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Host DNA repair response to oxidative damage is modulated by Trypanosoma cruzi in a strain-dependent manner
Acta Tropica ( IF 2.1 ) Pub Date : 2021-09-10 , DOI: 10.1016/j.actatropica.2021.106127
Ester Rose 1 , Aline Moraes 1 , Tatiana Shiroma 1 , Nadjar Nitz 1 , Ana de Cássia Rosa 1 , Riccardo Pratesi 1 , Luciana Hagström 1 , Juliana Lott de Carvalho 1 , Mariana Hecht 1
Affiliation  

The conservation of genomic integrity and stability is essential for cell survival. DNA Damage Responses (DDRs) are considered of paramount importance for all living beings and involve mechanisms of cell cycle regulation and damage-specific DNA repair pathways. Hydrogen peroxide (H2O2) is a compound that, in supraphysiological concentrations, damages biomolecules including the DNA, causing base modifications and strand breaks. There is evidence that Trypanosoma cruzi, the protozoan that causes Chagas disease, interferes in the host cell's DNA metabolism. In order to investigate the influence of T. cruzi infection over the host cell capacity to withstand and repair DNA damage, we analyzed L6 cells infected with Berenice, and Colombiana T. cruzi strains according to their viability, proliferation, morphology, DNA degradation, expression of DNA repair, and cell cycle genes following H2O2 treatment. It was noted that T. cruzi infection might act as either a stressor or a protective element of host DNA, depending on the strain and H2O2 concentration. Cells infected with Berenice strain and treated with 0.8 mM H2O2 presented a reduced DNA damage response intensity (e.g., BER and HR). Infection with T. cruzi Colombiana prevented the activation of DNA repair pathways in response to 0.8mM and 1.6mM H2O2 (NER and MMR). Nevertheless, since cellular viability was not significantly compromised in Colombiana-infected cells following the oxidative insult, it is possible that the parasite directly influenced the host DNA repair machinery. Our results support the notion that T. cruzi is able to modulate the host cell DNA metabolism in a strain-dependent manner, an event which can be explored in future drug development strategies.



中文翻译:

克氏锥虫以依赖菌株的方式调节宿主 DNA 对氧化损伤的修复反应

基因组完整性和稳定性的保护对于细胞存活至关重要。DNA 损伤反应 (DDR) 被认为对所有生物都至关重要,涉及细胞周期调节机制和损伤特异性 DNA 修复途径。过氧化氢 (H 2 O 2 ) 是一种化合物,在超生理浓度下,会破坏包括 DNA 在内的生物分子,导致碱基修饰和链断裂。有证据表明,导致南美锥虫病的原生动物克氏锥虫会干扰宿主细胞的 DNA 代谢。为了调查T. cruzi的影响感染超过宿主细胞承受和修复 DNA 损伤的能力,我们分析了感染 Berenice 和哥伦比亚T. cruzi菌株的L6 细胞,根据它们的活力、增殖、形态、DNA 降解、DNA 修复的表达和细胞周期基因在 H 2 O 2处理。注意到,根据菌株和 H 2 O 2浓度,T. cruzi感染可能充当宿主 DNA 的压力源或保护元素。用 Berenice 菌株感染并用 0.8 mM H 2 O 2处理的细胞表现出降低的 DNA 损伤反应强度(例如,BER 和 HR)。感染T. cruziColumbiana 阻止 DNA 修复途径的激活以响应 0.8mM 和 1.6mM H 2 O 2(NER 和 MMR)。尽管如此,由于在氧化损伤后哥伦比亚感染的细胞中细胞活力并未受到显着影响,因此寄生虫可能直接影响宿主 DNA 修复机制。我们的结果支持这样的观点,即T. cruzi能够以依赖菌株的方式调节宿主细胞 DNA 代谢,这一事件可以在未来的药物开发策略中进行探索。

更新日期:2021-09-27
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