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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

Titleβ-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
Authors
KeywordsAlternative Splicing
Aminophosphonovalerate
Aplp2
Cortex
Glur-B
Glutamate
Neurodegeneration
Nmda Receptor
Rat
Issue Date1995
Citation
Journal Of Molecular Neuroscience, 1995, v. 6 n. 4, p. 257-276 How to Cite?
AbstractAlternative 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 Identifierhttp://hdl.handle.net/10722/176343
ISSN
2015 Impact Factor: 2.352
2015 SCImago Journal Rankings: 0.988
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWilloughby, DAen_US
dc.contributor.authorRozovsky, Ien_US
dc.contributor.authorLo, ACYen_US
dc.contributor.authorFinch, CEen_US
dc.date.accessioned2012-11-26T09:10:42Z-
dc.date.available2012-11-26T09:10:42Z-
dc.date.issued1995en_US
dc.identifier.citationJournal Of Molecular Neuroscience, 1995, v. 6 n. 4, p. 257-276en_US
dc.identifier.issn0895-8696en_US
dc.identifier.urihttp://hdl.handle.net/10722/176343-
dc.description.abstractAlternative 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.languageengen_US
dc.relation.ispartofJournal of Molecular Neuroscienceen_US
dc.subjectAlternative Splicingen_US
dc.subjectAminophosphonovalerateen_US
dc.subjectAplp2en_US
dc.subjectCortexen_US
dc.subjectGlur-Ben_US
dc.subjectGlutamateen_US
dc.subjectNeurodegenerationen_US
dc.subjectNmda Receptoren_US
dc.subjectRaten_US
dc.titleβ-Amyloid precursor protein (APP) and APP-RNA are rapidly affected by glutamate in cultured neurons - Selective increase of mRNAs encoding a kunitz protease inhibitor domainen_US
dc.typeArticleen_US
dc.identifier.emailLo, ACY: amylo@hkucc.hku.hken_US
dc.identifier.authorityLo, ACY=rp00425en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1007/BF02736785en_US
dc.identifier.pmid8860237-
dc.identifier.scopuseid_2-s2.0-0029421109en_US
dc.identifier.hkuros13593-
dc.identifier.volume6en_US
dc.identifier.issue4en_US
dc.identifier.spage257en_US
dc.identifier.epage276en_US
dc.identifier.isiWOS:A1995UJ94700004-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridWilloughby, DA=7102836752en_US
dc.identifier.scopusauthoridRozovsky, I=6701472605en_US
dc.identifier.scopusauthoridLo, ACY=7102780640en_US
dc.identifier.scopusauthoridFinch, CE=7202276220en_US

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