16033417 |
Tokay T, Masmoudi O, Gandolfo P, Leprince J, Pelletier G, Vaudry H, Tonon MC: Beta-amyloid peptides stimulate endozepine biosynthesis in cultured rat astrocytes. J Neurochem. 2005 Aug;94(3):607-16. Accumulation of beta-amyloid peptide (Abeta), 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 Abeta on biosynthesis and release of diazepam-binding inhibitor (DBI), a polypeptide primarily expressed by astroglial cells in the CNS. Quantitative RT-PCR and specific radioimmunoassay demonstrated that aggregated Abeta (25-35), at concentrations up to 10 (-4) m, induced a dose-dependent increase in DBI mRNA expression and DBI-related peptide release from cultured rat astrocytes. These effects were totally suppressed when aggregation of Abeta (25-35) was prevented by Congo red. Measurement of the number of living cells revealed that Abeta (25-35) induced a trophic rather than a toxic effect on astrocytes. Administration of cycloheximide blocked Abeta (25-35)-induced increase of DBI gene expression and endozepine accumulation in astrocytes, indicating that protein synthesis is required for DBI gene expression. Altogether, the present data suggest that Abeta-induced activation of endozepine biosynthesis and release may contribute to astrocyte proliferation associated with Alzheimer's disease. |
84(1,1,1,4) |