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Mécanismes mis en jeu dans la libération d’endozépines induite par le peptide bêta amyloïde, rôle du gliopeptide ODN dans l’activité astrocytaire

Abstract : The diazepam-binding inhibitor and its processing products, including the octadecaneuropeptide ODN, are collectively designated by the term endozepines (EZ), and are exclusively produced by astroglial cells of the CNS. It has been shown that EZ concentration is increased in human cerebrospinal fluid of patients which Alzheimer’s disease which is characterized by beta-amyloid (bA) deposists. In addition, bA also stimulates the production of EZ from cultured astrocytes. In this work, we first demontrate that bA stimulates EZ release in cultured rat astrocytes through activation of N-formyl peptide receptors (FPR) positively coupled to adenylyl cyclase and phospholipase C. Activation of protein kinases A and C, and calcium influx are necessary to bA-induced EZ release. Finally, EZ secretion occurs through glyburide-sensitive ATP-binding cassette transporters. bA can also stimulate, with a delay, IL-1b-release from astrocytes. In contrast, ODN induces only a transient increase of IL-1b mRNA levels which is followed by an inhibition of IL-1b expression, suggesting that bA may independently stimulate EZ and IL-1b release. We also show that bA, through activation of FPR, induces astrocyte proliferation. Similarly, ODN, acting through pico- and nano-molar binding sites, stimulates astrocyte proliferation. Finally, ODN significantly reduces H2O2-induced ROS accumulation in cultured astrocytes, through an increase of both superoxyde dismutase and catalase activities. In addition, ODN abolishes the effects of H2O2 on mitochondrial membrane potential and caspase 3-activation indicating that ODN reduces apoptotic cell death and protects astrocytes from oxidative stress damages.
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Raya Hachem. Mécanismes mis en jeu dans la libération d’endozépines induite par le peptide bêta amyloïde, rôle du gliopeptide ODN dans l’activité astrocytaire. Sciences du Vivant [q-bio]. Université de Rouen, 2010. Français. ⟨tel-02295797⟩

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