Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR-induced depletion, and protects against the formation of DNA damage (8-hydroxy-2′-deoxyguanosine) in ex vivo human skin
Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR-induced depletion, and protects against the formation of DNA damage (8-hydroxy-2′-deoxyguanosine) in ex vivo human skin
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DOI：
10.1111/jpi.12018
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发表时间：
2013-04-01
影响因子：
10.3
通讯作者：
Zillikens, Detlef
中科院分区：
文献类型：
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作者：
Fischer, Tobias W.;Kleszczynski, Konrad;Zillikens, Detlef
紫外线辐射(UVR)会导致人体皮肤发生严重的结构和功能变化，导致皮肤衰老和致癌。在紫外光诱导的光损伤中，活性氧起着关键作用，并诱导DNA碱基氧化的中间体8-羟基-2‘-脱氧鸟苷(8-OHdG)。在这里，我们报道了褪黑素对UVR诱导的8-OHdG的形成和抗氧化酶的耗竭的保护作用，使用了剂量(0,100,300mJ/cm2)和时间依赖的方式(UVR后0，24，48小时后)的体外人全层皮肤。用实时定量聚合酶链式反应和免疫荧光/免疫组织化学染色方法研究了过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPX)和超氧化物歧化酶(SOD)等抗氧化酶(8-OHdG)的降解动态。紫外线照射后皮肤的基因表达显著降低(0HR 300mJ/cm2)，这种影响在紫外线照射后24小时内增强。8-OHdG阳性角质形成细胞在UVR后0HR已同时增加，100和300mJ/cm2分别上调71%和99%(P
UV radiation (UVR) induces serious structural and functional alterations in human skin leading to skin aging and carcinogenesis. Reactive oxygen species are key players in UVR-mediated photodamage and induce the DNA-base-oxidized, intermediate 8-hydroxy-2'-deoxyguanosine (8-OHdG). Herein, we report the protective action of melatonin against UVR-induced 8-OHdG formation and depletion of antioxidative enzymes using ex vivo human full-thickness skin exposed to UVR in a dose (0, 100, 300mJ/cm2)- and time-dependent manner (0, 24, 48hr post-UVR). Dynamics of depletion of antioxidative enzymes including catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), or 8-OHdG formation were studied by real-time PCR and immunofluorescence/immunohistochemical staining. UVR-treated skin revealed significant and immediate (0hr 300mJ/cm2) reduction of gene expression, and this effect intensified within 24hr post-UVR. Simultaneous increase in 8-OHdG-positive keratinocytes occurred already after 0hr post-UVR reaching 71% and 99% up-regulation at 100 and 300mJ/cm2, respectively (P