DNA damage and oxidative stress in human cells infected by Trypanosoma cruzi

• DOI: 10.1371/journal.ppat.1009502
• Publication Date: 2021-04-07T19:00:11Z
• Authors: Pilar T. V. Flore...; Davi Mendes; Francisca Nathali...; Davi J. Martins; Julia P. C. Cunha; Renato A. Mortara; Carlos F. M. Menck
• Keywords: PARP1

Trypanosoma cruzi is the etiologic agent of Chagas’ disease. Infected cells with T . activate several responses that promote unbalance reactive oxygen species (ROS) may cause DNA damage cellular including repair processes. In this work, HeLa and AC16 human cardiomyocyte cell line were infected to investigate host at genome level during parasites intracellular life cycle. fact, alkaline sensitive sites oxidized bases detected in genetic material particularly early stages infection. These lesions accompanied by phosphorylation histone H2Ax, inducing γH2Ax, a marker genotoxic stress. Moreover, Poly [ADP-ribose] polymerase-1 (PARP1) 8-oxoguanine glycosylase (OGG1) are recruited nuclei, indicating activation process. cells, chromatin-associated proteins carbonylated, as possible consequence oxidative stress nuclear factor erythroid 2–related 2 (NRF2) induced after infection, suggesting antioxidant defenses activated. However, late NRF2 downregulated. Interestingly, treated glutathione precursor, N-acetyl cysteine, activator (Sulforaphane), also Benznidonazol (BNZ) reduce parasite burst significantly, damage. data indicate balance induction play role process infection itself, interference these processes hamper revealing potential target pathways for therapy support.