Role of cyclooxygenase-2 in Trypanosoma cruzi survival in the early stages of parasite host-cell interaction

Chagas disease, caused by the intracellular protozoan Trypanosoma cruzi, is a serious health problem in Latin America. During this parasitic infection, the heart is one of the major organs affected. The pathogenesis of tissue remodelling, particularly regarding cardiomyocyte behaviour after parasite infection and the molecular mechanisms that occur immediately following parasite entry into host cells are not yet completely understood. When cells are infected with T. cruzi, they develop an inflammatory response, in which cyclooxygenase-2 (COX-2) catalyses rate-limiting steps in the arachidonic acid pathway. However, how the parasite interaction modulates COX-2 activity is poorly understood. In this study, the H9c2 cell line was used as our model and we investigated cellular and biochemical aspects during the initial 48 h of parasitic infection. Oscillatory activity of COX-2 was observed, which correlated with the control of the pro-inflammatory environment in infected cells. Interestingly, subcellular trafficking was also verified, correlated with the control of Cox-2 mRNA or the activated COX-2 protein in cells, which is directly connected with the assemble of stress granules structures. Our collective findings suggest that in the very early stage of the T. cruzi-host cell interaction, the parasite is able to modulate the cellular metabolism in order to survives.

• Publication year

  2015

• Venue

  Memórias do Instituto Oswaldo Cruz

• Publication date

  2015-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1590/0074-02760140311PMID 25946241PMCID 4489448
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2013influential reference
• Different parasite inocula determine the modulation of the immune response and outcome of experimental Trypanosoma cruzi infection

  2013cited by this paper
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  2012cited by this paper
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• Aspirin Treatment of Mice Infected with Trypanosoma cruzi and Implications for the Pathogenesis of Chagas Disease

  2011influential reference
• Bioactive lipids in Trypanosoma cruzi infection.

  2011cited by this paper
• The cardioprotective effects of zileuton, a 5-lipoxygenase inhibitor, are mediated by COX-2 via activation of PKC delta.

  2010cited by this paper
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  2010cited by this paper
• Posttranscriptional and posttranslational determinants of cyclooxygenase expression.

  2009cited by this paper
• Modulation of host cell mechanics by Trypanosoma cruzi

  2009cited by this paper
• Trypanosoma cruzi: the role of PGE2 in immune response during the acute phase of experimental infection.

  2008cited by this paper
• Molecular mechanisms of parasite invasion

  2008cited by this paper
• Elongation of polyunsaturated fatty acids in trypanosomatids

  2007cited by this paper
• Thromboxane A2 is a key regulator of pathogenesis during Trypanosoma cruzi infection

  2007influential reference
• Platelet-derived Growth Factor-induced Stabilization of Cyclooxygenase 2 mRNA in Rat Smooth Muscle Cells Requires the c-Src Family of Protein-tyrosine Kinases*

  2007cited by this paper
• Inhibition of the ubiquitin-proteasome system induces stress granule formation.

  2007cited by this paper
• The 19-amino Acid Cassette of Cyclooxygenase-2 Mediates Entry of the Protein into the Endoplasmic Reticulum-associated Degradation System*

  2006cited by this paper
• Molecular basis of mammalian cell invasion by Trypanosoma cruzi.

  2006cited by this paper
• Host Cell Signaling and Trypanosoma cruzi Invasion: Do All Roads Lead to Lysosomes?

  2005cited by this paper
• Cardiac gene expression profiling provides evidence for cytokinopathy as a molecular mechanism in Chagas' disease cardiomyopathy.

  2005influential reference
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  2005cited by this paper
• Stress granules and processing bodies are dynamically linked sites of mRNP remodeling

  2005cited by this paper
• Circulating levels of cyclooxygenase metabolites in experimental Trypanosoma cruzi infections.

  2004cited by this paper
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  2004influential reference
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  2003influential reference
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  2003influential reference
• Coupled mRNA stabilization and translational silencing of cyclooxygenase-2 by a novel RNA binding protein, CUGBP2.

  2003influential reference
• Role for interleukin-1 beta in Trypanosoma cruzi-induced cardiomyocyte hypertrophy.

  2003cited by this paper
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  2002cited by this paper
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  2002cited by this paper
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• RNA CUG Repeats Sequester CUGBP1 and Alter Protein Levels and Activity of CUGBP1*

  2001cited by this paper
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  2001influential reference
• Molecular Cloning: A Laboratory Manual

  2001cited by this paper
• Protein dynamics: implications for nuclear architecture and gene expression.

  2001cited by this paper
• Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy

  2001cited by this paper
• Many pathways to cardiac hypertrophy.

  2000cited by this paper
• Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages

  2000cited by this paper
• Expression of cardiac cytokines and inducible form of nitric oxide synthase (NOS2) in Trypanosoma cruzi-infected mice.

  1999cited by this paper
• Sequence and structure-based prediction of eukaryotic protein phosphorylation sites.

  1999influential reference
• Parasite persistence correlates with disease severity and localization in chronic Chagas' disease.

  1999cited by this paper
• Chagas disease or American trypanosomiasis.

  1998cited by this paper
• Localization of trinucleotide repeat sequences in myotonic dystrophy cells using a single fluorochrome-labeled PNA probe.

  1998cited by this paper
• Altered phosphorylation and intracellular distribution of a (CUG)n triplet repeat RNA-binding protein in patients with myotonic dystrophy and in myotonin protein kinase knockout mice.

  1997cited by this paper
• Lymphocyte muscarinic cholinergic activity and PGE2 involvement in experimental Trypanosoma cruzi infection.

  1996cited by this paper
• Lysophospholipase 1 in Trypanosoma brucei.

  1981cited by this paper
• Properties of a clonal muscle cell line from rat heart.

  1976cited by this paper

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  2018cites this paper
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  2018cites this paper
• Extracellular Vesicles Shed By Trypanosoma cruzi Potentiate Infection and Elicit Lipid Body Formation and PGE2 Production in Murine Macrophages

  2018cites this paper
• Differential expression of proteins in genetically distinct Trypanosoma cruzi samples (TcI and TcII DTUs) isolated from chronic Chagas disease cardiac patients

  2018cites this paper
• Response to Trypanosoma cruzi by Human Blood Cells Enriched with Dentritic Cells Is Controlled by Cyclooxygenase-2 Pathway

  2017influential citation
• Protective effect of aspirin treatment on mouse behavior in the acute phase of experimental infection with Trypanosoma cruzi

  2017cites this paper
• Trypanosoma cruzi: Inhibition of infection of human monocytes by aspirin.

  2017cites this paper
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  2017cites this paper
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