V642I APP-inducible neuronal cells: A model system for investigating Alzheimer's disorders

Takako Niikura, Norie Murayama, Yu Ichi Hashimoto, Yuko Ito, Yohichi Yamagishi, Masaaki Matsuoka, Yuji Takeuchi, Sadakazu Aiso, Ikuo Nishimoto

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

APP is a precursor of β amyloid deposited in Alzheimer's disease (AD). Although genetic studies established that mutations in APP cause familial AD (FAD), the mechanism for neuronal death by FAD mutants has not been well understood. We established neuronal cells (F11/EcR/V642I cells) in which V642I APP was inducibly expressed by ecdysone. Treatment with ecdysone, but not vehicle, killed most cells within a few days, with rounding, shrinkage, and detachment as well as nuclear fragmentation. Death was suppressed by Ac-DEVD-CHO and pertussis toxin. Electron microscopic analysis revealed that apoptosis occurred in ecdysone-treated cells. V642I-APP-induced death was suppressed by the anti-AD factors estrogen and apoE2. These data demonstrate not only that expression of this FAD gene causes neuronal apoptosis, but that F11/EcR/V642I cells, the first neuronal cells with inducible FAD gene expression, provide a useful model system in investigating AD disorders. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)445-454
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume274
Issue number2
DOIs
Publication statusPublished - 2000 Aug 2

Fingerprint

Ecdysone
Alzheimer Disease
Apolipoprotein E2
Apoptosis
Pertussis Toxin
Amyloid
Gene expression
Estrogens
Genes
Cells
Electrons
Gene Expression
Mutation

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • Anti-risk factor
  • Apoptosis
  • Caspase inhibitor
  • Disease mutation
  • Ecdysone-inducible system
  • Electron microscopy
  • Neuronal death
  • Pertussis toxin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Niikura, T., Murayama, N., Hashimoto, Y. I., Ito, Y., Yamagishi, Y., Matsuoka, M., ... Nishimoto, I. (2000). V642I APP-inducible neuronal cells: A model system for investigating Alzheimer's disorders. Biochemical and Biophysical Research Communications, 274(2), 445-454. https://doi.org/10.1006/bbrc.2000.3143

V642I APP-inducible neuronal cells : A model system for investigating Alzheimer's disorders. / Niikura, Takako; Murayama, Norie; Hashimoto, Yu Ichi; Ito, Yuko; Yamagishi, Yohichi; Matsuoka, Masaaki; Takeuchi, Yuji; Aiso, Sadakazu; Nishimoto, Ikuo.

In: Biochemical and Biophysical Research Communications, Vol. 274, No. 2, 02.08.2000, p. 445-454.

Research output: Contribution to journalArticle

Niikura, T, Murayama, N, Hashimoto, YI, Ito, Y, Yamagishi, Y, Matsuoka, M, Takeuchi, Y, Aiso, S & Nishimoto, I 2000, 'V642I APP-inducible neuronal cells: A model system for investigating Alzheimer's disorders', Biochemical and Biophysical Research Communications, vol. 274, no. 2, pp. 445-454. https://doi.org/10.1006/bbrc.2000.3143
Niikura, Takako ; Murayama, Norie ; Hashimoto, Yu Ichi ; Ito, Yuko ; Yamagishi, Yohichi ; Matsuoka, Masaaki ; Takeuchi, Yuji ; Aiso, Sadakazu ; Nishimoto, Ikuo. / V642I APP-inducible neuronal cells : A model system for investigating Alzheimer's disorders. In: Biochemical and Biophysical Research Communications. 2000 ; Vol. 274, No. 2. pp. 445-454.
@article{bb59135fa1964973aeb1cf18ab5acd54,
title = "V642I APP-inducible neuronal cells: A model system for investigating Alzheimer's disorders",
abstract = "APP is a precursor of β amyloid deposited in Alzheimer's disease (AD). Although genetic studies established that mutations in APP cause familial AD (FAD), the mechanism for neuronal death by FAD mutants has not been well understood. We established neuronal cells (F11/EcR/V642I cells) in which V642I APP was inducibly expressed by ecdysone. Treatment with ecdysone, but not vehicle, killed most cells within a few days, with rounding, shrinkage, and detachment as well as nuclear fragmentation. Death was suppressed by Ac-DEVD-CHO and pertussis toxin. Electron microscopic analysis revealed that apoptosis occurred in ecdysone-treated cells. V642I-APP-induced death was suppressed by the anti-AD factors estrogen and apoE2. These data demonstrate not only that expression of this FAD gene causes neuronal apoptosis, but that F11/EcR/V642I cells, the first neuronal cells with inducible FAD gene expression, provide a useful model system in investigating AD disorders. (C) 2000 Academic Press.",
keywords = "Alzheimer's disease, Amyloid precursor protein, Anti-risk factor, Apoptosis, Caspase inhibitor, Disease mutation, Ecdysone-inducible system, Electron microscopy, Neuronal death, Pertussis toxin",
author = "Takako Niikura and Norie Murayama and Hashimoto, {Yu Ichi} and Yuko Ito and Yohichi Yamagishi and Masaaki Matsuoka and Yuji Takeuchi and Sadakazu Aiso and Ikuo Nishimoto",
year = "2000",
month = "8",
day = "2",
doi = "10.1006/bbrc.2000.3143",
language = "English",
volume = "274",
pages = "445--454",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - V642I APP-inducible neuronal cells

T2 - A model system for investigating Alzheimer's disorders

AU - Niikura, Takako

AU - Murayama, Norie

AU - Hashimoto, Yu Ichi

AU - Ito, Yuko

AU - Yamagishi, Yohichi

AU - Matsuoka, Masaaki

AU - Takeuchi, Yuji

AU - Aiso, Sadakazu

AU - Nishimoto, Ikuo

PY - 2000/8/2

Y1 - 2000/8/2

N2 - APP is a precursor of β amyloid deposited in Alzheimer's disease (AD). Although genetic studies established that mutations in APP cause familial AD (FAD), the mechanism for neuronal death by FAD mutants has not been well understood. We established neuronal cells (F11/EcR/V642I cells) in which V642I APP was inducibly expressed by ecdysone. Treatment with ecdysone, but not vehicle, killed most cells within a few days, with rounding, shrinkage, and detachment as well as nuclear fragmentation. Death was suppressed by Ac-DEVD-CHO and pertussis toxin. Electron microscopic analysis revealed that apoptosis occurred in ecdysone-treated cells. V642I-APP-induced death was suppressed by the anti-AD factors estrogen and apoE2. These data demonstrate not only that expression of this FAD gene causes neuronal apoptosis, but that F11/EcR/V642I cells, the first neuronal cells with inducible FAD gene expression, provide a useful model system in investigating AD disorders. (C) 2000 Academic Press.

AB - APP is a precursor of β amyloid deposited in Alzheimer's disease (AD). Although genetic studies established that mutations in APP cause familial AD (FAD), the mechanism for neuronal death by FAD mutants has not been well understood. We established neuronal cells (F11/EcR/V642I cells) in which V642I APP was inducibly expressed by ecdysone. Treatment with ecdysone, but not vehicle, killed most cells within a few days, with rounding, shrinkage, and detachment as well as nuclear fragmentation. Death was suppressed by Ac-DEVD-CHO and pertussis toxin. Electron microscopic analysis revealed that apoptosis occurred in ecdysone-treated cells. V642I-APP-induced death was suppressed by the anti-AD factors estrogen and apoE2. These data demonstrate not only that expression of this FAD gene causes neuronal apoptosis, but that F11/EcR/V642I cells, the first neuronal cells with inducible FAD gene expression, provide a useful model system in investigating AD disorders. (C) 2000 Academic Press.

KW - Alzheimer's disease

KW - Amyloid precursor protein

KW - Anti-risk factor

KW - Apoptosis

KW - Caspase inhibitor

KW - Disease mutation

KW - Ecdysone-inducible system

KW - Electron microscopy

KW - Neuronal death

KW - Pertussis toxin

UR - http://www.scopus.com/inward/record.url?scp=0034596257&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034596257&partnerID=8YFLogxK

U2 - 10.1006/bbrc.2000.3143

DO - 10.1006/bbrc.2000.3143

M3 - Article

C2 - 10913358

AN - SCOPUS:0034596257

VL - 274

SP - 445

EP - 454

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -