Modulation of APP processing and secretion by okadaic acid in primary guinea pig neurons
Primary cultures of guinea pig neurons were used as a model system to study the influence of the protein phosphatase inhibitor okadaic acid (OA) on the secretion, processing and phosphorylation of the amyloid precursor protein (APP). This primary cell culture system mimics more closely than other ce...
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Veröffentlicht in: | Journal of Neural Transmission 2000-01, Vol.107 (4), p.451-461 |
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creator | HOLZER, M BRÜCKNER, M. K BECK, M BIGL, V ARENDT, T |
description | Primary cultures of guinea pig neurons were used as a model system to study the influence of the protein phosphatase inhibitor okadaic acid (OA) on the secretion, processing and phosphorylation of the amyloid precursor protein (APP). This primary cell culture system mimics more closely than other cell culture systems the human in vivo condition, as guinea pig APP is 98% homologous to human APP at the protein level, identical regarding the Abeta sequence and is processed in a similar manner as human APP. Both intracellular and secreted APP was upregulated by OA treatment (0.3 nM-10 nM) of 14 days old cultures in a concentration dependent manner while the amount of Abeta in the medium was decreased. OA treatment did not affect cell membrane integrity of primary neurons but induced DNA fragmentation. Phosphorylation of APP was unchanged by the low OA concentration used. These results show that OA treatment of guinea pig primary cultures might be used as a model to study the effects of modulation of signal transduction on secretion and processing of APP. |
doi_str_mv | 10.1007/s007020070087 |
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Phosphorylation of APP was unchanged by the low OA concentration used. These results show that OA treatment of guinea pig primary cultures might be used as a model to study the effects of modulation of signal transduction on secretion and processing of APP.</description><identifier>ISSN: 0300-9564</identifier><identifier>EISSN: 1435-1463</identifier><identifier>DOI: 10.1007/s007020070087</identifier><identifier>PMID: 11215756</identifier><identifier>CODEN: JNTMAH</identifier><language>eng</language><publisher>Wien: Springer</publisher><subject>Amyloid beta-Peptides - drug effects ; Amyloid beta-Peptides - secretion ; Amyloid beta-Protein Precursor - drug effects ; Amyloid beta-Protein Precursor - secretion ; Animals ; Biological and medical sciences ; Brain ; Cells, Cultured ; DNA Fragmentation - drug effects ; DNA Fragmentation - physiology ; Embryo, Mammalian ; Enzyme Inhibitors - pharmacology ; Fundamental and applied biological sciences. 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Neuroglia ; Mitogen-Activated Protein Kinases - drug effects ; Mitogen-Activated Protein Kinases - metabolism ; Neurons - drug effects ; Neurons - secretion ; Okadaic Acid - pharmacology ; Phosphorylation ; Vertebrates: nervous system and sense organs</subject><ispartof>Journal of Neural Transmission, 2000-01, Vol.107 (4), p.451-461</ispartof><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c349t-fb36c7821328c24e4564267b45dc6d25fb74aaffe70d8cb76ea1d0c0cc67fa9c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1331207$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11215756$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HOLZER, M</creatorcontrib><creatorcontrib>BRÜCKNER, M. K</creatorcontrib><creatorcontrib>BECK, M</creatorcontrib><creatorcontrib>BIGL, V</creatorcontrib><creatorcontrib>ARENDT, T</creatorcontrib><title>Modulation of APP processing and secretion by okadaic acid in primary guinea pig neurons</title><title>Journal of Neural Transmission</title><addtitle>J Neural Transm (Vienna)</addtitle><description>Primary cultures of guinea pig neurons were used as a model system to study the influence of the protein phosphatase inhibitor okadaic acid (OA) on the secretion, processing and phosphorylation of the amyloid precursor protein (APP). This primary cell culture system mimics more closely than other cell culture systems the human in vivo condition, as guinea pig APP is 98% homologous to human APP at the protein level, identical regarding the Abeta sequence and is processed in a similar manner as human APP. Both intracellular and secreted APP was upregulated by OA treatment (0.3 nM-10 nM) of 14 days old cultures in a concentration dependent manner while the amount of Abeta in the medium was decreased. OA treatment did not affect cell membrane integrity of primary neurons but induced DNA fragmentation. Phosphorylation of APP was unchanged by the low OA concentration used. These results show that OA treatment of guinea pig primary cultures might be used as a model to study the effects of modulation of signal transduction on secretion and processing of APP.</description><subject>Amyloid beta-Peptides - drug effects</subject><subject>Amyloid beta-Peptides - secretion</subject><subject>Amyloid beta-Protein Precursor - drug effects</subject><subject>Amyloid beta-Protein Precursor - secretion</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain</subject><subject>Cells, Cultured</subject><subject>DNA Fragmentation - drug effects</subject><subject>DNA Fragmentation - physiology</subject><subject>Embryo, Mammalian</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Guinea Pigs</subject><subject>Isolated neuron and nerve. Neuroglia</subject><subject>Mitogen-Activated Protein Kinases - drug effects</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Neurons - drug effects</subject><subject>Neurons - secretion</subject><subject>Okadaic Acid - pharmacology</subject><subject>Phosphorylation</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0300-9564</issn><issn>1435-1463</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkDtPwzAUhS0EoqUwsiIPiC1w_YidjhXiJRXRASS2yLm2K0PqlLgZ-u9JaaSK5dzhfjo6-gi5ZHDLAPRd6gP4LqDQR2TMpMgzJpU4JmMQANk0V3JEzlL6AgDGdHFKRoxxlutcjcnna2O72mxCE2nj6WyxoOu2QZdSiEtqoqXJYev-_tWWNt_GmoDUYLA0xJ4NK9Nu6bIL0Rm6DksaXdc2MZ2TE2_q5C6GOyEfjw_v98_Z_O3p5X42z1DI6SbzlVCoC84EL5BLJ_u1XOlK5haV5bmvtDTGe6fBFlhp5QyzgICotDdTFBNys-_tZ_90Lm3KVUjo6tpE13SpZAWAhL5_QrI9iG2TUut8OYwvGZQ7leU_lT1_NRR31crZAz2464HrATAJTe1bEzGkAycE46DFLyATe0U</recordid><startdate>20000101</startdate><enddate>20000101</enddate><creator>HOLZER, M</creator><creator>BRÜCKNER, M. 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K ; BECK, M ; BIGL, V ; ARENDT, T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c349t-fb36c7821328c24e4564267b45dc6d25fb74aaffe70d8cb76ea1d0c0cc67fa9c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Amyloid beta-Peptides - drug effects</topic><topic>Amyloid beta-Peptides - secretion</topic><topic>Amyloid beta-Protein Precursor - drug effects</topic><topic>Amyloid beta-Protein Precursor - secretion</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Brain</topic><topic>Cells, Cultured</topic><topic>DNA Fragmentation - drug effects</topic><topic>DNA Fragmentation - physiology</topic><topic>Embryo, Mammalian</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Guinea Pigs</topic><topic>Isolated neuron and nerve. Neuroglia</topic><topic>Mitogen-Activated Protein Kinases - drug effects</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Neurons - drug effects</topic><topic>Neurons - secretion</topic><topic>Okadaic Acid - pharmacology</topic><topic>Phosphorylation</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HOLZER, M</creatorcontrib><creatorcontrib>BRÜCKNER, M. K</creatorcontrib><creatorcontrib>BECK, M</creatorcontrib><creatorcontrib>BIGL, V</creatorcontrib><creatorcontrib>ARENDT, T</creatorcontrib><collection>Pascal-Francis</collection><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>Journal of Neural Transmission</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HOLZER, M</au><au>BRÜCKNER, M. 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This primary cell culture system mimics more closely than other cell culture systems the human in vivo condition, as guinea pig APP is 98% homologous to human APP at the protein level, identical regarding the Abeta sequence and is processed in a similar manner as human APP. Both intracellular and secreted APP was upregulated by OA treatment (0.3 nM-10 nM) of 14 days old cultures in a concentration dependent manner while the amount of Abeta in the medium was decreased. OA treatment did not affect cell membrane integrity of primary neurons but induced DNA fragmentation. Phosphorylation of APP was unchanged by the low OA concentration used. These results show that OA treatment of guinea pig primary cultures might be used as a model to study the effects of modulation of signal transduction on secretion and processing of APP.</abstract><cop>Wien</cop><cop>New York, NY</cop><pub>Springer</pub><pmid>11215756</pmid><doi>10.1007/s007020070087</doi><tpages>11</tpages></addata></record> |
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subjects | Amyloid beta-Peptides - drug effects Amyloid beta-Peptides - secretion Amyloid beta-Protein Precursor - drug effects Amyloid beta-Protein Precursor - secretion Animals Biological and medical sciences Brain Cells, Cultured DNA Fragmentation - drug effects DNA Fragmentation - physiology Embryo, Mammalian Enzyme Inhibitors - pharmacology Fundamental and applied biological sciences. Psychology Guinea Pigs Isolated neuron and nerve. Neuroglia Mitogen-Activated Protein Kinases - drug effects Mitogen-Activated Protein Kinases - metabolism Neurons - drug effects Neurons - secretion Okadaic Acid - pharmacology Phosphorylation Vertebrates: nervous system and sense organs |
title | Modulation of APP processing and secretion by okadaic acid in primary guinea pig neurons |
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