Institute of Life and Health Engineering, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632, China.
Toxicol In Vitro. 2010 Jun;24(4):1098-104. doi: 10.1016/j.tiv.2010.03.011. Epub 2010 Mar 21.
Heavy metals may exert their acute and chronic effects on the human skin through stress signals. In the present study, 2DE-based proteomics was used to analyze the protein expression in human keratinocytes exposed to heavy metals, chromium and neodymium, and 10 proteins with altered expression were identified. Among these proteins, small heat shock protein 27 (HSP27) was up-regulated significantly and the up-regulation was validated by Western blot and immunofluorescence. In addition, the mRNA expression level of HSP27 markedly increased as detected by quantitative PCR. More interestingly, the ratio of phosphorylated HSP27 and total HSP27 significantly decreased in keratinocytes treated with the heavy metals. These findings suggested that heavy metals reduced the phosphorylation level of HSP27, and that the ratio of p-HSP27 and HSP27 may represent a potential marker or additional endpoint for the hazard assessment of skin irritation caused by chemical products.
重金属可能通过应激信号对人体皮肤产生急性和慢性影响。在本研究中,采用基于 2DE 的蛋白质组学方法分析了暴露于重金属铬和钕的人角质形成细胞中的蛋白质表达,鉴定出 10 种表达发生改变的蛋白质。其中,小热休克蛋白 27(HSP27)显著上调,Western blot 和免疫荧光验证了这一点。此外,通过定量 PCR 检测到 HSP27 的 mRNA 表达水平明显增加。更有趣的是,重金属处理的角质形成细胞中 HSP27 的磷酸化水平显著降低。这些发现表明,重金属降低了 HSP27 的磷酸化水平,p-HSP27 和 HSP27 的比值可能代表化学产品引起皮肤刺激的危害评估的潜在标志物或附加终点。