Beta-amyloid peptides stimulate endozepine biosynthesis in cultured rat astrocytes.
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.
Tokay
Tursonjan
T
INSERM U413, European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and Molecular Neuroendocrinology, UA CNRS, University of Rouen, Mont-Saint-Aignan, France.
Masmoudi
Olfa
O
Gandolfo
Pierrick
P
Leprince
Jérôme
J
Pelletier
Georges
G
Vaudry
Hubert
H
Tonon
Marie-Christine
MC
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003224:Congo Red / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D026261:Diazepam Binding Inhibitor / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D007375:Interleukin-1 / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D016229:Amyloid beta-Peptides; D026261:Diazepam Binding Inhibitor; D007375:Interleukin-1; D010446:Peptide Fragments; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D003224:Congo Red; D003513:Cycloheximide