对于在许多细胞类型和组织中广泛表达的细胞内蛋白Paraoxonase-2 (PON2)，已知其水平受到氧化应激和由遗传和环境因素引起的细胞凋亡的调节。然而，迄今为止尚未探索的一个环境因素是紫外线A（UVA）辐射对人体皮肤成纤维细胞（HuDe）中PON2调节的影响，而UVA是阳光中的氧化成分。已知过量的UVA辐射通过经由氧化应激介导的活性氧（ROS）调节细胞内信号通路，进而对皮肤造成直接和间接的损伤，这些ROS调节了参与不同过程（例如皮肤光老化和癌症）的下游基因的表达。因此，本研究的目的是研究HuDe在接受UVA辐射（270 kJ/m2）后PON2在蛋白质表达和酶活性方面的调节。我们的结果显示，在UVA暴露后，PON2的表达上调，并且其水平和活性在后暴露阶段以时间依赖的方式下降（2-24小时）。PON2水平的趋势与UVA诱导的ROS的时间课程研究相一致。为了证实这一点，我们还在使用SPF30防晒霜作为屏障剂的情况下进行了实验，以逆转PON2在UVA暴露后0小时和2小时时的调节，并且还检查了其他光氧化应激标记物（NF-KB、γH2AX、高级糖基化终产物）。总体而言，我们的结果表明，PON2的上调可能与细胞内ROS增加有关，可能在减轻UVA介导损伤和预防UV暴露后果方面起到重要作用，因此在皮肤成纤维细胞中可能是UVA诱导损伤的早期反应的新标记物。版权所有©2023 Elsevier B.V.发表。

Paraoxonase-2 (PON2) is an intracellular protein widely expressed in many cell types and tissues, whose levels are known to be modulated by oxidative stress and apoptosis induced by genetic and environmental factors. However, an environmental factor that has not been previously explored is the effect of ultraviolet A radiation (UVA), the oxidizing component of sunlight, on the modulation of PON2 in human dermal fibroblasts (HuDe). Excessive UVA radiation is known to cause direct and indirect skin damage by influencing intracellular signalling pathways through oxidative stress mediated by reactive oxygen species (ROS) that modulate the expression of downstream genes involved in different processes, e.g. skin photoaging and cancer. The aim of this study was therefore to investigate the modulation of PON2 in terms of protein expression and enzyme activity in HuDe exposed to UVA (270 kJ/m2). Our results show that PON2 is up-regulated immediately after UVA exposure and that its levels and activity decrease in the post-exposure phase, in a time-dependent manner (2-24 h). The trend in PON2 levels mirror the time-course study of UVA-induced ROS. To confirm this, experiments were also performed in the presence of a SPF30 sunscreen used as shielding agent to revert modulation of PON2 at 0 and 2 h post-UVA exposure where other markers of photo-oxidative stress were also examined (NF-KB, γH2AX, advanced glycation end products). Overall, our results show that the upregulation of PON2 might be related to the increase in intracellular ROS and may play an important role in mitigation of UVA-mediated damage and in the prevention of the consequences of UV exposure, thus representing a new marker of early-response to UVA-induced damage in skin fibroblasts.Copyright © 2023. Published by Elsevier B.V.