Trypanosoma cruzi: Altered parasites after in vitro treatment with gangliosides, a therapeutic agent in experimental Chagas’ disease
Biochemical and structural modifications were investigated in axenic cultured Trypanosoma cruzi after treatment with gangliosides. Fluorescence anisotropy showed dose dependent increments in parasite membranes of ganglioside treated epimastigotes. NADP-GDH activity increased in parasites treated at...
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| Veröffentlicht in: | Experimental parasitology 2009-07, Vol.122 (3), p.218-225 |
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| creator | Cossy Isasi, S. Rodríguez, M. Pereira, B.M.I. Díaz-luján, C. Fretes, R.E. Haüen, D.I. |
| description | Biochemical and structural modifications were investigated in axenic cultured Trypanosoma cruzi after treatment with gangliosides. Fluorescence anisotropy showed dose dependent increments in parasite membranes of ganglioside treated epimastigotes. NADP-GDH activity increased in parasites treated at day 4 (13%), 7 (137.2%), and 14 (28.50%) while NAD-MDH but decreased from day 7 to 21 (−5.74%, −32.22%, −27.92%). Treated parasites presented electron-lucent vacuoles opposite to the cytostoma, multilamellar bodies and dilated mitochondrion cristae, disorganized kinetoplast and altered heterochromatin structure. Gangliosides inhibited fusogenic ability (80%) and PLA2 activity (>75%) from the parasite. The same occurred with anti-PLA2 antibodies. Trypomastigotes suffered loss of cytoplasmic material and organelles when GM1 was present in culture medium. We propose that exogenous gangliosides produced: altered lipid order, inhibited membrane enzymes, the parasite energy source shifted from glucose to amino acids, ending on a structural transformation which signals parasite cell death. |
| doi_str_mv | 10.1016/j.exppara.2009.03.017 |
| format | Article |
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Fluorescence anisotropy showed dose dependent increments in parasite membranes of ganglioside treated epimastigotes. NADP-GDH activity increased in parasites treated at day 4 (13%), 7 (137.2%), and 14 (28.50%) while NAD-MDH but decreased from day 7 to 21 (−5.74%, −32.22%, −27.92%). Treated parasites presented electron-lucent vacuoles opposite to the cytostoma, multilamellar bodies and dilated mitochondrion cristae, disorganized kinetoplast and altered heterochromatin structure. Gangliosides inhibited fusogenic ability (80%) and PLA2 activity (>75%) from the parasite. The same occurred with anti-PLA2 antibodies. Trypomastigotes suffered loss of cytoplasmic material and organelles when GM1 was present in culture medium. We propose that exogenous gangliosides produced: altered lipid order, inhibited membrane enzymes, the parasite energy source shifted from glucose to amino acids, ending on a structural transformation which signals parasite cell death.</description><identifier>ISSN: 0014-4894</identifier><identifier>EISSN: 1090-2449</identifier><identifier>DOI: 10.1016/j.exppara.2009.03.017</identifier><identifier>PMID: 19351532</identifier><identifier>CODEN: EXPAAA</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Calorimetry, Differential Scanning ; Cell Adhesion - drug effects ; Cell Membrane - chemistry ; Cell Membrane - drug effects ; Cell Membrane - metabolism ; Cercopithecus aethiops ; Chagas’ disease treatment ; Fundamental and applied biological sciences. Psychology ; Gangliosides ; Gangliosides - pharmacology ; GDH (EC 1.4.1.2) ; Glutamate Dehydrogenase (NADP+) - analysis ; Kinetoplastidae ; Life cycle. 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Pathogenesis ; Malate Dehydrogenase - analysis ; MDH (EC 1.1.1.37) ; Microscopy, Electron, Transmission ; Protozoa ; Protozoan Proteins - analysis ; Protozoan Proteins - chemistry ; Radiometry ; Trypanosoma cruzi ; Trypanosoma cruzi - drug effects ; Trypanosoma cruzi - physiology ; Trypanosoma cruzi - ultrastructure ; Ultrastructure ; Vero Cells ; Viscosity - drug effects</subject><ispartof>Experimental parasitology, 2009-07, Vol.122 (3), p.218-225</ispartof><rights>2009</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c424t-e9edb633062e313dda27b69e2e5583823d900d330ec84b87615db020cba840d3</citedby><cites>FETCH-LOGICAL-c424t-e9edb633062e313dda27b69e2e5583823d900d330ec84b87615db020cba840d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.exppara.2009.03.017$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21561320$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19351532$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cossy Isasi, S.</creatorcontrib><creatorcontrib>Rodríguez, M.</creatorcontrib><creatorcontrib>Pereira, B.M.I.</creatorcontrib><creatorcontrib>Díaz-luján, C.</creatorcontrib><creatorcontrib>Fretes, R.E.</creatorcontrib><creatorcontrib>Haüen, D.I.</creatorcontrib><title>Trypanosoma cruzi: Altered parasites after in vitro treatment with gangliosides, a therapeutic agent in experimental Chagas’ disease</title><title>Experimental parasitology</title><addtitle>Exp Parasitol</addtitle><description>Biochemical and structural modifications were investigated in axenic cultured Trypanosoma cruzi after treatment with gangliosides. Fluorescence anisotropy showed dose dependent increments in parasite membranes of ganglioside treated epimastigotes. NADP-GDH activity increased in parasites treated at day 4 (13%), 7 (137.2%), and 14 (28.50%) while NAD-MDH but decreased from day 7 to 21 (−5.74%, −32.22%, −27.92%). Treated parasites presented electron-lucent vacuoles opposite to the cytostoma, multilamellar bodies and dilated mitochondrion cristae, disorganized kinetoplast and altered heterochromatin structure. Gangliosides inhibited fusogenic ability (80%) and PLA2 activity (>75%) from the parasite. The same occurred with anti-PLA2 antibodies. Trypomastigotes suffered loss of cytoplasmic material and organelles when GM1 was present in culture medium. We propose that exogenous gangliosides produced: altered lipid order, inhibited membrane enzymes, the parasite energy source shifted from glucose to amino acids, ending on a structural transformation which signals parasite cell death.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Calorimetry, Differential Scanning</subject><subject>Cell Adhesion - drug effects</subject><subject>Cell Membrane - chemistry</subject><subject>Cell Membrane - drug effects</subject><subject>Cell Membrane - metabolism</subject><subject>Cercopithecus aethiops</subject><subject>Chagas’ disease treatment</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gangliosides</subject><subject>Gangliosides - pharmacology</subject><subject>GDH (EC 1.4.1.2)</subject><subject>Glutamate Dehydrogenase (NADP+) - analysis</subject><subject>Kinetoplastidae</subject><subject>Life cycle. Host-agent relationship. Pathogenesis</subject><subject>Malate Dehydrogenase - analysis</subject><subject>MDH (EC 1.1.1.37)</subject><subject>Microscopy, Electron, Transmission</subject><subject>Protozoa</subject><subject>Protozoan Proteins - analysis</subject><subject>Protozoan Proteins - chemistry</subject><subject>Radiometry</subject><subject>Trypanosoma cruzi</subject><subject>Trypanosoma cruzi - drug effects</subject><subject>Trypanosoma cruzi - physiology</subject><subject>Trypanosoma cruzi - ultrastructure</subject><subject>Ultrastructure</subject><subject>Vero Cells</subject><subject>Viscosity - drug effects</subject><issn>0014-4894</issn><issn>1090-2449</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2O0zAQxyMEYsvCI4B8YU8kjD-SJlzQquJLWolL79bEnrau0iTYzrLLiRPvwOvxJDhqBMc9WfL8_uMZ_7LsJYeCA6_eHgu6G0f0WAiApgBZAF8_ylYcGsiFUs3jbAXAVa7qRl1kz0I4AkDNhXqaXfBGlryUYpX92vr7EfshDCdkxk8_3Dt23UXyZNncPbhIgeEu3TDXs1sX_cCiJ4wn6iP77uKB7bHfd24IzlJ4w5DFA3kcaYrOMNzPWEqmacm7OYQd2xxwj-HPz9_MukAY6Hn2ZIddoBfLeZltP37Ybj7nN18_fdlc3-RGCRVzasi2lZRQCZJcWoti3VYNCSrLWtZC2gbApjqZWrX1uuKlbUGAabFWqXCZXZ3bjn74NlGI-uSCoa7DnoYp6GotuYCmeRAUUPG6VjKB5Rk0fgjB006PaUv095qDnkXpo15E6VmUBqmTqJR7tTwwtSey_1OLmQS8XgAMBrudx9648I8TvKy4FJC492eO0rfdOvI6GEe9Ies8majt4B4Y5S_XYLce</recordid><startdate>20090701</startdate><enddate>20090701</enddate><creator>Cossy Isasi, S.</creator><creator>Rodríguez, M.</creator><creator>Pereira, B.M.I.</creator><creator>Díaz-luján, C.</creator><creator>Fretes, R.E.</creator><creator>Haüen, D.I.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><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>M7N</scope><scope>7X8</scope></search><sort><creationdate>20090701</creationdate><title>Trypanosoma cruzi: Altered parasites after in vitro treatment with gangliosides, a therapeutic agent in experimental Chagas’ disease</title><author>Cossy Isasi, S. ; Rodríguez, M. ; Pereira, B.M.I. ; Díaz-luján, C. ; Fretes, R.E. ; Haüen, D.I.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c424t-e9edb633062e313dda27b69e2e5583823d900d330ec84b87615db020cba840d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Calorimetry, Differential Scanning</topic><topic>Cell Adhesion - drug effects</topic><topic>Cell Membrane - chemistry</topic><topic>Cell Membrane - drug effects</topic><topic>Cell Membrane - metabolism</topic><topic>Cercopithecus aethiops</topic><topic>Chagas’ disease treatment</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gangliosides</topic><topic>Gangliosides - pharmacology</topic><topic>GDH (EC 1.4.1.2)</topic><topic>Glutamate Dehydrogenase (NADP+) - analysis</topic><topic>Kinetoplastidae</topic><topic>Life cycle. Host-agent relationship. Pathogenesis</topic><topic>Malate Dehydrogenase - analysis</topic><topic>MDH (EC 1.1.1.37)</topic><topic>Microscopy, Electron, Transmission</topic><topic>Protozoa</topic><topic>Protozoan Proteins - analysis</topic><topic>Protozoan Proteins - chemistry</topic><topic>Radiometry</topic><topic>Trypanosoma cruzi</topic><topic>Trypanosoma cruzi - drug effects</topic><topic>Trypanosoma cruzi - physiology</topic><topic>Trypanosoma cruzi - ultrastructure</topic><topic>Ultrastructure</topic><topic>Vero Cells</topic><topic>Viscosity - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cossy Isasi, S.</creatorcontrib><creatorcontrib>Rodríguez, M.</creatorcontrib><creatorcontrib>Pereira, B.M.I.</creatorcontrib><creatorcontrib>Díaz-luján, C.</creatorcontrib><creatorcontrib>Fretes, R.E.</creatorcontrib><creatorcontrib>Haüen, D.I.</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>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cossy Isasi, S.</au><au>Rodríguez, M.</au><au>Pereira, B.M.I.</au><au>Díaz-luján, C.</au><au>Fretes, R.E.</au><au>Haüen, D.I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Trypanosoma cruzi: Altered parasites after in vitro treatment with gangliosides, a therapeutic agent in experimental Chagas’ disease</atitle><jtitle>Experimental parasitology</jtitle><addtitle>Exp Parasitol</addtitle><date>2009-07-01</date><risdate>2009</risdate><volume>122</volume><issue>3</issue><spage>218</spage><epage>225</epage><pages>218-225</pages><issn>0014-4894</issn><eissn>1090-2449</eissn><coden>EXPAAA</coden><abstract>Biochemical and structural modifications were investigated in axenic cultured Trypanosoma cruzi after treatment with gangliosides. Fluorescence anisotropy showed dose dependent increments in parasite membranes of ganglioside treated epimastigotes. NADP-GDH activity increased in parasites treated at day 4 (13%), 7 (137.2%), and 14 (28.50%) while NAD-MDH but decreased from day 7 to 21 (−5.74%, −32.22%, −27.92%). Treated parasites presented electron-lucent vacuoles opposite to the cytostoma, multilamellar bodies and dilated mitochondrion cristae, disorganized kinetoplast and altered heterochromatin structure. Gangliosides inhibited fusogenic ability (80%) and PLA2 activity (>75%) from the parasite. The same occurred with anti-PLA2 antibodies. Trypomastigotes suffered loss of cytoplasmic material and organelles when GM1 was present in culture medium. We propose that exogenous gangliosides produced: altered lipid order, inhibited membrane enzymes, the parasite energy source shifted from glucose to amino acids, ending on a structural transformation which signals parasite cell death.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>19351532</pmid><doi>10.1016/j.exppara.2009.03.017</doi><tpages>8</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Calorimetry, Differential Scanning Cell Adhesion - drug effects Cell Membrane - chemistry Cell Membrane - drug effects Cell Membrane - metabolism Cercopithecus aethiops Chagas’ disease treatment Fundamental and applied biological sciences. Psychology Gangliosides Gangliosides - pharmacology GDH (EC 1.4.1.2) Glutamate Dehydrogenase (NADP+) - analysis Kinetoplastidae Life cycle. Host-agent relationship. Pathogenesis Malate Dehydrogenase - analysis MDH (EC 1.1.1.37) Microscopy, Electron, Transmission Protozoa Protozoan Proteins - analysis Protozoan Proteins - chemistry Radiometry Trypanosoma cruzi Trypanosoma cruzi - drug effects Trypanosoma cruzi - physiology Trypanosoma cruzi - ultrastructure Ultrastructure Vero Cells Viscosity - drug effects |
| title | Trypanosoma cruzi: Altered parasites after in vitro treatment with gangliosides, a therapeutic agent in experimental Chagas’ disease |
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