Regulation of DHICA-mediated antioxidation by dopachrome tautomerase: Implication for skin photoprotection against UVA radiation
Regulation of DHICA-mediated antioxidation by dopachrome tautomerase: Implication for skin photoprotection against UVA radiation
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DOI：
10.1016/j.freeradbiomed.2010.01.033
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发表时间：
2010-05-01
影响因子：
7.4
通讯作者：
Xu, Shi-Zheng
中科院分区：
文献类型：
--
作者：
Jiang, Shan;Liu, Xiao-Ming;Xu, Shi-Zheng
多巴色素互变异构酶(DCT)是黑素合成途径中的一个关键酶，它将中间体多巴色素异构化为5，6-二羟基吲哚-2-羧酸(DHICA)，并影响5，6-二羟基吲哚(DHI)聚合物中DHICA单体在真黑素中的比例。为了研究DCT灭活是否影响皮肤对紫外线辐射的光保护作用，我们检测了DCT(-/-)基因敲除小鼠和野生型C57BL/6小鼠皮肤在UVA诱导的氧化应激下的活性氧(ROS)水平、晒伤细胞形成、表皮细胞凋亡和黑色素组成。结果表明，DCT灭活可提高慢性UVA照射小鼠皮肤ROS水平，增加晒伤细胞数和凋亡细胞数，降低真皮真黑素含量。此外，我们利用电子自旋共振技术研究了DHICA-黑色素、DHI-黑色素以及两者的混合物对Fenton反应中羟基自由基生成的影响。DHICA-黑色素显示出强大的羟基自由基清除活性，而DHI-黑色素则没有。因此，本研究表明DHICA单体需要被结合到真黑素的DHI聚合物骨架中，这突显了DCT在DHICA介导的抗氧化调节中的重要作用。(C)2010 Elsevier Inc.保留所有权利。
Dopachrome tautomerase (Dct) is a critical enzyme in the melanogenesis pathway that isomerizes the intermediate dopachrome to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and influences the proportion of DHICA monomer incorporated into the 5,6-dihydroxyindole (DHI) polymer in eumelanin. To investigate whether Dct inactivation affects skin photoprotection against ultraviolet radiation, we examined levels of reactive oxygen species (ROS), sunburn cell formation, epidermal cell apoptosis, and melanin composition in skins of Dct(-/-) knockout mice compared with skins of wild-type C57BL/6 mice under UVA-induced oxidative stress. The results demonstrate that Dct inactivation elevates the level of ROS, increases the numbers of sunburn cells and apoptotic cells, and decreases the amount of eumelanin in the epidermis upon exposure to chronic UVA radiation. Moreover, we determined the effects of DHICA-melanin, DHI-melanin, and a mixture of both on hydroxyl radical generation in the Fenton reaction utilizing an electron spin resonance assay. DHICA-melanin exhibits a potent hydroxyl radical-scavenging activity, whereas DHI-melanin does not. Thus, this study suggests that DHICA monomers are required to incorporate into the DHI polymer backbone of eumelanin, which highlights the important role of Dct in the regulation of DHICA-mediated antioxidation. (C) 2010 Elsevier Inc. All rights reserved.