title: Stressed neurons protect themselves by a tissue-type plasminogen activator-mediated EGFR-dependent mechanism.
abstract: In the central nervous system, tissue-type plasminogen activator (tPA) has been associated with both pro-death and prosurvival actions on neurons. In most cases, this has been related to exogenous tPA. In the present study, we addressed the influence of endogenous tPA. We first observed an increased transcription of tPA following either in vivo global brain ischemia in rats or in vitro oxygen glucose deprivation (OGD) on mice and rats hippocampal slices. Hippocampal slices from tPA-deficient mice were more sensitive to OGD than wild-type slices. Pharmacological approaches targeting the known receptors of tPA revealed that only the inhibition of phosphorylation of epidermal growth factor receptors (EGFRs) prevented the neuroprotective effect of endogenous tPA. This study shows that ischemic hippocampal neurons overproduce endogenous tPA as an intend to protect themselves from ischemic death, by a mechanism involving an activation of EGFRs. Thus, strategies contributing to promote either endogenous production of tPA or its associated EGFR-linked signaling pathway may have beneficial effects following brain injuries such as stroke.
authors.affiliation: INSERM UMR-S U919 Serine Proteases and Pathophysiology of the Neurovascular Unit, Université Caen Basse Normandie, Bd Henri Becquerel, GIP Cyceron, Caen, France.
authors.forename: E
authors.initials: E
authors.lastname: Lemarchand
authors.affiliation: INSERM UMR-S U919 Serine Proteases and Pathophysiology of the Neurovascular Unit, Université Caen Basse Normandie, Bd Henri Becquerel, GIP Cyceron, Caen, France.
authors.forename: E
authors.initials: E
authors.lastname: Maubert
authors.affiliation: ESRP (European Stroke Research Platform), Centre Universitaire de Ressources Biologiques (CURB), Université Caen Basse Normandie, Caen, France.
authors.forename: B
authors.initials: B
authors.lastname: Haelewyn
authors.affiliation: INSERM UMR-S U919 Serine Proteases and Pathophysiology of the Neurovascular Unit, Université Caen Basse Normandie, Bd Henri Becquerel, GIP Cyceron, Caen, France.
authors.forename: C
authors.initials: C
authors.lastname: Ali
authors.affiliation: INSERM UMR-S U919 Serine Proteases and Pathophysiology of the Neurovascular Unit, Université Caen Basse Normandie, Bd Henri Becquerel, GIP Cyceron, Caen, France.
authors.forename: M
authors.initials: M
authors.lastname: Rubio
authors.affiliation: INSERM UMR-S U919 Serine Proteases and Pathophysiology of the Neurovascular Unit, Université Caen Basse Normandie, Bd Henri Becquerel, GIP Cyceron, Caen, France.
authors.forename: D
authors.initials: D
authors.lastname: Vivien
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000235:genetics*; D002490:Central Nervous System / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D010959:Tissue Plasminogen Activator / Q000235:genetics* / Q000378:metabolism
chemical_list: C541485:EGFR protein, mouse; D066246:ErbB Receptors; D010959:Tissue Plasminogen Activator; D005947:Glucose; D010100:Oxygen