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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Autores principales: Tanos, Tamara, Coso, Omar Adrian
Publicado: 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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spelling 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 AT tanostamara arginaseinductionpromotestrypanosomacruziintracellularreplicationofcruzipaintreatedj774cellsthroughtheactivationofmultiplesignalingpathways
AT cosoomaradrian arginaseinductionpromotestrypanosomacruziintracellularreplicationofcruzipaintreatedj774cellsthroughtheactivationofmultiplesignalingpathways
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