| Full text | |
| Author(s): |
Florentino, P. T. V.
;
Vitorino, F. N. L.
;
Mendes, D.
;
da Cunha, J. P. C.
;
Menck, C. F. M.
Total Authors: 5
|
| Document type: | Journal article |
| Source: | JOURNAL OF PROTEOMICS; v. 272, p. 11-pg., 2023-02-10. |
| Abstract | |
Chagas disease is endemic in 22 Latin American countries, with approximately 8 million individuals infected worldwide and 10,000 deaths yearly. Trypanosoma cruzi presents an intracellular life cycle in mammalian hosts to sustain infection. Parasite infection activates host cell responses, promoting an unbalance in reactive oxygen species (ROS) in the intracellular environment inducing genomic DNA lesions in the host cell during infection. To further understand changes in host cell chromatin induced by parasite infection, we investigated alterations in chromatin caused by infection by performing quantitative proteomic analysis. DNA Damage Repair proteins, such as Poly-ADP-ribose Polymerase 1 (PARP-1) and X-Ray Repair Cross Complementing 6 (XRRC6), were recruited to the chromatin during infection. Also, changes in chromatin remodeling enzymes suggest that parasite infection may shape the epigenome of the host cells. Interestingly, the abundance of oxidative phosphorylation mitochondrial and vesicle-mediated transport proteins increased in the host chromatin at the final stages of infection. In addition, Apoptosis-inducing Factor (AIF) is translocated to the host cell nucleus upon infection, suggesting that cells enter parthanatos type of death. Altogether, this study reveals how parasites interfere with the host cells' responses at the chromatin level leading to significant crosstalk that support and disseminate infection. Significance: The present study provides novel insights into the effects of Trypanosoma cruzi on the chromatin from the host cell. This manuscript investigated proteomic alterations in chromatin caused by parasite infection at early and late infection phases by performing a quantitative proteomic analysis. In this study, we revealed that parasites interfere with DNA metabolism in the early and late stages of infection. We identified that proteins related to DNA damage repair, oxidative phosphorylation, and vesicle-mediated transport have increased abundance at the host chromatin. Additionally, we have observed that Apoptosis-inducing Factor is translocated to the host cell nucleus upon infection, suggesting that the parasites could lead the cells to enter Parthanatos as a form of programmed cell death. The findings improve our understanding on how the parasites modulate the host cell chromatin to disseminate infection. In this study, we suggest a mechanistic parasite action towards host nucleus that could be used to indicate targets for future treatments. (AU) | |
| FAPESP's process: | 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling |
| Grantee: | Hugo Aguirre Armelin |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg) |
| Grantee: | Carlos Frederico Martins Menck |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 17/18344-9 - Quantitative chromatin proteomics upon FGF2 treatment: analysis of transcriptional regulation and involvement of cdc42 |
| Grantee: | Francisca Nathália de Luna Vitorino |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center |
| Grantee: | Mayana Zatz |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 18/15553-9 - Going deeper into Trypanosoma cruzi chromatin regulation: identifying new players and quizzing its impact on a potential transcription control |
| Grantee: | Julia Pinheiro Chagas da Cunha |
| Support Opportunities: | Research Grants - Young Investigators Grants - Phase 2 |