Formation and remodeling of inositolphosphoceramide during differentiation of Trypanosoma cruzi from trypomastigote to amastigote
Differentiation of Trypanosoma cruzi trypomastigotes to amastigotes inside myoblasts or in vitro, at low extracellular pH, in the presence of [ 3H]palmitic acid or [3H]inositol revealed differential labeling of inositolphosphoceramide and phosphatidylinositol, suggesting that a remodeling process ta...
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todo:paper_15359778_v2_n4_p756_Salto2023-10-03T16:21:44Z Formation and remodeling of inositolphosphoceramide during differentiation of Trypanosoma cruzi from trypomastigote to amastigote Salto, M.L. Bertello, L.E. Vieira, M. Docampo, R. Moreno, S.N.J. De Lederkremer, R.M. aureobasidin A cyclopeptide depsipeptide enzyme inhibitor glycosphingolipid inositolphosphoceramides membrane lipid membrane protein phosphatidylinositol animal article cell culture cell differentiation cell membrane cell size Chagas disease drug effect electron microscopy metabolism parasitology pH physiology Trypanosoma cruzi ultrastructure Animals Cell Differentiation Cell Membrane Cell Size Cells, Cultured Chagas Disease Depsipeptides Enzyme Inhibitors Glycosphingolipids Hydrogen-Ion Concentration Membrane Glycoproteins Membrane Lipids Microscopy, Electron Peptides, Cyclic Phosphatidylinositols Trypanosoma cruzi Animalia Eukaryota Invertebrata Protozoa Trypanosoma Trypanosoma cruzi Differentiation of Trypanosoma cruzi trypomastigotes to amastigotes inside myoblasts or in vitro, at low extracellular pH, in the presence of [ 3H]palmitic acid or [3H]inositol revealed differential labeling of inositolphosphoceramide and phosphatidylinositol, suggesting that a remodeling process takes place in both lipids. Using 3H-labeled inositolphosphoceramide and phosphatidylinositol as substrates, we demonstrated the association of at least five enzymatic activities with the membranes of amastigotes and trypomastigotes. These included phospholipase A13, phospholipase A2, inositolphosphoceramide-fatty acid hydrolase, acyltransferase, and a phospholipase C releasing either ceramide or a glycerolipid from the inositolphospholipids. These enzymes may be acting in remodeling reactions leading to the anchor of mature glycoproteins or glycoinositolphospholipids and helping in the transformation of the plasma membrane, a necessary step in the differentiation of slender trypomastigotes to round amastigotes, Synthesis of inositolphosphoceramide and particularly of glycoinositolphospholipids was inhibited by aureobasidin A, a known inhibitor of fungal inositolphosphoceramide synthases. The antibiotic impaired the differentiation of trypomastigotes at acidic pH, as indicated by an increased appearance of intermediate forms and a decreased expression of the Ssp4 glycoprotein, a characteristic marker of amastigote forms. Aureobasidin A was also toxic to differentiating trypomastigotes at acidic pH but not to trypomastigotes maintained at neutral pH. Our data suggest that inositolphosphoceramide is implicated in T. cruzi differentiation and that its metabolism could provide important targets for the development of antiparasitic therapies. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_15359778_v2_n4_p756_Salto |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
aureobasidin A cyclopeptide depsipeptide enzyme inhibitor glycosphingolipid inositolphosphoceramides membrane lipid membrane protein phosphatidylinositol animal article cell culture cell differentiation cell membrane cell size Chagas disease drug effect electron microscopy metabolism parasitology pH physiology Trypanosoma cruzi ultrastructure Animals Cell Differentiation Cell Membrane Cell Size Cells, Cultured Chagas Disease Depsipeptides Enzyme Inhibitors Glycosphingolipids Hydrogen-Ion Concentration Membrane Glycoproteins Membrane Lipids Microscopy, Electron Peptides, Cyclic Phosphatidylinositols Trypanosoma cruzi Animalia Eukaryota Invertebrata Protozoa Trypanosoma Trypanosoma cruzi |
| spellingShingle |
aureobasidin A cyclopeptide depsipeptide enzyme inhibitor glycosphingolipid inositolphosphoceramides membrane lipid membrane protein phosphatidylinositol animal article cell culture cell differentiation cell membrane cell size Chagas disease drug effect electron microscopy metabolism parasitology pH physiology Trypanosoma cruzi ultrastructure Animals Cell Differentiation Cell Membrane Cell Size Cells, Cultured Chagas Disease Depsipeptides Enzyme Inhibitors Glycosphingolipids Hydrogen-Ion Concentration Membrane Glycoproteins Membrane Lipids Microscopy, Electron Peptides, Cyclic Phosphatidylinositols Trypanosoma cruzi Animalia Eukaryota Invertebrata Protozoa Trypanosoma Trypanosoma cruzi Salto, M.L. Bertello, L.E. Vieira, M. Docampo, R. Moreno, S.N.J. De Lederkremer, R.M. Formation and remodeling of inositolphosphoceramide during differentiation of Trypanosoma cruzi from trypomastigote to amastigote |
| topic_facet |
aureobasidin A cyclopeptide depsipeptide enzyme inhibitor glycosphingolipid inositolphosphoceramides membrane lipid membrane protein phosphatidylinositol animal article cell culture cell differentiation cell membrane cell size Chagas disease drug effect electron microscopy metabolism parasitology pH physiology Trypanosoma cruzi ultrastructure Animals Cell Differentiation Cell Membrane Cell Size Cells, Cultured Chagas Disease Depsipeptides Enzyme Inhibitors Glycosphingolipids Hydrogen-Ion Concentration Membrane Glycoproteins Membrane Lipids Microscopy, Electron Peptides, Cyclic Phosphatidylinositols Trypanosoma cruzi Animalia Eukaryota Invertebrata Protozoa Trypanosoma Trypanosoma cruzi |
| description |
Differentiation of Trypanosoma cruzi trypomastigotes to amastigotes inside myoblasts or in vitro, at low extracellular pH, in the presence of [ 3H]palmitic acid or [3H]inositol revealed differential labeling of inositolphosphoceramide and phosphatidylinositol, suggesting that a remodeling process takes place in both lipids. Using 3H-labeled inositolphosphoceramide and phosphatidylinositol as substrates, we demonstrated the association of at least five enzymatic activities with the membranes of amastigotes and trypomastigotes. These included phospholipase A13, phospholipase A2, inositolphosphoceramide-fatty acid hydrolase, acyltransferase, and a phospholipase C releasing either ceramide or a glycerolipid from the inositolphospholipids. These enzymes may be acting in remodeling reactions leading to the anchor of mature glycoproteins or glycoinositolphospholipids and helping in the transformation of the plasma membrane, a necessary step in the differentiation of slender trypomastigotes to round amastigotes, Synthesis of inositolphosphoceramide and particularly of glycoinositolphospholipids was inhibited by aureobasidin A, a known inhibitor of fungal inositolphosphoceramide synthases. The antibiotic impaired the differentiation of trypomastigotes at acidic pH, as indicated by an increased appearance of intermediate forms and a decreased expression of the Ssp4 glycoprotein, a characteristic marker of amastigote forms. Aureobasidin A was also toxic to differentiating trypomastigotes at acidic pH but not to trypomastigotes maintained at neutral pH. Our data suggest that inositolphosphoceramide is implicated in T. cruzi differentiation and that its metabolism could provide important targets for the development of antiparasitic therapies. |
| format |
JOUR |
| author |
Salto, M.L. Bertello, L.E. Vieira, M. Docampo, R. Moreno, S.N.J. De Lederkremer, R.M. |
| author_facet |
Salto, M.L. Bertello, L.E. Vieira, M. Docampo, R. Moreno, S.N.J. De Lederkremer, R.M. |
| author_sort |
Salto, M.L. |
| title |
Formation and remodeling of inositolphosphoceramide during differentiation of Trypanosoma cruzi from trypomastigote to amastigote |
| title_short |
Formation and remodeling of inositolphosphoceramide during differentiation of Trypanosoma cruzi from trypomastigote to amastigote |
| title_full |
Formation and remodeling of inositolphosphoceramide during differentiation of Trypanosoma cruzi from trypomastigote to amastigote |
| title_fullStr |
Formation and remodeling of inositolphosphoceramide during differentiation of Trypanosoma cruzi from trypomastigote to amastigote |
| title_full_unstemmed |
Formation and remodeling of inositolphosphoceramide during differentiation of Trypanosoma cruzi from trypomastigote to amastigote |
| title_sort |
formation and remodeling of inositolphosphoceramide during differentiation of trypanosoma cruzi from trypomastigote to amastigote |
| url |
http://hdl.handle.net/20.500.12110/paper_15359778_v2_n4_p756_Salto |
| work_keys_str_mv |
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