PDF(Pubmed)
Abstract：
Phthalates are extensively employed plasticizers crucial for conferring flexibility and plasticity to polyvinyl chloride. Phthalates, including DEHP (di(2-ethylhexyl)phthalate), present in diverse products, have been identified in fine dust and are capable of infiltrating the body, potentially posing health hazards. Importantly, melanocytes, existing at the basal layer of the epidermis, are susceptible to toxic substances. In our study, we employed the 3D human pigmented epidermis model, MelanoDerm™, along with the B16F10 murine melanoma cell line, to examine the influence of DEHP exposure on melanocytes. The exposure to low concentrations of DEHP (~ 5 μM), resulted in the extension of melanocyte dendrites, indicating the stimulation of melanocytes. Analysis of gene expression and protein profiles unveiled the up-regulation of MITF, Arpc2, and TRP1 genes subsequent to DEHP exposure, indicating alterations in cytoskeletal and melanosome-related genetic and protein components in melanocytes. Notably, increased pigmentation was observed in MelanoDerm™ following DEHP exposure. DEHP-stimulated reactive oxygen species generation appeared to be involved in these events since the antioxidant, ascorbic acid attenuated ROS generation and MITF upregulation. Collectively, our study demonstrated that DEHP exposure can induce cytoskeletal disturbance and skin pigmentation through oxidative stress.
摘要：
邻苯二甲酸酯是广泛使用的增塑剂，对于赋予聚氯乙烯柔韧性和可塑性至关重要。邻苯二甲酸酯,包括DEHP（邻苯二甲酸二（2-乙基己基）酯），在不同的产品中，已经被发现在细小的灰尘中，并且能够渗透到身体中，潜在的健康危害。重要的是,黑素细胞,存在于表皮的基底层，容易受到有毒物质的影响。在我们的研究中,我们使用了3D人类色素表皮模型，MelanoDerm™,以及B16F10鼠黑色素瘤细胞系，研究DEHP暴露对黑素细胞的影响。暴露于低浓度的DEHP（~5μM），导致黑素细胞树突的延伸，显示黑素细胞的刺激。基因表达和蛋白质谱分析揭示了MITF的上调，DEHP暴露后的Arpc2和TRP1基因，表明黑素细胞中细胞骨架和黑素相关遗传和蛋白质成分的改变。值得注意的是,在DEHP暴露后,在MelanoDerm™中观察到色素沉着增加。DEHP刺激的活性氧的产生似乎参与了这些事件，因为抗氧化剂，抗坏血酸减弱了ROS的产生和MITF的上调。总的来说，我们的研究表明，DEHP暴露可以通过氧化应激诱导细胞骨架紊乱和皮肤色素沉着。
