Department of Pharmacology, Medical University of Bialystok, Mickiewicza 2c, Bialystok 15-222, Poland.
Department of Pharmacology, Medical University of Bialystok, Mickiewicza 2c, Bialystok 15-222, Poland.
Respir Physiol Neurobiol. 2023 Oct;316:104140. doi: 10.1016/j.resp.2023.104140. Epub 2023 Aug 14.
Fine airborne particulate matter enter the respiratory system, induce oxidative stress and initiate DNA damage. The aim of our study was the estimation of cell viability, oxidative stress, DNA damage, cell cycle alterations and activation of histone H2A.X. Experiments were done on lung alveolar epithelial (A549) cells grown for 24 h with 200 µg mL coarse carbon black (CB), or nanoparticulate CB (NPCB). Neither CB nor glutathione depletion altered cell viability, growth rates, and H2A.X expression while NPCB decreased cell viability, increased oxidative stress and DNA damage. The cell cycle was blocked at G0/G1. NPCB but not CB increased expression and activation of H2A.X at mRNA and protein levels. Co-expression data point to γH2A.X as a major NPCB target, and show the interdependence of γH2A.X and oxidative stress. We conclude, that NPCB increases γ-H2A.X expression in A549 cells at mRNA and protein levels and stimulates H2A.X (Ser139), phosphorylation, associated with oxidative stress, the DNA damage response and G1 cell cycle arrest.
细颗粒物进入呼吸系统，引起氧化应激并引发 DNA 损伤。我们的研究目的是评估细胞活力、氧化应激、DNA 损伤、细胞周期改变和组蛋白 H2A.X 的激活。将培养 24 小时的肺肺泡上皮（A549）细胞与 200µg mL 的粗碳黑（CB）或纳米颗粒碳黑（NPCB）一起进行实验。CB 或谷胱甘肽耗竭既不改变细胞活力、生长速率，也不改变 H2A.X 的表达，而 NPCB 则降低细胞活力，增加氧化应激和 DNA 损伤。细胞周期被阻滞在 G0/G1 期。NPCB 但不是 CB 增加了 mRNA 和蛋白质水平的 H2A.X 的表达和激活。共表达数据表明 γH2A.X 是 NPCB 的主要靶标，并显示了 γH2A.X 和氧化应激的相互依赖性。我们得出结论，NPCB 在 A549 细胞中增加 γ-H2A.X 的 mRNA 和蛋白质水平的表达，并刺激 H2A.X（Ser139）磷酸化，与氧化应激、DNA 损伤反应和 G1 细胞周期阻滞相关。
