Amyloid beta-protein(25-35) increases cellular APP and inhibits the secretion of APPs in human extraneuronal cells.
Amyloid beta-protein (A beta) is the core component of the senile plaques occurring during Alzheimer's disease and in its aggregated form is cytotoxic for neuronal and extraneuronal cells. In this study, the influence of the spontaneously aggregating fragment A beta(25-35) on the expression and metabolism of beta-amyloid precursor protein (APP) was investigated in human extraneuronal cells. Cellular extracts and conditioned supernatants were analyzed by immunoblotting. A beta(25-35) strongly increased the cellular content of APP in cultured epithelial cells from thyroid glands and kidneys as well as in the promyelogranulocytotic cell line HL-60. At the same time A beta reduced the secretion of soluble APPs to less than one-third of its control value, but did not alter the secretion of fibronectin, which was used as a control protein. Despite these changes, APP transcription was not changed following A beta(25-35) treatment. These results demonstrate that A beta(25-35) strongly increases the APP content of extraneuronal cells by inhibiting its secretory processing. This may result in a deviation of APP metabolism towards an internal, potentially amyloidogenic pathway.
Schmitt
T L
TL
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck. Thomas.Schmitt@oeaw.ac.at
Steiner
E
E
Trieb
K
K
Grubeck-Loebenstein
B
B
D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000494:pharmacology* / Q000633:toxicity; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005260:Female; D018922:HL-60 Cells / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology* / Q000633:toxicity; D012333:RNA, Messenger / Q000032:analysis; D013961:Thyroid Gland / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D012333:RNA, Messenger; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35)