BetaA amyloid peptide (25-35) induced APP expression in cultured astrocytes.
Alzheimer's disease is characterized by an accumulation of senile or neuritic plaques surrounded by activated microglia and reactive astrocytes, the cell processes of which are frequently in contact with the amyloid core. The major component of this amyloid deposit is the amyloid peptide (betaA or betaA4). These reactive glia are characterized by their hypertrophic phenotype and by the overexpression of some molecules such as glial fibrillary acidic protein and the amyloid precursor protein (APP). The purpose of this work was to analyze whether APP expression was modified in astrocytes by the presence of betaA peptide. To study this, the effects of beta-Amyloid (25-35) on cultured astrocytes were analyzed and compared with those of a scrambled peptide. Our data indicated that the addition of previously polymerized betaA peptide induced a marked morphological change from a flat, polygonal shape to a stellated, process-bearing morphology. This change occurred with an increase in APP immunoreactivity that is dependent of phosphatases PP2A or PP1, since it was inhibited by okadaic acid. Upregulation of APP protein expression appears to be mainly nontranscriptional, because the increase of APP protein precedes the increase of mRNA expression. The analysis of several APP isoforms indicated that this increment is not due to changes of a single isoform. Our data may correlate with some in vivo reports of astrocytic APP induction after brain insult, suggesting an important role for betaA peptide in the initial process and/or maintenance of the reactive phenotype in vivo.
Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Cantoblanco-Madrid, Spain.
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Moreno-Flores
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Salinero
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Wandosell
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D007536:Isomerism; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D012333:RNA, Messenger; C074636:amyloid beta-protein (25-35)