurovascular Unit (SP2U), Cyceron, Caen Cedex F-14074, France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Baron
authors.forename: Yannick
authors.initials: Y
authors.lastname: Hommet
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cassé
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
mesh_terms: D000818:Animals; D005341:Fibrinolysin / Q000378:metabolism*; D051379:Mice; D016202:N-Methylaspartate / Q000378:metabolism; D009474:Neurons / Q000201:enzymology* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D015398:Signal Transduction; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D016202:N-Methylaspartate; D052248:Nitric Oxide Synthase Type I; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin