TY - JOUR
T1 - β-Amyloid-induced neurotoxicity of a hybrid septal cell line associated with increased tau phosphorylation and expression of β-amyloid precursor protein
AU - Le, Weidong
AU - Xie, Wen Jie
AU - Kong, Rong
AU - Appel, Stanley H.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1997/9
Y1 - 1997/9
N2 - Recent evidence suggests that β-amyloid peptide (β-AP) may induce tau protein phosphorylation, resulting in loss of microtubule binding capacity and formation of paired helical filaments. The mechanism by which β-AP increases tau phosphorylation, however, is unclear. Using a hybrid septal cell line, SN56, we demonstrate that aggregated β-AP1-40 treatment caused cell injury. Accompanying the cell injury, the levels of phosphorylated tau as well as total tau were enhanced as detected immunochemically by AT8, PHF-1, Tau-1, and Tau-5 antibodies. Alkaline phosphatase treatment abolished AT8 and PHF-1 immunoreactivity, confirming that the tau phosphorylation sites were at least at Ser(199/202) and Ser(396). In association with the increase in tau phosphorylation, the immunoreactivity of cell-associated and secreted β-amyloid precursor protein (β-APP) was markedly elevated. Application of antisense oligonucleotide to β-APP reduced expression of β-APP and immunoreactivity of phosphorylated tau. Control peptide β-AP1-28 did not produce significant effects on tau phosphorylation, although it slightly increased cell-associated β-APP. These results suggest that βAP1-40-induced tau phosphorylation may be associated with increased β-APP expression in degenerated neurons.
AB - Recent evidence suggests that β-amyloid peptide (β-AP) may induce tau protein phosphorylation, resulting in loss of microtubule binding capacity and formation of paired helical filaments. The mechanism by which β-AP increases tau phosphorylation, however, is unclear. Using a hybrid septal cell line, SN56, we demonstrate that aggregated β-AP1-40 treatment caused cell injury. Accompanying the cell injury, the levels of phosphorylated tau as well as total tau were enhanced as detected immunochemically by AT8, PHF-1, Tau-1, and Tau-5 antibodies. Alkaline phosphatase treatment abolished AT8 and PHF-1 immunoreactivity, confirming that the tau phosphorylation sites were at least at Ser(199/202) and Ser(396). In association with the increase in tau phosphorylation, the immunoreactivity of cell-associated and secreted β-amyloid precursor protein (β-APP) was markedly elevated. Application of antisense oligonucleotide to β-APP reduced expression of β-APP and immunoreactivity of phosphorylated tau. Control peptide β-AP1-28 did not produce significant effects on tau phosphorylation, although it slightly increased cell-associated β-APP. These results suggest that βAP1-40-induced tau phosphorylation may be associated with increased β-APP expression in degenerated neurons.
KW - β-Amyloid
KW - β-Amyloid precursor protein
KW - Alzheimer's disease
KW - Tau phosphorylation
UR - http://www.scopus.com/inward/record.url?scp=1842404212&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1842404212&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.1997.69030978.x
DO - 10.1046/j.1471-4159.1997.69030978.x
M3 - Article
C2 - 9282919
AN - SCOPUS:1842404212
SN - 0022-3042
VL - 69
SP - 978
EP - 985
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 3
ER -