Traynor Nicola J, McKenzie Roddie C, Beckett Geoffrey J, Gibbs Neil K
Photobiology Unit, Ninewells Hospital, University of Dundee, Dundee, UK.
Photodermatol Photoimmunol Photomed. 2006 Dec;22(6):297-303. doi: 10.1111/j.1600-0781.2006.00256.x.
Ultraviolet (UV) radiation damages the cellular DNA of skin cells. In response, wild-type p53 protein accumulates in irradiated cells and the stabilized and transactivated protein can then induce genes involved in cell cycle arrest in G1, or in the initiation of apoptosis. Selenium protects cells from UVB-induced cell death and apoptosis by mechanisms which are unclear, although recent reports suggest that selenium protects against UV-induced cell damage by inducing DNA repair enzymes and transactivating p53.
We examined whether selenomethionine could protect human skin cells from UV radiation-induced p53 transactivation, using a pRGCDeltafos-lacZ p53-dependent reporter construct stably transfected in an amelanotic melanoma cell line (Arn-8) which expresses wild-type p53. Cells were pretreated with or without selenomethionine and then irradiated with broadband UVB (approximately 270-350 nm); 0-30 mJ/cm2 from a Phillips TL100 W/12 lamp.
The percentage of cells with transcriptionally active p53 increased dose dependently up to 20 mJ/cm2 UVB. Treatment with 50 microM selenomethionine for 24 h both pre- and post-irradiation, significantly diminished p53 activation by 30-43% across the UV dose range (P=0.0085, n=5 independent experiments) and decreased UV-induced p53 protein accumulation as assessed by Western blotting.
We conclude that selenomethionine inhibits broad band UVB-induced p53 transactivation and protein accumulation and that this effect correlates with reported protective effects of selenium against UV-induced DNA damage.
紫外线（UV）辐射会损伤皮肤细胞的细胞核DNA。作为响应，野生型p53蛋白会在受辐射的细胞中积累，然后稳定并被激活的该蛋白能够诱导参与G1期细胞周期停滞或凋亡起始的基因。尽管最近的报道表明硒通过诱导DNA修复酶和激活p53来保护细胞免受紫外线诱导的损伤，但硒通过何种机制保护细胞免受UVB诱导的细胞死亡和凋亡尚不清楚。
我们使用稳定转染入表达野生型p53的无黑色素黑色素瘤细胞系（Arn-8）中的pRGCDeltafos-lacZ p53依赖性报告构建体，研究了硒代蛋氨酸是否能保护人类皮肤细胞免受紫外线辐射诱导的p53激活。细胞在有无硒代蛋氨酸的情况下进行预处理，然后用宽带UVB（约270 - 350nm）照射；来自飞利浦TL100 W/12灯的0 - 30 mJ/cm²。
转录活性p53的细胞百分比在UVB剂量高达20 mJ/cm²时呈剂量依赖性增加。在照射前和照射后用50 microM硒代蛋氨酸处理24小时，在整个紫外线剂量范围内，p53激活显著降低了30 - 43%（P = 0.0085，n = 5个独立实验），并且通过蛋白质印迹法评估，紫外线诱导的p53蛋白积累减少。
我们得出结论，硒代蛋氨酸可抑制宽带UVB诱导的p53激活和蛋白积累，并且这种作用与报道的硒对紫外线诱导的DNA损伤的保护作用相关。
