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DNA damage and oxidative stress in human cells infected by Trypanosoma cruzi
Trypanosoma cruzi is the etiologic agent of Chagas’ disease. Infected cells with T. cruzi activate several responses that promote unbalance of reactive oxygen species (ROS) that may cause DNA damage that activate cellular responses including DNA repair processes. In this work, HeLa cells and AC16 hu...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087042/ https://www.ncbi.nlm.nih.gov/pubmed/33826673 http://dx.doi.org/10.1371/journal.ppat.1009502 |
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author | Florentino, Pilar T. V. Mendes, Davi Vitorino, Francisca Nathalia L. Martins, Davi J. Cunha, Julia P. C. Mortara, Renato A. Menck, Carlos F. M. |
author_facet | Florentino, Pilar T. V. Mendes, Davi Vitorino, Francisca Nathalia L. Martins, Davi J. Cunha, Julia P. C. Mortara, Renato A. Menck, Carlos F. M. |
author_sort | Florentino, Pilar T. V. |
collection | PubMed |
description | Trypanosoma cruzi is the etiologic agent of Chagas’ disease. Infected cells with T. cruzi activate several responses that promote unbalance of reactive oxygen species (ROS) that may cause DNA damage that activate cellular responses including DNA repair processes. In this work, HeLa cells and AC16 human cardiomyocyte cell line were infected with T. cruzi to investigate host cell responses at genome level during parasites intracellular life cycle. In fact, alkaline sensitive sites and oxidized DNA bases were detected in the host cell genetic material particularly in early stages of infection. These DNA lesions were accompanied by phosphorylation of the histone H2Ax, inducing γH2Ax, a marker of genotoxic stress. Moreover, Poly [ADP-ribose] polymerase-1 (PARP1) and 8-oxoguanine glycosylase (OGG1) are recruited to host cell nuclei, indicating activation of the DNA repair process. In infected cells, chromatin-associated proteins are carbonylated, as a possible consequence of oxidative stress and the nuclear factor erythroid 2–related factor 2 (NRF2) is induced early after infection, suggesting that the host cell antioxidant defenses are activated. However, at late stages of infection, NRF2 is downregulated. Interestingly, host cells treated with glutathione precursor, N-acetyl cysteine, NRF2 activator (Sulforaphane), and also Benznidonazol (BNZ) reduce parasite burst significantly, and DNA damage. These data indicate that the balance of oxidative stress and DNA damage induction in host cells may play a role during the process of infection itself, and interference in these processes may hamper T. cruzi infection, revealing potential target pathways for the therapy support. |
format | Online Article Text |
id | pubmed-8087042 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-80870422021-05-06 DNA damage and oxidative stress in human cells infected by Trypanosoma cruzi Florentino, Pilar T. V. Mendes, Davi Vitorino, Francisca Nathalia L. Martins, Davi J. Cunha, Julia P. C. Mortara, Renato A. Menck, Carlos F. M. PLoS Pathog Research Article Trypanosoma cruzi is the etiologic agent of Chagas’ disease. Infected cells with T. cruzi activate several responses that promote unbalance of reactive oxygen species (ROS) that may cause DNA damage that activate cellular responses including DNA repair processes. In this work, HeLa cells and AC16 human cardiomyocyte cell line were infected with T. cruzi to investigate host cell responses at genome level during parasites intracellular life cycle. In fact, alkaline sensitive sites and oxidized DNA bases were detected in the host cell genetic material particularly in early stages of infection. These DNA lesions were accompanied by phosphorylation of the histone H2Ax, inducing γH2Ax, a marker of genotoxic stress. Moreover, Poly [ADP-ribose] polymerase-1 (PARP1) and 8-oxoguanine glycosylase (OGG1) are recruited to host cell nuclei, indicating activation of the DNA repair process. In infected cells, chromatin-associated proteins are carbonylated, as a possible consequence of oxidative stress and the nuclear factor erythroid 2–related factor 2 (NRF2) is induced early after infection, suggesting that the host cell antioxidant defenses are activated. However, at late stages of infection, NRF2 is downregulated. Interestingly, host cells treated with glutathione precursor, N-acetyl cysteine, NRF2 activator (Sulforaphane), and also Benznidonazol (BNZ) reduce parasite burst significantly, and DNA damage. These data indicate that the balance of oxidative stress and DNA damage induction in host cells may play a role during the process of infection itself, and interference in these processes may hamper T. cruzi infection, revealing potential target pathways for the therapy support. Public Library of Science 2021-04-07 /pmc/articles/PMC8087042/ /pubmed/33826673 http://dx.doi.org/10.1371/journal.ppat.1009502 Text en © 2021 Florentino et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Florentino, Pilar T. V. Mendes, Davi Vitorino, Francisca Nathalia L. Martins, Davi J. Cunha, Julia P. C. Mortara, Renato A. Menck, Carlos F. M. DNA damage and oxidative stress in human cells infected by Trypanosoma cruzi |
title | DNA damage and oxidative stress in human cells infected by Trypanosoma cruzi |
title_full | DNA damage and oxidative stress in human cells infected by Trypanosoma cruzi |
title_fullStr | DNA damage and oxidative stress in human cells infected by Trypanosoma cruzi |
title_full_unstemmed | DNA damage and oxidative stress in human cells infected by Trypanosoma cruzi |
title_short | DNA damage and oxidative stress in human cells infected by Trypanosoma cruzi |
title_sort | dna damage and oxidative stress in human cells infected by trypanosoma cruzi |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087042/ https://www.ncbi.nlm.nih.gov/pubmed/33826673 http://dx.doi.org/10.1371/journal.ppat.1009502 |
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