Gold nanoparticles (AuNPs) are considered nontoxic upon acute exposure, at least when they are equal or above 5 nm size. However, the safeguard mechanisms contributing to maintain cell viability are scarcely explored so far. Here, we investigated the cyto-protective role of Glyoxalase 1 (Glo1), a key enzyme involved in the control of deleterious dicarbonyl stress, in two human cell types of the respiratory tract, after an acute exposure to AuNPs with a main size of 5 nm. We found that the redox sensitive Nrf-2-mediated up-regulation of Glo1 was crucial to protect cells from AuNPs-induced toxicity. However, cells challenged with a pro-inflammatory/pro-oxidative insult become susceptible to the pro-apoptotic effect of AuNPs. Notably, the surviving cells undergo epigenetic changes associated with the onset of a partial epithelial to mesenchymal transition (EMT) process (metastable phenotype), driven by the increase in dicarbonyl stress, consequent to Glo1 inactivation. As a physiological respiratory epithelium is required for the normal respiratory function, the knowledge of the protective mechanisms avoiding or (when challenged) promoting its modification/damage might provide insight into the genesis, and, most importantly, prevention of potential health effects that might occur in subjects exposed to AuNPs, through targeted surveillance programs, at least under specific influencing factors.

中文翻译：

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氧化还原敏感的乙二醛酶1上调对于保护人的肺细胞免受金纳米颗粒的毒性至关重要。

金纳米颗粒（AuNP）至少在当其等于或大于5 nm大小时，被认为无毒。然而，迄今为止几乎没有探索有助于维持细胞生存力的保护机制。在这里，我们研究了乙二醛酶1（Glo1）的细胞保护作用，该酶是控制两种人呼吸道细胞中的有害二羰基应激的关键酶，急性暴露于主要大小为5的AuNP后纳米 我们发现，氧化还原敏感的Nrf-2介导的Glo1的上调对于保护细胞免受AuNPs诱导的毒性至关重要。然而，受到促炎/促氧化损伤的细胞变得易受AuNPs促凋亡作用的影响。值得注意的是 存活的细胞经历表观遗传学变化，这种变化与部分上皮向间充质转变（EMT）过程（可转移表型）的发生有关，这是由于Glo1失活导致二羰基应力增加所致。由于生理呼吸道上皮是正常呼吸功能所必需的，因此了解避免或（当受到挑战时）促进其修饰/破坏的保护机制的知识可能会提供其发生的见解，最重要的是，防止可能发生的潜在健康影响至少在特定的影响因素下，通过有针对性的监测计划对暴露于AuNPs的受试者进行治疗。