Activation of protein kinase C inhibits cellular production of the amyloid beta-protein
The 39-43-amino acid amyloid beta-protein (A beta), which is progressively deposited in cerebral plaques and blood vessels in Alzheimer's disease (AD), is released by cultured human cells during normal metabolism. Here we show that agents which activate protein kinase C or otherwise enhance pro...
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| Veröffentlicht in: | The Journal of biological chemistry 1993-11, Vol.268 (31), p.22959-22962 |
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| container_issue | 31 |
| container_start_page | 22959 |
| container_title | The Journal of biological chemistry |
| container_volume | 268 |
| creator | HUNG, A. Y HAASS, C NITSCH, R. M WEI QIAO QIU CITRON, M WURTMAN, R. J GROWDON, J. H SELKOE, D. J |
| description | The 39-43-amino acid amyloid beta-protein (A beta), which is progressively deposited in cerebral plaques and blood vessels
in Alzheimer's disease (AD), is released by cultured human cells during normal metabolism. Here we show that agents which
activate protein kinase C or otherwise enhance protein phosphorylation caused a substantial decrease in A beta production
in vitro. Protein kinase C activation also markedly decreased A beta release from cells that express mutant forms of the beta-amyloid
precursor protein genetically linked to familial AD. Inhibition of A beta secretion could also be effected by direct stimulation
of m1 muscarinic acetylcholine receptors with carbachol. These results demonstrate that activation of the protein kinase C
signal transduction pathways down-regulates the generation of the amyloidogenic A beta peptide. Pharmacologic agents that
activate this system, including a variety of first messengers, could potentially slow the development or growth of some A
beta plaques during the early stages of AD. |
| doi_str_mv | 10.1016/s0021-9258(19)49409-x |
| format | Article |
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in Alzheimer's disease (AD), is released by cultured human cells during normal metabolism. Here we show that agents which
activate protein kinase C or otherwise enhance protein phosphorylation caused a substantial decrease in A beta production
in vitro. Protein kinase C activation also markedly decreased A beta release from cells that express mutant forms of the beta-amyloid
precursor protein genetically linked to familial AD. Inhibition of A beta secretion could also be effected by direct stimulation
of m1 muscarinic acetylcholine receptors with carbachol. These results demonstrate that activation of the protein kinase C
signal transduction pathways down-regulates the generation of the amyloidogenic A beta peptide. Pharmacologic agents that
activate this system, including a variety of first messengers, could potentially slow the development or growth of some A
beta plaques during the early stages of AD.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1016/s0021-9258(19)49409-x</identifier><identifier>PMID: 8226807</identifier><identifier>CODEN: JBCHA3</identifier><language>eng</language><publisher>Bethesda, MD: American Society for Biochemistry and Molecular Biology</publisher><subject>Amino Acid Sequence ; Amyloid beta-Peptides - biosynthesis ; Biological and medical sciences ; Cell Line ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Enzyme Activation ; Ethers, Cyclic - pharmacology ; Humans ; In Vitro Techniques ; Medical sciences ; Molecular Sequence Data ; Neurology ; Okadaic Acid ; Phorbol Esters - pharmacology ; Phosphoproteins - physiology ; Protein Kinase C - physiology ; Receptors, Muscarinic - physiology ; Type C Phospholipases - metabolism</subject><ispartof>The Journal of biological chemistry, 1993-11, Vol.268 (31), p.22959-22962</ispartof><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c506t-103ec5230d2769df4aac03f135fef325b7015e35ff5843279bb5817ebf837bde3</citedby><cites>FETCH-LOGICAL-c506t-103ec5230d2769df4aac03f135fef325b7015e35ff5843279bb5817ebf837bde3</cites></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=3855498$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8226807$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HUNG, A. Y</creatorcontrib><creatorcontrib>HAASS, C</creatorcontrib><creatorcontrib>NITSCH, R. M</creatorcontrib><creatorcontrib>WEI QIAO QIU</creatorcontrib><creatorcontrib>CITRON, M</creatorcontrib><creatorcontrib>WURTMAN, R. J</creatorcontrib><creatorcontrib>GROWDON, J. H</creatorcontrib><creatorcontrib>SELKOE, D. J</creatorcontrib><title>Activation of protein kinase C inhibits cellular production of the amyloid beta-protein</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The 39-43-amino acid amyloid beta-protein (A beta), which is progressively deposited in cerebral plaques and blood vessels
in Alzheimer's disease (AD), is released by cultured human cells during normal metabolism. Here we show that agents which
activate protein kinase C or otherwise enhance protein phosphorylation caused a substantial decrease in A beta production
in vitro. Protein kinase C activation also markedly decreased A beta release from cells that express mutant forms of the beta-amyloid
precursor protein genetically linked to familial AD. Inhibition of A beta secretion could also be effected by direct stimulation
of m1 muscarinic acetylcholine receptors with carbachol. These results demonstrate that activation of the protein kinase C
signal transduction pathways down-regulates the generation of the amyloidogenic A beta peptide. Pharmacologic agents that
activate this system, including a variety of first messengers, could potentially slow the development or growth of some A
beta plaques during the early stages of AD.</description><subject>Amino Acid Sequence</subject><subject>Amyloid beta-Peptides - biosynthesis</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Enzyme Activation</subject><subject>Ethers, Cyclic - pharmacology</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Medical sciences</subject><subject>Molecular Sequence Data</subject><subject>Neurology</subject><subject>Okadaic Acid</subject><subject>Phorbol Esters - pharmacology</subject><subject>Phosphoproteins - physiology</subject><subject>Protein Kinase C - physiology</subject><subject>Receptors, Muscarinic - physiology</subject><subject>Type C Phospholipases - metabolism</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM1O3DAURq0KBFPaR0DKAqF2EfC148ReolFbKiGxANTZWbZz3bjkB-KkwNuTMGHwxrLu-b5rHUKOgZ4Bhfw8UsogVUzIb6C-ZyqjKn3-RFZAJU-5gM0eWe2QQ_I5xn90OpmCA3IgGcslLVbkz4Ubwn8zhK5NOp889N2AoU3uQ2siJusktFWwYYiJw7oea9PPSDm698BQYWKal7oLZWJxMOnS8IXse1NH_LrcR-Tu54_b9WV6df3r9_riKnWC5kMKlKMTjNOSFbkqfWaMo9wDFx49Z8IWFAROLy9kxlmhrBUSCrRe8sKWyI_I6bZ32vs4Yhx0E-L8V9NiN0YNecELoNkEii3o-i7GHr1-6ENj-hcNVM9C9c1sS8-2NCj9JlRvptzxsmC0DZa71GJwmp8scxOdqX1vWhfiDuNSiEzJD6wKf6un0KO2oXMVNnqq0Rw0Y0oo_gqPQYqp</recordid><startdate>19931105</startdate><enddate>19931105</enddate><creator>HUNG, A. 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Prion diseases</topic><topic>Enzyme Activation</topic><topic>Ethers, Cyclic - pharmacology</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>Neurology</topic><topic>Okadaic Acid</topic><topic>Phorbol Esters - pharmacology</topic><topic>Phosphoproteins - physiology</topic><topic>Protein Kinase C - physiology</topic><topic>Receptors, Muscarinic - physiology</topic><topic>Type C Phospholipases - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HUNG, A. Y</creatorcontrib><creatorcontrib>HAASS, C</creatorcontrib><creatorcontrib>NITSCH, R. M</creatorcontrib><creatorcontrib>WEI QIAO QIU</creatorcontrib><creatorcontrib>CITRON, M</creatorcontrib><creatorcontrib>WURTMAN, R. J</creatorcontrib><creatorcontrib>GROWDON, J. H</creatorcontrib><creatorcontrib>SELKOE, D. 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J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of protein kinase C inhibits cellular production of the amyloid beta-protein</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1993-11-05</date><risdate>1993</risdate><volume>268</volume><issue>31</issue><spage>22959</spage><epage>22962</epage><pages>22959-22962</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><coden>JBCHA3</coden><abstract>The 39-43-amino acid amyloid beta-protein (A beta), which is progressively deposited in cerebral plaques and blood vessels
in Alzheimer's disease (AD), is released by cultured human cells during normal metabolism. Here we show that agents which
activate protein kinase C or otherwise enhance protein phosphorylation caused a substantial decrease in A beta production
in vitro. Protein kinase C activation also markedly decreased A beta release from cells that express mutant forms of the beta-amyloid
precursor protein genetically linked to familial AD. Inhibition of A beta secretion could also be effected by direct stimulation
of m1 muscarinic acetylcholine receptors with carbachol. These results demonstrate that activation of the protein kinase C
signal transduction pathways down-regulates the generation of the amyloidogenic A beta peptide. Pharmacologic agents that
activate this system, including a variety of first messengers, could potentially slow the development or growth of some A
beta plaques during the early stages of AD.</abstract><cop>Bethesda, MD</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>8226807</pmid><doi>10.1016/s0021-9258(19)49409-x</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Amino Acid Sequence Amyloid beta-Peptides - biosynthesis Biological and medical sciences Cell Line Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Enzyme Activation Ethers, Cyclic - pharmacology Humans In Vitro Techniques Medical sciences Molecular Sequence Data Neurology Okadaic Acid Phorbol Esters - pharmacology Phosphoproteins - physiology Protein Kinase C - physiology Receptors, Muscarinic - physiology Type C Phospholipases - metabolism |
| title | Activation of protein kinase C inhibits cellular production of the amyloid beta-protein |
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