V642I APP-Inducible Neuronal Cells: A Model System for Investigating Alzheimer's Disorders
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 V...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2000-08, Vol.274 (2), p.445-454 |
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| creator | Niikura, Takako Murayama, Norie Hashimoto, Yu-ichi Ito, Yuko Yamagishi, Yohichi Matsuoka, Masaaki Takeuchi, Yuji Aiso, Sadakazu Nishimoto, Ikuo |
| description | 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. |
| doi_str_mv | 10.1006/bbrc.2000.3143 |
| format | Article |
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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.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1006/bbrc.2000.3143</identifier><identifier>PMID: 10913358</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alzheimer Disease - genetics ; Alzheimer Disease - metabolism ; Alzheimer's disease ; Amino Acid Chloromethyl Ketones - pharmacology ; Amino Acid Substitution ; Amyloid beta-Protein Precursor - genetics ; Amyloid beta-Protein Precursor - metabolism ; Amyloid beta-Protein Precursor - pharmacology ; amyloid precursor protein ; Animals ; anti-risk factor ; Apolipoprotein E2 ; Apolipoprotein E4 ; Apolipoproteins E - pharmacology ; apoptosis ; Apoptosis - drug effects ; Apoptosis - genetics ; caspase inhibitor ; Cell Line ; Cell Survival - drug effects ; Cell Survival - genetics ; Cysteine Proteinase Inhibitors - pharmacology ; disease mutation ; Dose-Response Relationship, Drug ; Ecdysone - antagonists & inhibitors ; Ecdysone - pharmacology ; ecdysone-inducible system ; electron microscopy ; Estradiol - pharmacology ; Gene Expression - drug effects ; Hybrid Cells ; Mice ; Models, Biological ; neuronal death ; Neurons - drug effects ; Neurons - metabolism ; Neurons - ultrastructure ; Oligopeptides - pharmacology ; Pertussis Toxin ; Rats ; Receptors, Steroid - biosynthesis ; Recombinant Proteins - biosynthesis ; Transfection ; Virulence Factors, Bordetella - pharmacology</subject><ispartof>Biochemical and biophysical research communications, 2000-08, Vol.274 (2), p.445-454</ispartof><rights>2000 Academic Press</rights><rights>Copyright 2000 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c255t-bcd0c3a962630a68203cbd1e09704cf777bf171a5119f5f520ff9486d52a62fa3</citedby><cites>FETCH-LOGICAL-c255t-bcd0c3a962630a68203cbd1e09704cf777bf171a5119f5f520ff9486d52a62fa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/bbrc.2000.3143$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10913358$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Niikura, Takako</creatorcontrib><creatorcontrib>Murayama, Norie</creatorcontrib><creatorcontrib>Hashimoto, Yu-ichi</creatorcontrib><creatorcontrib>Ito, Yuko</creatorcontrib><creatorcontrib>Yamagishi, Yohichi</creatorcontrib><creatorcontrib>Matsuoka, Masaaki</creatorcontrib><creatorcontrib>Takeuchi, Yuji</creatorcontrib><creatorcontrib>Aiso, Sadakazu</creatorcontrib><creatorcontrib>Nishimoto, Ikuo</creatorcontrib><title>V642I APP-Inducible Neuronal Cells: A Model System for Investigating Alzheimer's Disorders</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>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.</description><subject>Alzheimer Disease - genetics</subject><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer's disease</subject><subject>Amino Acid Chloromethyl Ketones - pharmacology</subject><subject>Amino Acid Substitution</subject><subject>Amyloid beta-Protein Precursor - genetics</subject><subject>Amyloid beta-Protein Precursor - metabolism</subject><subject>Amyloid beta-Protein Precursor - pharmacology</subject><subject>amyloid precursor protein</subject><subject>Animals</subject><subject>anti-risk factor</subject><subject>Apolipoprotein E2</subject><subject>Apolipoprotein E4</subject><subject>Apolipoproteins E - pharmacology</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - genetics</subject><subject>caspase inhibitor</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - genetics</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>disease mutation</subject><subject>Dose-Response Relationship, Drug</subject><subject>Ecdysone - antagonists & inhibitors</subject><subject>Ecdysone - pharmacology</subject><subject>ecdysone-inducible system</subject><subject>electron microscopy</subject><subject>Estradiol - pharmacology</subject><subject>Gene Expression - drug effects</subject><subject>Hybrid Cells</subject><subject>Mice</subject><subject>Models, Biological</subject><subject>neuronal death</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Neurons - ultrastructure</subject><subject>Oligopeptides - pharmacology</subject><subject>Pertussis Toxin</subject><subject>Rats</subject><subject>Receptors, Steroid - biosynthesis</subject><subject>Recombinant Proteins - biosynthesis</subject><subject>Transfection</subject><subject>Virulence Factors, Bordetella - pharmacology</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kElPwzAQRi0EgrJcOSKf4JQydhIn4VaVrRJLJRYhLpZjj8EoS7ETpPLrSVUOXDiNNHrz6ZtHyCGDMQMQp2Xp9ZgDwDhmSbxBRgwKiDiDZJOMhrWIeMFedshuCB8AjCWi2CY7A8TiOM1H5PVZJHxGJ_N5NGtMr11ZIb3D3reNqugUqyqc0Qm9bQ1W9GEZOqypbT2dNV8YOvemOte80Un1_Y6uRn8S6LkLrTfowz7ZsqoKePA798jT5cXj9Dq6ub-aTSc3keZp2kWlNqBjVQguYlAi5xDr0jCEIoNE2yzLSssyplLGCpvalIO1RZILk3IluFXxHjle5y58-9kPrWTtgh6aqwbbPkiWp3mWi2wAx2tQ-zYEj1YuvKuVX0oGcmVTrmzKlU25sjkcHP0m92WN5g--1jcA-RrA4b8vh14G7bDRaJxH3UnTuv-yfwC5-4IB</recordid><startdate>20000802</startdate><enddate>20000802</enddate><creator>Niikura, Takako</creator><creator>Murayama, Norie</creator><creator>Hashimoto, Yu-ichi</creator><creator>Ito, Yuko</creator><creator>Yamagishi, Yohichi</creator><creator>Matsuoka, Masaaki</creator><creator>Takeuchi, Yuji</creator><creator>Aiso, Sadakazu</creator><creator>Nishimoto, Ikuo</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope></search><sort><creationdate>20000802</creationdate><title>V642I APP-Inducible Neuronal Cells: A Model System for Investigating Alzheimer's Disorders</title><author>Niikura, Takako ; Murayama, Norie ; Hashimoto, Yu-ichi ; Ito, Yuko ; Yamagishi, Yohichi ; Matsuoka, Masaaki ; Takeuchi, Yuji ; Aiso, Sadakazu ; Nishimoto, Ikuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c255t-bcd0c3a962630a68203cbd1e09704cf777bf171a5119f5f520ff9486d52a62fa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Alzheimer Disease - genetics</topic><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer's disease</topic><topic>Amino Acid Chloromethyl Ketones - pharmacology</topic><topic>Amino Acid Substitution</topic><topic>Amyloid beta-Protein Precursor - genetics</topic><topic>Amyloid beta-Protein Precursor - metabolism</topic><topic>Amyloid beta-Protein Precursor - pharmacology</topic><topic>amyloid precursor protein</topic><topic>Animals</topic><topic>anti-risk factor</topic><topic>Apolipoprotein E2</topic><topic>Apolipoprotein E4</topic><topic>Apolipoproteins E - pharmacology</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - genetics</topic><topic>caspase inhibitor</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - genetics</topic><topic>Cysteine Proteinase Inhibitors - pharmacology</topic><topic>disease mutation</topic><topic>Dose-Response Relationship, Drug</topic><topic>Ecdysone - antagonists & inhibitors</topic><topic>Ecdysone - pharmacology</topic><topic>ecdysone-inducible system</topic><topic>electron microscopy</topic><topic>Estradiol - pharmacology</topic><topic>Gene Expression - drug effects</topic><topic>Hybrid Cells</topic><topic>Mice</topic><topic>Models, Biological</topic><topic>neuronal death</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Neurons - ultrastructure</topic><topic>Oligopeptides - pharmacology</topic><topic>Pertussis Toxin</topic><topic>Rats</topic><topic>Receptors, Steroid - biosynthesis</topic><topic>Recombinant Proteins - biosynthesis</topic><topic>Transfection</topic><topic>Virulence Factors, Bordetella - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Niikura, Takako</creatorcontrib><creatorcontrib>Murayama, Norie</creatorcontrib><creatorcontrib>Hashimoto, Yu-ichi</creatorcontrib><creatorcontrib>Ito, Yuko</creatorcontrib><creatorcontrib>Yamagishi, Yohichi</creatorcontrib><creatorcontrib>Matsuoka, Masaaki</creatorcontrib><creatorcontrib>Takeuchi, Yuji</creatorcontrib><creatorcontrib>Aiso, Sadakazu</creatorcontrib><creatorcontrib>Nishimoto, Ikuo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Niikura, Takako</au><au>Murayama, Norie</au><au>Hashimoto, Yu-ichi</au><au>Ito, Yuko</au><au>Yamagishi, Yohichi</au><au>Matsuoka, Masaaki</au><au>Takeuchi, Yuji</au><au>Aiso, Sadakazu</au><au>Nishimoto, Ikuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>V642I APP-Inducible Neuronal Cells: A Model System for Investigating Alzheimer's Disorders</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2000-08-02</date><risdate>2000</risdate><volume>274</volume><issue>2</issue><spage>445</spage><epage>454</epage><pages>445-454</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>10913358</pmid><doi>10.1006/bbrc.2000.3143</doi><tpages>10</tpages></addata></record> |
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| subjects | Alzheimer Disease - genetics Alzheimer Disease - metabolism Alzheimer's disease Amino Acid Chloromethyl Ketones - pharmacology Amino Acid Substitution Amyloid beta-Protein Precursor - genetics Amyloid beta-Protein Precursor - metabolism Amyloid beta-Protein Precursor - pharmacology amyloid precursor protein Animals anti-risk factor Apolipoprotein E2 Apolipoprotein E4 Apolipoproteins E - pharmacology apoptosis Apoptosis - drug effects Apoptosis - genetics caspase inhibitor Cell Line Cell Survival - drug effects Cell Survival - genetics Cysteine Proteinase Inhibitors - pharmacology disease mutation Dose-Response Relationship, Drug Ecdysone - antagonists & inhibitors Ecdysone - pharmacology ecdysone-inducible system electron microscopy Estradiol - pharmacology Gene Expression - drug effects Hybrid Cells Mice Models, Biological neuronal death Neurons - drug effects Neurons - metabolism Neurons - ultrastructure Oligopeptides - pharmacology Pertussis Toxin Rats Receptors, Steroid - biosynthesis Recombinant Proteins - biosynthesis Transfection Virulence Factors, Bordetella - pharmacology |
| title | V642I APP-Inducible Neuronal Cells: A Model System for Investigating Alzheimer's Disorders |
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