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

SUBMITTER: Lemarchand E 

PROVIDER: S-EPMC4815983 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature