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- Publisher Website: 10.1007/BF02736785
- Scopus: eid_2-s2.0-0029421109
- PMID: 8860237
- WOS: WOS:A1995UJ94700004
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Article: β-Amyloid precursor protein (APP) and APP-RNA are rapidly affected by glutamate in cultured neurons - Selective increase of mRNAs encoding a kunitz protease inhibitor domain
Title | β-Amyloid precursor protein (APP) and APP-RNA are rapidly affected by glutamate in cultured neurons - Selective increase of mRNAs encoding a kunitz protease inhibitor domain |
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Authors | |
Keywords | Alternative Splicing Aminophosphonovalerate Aplp2 Cortex Glur-B Glutamate Neurodegeneration Nmda Receptor Rat |
Issue Date | 1995 |
Citation | Journal Of Molecular Neuroscience, 1995, v. 6 n. 4, p. 257-276 How to Cite? |
Abstract | Alternative splicing of β-amyloid precursor protein (APP) RNA generates APP isoforms with or without a Kunitz protease inhibitor (KPI) domain. Previously, we showed that KPI (+) APP RNA, but not KPI (-) APP RNA, is upregulated in response to experimental lesions in which neurotoxicity is dependent on NMDA receptor activation and in Alzheimer's disease hippocampus. Recent studies by Mucke et al. (1995) showed that neuronal expression of human KPI (+) APP, but not KPI (-) APP, in transgenic mice is neuroprotective against experimental lesions. In this study we examined the direct effects of the excitotoxic amino acid Glu on alternatively spliced APP RNAs and the corresponding protein isoforms in cultured rat cortical neurons. Glu treatment rapidly induced (4.5 h) KPI (+) APP RNA but not KPI (-) APP RNA. Induction of KPI (+) RNA preceded Glu-induced neuronal cell death and was partially blocked by an NMDA-receptor antagonist. In contrast to the RNA, cellular levels of KPI (+) APP were not changed by 4.5 h of Glu treatment. Instead, the cellular full-length form of the protein KPI (-) APP was reduced by ∼50% after 2 h of Glu treatment and remained depleted after 24 h of treatment. Cellular levels of KPI (+) forms of amyloid precursor-like protein 2 (APLP2) were not changed by Glu treatment. Our data are consistent with the hypothesis that sustained NMDA-receptor activation can regulate alternative splicing of the APP pre-mRNA in neurons. © 1996 Humana Press Inc. |
Persistent Identifier | http://hdl.handle.net/10722/176343 |
ISSN | 2023 Impact Factor: 2.8 2023 SCImago Journal Rankings: 0.747 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Willoughby, DA | en_US |
dc.contributor.author | Rozovsky, I | en_US |
dc.contributor.author | Lo, ACY | en_US |
dc.contributor.author | Finch, CE | en_US |
dc.date.accessioned | 2012-11-26T09:10:42Z | - |
dc.date.available | 2012-11-26T09:10:42Z | - |
dc.date.issued | 1995 | en_US |
dc.identifier.citation | Journal Of Molecular Neuroscience, 1995, v. 6 n. 4, p. 257-276 | en_US |
dc.identifier.issn | 0895-8696 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/176343 | - |
dc.description.abstract | Alternative splicing of β-amyloid precursor protein (APP) RNA generates APP isoforms with or without a Kunitz protease inhibitor (KPI) domain. Previously, we showed that KPI (+) APP RNA, but not KPI (-) APP RNA, is upregulated in response to experimental lesions in which neurotoxicity is dependent on NMDA receptor activation and in Alzheimer's disease hippocampus. Recent studies by Mucke et al. (1995) showed that neuronal expression of human KPI (+) APP, but not KPI (-) APP, in transgenic mice is neuroprotective against experimental lesions. In this study we examined the direct effects of the excitotoxic amino acid Glu on alternatively spliced APP RNAs and the corresponding protein isoforms in cultured rat cortical neurons. Glu treatment rapidly induced (4.5 h) KPI (+) APP RNA but not KPI (-) APP RNA. Induction of KPI (+) RNA preceded Glu-induced neuronal cell death and was partially blocked by an NMDA-receptor antagonist. In contrast to the RNA, cellular levels of KPI (+) APP were not changed by 4.5 h of Glu treatment. Instead, the cellular full-length form of the protein KPI (-) APP was reduced by ∼50% after 2 h of Glu treatment and remained depleted after 24 h of treatment. Cellular levels of KPI (+) forms of amyloid precursor-like protein 2 (APLP2) were not changed by Glu treatment. Our data are consistent with the hypothesis that sustained NMDA-receptor activation can regulate alternative splicing of the APP pre-mRNA in neurons. © 1996 Humana Press Inc. | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Journal of Molecular Neuroscience | en_US |
dc.subject | Alternative Splicing | en_US |
dc.subject | Aminophosphonovalerate | en_US |
dc.subject | Aplp2 | en_US |
dc.subject | Cortex | en_US |
dc.subject | Glur-B | en_US |
dc.subject | Glutamate | en_US |
dc.subject | Neurodegeneration | en_US |
dc.subject | Nmda Receptor | en_US |
dc.subject | Rat | en_US |
dc.title | β-Amyloid precursor protein (APP) and APP-RNA are rapidly affected by glutamate in cultured neurons - Selective increase of mRNAs encoding a kunitz protease inhibitor domain | en_US |
dc.type | Article | en_US |
dc.identifier.email | Lo, ACY: amylo@hkucc.hku.hk | en_US |
dc.identifier.authority | Lo, ACY=rp00425 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1007/BF02736785 | en_US |
dc.identifier.pmid | 8860237 | - |
dc.identifier.scopus | eid_2-s2.0-0029421109 | en_US |
dc.identifier.hkuros | 13593 | - |
dc.identifier.volume | 6 | en_US |
dc.identifier.issue | 4 | en_US |
dc.identifier.spage | 257 | en_US |
dc.identifier.epage | 276 | en_US |
dc.identifier.isi | WOS:A1995UJ94700004 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Willoughby, DA=7102836752 | en_US |
dc.identifier.scopusauthorid | Rozovsky, I=6701472605 | en_US |
dc.identifier.scopusauthorid | Lo, ACY=7102780640 | en_US |
dc.identifier.scopusauthorid | Finch, CE=7202276220 | en_US |
dc.identifier.issnl | 0895-8696 | - |