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Abstract:

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.

Registro:

Documento: Artículo
Título:Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein
Autor:Aoki, M.d.P.; Cano, R.C.; Pellegrini, A.V.; Tanos, T.; Guiñazú, N.L.; Coso, O.A.; Gea, S.
Filiación:CIBICI-CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Haya la Torre Medina Allende, CP 5000 Córdoba, Argentina
IFIBYNE-CONICET, Laboratorio de Fisiología y Biología Molecular, Facultad de Ciencias Exactas y Naturales, Ciudad Universitaria Pabellon 2, Buenos Aires, Argentina
Palabras clave: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
Año:2006
Volumen:8
Número:7
Página de inicio:1723
Página de fin:1731
DOI: http://dx.doi.org/10.1016/j.micinf.2006.02.010
Título revista:Microbes and Infection
Título revista abreviado:Microbes Infect.
ISSN:12864579
CODEN:MCINF
CAS:2 (2 amino 3 methoxyphenyl)chromone, 167869-21-8; 2 morpholino 8 phenylchromone, 154447-36-6; 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole, 152121-47-6; anthra[1,9 cd]pyrazol 6(2h) one, 129-56-6; mitogen activated protein kinase, 142243-02-5; phosphatidylinositol 3 kinase, 115926-52-8; protein bcl 2, 219306-68-0; protein bcl xl, 151033-38-4; protein kinase B, 148640-14-6; stress activated protein kinase, 155215-87-5; 1-Phosphatidylinositol 3-Kinase, EC 2.7.1.137; 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, 154447-36-6; Bad protein, mouse; bcl-Associated Death Protein; bcl-X Protein; Bcl2l1 protein, mouse; CASP3 protein, human, EC 3.4.22.-; Casp3 protein, mouse, EC 3.4.22.-; Caspase 3, EC 3.4.22.-; Caspases, EC 3.4.22.-; Chromones; cruzipain, EC 3.4.22.-; Cysteine Endopeptidases, EC 3.4.22.-; Enzyme Inhibitors; Flavonoids; Imidazoles; JNK Mitogen-Activated Protein Kinases, EC 2.7.1.37; MAP Kinase Kinase 1, EC 2.7.1.-; Morpholines; p38 Mitogen-Activated Protein Kinases, EC 2.7.1.37; PD 98059; Pyridines; SB 203580
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_12864579_v8_n7_p1723_Aoki

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Citas:

---------- APA ----------
Aoki, M.d.P., Cano, R.C., Pellegrini, A.V., Tanos, T., Guiñazú, N.L., Coso, O.A. & Gea, S. (2006) . Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein. Microbes and Infection, 8(7), 1723-1731.
http://dx.doi.org/10.1016/j.micinf.2006.02.010
---------- CHICAGO ----------
Aoki, M.d.P., Cano, R.C., Pellegrini, A.V., Tanos, T., Guiñazú, N.L., Coso, O.A., et al. "Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein" . Microbes and Infection 8, no. 7 (2006) : 1723-1731.
http://dx.doi.org/10.1016/j.micinf.2006.02.010
---------- MLA ----------
Aoki, M.d.P., Cano, R.C., Pellegrini, A.V., Tanos, T., Guiñazú, N.L., Coso, O.A., et al. "Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein" . Microbes and Infection, vol. 8, no. 7, 2006, pp. 1723-1731.
http://dx.doi.org/10.1016/j.micinf.2006.02.010
---------- VANCOUVER ----------
Aoki, M.d.P., Cano, R.C., Pellegrini, A.V., Tanos, T., Guiñazú, N.L., Coso, O.A., et al. Different signaling pathways are involved in cardiomyocyte survival induced by a Trypanosoma cruzi glycoprotein. Microbes Infect. 2006;8(7):1723-1731.
http://dx.doi.org/10.1016/j.micinf.2006.02.010