Arginase induction promotes Trypanosoma cruzi intracellular replication of Cruzipain-treated J774 cells through the activation of multiple signaling pathways
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 argi...
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2004
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Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142980_v34_n1_p200_Stempin http://hdl.handle.net/20.500.12110/paper_00142980_v34_n1_p200_Stempin |
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paper:paper_00142980_v34_n1_p200_Stempin2023-06-08T14:36:47Z Arginase induction promotes Trypanosoma cruzi intracellular replication of Cruzipain-treated J774 cells through the activation of multiple signaling pathways Tanos, Tamara Coso, Omar Adrian 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 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. Fil:Tanos, T.B. 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. 2004 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142980_v34_n1_p200_Stempin http://hdl.handle.net/20.500.12110/paper_00142980_v34_n1_p200_Stempin |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
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 |
spellingShingle |
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 Tanos, Tamara Coso, Omar Adrian Arginase induction promotes Trypanosoma cruzi intracellular replication of Cruzipain-treated J774 cells through the activation of multiple signaling pathways |
topic_facet |
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 |
description |
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. |
author |
Tanos, Tamara Coso, Omar Adrian |
author_facet |
Tanos, Tamara Coso, Omar Adrian |
author_sort |
Tanos, Tamara |
title |
Arginase induction promotes Trypanosoma cruzi intracellular replication of Cruzipain-treated J774 cells through the activation of multiple signaling pathways |
title_short |
Arginase induction promotes Trypanosoma cruzi intracellular replication of Cruzipain-treated J774 cells through the activation of multiple signaling pathways |
title_full |
Arginase induction promotes Trypanosoma cruzi intracellular replication of Cruzipain-treated J774 cells through the activation of multiple signaling pathways |
title_fullStr |
Arginase induction promotes Trypanosoma cruzi intracellular replication of Cruzipain-treated J774 cells through the activation of multiple signaling pathways |
title_full_unstemmed |
Arginase induction promotes Trypanosoma cruzi intracellular replication of Cruzipain-treated J774 cells through the activation of multiple signaling pathways |
title_sort |
arginase induction promotes trypanosoma cruzi intracellular replication of cruzipain-treated j774 cells through the activation of multiple signaling pathways |
publishDate |
2004 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142980_v34_n1_p200_Stempin http://hdl.handle.net/20.500.12110/paper_00142980_v34_n1_p200_Stempin |
work_keys_str_mv |
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_version_ |
1768545401651068928 |