Estrogens can contribute to hydrogen peroxide generation and quinone-mediated DNA damage in peripheral blood lymphocytes from patients with vitiligo
Estrogens can contribute to hydrogen peroxide generation and quinone-mediated DNA damage in peripheral blood lymphocytes from patients with vitiligo
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DOI：
10.1038/sj.jid.5700257
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发表时间：
2006-05-01
影响因子：
6.5
通讯作者：
Anderson, Diana
中科院分区：
文献类型：
--
作者：
Schallreuter, Karin U.;Chiuchiarelli, Georgia;Anderson, Diana
迄今为止，有大量的体内和体外证据表明白癜风中表皮和全身过氧化氢（H2 O2）水平升高，局部应用假过氧化氢酶-K可以降低过氧化氢水平。联合Sbergreuter（PC-KUS）导致表皮过氧化氢酶水平以及外周血细胞中其他酶的恢复。最近，通过雌激素和其他芳香族类固醇的氧化代谢产生H2 O2被记录。因此，这是诱人的，以遵循雌激素产生的H2 O2和其可能的影响，在白癜风患者的外周血淋巴细胞的DNA损伤之前和之后，减少表皮H2 O2与pseudocatalase PC-KUS相比，对照。为此，将20例高加索患者分为治疗的应答者（A组，n = 11）和未治疗的活动性/急性疾病（B组，n = 9），并与高加索健康对照（C组，n = 7）进行比较。因此，表皮过氧化氢酶蛋白的表达，在整个皮肤活检进行了评估，使用免疫荧光标记与测定基础H2 O2水平在外周血淋巴细胞。为了测试雌激素对H2 O2生成和DNA损伤的影响，在存在和不存在过氧化氢酶的情况下，将来自所有三个组的新鲜制备的外周血淋巴细胞用于碱性彗星试验。这项研究的结果表明，减少表皮H2 O2导致表皮过氧化氢酶蛋白表达增加，以及淋巴细胞中H2 O2浓度降低。此外，在两个患者组中均发现了直接的雌激素介导的DNA损伤，而健康对照组中不存在这种损伤。这种作用没有被过氧化氢酶消除，这表明白癜风患者外周血淋巴细胞中雌激素直接介导的DNA损伤。
To date there is ample in vivo and in vitro evidence for increased epidermal and systemic hydrogen peroxide (H2O2) levels in vitiligo, which can be reduced with a topical application of a pseudocatalase-K. U. Schallreuter (PC-KUS) leading to the recovery of epidermal catalase levels as well as other enzymes in peripheral blood cells. Recently, the generation of H2O2 by oxidative metabolism of estrogens and other aromatic steroids was documented. Therefore, it was tempting to follow estrogen-generated H2O2 and its possible effect on DNA damage in peripheral blood lymphocytes from patients with vitiligo before and after the reduction of epidermal H2O2 with pseudocatalase PC-KUS compared to controls. For this purpose, 20 Caucasian patients were grouped in treated responders (group A, n = 11) and untreated active/acute disease (group B, n = 9) and compared to Caucasian healthy controls (group C, n = 7). Consequently, epidermal catalase protein expression in full skin biopsies was assessed using immunofluorescence labelling together with determination of basal H2O2 levels in peripheral blood lymphocytes. To test the influence of estrogen on H2O2 generation and DNA damage, freshly prepared peripheral blood lymphocytes from all three groups were used for the alkaline comet assay in the presence and absence of catalase. The results of this study demonstrated that reduction of epidermal H2O2 leads to both increased epidermal catalase protein expression as well as decreased H2O2 concentrations in lymphocytes. Moreover, a direct estrogen-mediated DNA damage was identified in both patient groups, which was absent in healthy controls. This effect was not abolished by catalase pointing to direct quinone-mediated DNA damage by estrogens in peripheral blood lymphocytes in vitiligo.