PMID- 33826673
OWN - NLM
STAT- MEDLINE
DCOM- 20210823
LR  - 20240401
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 17
IP  - 4
DP  - 2021 Apr
TI  - DNA damage and oxidative stress in human cells infected by Trypanosoma cruzi.
PG  - e1009502
LID - 10.1371/journal.ppat.1009502 [doi]
LID - e1009502
AB  - 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 gammaH2Ax, 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.
FAU - Florentino, Pilar T V
AU  - Florentino PTV
AUID- ORCID: 0000-0001-8077-8100
AD  - Department of Microbiology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
FAU - Mendes, Davi
AU  - Mendes D
AUID- ORCID: 0000-0002-9524-4424
AD  - Department of Microbiology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
FAU - Vitorino, Francisca Nathalia L
AU  - Vitorino FNL
AUID- ORCID: 0000-0001-8543-2299
AD  - Special Laboratory of Cell Cycle, Butantan Institute, Sao Paulo, Brazil.
FAU - Martins, Davi J
AU  - Martins DJ
AUID- ORCID: 0000-0003-2946-5162
AD  - Department of Microbiology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
FAU - Cunha, Julia P C
AU  - Cunha JPC
AD  - Special Laboratory of Cell Cycle, Butantan Institute, Sao Paulo, Brazil.
FAU - Mortara, Renato A
AU  - Mortara RA
AUID- ORCID: 0000-0002-2311-8349
AD  - Department of Microbiology, Imunology & Parasitology, Escola Paulista de Medicina 
      Federal University of Sao Paulo, Sao Paulo, Brazil.
FAU - Menck, Carlos F M
AU  - Menck CFM
AUID- ORCID: 0000-0003-1941-0694
AD  - Department of Microbiology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210407
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Antioxidants)
RN  - 0 (H2AX protein, human)
RN  - 0 (Histones)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.4.2.30 (PARP1 protein, human)
RN  - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
RN  - EC 3.2.2.- (DNA Glycosylases)
RN  - EC 3.2.2.- (oxoguanine glycosylase 1, human)
SB  - IM
MH  - Antioxidants/metabolism
MH  - Cell Death
MH  - Cell Line
MH  - Chagas Disease/*parasitology
MH  - *DNA Damage
MH  - DNA Glycosylases/genetics/metabolism
MH  - DNA Repair
MH  - Down-Regulation
MH  - HeLa Cells
MH  - Histones/genetics/metabolism
MH  - *Host-Parasite Interactions
MH  - Humans
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - *Oxidative Stress
MH  - Phosphorylation
MH  - Poly (ADP-Ribose) Polymerase-1/genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Trypanosoma cruzi/pathogenicity/*physiology
PMC - PMC8087042
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/04/08 06:00
MHDA- 2021/08/24 06:00
PMCR- 2021/04/07
CRDT- 2021/04/07 17:30
PHST- 2020/08/10 00:00 [received]
PHST- 2021/03/25 00:00 [accepted]
PHST- 2021/04/30 00:00 [revised]
PHST- 2021/04/08 06:00 [pubmed]
PHST- 2021/08/24 06:00 [medline]
PHST- 2021/04/07 17:30 [entrez]
PHST- 2021/04/07 00:00 [pmc-release]
AID - PPATHOGENS-D-20-01757 [pii]
AID - 10.1371/journal.ppat.1009502 [doi]
PST - epublish
SO  - PLoS Pathog. 2021 Apr 7;17(4):e1009502. doi: 10.1371/journal.ppat.1009502. 
      eCollection 2021 Apr.