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Given that arginase activation may effectively influence nitric oxide (NO) production in macrophages, we have investigated the intracellular signals that regulate L-arginine metabolism and its influence on Trypanosoma cruzi growth. We demonstrate that cruzipain (Cz), a parasite antigen, induces arginase I expression in J774 cells, and the pretreatment of Cz-treated cells with N-omega-hydroxy-L-arginine (arginase inhibitor) leads to a dramatic decrease in amastigote growth. The study of intracellular signals shows that genistein [tyrosine kinase (TK) inhibitor], KT5720 [protein kinase (PK) A inhibitor] and SB203580 [p38 mitogen-activated protein kinase (MAPK) inhibitor] significantly decrease Cz-induced arginase activation. However, calphostin C (PKC inhibitor) and PD98059 [p44/p42 MAPK kinase (MEK) inhibitor] did not cause a significant change. To determine if signaling pathways triggered by Cz were involved in the T. cruzi growth, we studied the effect of those inhibitors. In Cz-treated cells- pre-incubated with TK, PKA or p38 MAPK inhibitors - the balance of NO/urea was biased towards NO, and the amastigote growth was diminished. Besides, genistein and mainly KT5720 induced down-regulation of arginase I expression in Cz-treated cells. Thus, activation of TK, PKA and p38 MAPK by Cz induces an increase of arginase activity in macrophages and the subsequent T. cruzi growth.


Documento: Artículo
Título:Arginase induction promotes Trypanosoma cruzi intracellular replication of Cruzipain-treated J774 cells through the activation of multiple signaling pathways
Autor:Stempin, C.C.; Tanos, T.B.; Coso, O.A.; Cerbán, F.M.
Filiación:Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre Medina Allende s/n, 5000 Cordoba, Argentina
Dept. de Fisiol. Biol. Molec. y Cel., Fac. de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:Arginase; Macrophage; Parasite antigen; Protein kinase; Trypanosoma cruzi; 2 (2 amino 3 methoxyphenyl)chromone; 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole; arginase; arginine; calphostin C; carbazole derivative; cruzipain; cyclic AMP dependent protein kinase; cyclic AMP dependent protein kinase inhibitor; cysteine proteinase; drug derivative; genistein; growth inhibitor; imidazole derivative; indole derivative; kt 5720; mitogen activated protein kinase; mitogen activated protein kinase inhibitor; mitogen activated protein kinase p38; n(g) hydroxyarginine; N(omega) hydroxyarginine; N(omega)-hydroxyarginine; nitric oxide; parasite antigen; protein kinase C inhibitor; protein p42; protein p44; protein tyrosine kinase; protein tyrosine kinase inhibitor; pyridine derivative; pyrrole derivative; unclassified drug; urea; amastigote; amino acid metabolism; animal; animal cell; article; biosynthesis; cell division; cell line; controlled study; developmental stage; down regulation; drug effect; enzyme activation; enzyme induction; enzyme inhibition; enzymology; growth, development and aging; incubation time; macrophage; metabolism; mouse; nonhuman; physiology; priority journal; protein expression; signal transduction; Trypanosoma cruzi; Animals; Arginase; Arginine; Carbazoles; Cell Division; Cyclic AMP-Dependent Protein Kinases; Cysteine Endopeptidases; Enzyme Induction; Genistein; Growth Inhibitors; Imidazoles; Indoles; Mitogen-Activated Protein Kinases; p38 Mitogen-Activated Protein Kinases; Protein-Tyrosine Kinases; Pyridines; Pyrroles; Signal Transduction; Trypanosoma cruzi
Página de inicio:200
Página de fin:209
Título revista:European Journal of Immunology
Título revista abreviado:Eur. J. Immunol.
CAS:2 (2 amino 3 methoxyphenyl)chromone, 167869-21-8; 4 (4 fluorophenyl) 2 (4 methylsulfinylphenyl) 5 (4 pyridyl)imidazole, 152121-47-6; arginase, 9000-96-8; arginine, 1119-34-2, 15595-35-4, 7004-12-8, 74-79-3; calphostin C, 121263-19-2; cysteine proteinase, 37353-41-6; genistein, 446-72-0; kt 5720, 108068-98-0; mitogen activated protein kinase, 142243-02-5; nitric oxide, 10102-43-9; protein tyrosine kinase, 80449-02-1; urea, 57-13-6; Arginase, EC; Arginine, 74-79-3; Carbazoles; cruzipain, EC 3.4.22.-; Cyclic AMP-Dependent Protein Kinases, EC; Cysteine Endopeptidases, EC 3.4.22.-; Genistein, 446-72-0; Growth Inhibitors; Imidazoles; Indoles; KT 5720, 108068-98-0; Mitogen-Activated Protein Kinases, EC; N(omega)-hydroxyarginine, 53054-07-2; p38 Mitogen-Activated Protein Kinases, EC; Protein-Tyrosine Kinases, EC; Pyridines; Pyrroles; SB 203580


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---------- APA ----------
Stempin, C.C., Tanos, T.B., Coso, O.A. & Cerbán, F.M. (2004) . Arginase induction promotes Trypanosoma cruzi intracellular replication of Cruzipain-treated J774 cells through the activation of multiple signaling pathways. European Journal of Immunology, 34(1), 200-209.
---------- CHICAGO ----------
Stempin, C.C., Tanos, T.B., Coso, O.A., Cerbán, F.M. "Arginase induction promotes Trypanosoma cruzi intracellular replication of Cruzipain-treated J774 cells through the activation of multiple signaling pathways" . European Journal of Immunology 34, no. 1 (2004) : 200-209.
---------- MLA ----------
Stempin, C.C., Tanos, T.B., Coso, O.A., Cerbán, F.M. "Arginase induction promotes Trypanosoma cruzi intracellular replication of Cruzipain-treated J774 cells through the activation of multiple signaling pathways" . European Journal of Immunology, vol. 34, no. 1, 2004, pp. 200-209.
---------- VANCOUVER ----------
Stempin, C.C., Tanos, T.B., Coso, O.A., Cerbán, F.M. Arginase induction promotes Trypanosoma cruzi intracellular replication of Cruzipain-treated J774 cells through the activation of multiple signaling pathways. Eur. J. Immunol. 2004;34(1):200-209.