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

Tursonjan Tokay (1, 2) , Raya Hachem (1, 2) , Olfa Masmoudi-Kouki (2, 1, 3) , Pierrick Gandolfo (1, 2) , Laurence Desrues (1, 2) , Jérôme Leprince (1, 2) , Hélène Castel (1, 2) , Mickael Diallo (1, 2) , Mohamed Amri (3) , Hubert Vaudry (1, 2) , Marie-Christine Tonon (1, 2)

1 Neuroendocrinologie cellulaire et moléculaire
2 IFRMP 23 - Institut Fédératif de Recherches Multidisciplinaires sur les Peptides
3 FST - Faculté des Sciences Mathématiques, Physiques et Naturelles de Tunis

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.

Domaines: Chimie thérapeutique; Interactions cellulaires [q-bio.CB]; Neurobiologie; Pharmacologie

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, 2008, 56 (13), pp.1380-1389. ⟨10.1002/glia.20705⟩. ⟨hal-01974262⟩