beta-Amyloid1-40 increases expression of beta-amyloid precursor protein in neuronal hybrid cells.
Studies of cell injury and death in Alzheimer's disease have suggested a prominent role for beta-amyloid peptide (beta-AP), a 40-43-amino-acid peptide derived from a larger membrane glycoprotein, beta-amyloid precursor protein (beta-APP). Previous experiments have demonstrated that beta-AP induces cytotoxicity in a neuronal hybrid cell line (MES 23.5) in vitro. Here, we demonstrate that beta-APP mRNA content is increased 3.5-fold in 24 h after treatment with beta-AP1-40. Accompanying beta-AP1-40-induced cell injury, levels of cell-associated beta-APP and a C-terminal intermediate fragment are increased up to 15-fold, and levels of secreted forms of beta-APP and 12- and 4-kDa fragments are also increased. Application of beta-APP antisense oligodeoxynucleotide reduces both cytotoxicity and beta-APP expression. 6-Hydroxydopamine application or glucose deprivation causes extensive cell damage, but they do not increase beta-APP expression. These results suggest a selective positive feedback mechanism whereby beta-AP may induce cytotoxicity and increase levels of potentially neurotrophic as well as amyloidogenic fragments of beta-APP with the net consequence of further neuronal damage.
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Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Xie
W J
WJ
Nyormoi
O
O
Ho
B K
BK
Smith
R G
RG
Appel
S H
SH
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006822:Hybrid Cells / Q000378:metabolism*; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015335:Molecular Probes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)