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

doi:10.1006/bbrc.2000.3143

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 journal › Article › peer-review

28 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 language	English
Pages (from-to)	445-454
Number of pages	10
Journal	Biochemical and Biophysical Research Communications
Volume	274
Issue number	2
DOIs	https://doi.org/10.1006/bbrc.2000.3143
Publication status	Published - 2000 Aug 2
Externally published	Yes

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

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1006/bbrc.2000.3143

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@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",

note = "Funding Information: We thank Yasuko Homma and Ugo Giambarella for indispensable technical assistance; John T. Potts Jr., Mark C. Fishman, and Shigeaki Kato for helping us with this study and critical reading; Yumi and Yoshiomi Tamai for encouragement; and Ko-ichi Tsuchiya, Kazumi Nishihara, and other department members for technical assistance. We are especially indebted to Takako Hiraki for indispensable assistance and Dovie Wylie for excellent technical assistance. This work was supported in part by grants from Naito Foundation, Brain Science Foundation, Takeda Medical Research Foundation, Takeda Science Foundation, the Ministry of Health and Welfare of Japan, the Ministry of Education, Science, and Culture of Japan and the Organization for Pharmaceutical Safety and Research.",

year = "2000",

month = aug,

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 = "Elsevier B.V.",

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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

N1 - Funding Information: We thank Yasuko Homma and Ugo Giambarella for indispensable technical assistance; John T. Potts Jr., Mark C. Fishman, and Shigeaki Kato for helping us with this study and critical reading; Yumi and Yoshiomi Tamai for encouragement; and Ko-ichi Tsuchiya, Kazumi Nishihara, and other department members for technical assistance. We are especially indebted to Takako Hiraki for indispensable assistance and Dovie Wylie for excellent technical assistance. This work was supported in part by grants from Naito Foundation, Brain Science Foundation, Takeda Medical Research Foundation, Takeda Science Foundation, the Ministry of Health and Welfare of Japan, the Ministry of Education, Science, and Culture of Japan and the Organization for Pharmaceutical Safety and Research.

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

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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

SN - 0006-291X

VL - 274

SP - 445

EP - 454

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -

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

Abstract

Keywords

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