Melanin acts as a cause an atypical potent UVB photosensitizer to mode of cell death in murine skin
Melanin acts as a cause an atypical potent UVB photosensitizer to mode of cell death in murine skin
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DOI：
10.1073/pnas.0403994101
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发表时间：
2004-10-19
影响因子：
11.1
通讯作者：
Brash, DE
中科院分区：
文献类型：
--
作者：
Takeuchi, S;Zhang, WG;Brash, DE
黑色素保护皮肤免受阳光紫外线直接吸收造成的DNA损伤。然而，在体外或在培养细胞中照射黑色素也会产生活性氧物种，如超氧化物，这可以间接地导致氧化碱基损伤和DNA链断裂。这种光敏作用对褐黑素(黄色和红色黑色素)比真黑素(棕色和黑色)更强。黑色素在体内的光敏能力尚不清楚。我们使用黑色、黄色和白化毛色的同源小鼠来研究主要暴露于UVB(280-320 nm)或UVA(320-400 nm)辐射后DNA损伤和细胞凋亡的诱导。由UVB直接吸收诱导的环丁烷嘧啶二聚体在所有三个菌株中都是相同的，作为晒伤细胞或含有活性caspase-3的角质形成细胞的凋亡率。然而，经UVB或UVA照射后，黑鼠和黄鼠的末端脱氧核糖核酸基转移酶介导的dUTP缺口末端标记(TUNEL)阳性细胞的出现率约为白鼠的3倍。在表皮层中，TUNEL阳性细胞排列在毛囊的上部，与毛干中黑色素诱导的紫外线光敏作用一致。由于黑鼠体内的真黑素浓度是黄鼠体内真黑素浓度的三倍，因此真黑素的比活力高出三倍。我们得出的结论是，紫外线照射的黑色素，特别是黑色素，使邻近细胞对caspase-3独立的凋亡变得光敏，而且这种光敏发生的频率高于紫外线直接DNA吸收诱导的凋亡。黑色素诱导的细胞凋亡可能导致金发和红发的人对晒伤和皮肤癌的敏感性增加。
Melanin protects the skin against DNA damage induced by direct absorption of sunlight's UV radiation. Yet, irradiating melanin in vitro or in cultured cells also generates active oxygen species such as superoxide, which can indirectly induce oxidative base lesions and DNA strand breaks. This photosensitization is greater for pheomelanin (yellow and red melanin) than for eumelanin (brown and black). The in vivo photosensitizing ability of melanin is unknown. We used congenic mice of black, yellow, and albino coat colors to investigate the induction of DNA lesions and apoptosis after exposure to predominantly UVB (280-320 nm) or UVA (320-400 nm) radiation. Cyclobutane pyrimidine dimers induced by direct UVB absorption were equal in all three strains, as was apoptosis measured as sunburn cells or as keratinocytes containing active caspase-3. However, terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL)-positive cells were approximate to 3-fold more frequent in black and yellow mice after UVB or UVA irradiation than in albino. In epidermal sheets, TUNEL-positive cells lined the upper portion of the hair follicle, consistent with UV-induced photosensitization by melanin in the hair shaft. Because the concentration of eumelanin in black mice was three times that of pheomelanin in yellow mice, pheomelanin had 3-fold greater specific activity. We conclude that UV-irradiated melanin, particularly pheomelanin, photosensitizes adjacent cells to caspase-3 independent apoptosis, and this occurs at a frequency greater than the apoptosis induced by direct DNA absorption of UV. Melanin-induced apoptosis may contribute to the increased sensitivity of individuals with blonde and red hair to sunburn and skin cancer.