Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis
Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis
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DOI：
10.1096/fj.06-5725fje
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发表时间：
2006-07-01
期刊：
影响因子：
4.8
通讯作者：
Hearing, Vincent J.
中科院分区：
文献类型：
--
作者：
Yamaguchi, Yuji;Takahashi, Kaoruko;Hearing, Vincent J.
黑色素在保护皮肤免受紫外线辐射方面起着重要作用，而黑色素瘤和基底/鳞状细胞癌在白皙/浅色皮肤的个体中更容易发生。我们之前曾报道，黑色素水平与紫外线对不同种族/民族的正常人皮肤的DNA损伤量呈负相关。我们现在已经分别检测了紫外线照射前后不同类型皮肤上、下表皮层的DNA损伤，并检测了随后的细胞凋亡和P53的磷酸化。结果表明，白/白皮肤的光致癌增加有两个主要机制。首先，在较暗的皮肤中，紫外线诱导的下表皮(包括角质形成细胞干细胞和黑素细胞)的DNA损伤可以更有效地防止，这表明有色表皮是一种有效的紫外线过滤器。其次，紫外线诱导的细胞凋亡在较暗的皮肤中明显较大，这表明紫外线损伤的细胞可能在有色的表皮中被更有效地去除。DNA损伤的减少和紫外线损伤细胞的更有效去除的结合，可能在深色皮肤的人减少光癌发生方面发挥了关键作用。
Melanin plays an important role in protecting the skin against UV radiation, and melanomas and basal/squamous cell carcinomas occur more frequently in individuals with fair/light skin. We previously reported that levels of melanin correlate inversely with amounts of DNA damage induced by UV in normal human skin of different racial/ethnic groups. We have now separately examined DNA damage in the upper and lower epidermal layers in various types of skin before and after exposure to UV and have measured subsequent apoptosis and phosphorylation of p53. The results show that two major mechanisms underlie the increased photocarcinogenesis in fair/light skin. First, UV-induced DNA damage in the lower epidermis (including keratinocyte stem cells and melanocytes) is more effectively prevented in darker skin, suggesting that the pigmented epidermis is an efficient UV filter. Second, UV-induced apoptosis is significantly greater in darker skin, which suggests that UV-damaged cells may be removed more efficiently in pigmented epidermis. The combination of decreased DNA damage and more efficient removal of UV-damaged cells may play a critical role in the decreased photocarcinogenesis seen in individuals with darker skin.