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β‐Amyloid 1–40 Increases Expression of β‐Amyloid Precursor Protein in Neuronal Hybrid Cells
Author(s) -
Le Weidong,
Xie Wen Jie,
Nyormoi Okot,
Ho Bao Kuang,
Smith R. Glenn,
Appel Stanley H.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65052373.x
Subject(s) - amyloid precursor protein , cytotoxicity , p3 peptide , cell culture , peptide , programmed cell death , amyloid (mycology) , microbiology and biotechnology , chemistry , cell , biochemistry , in vitro , biology , alzheimer's disease , apoptosis , medicine , genetics , disease , inorganic chemistry
Studies of cell injury and death in Alzheimer's disease have suggested a prominent role for β‐amyloid peptide (β‐AP), a 40–43‐amino‐acid peptide derived from a larger membrane glycoprotein, β‐amyloid precursor protein (β‐APP). Previous experiments have demonstrated that β‐AP induces cytotoxicity in a neuronal hybrid cell line (MES 23.5) in vitro. Here, we demonstrate that β‐APP mRNA content is increased 3.5‐fold in 24 h after treatment with β‐AP 1–40 . Accompanying β‐AP 1–40 ‐induced cell injury, levels of cell‐associated β‐APP and a C‐terminal intermediate fragment are increased up to 15‐fold, and levels of secreted forms of β‐APP and 12‐ and 4‐kDa fragments are also increased. Application of β‐APP antisense oligodeoxynucleotide reduces both cytotoxicity and β‐APP expression. 6‐Hydroxydopamine application or glucose deprivation causes extensive cell damage, but they do not increase β‐APP expression. These results suggest a selective positive feedback mechanism whereby β‐AP may induce cytotoxicity and increase levels of potentially neurotrophic as well as amyloidogenic fragments of β‐APP with the net consequence of further neuronal damage.