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Beta-amyloid peptide stimulates endozepine release in cultured rat astrocytes through activation of N -formyl peptide receptors

Abstract : Astroglial cells synthesize and release endozepines, a family of neuropeptides derived from diazepam-binding inhibitor (DBI). The authors have recently shown that beta-amyloid peptide (Abeta) stimulates DBI gene expression and endozepine release. The purpose of this study was to determine the mechanism of action of Abeta in cultured rat astrocytes. Abeta(25-35) and the N-formyl peptide receptor (FPR) agonist N-formyl-Met-Leu-Phe (fMLF) increased the secretion of endozepines in a dose-dependent manner with EC(50) value of approximately 2 microM. The stimulatory effects of Abeta(25-35) and the FPR agonists fMLF and N-formyl-Met-Met-Met (fMMM) on endozepine release were abrogated by the FPR antagonist N-t-Boc-Phe-Leu-Phe-Leu-Phe. In contrast, Abeta(25-35) increased DBI mRNA expression through a FPR-independent mechanism. Abeta(25-35) induced a transient stimulation of cAMP formation and a sustained activation of polyphosphoinositide turnover. The stimulatory effect of Abeta(25-35) on endozepine release was blocked by the adenylyl cyclase inhibitor somatostatin, the protein kinase A (PKA) inhibitor H89, the phospholipase C inhibitor U73122, the protein kinase C (PKC) inhibitor chelerythrine and the ATP binding cassette transporter blocker glyburide. Taken together, these data demonstrate for the first time that Abeta(25-35) stimulates endozepine release from rat astrocytes through a FPR receptor positively coupled to PKA and PKC.
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https://hal-normandie-univ.archives-ouvertes.fr/hal-01974262
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Submitted on : Tuesday, January 8, 2019 - 4:39:58 PM
Last modification on : Monday, May 25, 2020 - 11:24:02 PM

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Tursonjan Tokay, Raya Hachem, Olfa Masmoudi-Kouki, Pierrick Gandolfo, Laurence Desrues, et al.. Beta-amyloid peptide stimulates endozepine release in cultured rat astrocytes through activation of N -formyl peptide receptors. Glia, Wiley, 2008, 56 (13), pp.1380-1389. ⟨10.1002/glia.20705⟩. ⟨hal-01974262⟩

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