Amyloid beta peptide 25-35 modulates hydrolysis of phosphoinositides by membrane phospholipase(s) C of adult brain cortex
Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal transduction. A subset of muscarinic cholinergic receptors are linked to G-proteins that activate phospholipase C. Cholinergic pathways are important in learning and memory, and deficits in cholinergic transmission have been i...
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| Veröffentlicht in: | Journal of molecular neuroscience 1999-04, Vol.12 (2), p.101-109 |
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| description | Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal transduction. A subset of muscarinic cholinergic receptors are linked to G-proteins that activate phospholipase C. Cholinergic pathways are important in learning and memory, and deficits in cholinergic transmission have been implicated in Alzheimer's disease (AD). AD is also associated with increased beta-amyloid plaques. In the present study, we have investigated the effect of the amyloid beta (A beta) synthetic peptide homologous to residue 25-35 of A beta in nonaggregated and aggregated forms on the degradation of inositol phospholipids. Synaptic plasma membranes (SPM) and the cytosolic fraction from rat brain cortex served as a source of enzymes. The studies were carried out with radioactive inositol phospholipids in the presence of endogenous and 2 mM CaCl2. The enzyme(s) activity was evaluated by determination of the product formation of [3H]inositol-1-phosphate (IP1) or [3H]inositol-1,4,5-trisphosphate (IP3). Results show that the PI-PLC activity was significantly higher in cytosol compared to SPM, and this enzyme was stimulated by 2 mM CaCl2, but not by GTPgammaS or carbachol, a cholinergic receptor agonist. Activity of the SPM-bound PIP2-PLC was similar to that in cytosol and was not activated by 2 mM CaCl2. The SPM PIP2-PLC was significantly stimulated by GTPgammaS together with the cholinergic agonist, carbachol. Fresh-water-soluble A beta 25-35 activated PI-PLC in SPM markedly by two- to threefold, but this effect was absent in the presence of 2 mM CaCl2. Moreover, A beta 25-35 had no effect on basal PIP2-PLC activity and cytosolic PI-PLC and PIP2-PLC. The aggregated form of A beta 25-35 significantly inhibited PIP2-PLC only in the presence of endogenous CaCl2. It also inhibited the carbachol and GTP(gamma)S-stimulated PIP2-PLC. Our findings show that depending on the aggregation state and Ca2+ concentration, A beta modulates phosphoinositide degradation differently and exclusively in brain synaptic plasma membranes. Our data suggested that aggregated A beta peptide may be responsible for the significant impairment of phosphoinositide signaling found in brain membranes during AD. |
| doi_str_mv | 10.1007/BF02736924 |
| format | Article |
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A subset of muscarinic cholinergic receptors are linked to G-proteins that activate phospholipase C. Cholinergic pathways are important in learning and memory, and deficits in cholinergic transmission have been implicated in Alzheimer's disease (AD). AD is also associated with increased beta-amyloid plaques. In the present study, we have investigated the effect of the amyloid beta (A beta) synthetic peptide homologous to residue 25-35 of A beta in nonaggregated and aggregated forms on the degradation of inositol phospholipids. Synaptic plasma membranes (SPM) and the cytosolic fraction from rat brain cortex served as a source of enzymes. The studies were carried out with radioactive inositol phospholipids in the presence of endogenous and 2 mM CaCl2. The enzyme(s) activity was evaluated by determination of the product formation of [3H]inositol-1-phosphate (IP1) or [3H]inositol-1,4,5-trisphosphate (IP3). Results show that the PI-PLC activity was significantly higher in cytosol compared to SPM, and this enzyme was stimulated by 2 mM CaCl2, but not by GTPgammaS or carbachol, a cholinergic receptor agonist. Activity of the SPM-bound PIP2-PLC was similar to that in cytosol and was not activated by 2 mM CaCl2. The SPM PIP2-PLC was significantly stimulated by GTPgammaS together with the cholinergic agonist, carbachol. Fresh-water-soluble A beta 25-35 activated PI-PLC in SPM markedly by two- to threefold, but this effect was absent in the presence of 2 mM CaCl2. Moreover, A beta 25-35 had no effect on basal PIP2-PLC activity and cytosolic PI-PLC and PIP2-PLC. The aggregated form of A beta 25-35 significantly inhibited PIP2-PLC only in the presence of endogenous CaCl2. It also inhibited the carbachol and GTP(gamma)S-stimulated PIP2-PLC. Our findings show that depending on the aggregation state and Ca2+ concentration, A beta modulates phosphoinositide degradation differently and exclusively in brain synaptic plasma membranes. Our data suggested that aggregated A beta peptide may be responsible for the significant impairment of phosphoinositide signaling found in brain membranes during AD.</description><identifier>ISSN: 0895-8696</identifier><identifier>EISSN: 1559-1166</identifier><identifier>DOI: 10.1007/BF02736924</identifier><identifier>PMID: 10527454</identifier><language>eng</language><publisher>United States: Springer Nature B.V</publisher><subject>Acetylcholine receptors ; Acetylcholine receptors (muscarinic) ; Age Factors ; Agonists ; Alzheimer's disease ; Amyloid beta-Peptides - pharmacology ; Animals ; Brain ; Calcium chloride ; Calcium Chloride - pharmacology ; Calcium ions ; Carbachol ; Cell Membrane - drug effects ; Cell Membrane - enzymology ; Cerebral Cortex - enzymology ; Cholinergic transmission ; Cholinergics ; Cytosol ; Cytosol - drug effects ; Cytosol - enzymology ; Degradation ; Enzyme Activation - drug effects ; Enzyme Activation - physiology ; Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology ; Hydrolysis ; Inositol 1,4,5-trisphosphate receptors ; Inositol trisphosphate ; Inositols ; Membranes ; Neurodegenerative diseases ; Peptide Fragments - pharmacology ; Peptides ; Phosphatidylinositol 4,5-diphosphate ; Phosphatidylinositols - metabolism ; Phosphoinositides ; Phospholipase ; Phospholipase C ; Phospholipids ; Plasma membranes ; Proteins ; Rats ; Rats, Wistar ; Receptors ; Rodents ; Signal transduction ; Signal Transduction - physiology ; Synaptic Membranes - drug effects ; Synaptic Membranes - enzymology ; Type C Phospholipases - metabolism ; β-Amyloid</subject><ispartof>Journal of molecular neuroscience, 1999-04, Vol.12 (2), p.101-109</ispartof><rights>Humana Press Inc 1999.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c311t-daf15cedd9956d56edc29b4a8063182e2997ea5d1a34db40da23371ce5f2167a3</citedby><cites>FETCH-LOGICAL-c311t-daf15cedd9956d56edc29b4a8063182e2997ea5d1a34db40da23371ce5f2167a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10527454$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Strosznajder, J B</creatorcontrib><creatorcontrib>Zambrzycka, A</creatorcontrib><creatorcontrib>Kacprzak, M D</creatorcontrib><creatorcontrib>Strosznajder, R P</creatorcontrib><title>Amyloid beta peptide 25-35 modulates hydrolysis of phosphoinositides by membrane phospholipase(s) C of adult brain cortex</title><title>Journal of molecular neuroscience</title><addtitle>J Mol Neurosci</addtitle><description>Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal transduction. A subset of muscarinic cholinergic receptors are linked to G-proteins that activate phospholipase C. Cholinergic pathways are important in learning and memory, and deficits in cholinergic transmission have been implicated in Alzheimer's disease (AD). AD is also associated with increased beta-amyloid plaques. In the present study, we have investigated the effect of the amyloid beta (A beta) synthetic peptide homologous to residue 25-35 of A beta in nonaggregated and aggregated forms on the degradation of inositol phospholipids. Synaptic plasma membranes (SPM) and the cytosolic fraction from rat brain cortex served as a source of enzymes. The studies were carried out with radioactive inositol phospholipids in the presence of endogenous and 2 mM CaCl2. The enzyme(s) activity was evaluated by determination of the product formation of [3H]inositol-1-phosphate (IP1) or [3H]inositol-1,4,5-trisphosphate (IP3). Results show that the PI-PLC activity was significantly higher in cytosol compared to SPM, and this enzyme was stimulated by 2 mM CaCl2, but not by GTPgammaS or carbachol, a cholinergic receptor agonist. Activity of the SPM-bound PIP2-PLC was similar to that in cytosol and was not activated by 2 mM CaCl2. The SPM PIP2-PLC was significantly stimulated by GTPgammaS together with the cholinergic agonist, carbachol. Fresh-water-soluble A beta 25-35 activated PI-PLC in SPM markedly by two- to threefold, but this effect was absent in the presence of 2 mM CaCl2. Moreover, A beta 25-35 had no effect on basal PIP2-PLC activity and cytosolic PI-PLC and PIP2-PLC. The aggregated form of A beta 25-35 significantly inhibited PIP2-PLC only in the presence of endogenous CaCl2. It also inhibited the carbachol and GTP(gamma)S-stimulated PIP2-PLC. Our findings show that depending on the aggregation state and Ca2+ concentration, A beta modulates phosphoinositide degradation differently and exclusively in brain synaptic plasma membranes. Our data suggested that aggregated A beta peptide may be responsible for the significant impairment of phosphoinositide signaling found in brain membranes during AD.</description><subject>Acetylcholine receptors</subject><subject>Acetylcholine receptors (muscarinic)</subject><subject>Age Factors</subject><subject>Agonists</subject><subject>Alzheimer's disease</subject><subject>Amyloid beta-Peptides - pharmacology</subject><subject>Animals</subject><subject>Brain</subject><subject>Calcium chloride</subject><subject>Calcium Chloride - pharmacology</subject><subject>Calcium ions</subject><subject>Carbachol</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane - enzymology</subject><subject>Cerebral Cortex - enzymology</subject><subject>Cholinergic transmission</subject><subject>Cholinergics</subject><subject>Cytosol</subject><subject>Cytosol - drug effects</subject><subject>Cytosol - enzymology</subject><subject>Degradation</subject><subject>Enzyme Activation - drug effects</subject><subject>Enzyme Activation - physiology</subject><subject>Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology</subject><subject>Hydrolysis</subject><subject>Inositol 1,4,5-trisphosphate receptors</subject><subject>Inositol trisphosphate</subject><subject>Inositols</subject><subject>Membranes</subject><subject>Neurodegenerative diseases</subject><subject>Peptide Fragments - pharmacology</subject><subject>Peptides</subject><subject>Phosphatidylinositol 4,5-diphosphate</subject><subject>Phosphatidylinositols - metabolism</subject><subject>Phosphoinositides</subject><subject>Phospholipase</subject><subject>Phospholipase C</subject><subject>Phospholipids</subject><subject>Plasma membranes</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptors</subject><subject>Rodents</subject><subject>Signal transduction</subject><subject>Signal Transduction - physiology</subject><subject>Synaptic Membranes - drug effects</subject><subject>Synaptic Membranes - enzymology</subject><subject>Type C Phospholipases - metabolism</subject><subject>β-Amyloid</subject><issn>0895-8696</issn><issn>1559-1166</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpd0U1r3DAQBmARUpJt2kt_QBEEQltwq9GndUyX5gMCubRnI1tjomCvHMmG-N9Hy6Y09DDoMI9ehhlCPgH7DoyZHz-vGDdCWy6PyAaUshWA1sdkw2qrqlpbfUre5_zIGAcJ9Qk5Baa4kUpuyHo5rkMMnrY4OzrhNAePlKtKKDpGvwxuxkwfVp_isOaQaezp9BBzqbCLOex5pu1KRxzb5Hb4tzuEyWX8kr_S7f6PK1EzLSLsaBfTjM8fyLveDRk_vr5n5M_Vr9_bm-ru_vp2e3lXdQJgrrzrQXXovbVKe6XRd9y20tVMC6g5cmsNOuXBCelbybzjQhjoUPUctHHijFwccqcUnxbMczOG3OEwlGHjkhvDalELqQo8_w8-xiXtymwNMDBMaTCyqG8H1aWYc8K-mVIYXVoLavbnaP6do-DPr5FLO6J_Qw_7Fy93CIUk</recordid><startdate>19990401</startdate><enddate>19990401</enddate><creator>Strosznajder, J B</creator><creator>Zambrzycka, A</creator><creator>Kacprzak, M D</creator><creator>Strosznajder, R P</creator><general>Springer Nature B.V</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>3V.</scope><scope>7QL</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7N</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>19990401</creationdate><title>Amyloid beta peptide 25-35 modulates hydrolysis of phosphoinositides by membrane phospholipase(s) C of adult brain cortex</title><author>Strosznajder, J B ; Zambrzycka, A ; Kacprzak, M D ; Strosznajder, R P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c311t-daf15cedd9956d56edc29b4a8063182e2997ea5d1a34db40da23371ce5f2167a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Acetylcholine receptors</topic><topic>Acetylcholine receptors (muscarinic)</topic><topic>Age Factors</topic><topic>Agonists</topic><topic>Alzheimer's disease</topic><topic>Amyloid beta-Peptides - pharmacology</topic><topic>Animals</topic><topic>Brain</topic><topic>Calcium chloride</topic><topic>Calcium Chloride - pharmacology</topic><topic>Calcium ions</topic><topic>Carbachol</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - enzymology</topic><topic>Cerebral Cortex - enzymology</topic><topic>Cholinergic transmission</topic><topic>Cholinergics</topic><topic>Cytosol</topic><topic>Cytosol - drug effects</topic><topic>Cytosol - enzymology</topic><topic>Degradation</topic><topic>Enzyme Activation - drug effects</topic><topic>Enzyme Activation - physiology</topic><topic>Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology</topic><topic>Hydrolysis</topic><topic>Inositol 1,4,5-trisphosphate receptors</topic><topic>Inositol trisphosphate</topic><topic>Inositols</topic><topic>Membranes</topic><topic>Neurodegenerative diseases</topic><topic>Peptide Fragments - pharmacology</topic><topic>Peptides</topic><topic>Phosphatidylinositol 4,5-diphosphate</topic><topic>Phosphatidylinositols - metabolism</topic><topic>Phosphoinositides</topic><topic>Phospholipase</topic><topic>Phospholipase C</topic><topic>Phospholipids</topic><topic>Plasma membranes</topic><topic>Proteins</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptors</topic><topic>Rodents</topic><topic>Signal transduction</topic><topic>Signal Transduction - physiology</topic><topic>Synaptic Membranes - drug effects</topic><topic>Synaptic Membranes - enzymology</topic><topic>Type C Phospholipases - metabolism</topic><topic>β-Amyloid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Strosznajder, J B</creatorcontrib><creatorcontrib>Zambrzycka, A</creatorcontrib><creatorcontrib>Kacprzak, M D</creatorcontrib><creatorcontrib>Strosznajder, R P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Chemoreception Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of molecular neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Strosznajder, J B</au><au>Zambrzycka, A</au><au>Kacprzak, M D</au><au>Strosznajder, R P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Amyloid beta peptide 25-35 modulates hydrolysis of phosphoinositides by membrane phospholipase(s) C of adult brain cortex</atitle><jtitle>Journal of molecular neuroscience</jtitle><addtitle>J Mol Neurosci</addtitle><date>1999-04-01</date><risdate>1999</risdate><volume>12</volume><issue>2</issue><spage>101</spage><epage>109</epage><pages>101-109</pages><issn>0895-8696</issn><eissn>1559-1166</eissn><abstract>Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal transduction. A subset of muscarinic cholinergic receptors are linked to G-proteins that activate phospholipase C. Cholinergic pathways are important in learning and memory, and deficits in cholinergic transmission have been implicated in Alzheimer's disease (AD). AD is also associated with increased beta-amyloid plaques. In the present study, we have investigated the effect of the amyloid beta (A beta) synthetic peptide homologous to residue 25-35 of A beta in nonaggregated and aggregated forms on the degradation of inositol phospholipids. Synaptic plasma membranes (SPM) and the cytosolic fraction from rat brain cortex served as a source of enzymes. The studies were carried out with radioactive inositol phospholipids in the presence of endogenous and 2 mM CaCl2. The enzyme(s) activity was evaluated by determination of the product formation of [3H]inositol-1-phosphate (IP1) or [3H]inositol-1,4,5-trisphosphate (IP3). Results show that the PI-PLC activity was significantly higher in cytosol compared to SPM, and this enzyme was stimulated by 2 mM CaCl2, but not by GTPgammaS or carbachol, a cholinergic receptor agonist. Activity of the SPM-bound PIP2-PLC was similar to that in cytosol and was not activated by 2 mM CaCl2. The SPM PIP2-PLC was significantly stimulated by GTPgammaS together with the cholinergic agonist, carbachol. Fresh-water-soluble A beta 25-35 activated PI-PLC in SPM markedly by two- to threefold, but this effect was absent in the presence of 2 mM CaCl2. Moreover, A beta 25-35 had no effect on basal PIP2-PLC activity and cytosolic PI-PLC and PIP2-PLC. The aggregated form of A beta 25-35 significantly inhibited PIP2-PLC only in the presence of endogenous CaCl2. It also inhibited the carbachol and GTP(gamma)S-stimulated PIP2-PLC. Our findings show that depending on the aggregation state and Ca2+ concentration, A beta modulates phosphoinositide degradation differently and exclusively in brain synaptic plasma membranes. Our data suggested that aggregated A beta peptide may be responsible for the significant impairment of phosphoinositide signaling found in brain membranes during AD.</abstract><cop>United States</cop><pub>Springer Nature B.V</pub><pmid>10527454</pmid><doi>10.1007/BF02736924</doi><tpages>9</tpages></addata></record> |
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| ispartof | Journal of molecular neuroscience, 1999-04, Vol.12 (2), p.101-109 |
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| subjects | Acetylcholine receptors Acetylcholine receptors (muscarinic) Age Factors Agonists Alzheimer's disease Amyloid beta-Peptides - pharmacology Animals Brain Calcium chloride Calcium Chloride - pharmacology Calcium ions Carbachol Cell Membrane - drug effects Cell Membrane - enzymology Cerebral Cortex - enzymology Cholinergic transmission Cholinergics Cytosol Cytosol - drug effects Cytosol - enzymology Degradation Enzyme Activation - drug effects Enzyme Activation - physiology Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology Hydrolysis Inositol 1,4,5-trisphosphate receptors Inositol trisphosphate Inositols Membranes Neurodegenerative diseases Peptide Fragments - pharmacology Peptides Phosphatidylinositol 4,5-diphosphate Phosphatidylinositols - metabolism Phosphoinositides Phospholipase Phospholipase C Phospholipids Plasma membranes Proteins Rats Rats, Wistar Receptors Rodents Signal transduction Signal Transduction - physiology Synaptic Membranes - drug effects Synaptic Membranes - enzymology Type C Phospholipases - metabolism β-Amyloid |
| title | Amyloid beta peptide 25-35 modulates hydrolysis of phosphoinositides by membrane phospholipase(s) C of adult brain cortex |
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