Beta‐amyloid peptides stimulate endozepine biosynthesis in cultured rat astrocytes

Abstract

Accumulation of b-amyloid peptide (Ab), which is a landmark of Alzheimer's disease, may alter astrocyte functions before any visible symptoms of the disease occur. Here, we examined the effects of Ab on biosynthesis and release of diazepam-binding inhibitor (DBI) There is now clear evidence that, in the brain, the DBI gene is primarily expressed in glial cells (Tong et al. 1991;Lihrmann et al. 1994;Alho et al. 1995;Bürgi et al. 1999) and the presence of DBI-related peptides has been visualized by immunohistochemistry in astroglial cells in various regions of the central nervous system, notably in the cerebral cortex (Tonon et al. 1990), in ependymocytes lining the third ventricle (Tonon et al. 1990;Malagon et al. 1993;Do-Rego et al. 2001), in tanycytes in the median eminence (Tonon et al. 1990;Malagon et al. 1993) and in Bergmann cells in the cerebellum (Tonon et al. 1990;Vidnyanszky et al. 1994;Yanase et al. 2002). In vitro studies have shown that cultured rat astrocytes contain and release substantial amounts of endozepines (Lamacz et al. 1996;Patte et al. 1999;Masmoudi et al. 2003Masmoudi et al. , 2005 and that endozepines act as autocrine factors modulating intracellular calcium concentration in astroglial cells (Gandolfo et al. 1997(Gandolfo et al. , 2001Leprince et al. 1998Leprince et al. , 2001).Alzheimer's disease is a neurogenerative disorder characterized by the presence of senile plaques in the brain

The Octadecaneuropeptide ODN Protects Astrocytes against Hydrogen Peroxide-Induced Apoptosis via a PKA/MAPK-Dependent Mechanism

“…The concentration of endozepines is elevated in the cerebral spinal fluid of patients with Alzheimer's and Parkinson's diseases [60] and it has been reported that β-amyloid peptide, the major constituent of senile plaques, induces endozepine biosynthesis and release from cultured astrocytes [61], [62]. Moreover, ODN exerts a proliferative effect on some cell types, notably astroglial cells [35], [62], suggesting that over-production of ODN may contribute to astrocyte proliferation observed in various neurodegenerative diseases. Besides, the present data indicate that ODN prevents H 2 O 2 -induced astrocyte apoptosis which is in agreement with a study showing that DBI silencing with siRNA leads to growth arrest and apoptosis in various mammalian cell lines [63].…”

Protective effect of the octadecaneuropeptide on hydrogen peroxide‐induced oxidative stress and cell death in cultured rat astrocytes

“…2008). We have recently found that the endozepine ODN induces a concentration‐dependent increase of the number of astrocytes in primary culture (Tokay et al. 2005), suggesting that ODN may be involved in the control of survival or/and cell proliferation.…”

“…1990). We have recently shown that β‐amyloid peptide induces activation of endozepine biosynthesis and release, suggesting that over production of ODN may contribute to astrocyte proliferation associated with AD (Tokay et al. 2005, 2008).…”

Acyl coenzyme A‐binding protein (ACBP) is phosphorylated and secreted by retinal Müller astrocytes following protein kinase C activation

“…1993). Stimulation of cultured astrocytes by either β‐amyloid peptides or pituitary adenylate cyclase activating polypeptide evokes expression and secretion of ACBP (Tokay et al. 2005).…”

“…1999). Treatment of astrocytes with β‐amyloid peptides not only induces secretion of ACBP (Tokay et al. 2005) it also increases intracellular calcium (Jalonen et al.…”