Daily exposure of the skin to UVA radiation causes oxidative modifications to cellular components and biomolecules. These include proteins involved in the metabolism and cytoprotection of fibroblasts, and their modification can contribute to the disruption of cell function and the development of skin disorders. Therefore, there remains a need for highly active cytoprotective compounds with antioxidant properties. The purpose of this study was to investigate the effect of ascorbic acid on the activity of rutin against UVA-induced changes in the proteome of human fibroblasts. All analyses were carried out on fibroblasts cultured in a three-dimensional system exposed to UVA radiation and incubated with rutin and ascorbic acid. Their proteomic profile was analyzed using nano-HPLC, which revealed 150 proteins whose expression was significantly altered between treatment conditions. UVA radiation led to changes in the expression of 82 proteins. However, some of these changes were mitigated by rutin and ascorbic acid separately (23 and 25 proteins, respectively) and rutin and ascorbic acid together (23 proteins). UVA radiation has led to the upregulation of proteins involved in gene expression, catalytic processes and antioxidant pathways, and downregulation of proteins with binding activity. Nevertheless, rutin and ascorbic acid used separately or together have countered these changes to varying degrees. Moreover, rutin and ascorbic acid stimulated fibroblasts irradiated by UVA to increase the expression of the signalling molecules responsible for the opening of the transmembrane channels. In the context of the results obtained, the observed cytoprotective effect of the cooperation of rutin and ascorbic acid results not only from the overlapping properties of the compounds. The effect of rutin alone is probably inhibited by its limited bioavailability. Therefore, its interaction with ascorbic acid increases membrane penetration and improves the cytoprotective effect on skin fibroblasts.

中文翻译：

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天然外源抗氧化剂防御UVA辐射干扰的人类皮肤成纤维细胞蛋白质组的变化

皮肤每天暴露于UVA辐射会引起细胞成分和生物分子的氧化修饰。这些包括参与成纤维细胞代谢和细胞保护的蛋白质，其修饰可导致细胞功能破坏和皮肤疾病的发展。因此，仍然需要具有抗氧化剂性质的高活性细胞保护化合物。这项研究的目的是研究抗坏血酸对芦丁活性的抗紫外线作用的影响，该活性对人成纤维细胞蛋白质组中的UVA诱导的变化有帮助。所有分析都是在暴露于UVA辐射的三维系统中培养的成纤维细胞上进行的，并与芦丁和抗坏血酸一起孵育。使用纳米HPLC分析了它们的蛋白质组图谱，它揭示了150种蛋白质，其表达在不同处理条件之间显着改变。UVA辐射导致82种蛋白表达的变化。但是，其中一些变化被芦丁和抗坏血酸（分别为23和25个蛋白质）以及芦丁和抗坏血酸（分别为23个蛋白质）减轻了。UVA辐射导致涉及基因表达，催化过程和抗氧化剂途径的蛋白质上调，以及具有结合活性的蛋白质下调。尽管如此，单独或一起使用的芦丁和抗坏血酸已在不同程度上抵消了这些变化。此外，芦丁和抗坏血酸刺激了被UVA照射的成纤维细胞，从而增加了负责跨膜通道开放的信号分子的表达。在获得的结果的背景下，观察到的芦丁和抗坏血酸协同作用的细胞保护作用不仅是由于化合物的重叠性质。单独的芦丁的作用可能被其有限的生物利用度所抑制。因此，其与抗坏血酸的相互作用增加了膜的渗透性并改善了对皮肤成纤维细胞的细胞保护作用。