Fluorescence Polarization Analysis, Lipid Composition, and Na+, K+‐ATPase Kinetics of Synaptosomal Membranes in Feline GM1 and GM2 Gangliosidosis
: Neurochemical studies were performed on synaptosomal membranes from cats with GM1 or GM2 gangliosidosis to examine possible mechanisms of neuronal dysfunction in these disorders. The basic hypothesis tested was that deficient ganglioside catabolism causes increased ganglioside content of synaptoso...
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Veröffentlicht in: | Journal of neurochemistry 1985-03, Vol.44 (3), p.947-956 |
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description | : Neurochemical studies were performed on synaptosomal membranes from cats with GM1 or GM2 gangliosidosis to examine possible mechanisms of neuronal dysfunction in these disorders. The basic hypothesis tested was that deficient ganglioside catabolism causes increased ganglioside content of synaptosomal plasma membrane which in turn disrupts normal function. Fluidity characteristics of synaptosomal membranes were examined using fluorescence polarization. Results showed markedly reduced membrane fluidity in both GM1 and GM2 gangliosidosis. These results were supported by a second study which revealed that isolated synaptosomal membranes of GM1 gangliosidosis cats had a 24‐fold increase in total ganglioside content caused predominantly by excess GM1, a 2.3‐fold increased cholesterol content, and a 1.4‐fold increased phospholipid content. Finally, kinetic analysis of synaptosomal plasma membrane Na+, K+‐ATPase from cats with GM1 gangliosidosis showed negligible differences in kinetic parameters compared with controls. Thus, the enzyme appeared protected from the global membrane changes in fluidity and composition. These observations provide evidence for a pathogenetic mechanism of neuronal dysfunction in the gangliosidoses while demonstrating protection of certain vital functional components, such as Na+, K+‐ATPase. |
doi_str_mv | 10.1111/j.1471-4159.1985.tb12909.x |
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The basic hypothesis tested was that deficient ganglioside catabolism causes increased ganglioside content of synaptosomal plasma membrane which in turn disrupts normal function. Fluidity characteristics of synaptosomal membranes were examined using fluorescence polarization. Results showed markedly reduced membrane fluidity in both GM1 and GM2 gangliosidosis. These results were supported by a second study which revealed that isolated synaptosomal membranes of GM1 gangliosidosis cats had a 24‐fold increase in total ganglioside content caused predominantly by excess GM1, a 2.3‐fold increased cholesterol content, and a 1.4‐fold increased phospholipid content. Finally, kinetic analysis of synaptosomal plasma membrane Na+, K+‐ATPase from cats with GM1 gangliosidosis showed negligible differences in kinetic parameters compared with controls. Thus, the enzyme appeared protected from the global membrane changes in fluidity and composition. These observations provide evidence for a pathogenetic mechanism of neuronal dysfunction in the gangliosidoses while demonstrating protection of certain vital functional components, such as Na+, K+‐ATPase.</description><identifier>ISSN: 0022-3042</identifier><identifier>EISSN: 1471-4159</identifier><identifier>DOI: 10.1111/j.1471-4159.1985.tb12909.x</identifier><identifier>PMID: 2983023</identifier><identifier>CODEN: JONRA9</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; Applied sciences ; Biological and medical sciences ; Brain - ultrastructure ; Cats ; Cholesterol - analysis ; Errors of metabolism ; Exact sciences and technology ; Fluorescence Polarization ; G(M1) Ganglioside ; G(M2) Ganglioside ; Gangliosides ; Gangliosidoses - enzymology ; GM1 gangliosidosis ; GM2 gangliosidosis ; Humans ; Lipids (lysosomal enzyme disorders, storage diseases) ; Lipids - analysis ; Medical sciences ; Membrane Fluidity ; Metabolic diseases ; Other techniques and industries ; Phospholipids - analysis ; Sodium-Potassium-Exchanging ATPase - metabolism ; Synaptic Membranes - enzymology ; Synaptosomal membranes ; Temperature</subject><ispartof>Journal of neurochemistry, 1985-03, Vol.44 (3), p.947-956</ispartof><rights>1986 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1471-4159.1985.tb12909.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1471-4159.1985.tb12909.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=8574035$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=8835702$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/2983023$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wood, Philip A.</creatorcontrib><creatorcontrib>McBride, Michael R.</creatorcontrib><creatorcontrib>Baker, Henry J.</creatorcontrib><creatorcontrib>Christian, Samuel T.</creatorcontrib><title>Fluorescence Polarization Analysis, Lipid Composition, and Na+, K+‐ATPase Kinetics of Synaptosomal Membranes in Feline GM1 and GM2 Gangliosidosis</title><title>Journal of neurochemistry</title><addtitle>J Neurochem</addtitle><description>: Neurochemical studies were performed on synaptosomal membranes from cats with GM1 or GM2 gangliosidosis to examine possible mechanisms of neuronal dysfunction in these disorders. The basic hypothesis tested was that deficient ganglioside catabolism causes increased ganglioside content of synaptosomal plasma membrane which in turn disrupts normal function. Fluidity characteristics of synaptosomal membranes were examined using fluorescence polarization. Results showed markedly reduced membrane fluidity in both GM1 and GM2 gangliosidosis. These results were supported by a second study which revealed that isolated synaptosomal membranes of GM1 gangliosidosis cats had a 24‐fold increase in total ganglioside content caused predominantly by excess GM1, a 2.3‐fold increased cholesterol content, and a 1.4‐fold increased phospholipid content. Finally, kinetic analysis of synaptosomal plasma membrane Na+, K+‐ATPase from cats with GM1 gangliosidosis showed negligible differences in kinetic parameters compared with controls. Thus, the enzyme appeared protected from the global membrane changes in fluidity and composition. These observations provide evidence for a pathogenetic mechanism of neuronal dysfunction in the gangliosidoses while demonstrating protection of certain vital functional components, such as Na+, K+‐ATPase.</description><subject>Animals</subject><subject>Applied sciences</subject><subject>Biological and medical sciences</subject><subject>Brain - ultrastructure</subject><subject>Cats</subject><subject>Cholesterol - analysis</subject><subject>Errors of metabolism</subject><subject>Exact sciences and technology</subject><subject>Fluorescence Polarization</subject><subject>G(M1) Ganglioside</subject><subject>G(M2) Ganglioside</subject><subject>Gangliosides</subject><subject>Gangliosidoses - enzymology</subject><subject>GM1 gangliosidosis</subject><subject>GM2 gangliosidosis</subject><subject>Humans</subject><subject>Lipids (lysosomal enzyme disorders, storage diseases)</subject><subject>Lipids - analysis</subject><subject>Medical sciences</subject><subject>Membrane Fluidity</subject><subject>Metabolic diseases</subject><subject>Other techniques and industries</subject><subject>Phospholipids - analysis</subject><subject>Sodium-Potassium-Exchanging ATPase - metabolism</subject><subject>Synaptic Membranes - enzymology</subject><subject>Synaptosomal membranes</subject><subject>Temperature</subject><issn>0022-3042</issn><issn>1471-4159</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1985</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkdGK1DAYhYMo6-zqIwhBxJud1vxJ2iY3wjA4o-7MuuB6HdI2lQxp0206uLNXPoLgG_okpu4wtwZ-ws_5OCTnIPQaSArxvNulwAtIOGQyBSmydCyBSiLT-ydodpKeohkhlCaMcPocnYewIwRynsMZOqNSMELZDP1eub0fTKhMVxl8450e7IMere_wotPuEGyY443tbY2Xvu19sJM2x7qr8bW-nOOryz8_fy1ub3Qw-Mp2ZrRVwL7BXw-d7kcffKsd3pq2HHRnArYdXhkXObzewj-X9Zbite6-OxvN6zjhBXrWaBfMy-N9gb6tPtwuPyabL-tPy8Um6RnIIuFNzRpeaFlJIUVeCmpKUVAoc9CQZTmYmseFCpJluqhyLrkuBdMgpJS0IewCvX307Qd_tzdhVK2NQTgXX-r3QRV5DAwkRPDVEdyXralVP9hWDwd1TDHqb466DpV2TfxqZcMJE4JlReT-h2UFJyyL2PtH7Id15nCSgaipfLVTU8NqalhN5atj-epefb5eSl6wv1ESotU</recordid><startdate>198503</startdate><enddate>198503</enddate><creator>Wood, Philip A.</creator><creator>McBride, Michael R.</creator><creator>Baker, Henry J.</creator><creator>Christian, Samuel T.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>198503</creationdate><title>Fluorescence Polarization Analysis, Lipid Composition, and Na+, K+‐ATPase Kinetics of Synaptosomal Membranes in Feline GM1 and GM2 Gangliosidosis</title><author>Wood, Philip A. ; McBride, Michael R. ; Baker, Henry J. ; Christian, Samuel T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p3197-4fd3f47a9c98986b82eb8721b61a15561ed41b628055a7c6494ab83a189992f03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1985</creationdate><topic>Animals</topic><topic>Applied sciences</topic><topic>Biological and medical sciences</topic><topic>Brain - ultrastructure</topic><topic>Cats</topic><topic>Cholesterol - analysis</topic><topic>Errors of metabolism</topic><topic>Exact sciences and technology</topic><topic>Fluorescence Polarization</topic><topic>G(M1) Ganglioside</topic><topic>G(M2) Ganglioside</topic><topic>Gangliosides</topic><topic>Gangliosidoses - enzymology</topic><topic>GM1 gangliosidosis</topic><topic>GM2 gangliosidosis</topic><topic>Humans</topic><topic>Lipids (lysosomal enzyme disorders, storage diseases)</topic><topic>Lipids - analysis</topic><topic>Medical sciences</topic><topic>Membrane Fluidity</topic><topic>Metabolic diseases</topic><topic>Other techniques and industries</topic><topic>Phospholipids - analysis</topic><topic>Sodium-Potassium-Exchanging ATPase - metabolism</topic><topic>Synaptic Membranes - enzymology</topic><topic>Synaptosomal membranes</topic><topic>Temperature</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wood, Philip A.</creatorcontrib><creatorcontrib>McBride, Michael R.</creatorcontrib><creatorcontrib>Baker, Henry J.</creatorcontrib><creatorcontrib>Christian, Samuel 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>MEDLINE - Academic</collection><jtitle>Journal of neurochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wood, Philip A.</au><au>McBride, Michael R.</au><au>Baker, Henry J.</au><au>Christian, Samuel T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fluorescence Polarization Analysis, Lipid Composition, and Na+, K+‐ATPase Kinetics of Synaptosomal Membranes in Feline GM1 and GM2 Gangliosidosis</atitle><jtitle>Journal of neurochemistry</jtitle><addtitle>J Neurochem</addtitle><date>1985-03</date><risdate>1985</risdate><volume>44</volume><issue>3</issue><spage>947</spage><epage>956</epage><pages>947-956</pages><issn>0022-3042</issn><eissn>1471-4159</eissn><coden>JONRA9</coden><abstract>: Neurochemical studies were performed on synaptosomal membranes from cats with GM1 or GM2 gangliosidosis to examine possible mechanisms of neuronal dysfunction in these disorders. The basic hypothesis tested was that deficient ganglioside catabolism causes increased ganglioside content of synaptosomal plasma membrane which in turn disrupts normal function. Fluidity characteristics of synaptosomal membranes were examined using fluorescence polarization. Results showed markedly reduced membrane fluidity in both GM1 and GM2 gangliosidosis. These results were supported by a second study which revealed that isolated synaptosomal membranes of GM1 gangliosidosis cats had a 24‐fold increase in total ganglioside content caused predominantly by excess GM1, a 2.3‐fold increased cholesterol content, and a 1.4‐fold increased phospholipid content. Finally, kinetic analysis of synaptosomal plasma membrane Na+, K+‐ATPase from cats with GM1 gangliosidosis showed negligible differences in kinetic parameters compared with controls. Thus, the enzyme appeared protected from the global membrane changes in fluidity and composition. These observations provide evidence for a pathogenetic mechanism of neuronal dysfunction in the gangliosidoses while demonstrating protection of certain vital functional components, such as Na+, K+‐ATPase.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>2983023</pmid><doi>10.1111/j.1471-4159.1985.tb12909.x</doi><tpages>10</tpages></addata></record> |
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subjects | Animals Applied sciences Biological and medical sciences Brain - ultrastructure Cats Cholesterol - analysis Errors of metabolism Exact sciences and technology Fluorescence Polarization G(M1) Ganglioside G(M2) Ganglioside Gangliosides Gangliosidoses - enzymology GM1 gangliosidosis GM2 gangliosidosis Humans Lipids (lysosomal enzyme disorders, storage diseases) Lipids - analysis Medical sciences Membrane Fluidity Metabolic diseases Other techniques and industries Phospholipids - analysis Sodium-Potassium-Exchanging ATPase - metabolism Synaptic Membranes - enzymology Synaptosomal membranes Temperature |
title | Fluorescence Polarization Analysis, Lipid Composition, and Na+, K+‐ATPase Kinetics of Synaptosomal Membranes in Feline GM1 and GM2 Gangliosidosis |
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