ArticleThe Journal of biological chemistry2010
Trypanosoma cruzi induces the reactive oxygen species-PARP-1-RelA pathway for up-regulation of cytokine expression in cardiomyocytes.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 118 citations in OpenAlex.
- T cells responding to Trypanosoma cruzi detected by membrane TNF-α and CD154 in chagasic patients.Immunity, inflammation and disease · 2018Trial
- Empagliflozin improves metabolism and prevents myocardial and coronary dysfunction in streptozotocin-diabetic and non-diabetic rats subjected to ischemia/reperfusion.Basic research in cardiology · 2026Article
- Harnessing the novel safeguarding role of Selenoprotein T in age-related myocardial left and right decline through the ferroptosis-mitochondrial axis.Journal of translational medicine · 2026Article
- Effect of curcumin on methotrexate-induced ovarian damage and follicle reserve in rats: the role of PARP-1 and P53.Annals of medicine · 2025Article
- Effect of heme oxygenase-1 on the expression of interferon-stimulated genes.Journal of inflammation (London, England) · 2025Article
- Fexinidazole results in specific effects on DNA synthesis and DNA damage in the African trypanosome.PLoS neglected tropical diseases · 2025Article
- PARP1-NFATc1-PD1 pathway of maturation and stability of CD8iScience · 2025Article
- Cardiac alterations induced by Trypanosoma cruzi extracellular vesicles and immune complexes.PLoS neglected tropical diseases · 2025Article
- Single-cell transcriptome profiling implicates the psychological stress-induced disruption of spermatogenesis.Molecular therapy. Nucleic acids · 2024Article
- Trypanosoma cruzi infection induces DNA double-strand breaks and activates DNA damage response pathway in host epithelial cells.Scientific reports · 2024Article
- PARPs and ADP-Ribosylation in Chronic Inflammation: A Focus on Macrophages.Pathogens (Basel, Switzerland) · 2023Review
- Roles of ADP-Ribosylation during Infection Establishment byPathogens (Basel, Switzerland) · 2023Review
- The roles of COX-2 in protozoan infection.Frontiers in immunology · 2023Review
- mTOR regulation of metabolism limits LPS-induced monocyte inflammatory and procoagulant responses.Communications biology · 2022Article
- Cellular Stress and Senescence Induction duringTropical medicine and infectious disease · 2022Review
- The Role of Nuclear Factor Kappa B (NF-κB) in the Immune Response against Parasites.Pathogens (Basel, Switzerland) · 2022Review
- Article
- Platelets, Macrophages, and Thromboinflammation in Chagas Disease.Journal of inflammation research · 2022Review
- The state of the art of extracellular vesicle research in protozoan infection.Frontiers in genetics · 2022Review
- The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance.Frontiers in cellular and infection microbiology · 2022Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
In this study, we demonstrate that human cardiomyocytes (AC16) produce reactive oxygen species (ROS) and inflammatory cytokines in response to Trypanosoma cruzi. ROS were primarily produced by mitochondria, some of which diffused to cytosol of infected cardiomyocytes. These ROS resulted in an increase in 8-hydroxyguanine lesions and DNA fragmentation that signaled PARP-1 activation evidenced by poly(ADP-ribose) (PAR) modification of PARP-1 and other proteins in infected cardiomyocytes. Phenyl-alpha-tert-butylnitrone blocked the mitochondrial ROS (mtROS) formation, DNA damage, and PARP-1 activation in infected cardiomyocytes. Further inhibition studies demonstrated that ROS and PARP-1 signaled TNF-alpha and IL-1beta expression in infected cardiomyocytes. ROS directly signaled the nuclear translocation of RelA (p65), NF-kappaB activation, and cytokine gene expression. PARP-1 exhibited no direct interaction with p65 and did not signal its translocation to nuclei in infected cardiomyocytes. Instead, PARP-1 contributed to PAR modification of p65-interacting nuclear proteins and assembly of the NF-kappaB transcription complex. PJ34 (PARP-1 inhibitor) also prevented mitochondrial poly(ADP-ribosyl)ation (PARylation) and ROS formation. We conclude that T. cruzi-mediated mtROS provide primary stimulus for PARP-1-NF-kappaB activation and cytokine gene expression in infected cardiomyocytes. PAR modification of mitochondrial membranes then results in a feedback cycle of mtROS formation and DNA damage/PARP-1 activation. ROS, either through direct modulation of cytosolic NF-kappaB, or via PARP-1-dependent PAR modification of p65-interacting nuclear proteins, contributes to cytokine gene expression. Our results demonstrate a link between ROS and inflammatory responses in cardiomyocytes infected by T. cruzi and provide a clue to the pathomechanism of sustained inflammation in Chagas disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.