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

Tursonjan Tokay, Raya Hachem, Olfa Masmoudi-Kouki, Pierrick Gandolfo, Laurence Desrues, Jerome Leprince, Helene Castel, Mickael Diallo, Mohamed Amri, Hubert Vaudry, Marie Christine Tonon

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19 Citations (Scopus)

Abstract

Astroglial cells synthesize and release endozepines, a family of neuropeptides derived from diazepam-binding inhibitor (DBI). The authors have recently shown that β-amyloid peptide (Aβ) stimulates DBI gene expression and endozepine release. The purpose of this study was to determine the mechanism of action of Aβ in cultured rat astrocytes. Aβ25-35 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 EC50 value of ≈2 μM. The stimulatory effects of Aβ25-35 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, Aβ 25-35 increased DBI mRNA expression through a FPR-independent mechanism. Aβ25-35 induced a transient stimulation of cAMP formation and a sustained activation of polyphosphoinositide turnover. The stimulatory effect of Aβ 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 Aβ25-35 stimulates endozepine release from rat astrocytes through a FPR receptor positively coupled to PKA and PKC.

Original languageEnglish
Pages (from-to)1380-1389
Number of pages10
JournalGLIA
Volume56
Issue number13
DOIs
Publication statusPublished - Oct 1 2008

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Keywords

  • Astroglial cells
  • Endozepines
  • N-formyl peptide receptors
  • β-amyloid peptide

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Tokay, T., Hachem, R., Masmoudi-Kouki, O., Gandolfo, P., Desrues, L., Leprince, J., Castel, H., Diallo, M., Amri, M., Vaudry, H., & Tonon, M. C. (2008). Beta-amyloid peptide stimulates endozepine release in cultured rat astrocytes through activation of N-formyl peptide receptors. GLIA, 56(13), 1380-1389. https://doi.org/10.1002/glia.20705