Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein

We have recently reported that Trypanosoma cruzi infection protects cardiomyocytes against apoptosis induced by growth factor deprivation. Cruzipain, a major parasite antigen, reproduced this survival effect by a Bcl-2-dependent mechanism. In this study, we have investigated the molecular mechanisms...

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Autores principales:	Tanos, Tamara, Coso, Omar Adrian
Publicado:	2006
Materias:	Cardiomyocyte MAPKs PI3K/Akt Trypanosoma cruzi 2 (2 amino 3 methoxyphenyl)chromone 2 morpholino 8 phenylchromone 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole anthra[1,9 cd]pyrazol 6(2h) one cruzipain glycoprotein mitogen activated protein kinase mitogen activated protein kinase p38 phosphatidylinositol 3 kinase protein BAD protein bcl 2 protein bcl xl protein kinase B protozoal protein stress activated protein kinase animal cell animal model apoptosis article cell protection cell survival controlled study enzyme inhibition enzyme phosphorylation heart cell culture heart muscle cell molecular mechanics mouse newborn nonhuman premedication priority journal protein expression protozoal infection signal transduction 1-Phosphatidylinositol 3-Kinase Animals Apoptosis bcl-Associated Death Protein bcl-X Protein Caspase 3 Caspases Cell Survival Cells, Cultured Chromones Cysteine Endopeptidases Enzyme Inhibitors Flavonoids Gene Expression Genes, bcl-2 Humans Imidazoles JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase 1 Mice Morpholines Myocytes, Cardiac p38 Mitogen-Activated Protein Kinases Phosphorylation Pyridines Signal Transduction
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_12864579_v8_n7_p1723_Aoki http://hdl.handle.net/20.500.12110/paper_12864579_v8_n7_p1723_Aoki
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_12864579_v8_n7_p1723_Aoki
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spelling	paper:paper_12864579_v8_n7_p1723_Aoki2023-06-08T16:10:14Z Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein Tanos, Tamara Coso, Omar Adrian Cardiomyocyte MAPKs PI3K/Akt Trypanosoma cruzi 2 (2 amino 3 methoxyphenyl)chromone 2 morpholino 8 phenylchromone 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole anthra[1,9 cd]pyrazol 6(2h) one cruzipain glycoprotein mitogen activated protein kinase mitogen activated protein kinase p38 phosphatidylinositol 3 kinase protein BAD protein bcl 2 protein bcl xl protein kinase B protozoal protein stress activated protein kinase animal cell animal model apoptosis article cell protection cell survival controlled study enzyme inhibition enzyme phosphorylation heart cell culture heart muscle cell molecular mechanics mouse newborn nonhuman premedication priority journal protein expression protozoal infection signal transduction Trypanosoma cruzi 1-Phosphatidylinositol 3-Kinase Animals Apoptosis bcl-Associated Death Protein bcl-X Protein Caspase 3 Caspases Cell Survival Cells, Cultured Chromones Cysteine Endopeptidases Enzyme Inhibitors Flavonoids Gene Expression Genes, bcl-2 Humans Imidazoles JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase 1 Mice Morpholines Myocytes, Cardiac p38 Mitogen-Activated Protein Kinases Phosphorylation Pyridines Signal Transduction Trypanosoma cruzi Trypanosoma cruzi We have recently reported that Trypanosoma cruzi infection protects cardiomyocytes against apoptosis induced by growth factor deprivation. Cruzipain, a major parasite antigen, reproduced this survival effect by a Bcl-2-dependent mechanism. In this study, we have investigated the molecular mechanisms of cruzipain-induced cardiomyocyte protection. Neonatal BALB/c mouse cardiac myocytes were cultured under minimum serum conditions in the presence of cruzipain or T. cruzi (Tulahuen strain). Some cultures were pretreated with the phosphatidylinositol 3-kinase (PI3K) inhibitor Ly294002 or specific inhibitors of the mitogen-activated protein kinase (MAPK) family members such as the mitogen-activated protein kinase kinase (MEK1) inhibitor PD098059, Jun N-terminal kinase (JNK) inhibitor SP600125, p38 MAPK inhibitor SB203580. Inhibition of PI3K and MEK1 but not JNK or p38 MAPK increased the apoptotic rate of cardiomyocytes treated with cruzipain. Phosphorylation of Akt, a major target of PI3K, and ERK1/2, MEK1-targets, was achieved at 15 min and 5 min, respectively. In parallel, these kinases were strongly phosphorylated by T. cruzi infection. In cultures treated with cruzipain, cleavage of caspase 3 was considerably diminished after serum starvation; Bcl-2 overexpression was inhibited by PD098059 but not by Ly294002, whereas Bad phosphorylation and Bcl-xL expression were increased and differentially modulated by both inhibitors. The results suggest that cruzipain exerts its anti-apoptotic property in cardiac myocytes at least by PI3K/Akt and MEK1/ERK1/2 signaling pathways. We further identified a differential modulation of Bcl-2 family members by these two signaling pathways. © 2006 Elsevier SAS. All rights reserved. Fil:Tanos, T. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Coso, O.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2006 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_12864579_v8_n7_p1723_Aoki http://hdl.handle.net/20.500.12110/paper_12864579_v8_n7_p1723_Aoki
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Cardiomyocyte MAPKs PI3K/Akt Trypanosoma cruzi 2 (2 amino 3 methoxyphenyl)chromone 2 morpholino 8 phenylchromone 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole anthra[1,9 cd]pyrazol 6(2h) one cruzipain glycoprotein mitogen activated protein kinase mitogen activated protein kinase p38 phosphatidylinositol 3 kinase protein BAD protein bcl 2 protein bcl xl protein kinase B protozoal protein stress activated protein kinase animal cell animal model apoptosis article cell protection cell survival controlled study enzyme inhibition enzyme phosphorylation heart cell culture heart muscle cell molecular mechanics mouse newborn nonhuman premedication priority journal protein expression protozoal infection signal transduction Trypanosoma cruzi 1-Phosphatidylinositol 3-Kinase Animals Apoptosis bcl-Associated Death Protein bcl-X Protein Caspase 3 Caspases Cell Survival Cells, Cultured Chromones Cysteine Endopeptidases Enzyme Inhibitors Flavonoids Gene Expression Genes, bcl-2 Humans Imidazoles JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase 1 Mice Morpholines Myocytes, Cardiac p38 Mitogen-Activated Protein Kinases Phosphorylation Pyridines Signal Transduction Trypanosoma cruzi Trypanosoma cruzi
spellingShingle	Cardiomyocyte MAPKs PI3K/Akt Trypanosoma cruzi 2 (2 amino 3 methoxyphenyl)chromone 2 morpholino 8 phenylchromone 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole anthra[1,9 cd]pyrazol 6(2h) one cruzipain glycoprotein mitogen activated protein kinase mitogen activated protein kinase p38 phosphatidylinositol 3 kinase protein BAD protein bcl 2 protein bcl xl protein kinase B protozoal protein stress activated protein kinase animal cell animal model apoptosis article cell protection cell survival controlled study enzyme inhibition enzyme phosphorylation heart cell culture heart muscle cell molecular mechanics mouse newborn nonhuman premedication priority journal protein expression protozoal infection signal transduction Trypanosoma cruzi 1-Phosphatidylinositol 3-Kinase Animals Apoptosis bcl-Associated Death Protein bcl-X Protein Caspase 3 Caspases Cell Survival Cells, Cultured Chromones Cysteine Endopeptidases Enzyme Inhibitors Flavonoids Gene Expression Genes, bcl-2 Humans Imidazoles JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase 1 Mice Morpholines Myocytes, Cardiac p38 Mitogen-Activated Protein Kinases Phosphorylation Pyridines Signal Transduction Trypanosoma cruzi Trypanosoma cruzi Tanos, Tamara Coso, Omar Adrian Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein
topic_facet	Cardiomyocyte MAPKs PI3K/Akt Trypanosoma cruzi 2 (2 amino 3 methoxyphenyl)chromone 2 morpholino 8 phenylchromone 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole anthra[1,9 cd]pyrazol 6(2h) one cruzipain glycoprotein mitogen activated protein kinase mitogen activated protein kinase p38 phosphatidylinositol 3 kinase protein BAD protein bcl 2 protein bcl xl protein kinase B protozoal protein stress activated protein kinase animal cell animal model apoptosis article cell protection cell survival controlled study enzyme inhibition enzyme phosphorylation heart cell culture heart muscle cell molecular mechanics mouse newborn nonhuman premedication priority journal protein expression protozoal infection signal transduction Trypanosoma cruzi 1-Phosphatidylinositol 3-Kinase Animals Apoptosis bcl-Associated Death Protein bcl-X Protein Caspase 3 Caspases Cell Survival Cells, Cultured Chromones Cysteine Endopeptidases Enzyme Inhibitors Flavonoids Gene Expression Genes, bcl-2 Humans Imidazoles JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase 1 Mice Morpholines Myocytes, Cardiac p38 Mitogen-Activated Protein Kinases Phosphorylation Pyridines Signal Transduction Trypanosoma cruzi Trypanosoma cruzi
description	We have recently reported that Trypanosoma cruzi infection protects cardiomyocytes against apoptosis induced by growth factor deprivation. Cruzipain, a major parasite antigen, reproduced this survival effect by a Bcl-2-dependent mechanism. In this study, we have investigated the molecular mechanisms of cruzipain-induced cardiomyocyte protection. Neonatal BALB/c mouse cardiac myocytes were cultured under minimum serum conditions in the presence of cruzipain or T. cruzi (Tulahuen strain). Some cultures were pretreated with the phosphatidylinositol 3-kinase (PI3K) inhibitor Ly294002 or specific inhibitors of the mitogen-activated protein kinase (MAPK) family members such as the mitogen-activated protein kinase kinase (MEK1) inhibitor PD098059, Jun N-terminal kinase (JNK) inhibitor SP600125, p38 MAPK inhibitor SB203580. Inhibition of PI3K and MEK1 but not JNK or p38 MAPK increased the apoptotic rate of cardiomyocytes treated with cruzipain. Phosphorylation of Akt, a major target of PI3K, and ERK1/2, MEK1-targets, was achieved at 15 min and 5 min, respectively. In parallel, these kinases were strongly phosphorylated by T. cruzi infection. In cultures treated with cruzipain, cleavage of caspase 3 was considerably diminished after serum starvation; Bcl-2 overexpression was inhibited by PD098059 but not by Ly294002, whereas Bad phosphorylation and Bcl-xL expression were increased and differentially modulated by both inhibitors. The results suggest that cruzipain exerts its anti-apoptotic property in cardiac myocytes at least by PI3K/Akt and MEK1/ERK1/2 signaling pathways. We further identified a differential modulation of Bcl-2 family members by these two signaling pathways. © 2006 Elsevier SAS. All rights reserved.
author	Tanos, Tamara Coso, Omar Adrian
author_facet	Tanos, Tamara Coso, Omar Adrian
author_sort	Tanos, Tamara
title	Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein
title_short	Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein
title_full	Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein
title_fullStr	Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein
title_full_unstemmed	Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein
title_sort	different signaling pathways are involved in cardiomyocyte survival induced by a trypanosoma cruzi glycoprotein
publishDate	2006
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_12864579_v8_n7_p1723_Aoki http://hdl.handle.net/20.500.12110/paper_12864579_v8_n7_p1723_Aoki
work_keys_str_mv	AT tanostamara differentsignalingpathwaysareinvolvedincardiomyocytesurvivalinducedbyatrypanosomacruziglycoprotein AT cosoomaradrian differentsignalingpathwaysareinvolvedincardiomyocytesurvivalinducedbyatrypanosomacruziglycoprotein
_version_	1768545476647321600

Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein

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