Malondialdehyde-derived epitopes in human skin result from acute exposure to solar UV and occur in nonmelanoma skin cancer tissue.
Malondialdehyde-derived epitopes in human skin result from acute exposure to solar UV and occur in nonmelanoma skin cancer tissue.
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DOI：
10.1016/j.jphotobiol.2014.01.019
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发表时间：
2014-03-05
影响因子：
5.4
通讯作者：
Wondrak, Georg T.
中科院分区：
文献类型：
--
作者：
Williams, Joshua D.;Bermudez, Yira;Park, Sophia L.;Stratton, Steven P.;Uchida, Koji;Hurst, Craig A.;Wondrak, Georg T.
关键词：
皮肤暴露于太阳紫外线辐射(UVR)是光老化和光致癌的一个致病因素。在人类皮肤中，氧化应激被广泛认为是急性和慢性紫外线照射有害影响的关键机制。脂质过氧化产物丙二醛(MDA)在氧化应激增加的条件下积聚在组织中，最近在人类皮肤中证实了包括二氢吡啶赖氨酸(DHP)在内的丙二醛衍生蛋白表位的存在。在这里，我们首次证明，在培养的人角质形成细胞和健康皮肤中，急性暴露于亚致凋亡剂量的太阳模拟紫外线(SSL)会导致游离的丙二醛和蛋白结合的丙二醛衍生表位的形成。免疫组织化学染色显示，急性暴露于SSL足以导致人类皮肤中总的丙二醛和特定的DHP表位含量增加近20倍。与剂量匹配的太阳模拟UVA相比，完整的SSL更有效地产生了游离的丙二醛和丙二醛衍生的表位。随后的组织微阵列(TMA)分析揭示了非黑色素瘤皮肤癌(NMSC)中普遍存在的MDA和DHP表位。在鳞状细胞癌组织中，与邻近正常组织相比，丙二醛和DHP表位都增加了三倍以上。综上所述，这些数据表明，丙二醛衍生的表位在暴露在紫外线照射下的健康人体皮肤和NMSC TMA组织中都存在；然而，这些表位作为皮肤光损伤的新生物标记物的潜在用途以及在皮肤光癌发生过程中的功能作用仍有待探索。
Cutaneous exposure to solar ultraviolet radiation (UVR) is a causative factor in photoaging and photocarcinogenesis. In human skin, oxidative stress is widely considered a key mechanism underlying the detrimental effects of acute and chronic UVR exposure. The lipid peroxidation product malondialdehyde (MDA) accumulates in tissue under conditions of increased oxidative stress, and the occurrence of MDA-derived protein epitopes, including dihydropyridine-lysine (DHP), has recently been substantiated in human skin. Here we demonstrate for the first time that acute exposure to sub-apoptogenic doses of solar simulated UV light (SSL) causes the formation of free MDA and protein-bound MDA-derived epitopes in cultured human HaCaT keratinocytes and healthy human skin. Immunohistochemical staining revealed that acute exposure to SSL is sufficient to cause an almost twenty-fold increase in general MDA- and specific DHP-epitope content in human skin. When compared to dose-matched solar simulated UVA, complete SSL was more efficient generating both free MDA and MDA-derived epitopes. Subsequent tissue microarray (TMA) analysis revealed the prevalence of MDA- and DHP-epitopes in nonmelanoma skin cancer (NMSC). In squamous cell carcinoma tissue, both MDA- and DHP-epitopes were increased more than three-fold as compared to adjacent normal tissue. Taken together, these date demonstrate the occurrence of MDA-derived epitopes in both solar UVR-exposed healthy human skin and NMSC TMA tissue; however, the potential utility of these epitopes as novel biomarkers of cutaneous photodamage and a functional role in the process of skin photocarcinogenesis remain to be explored.
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影响因子：
3.1
作者：
Cadet, Jean;Douki, Thierry;Di Mascio, Paolo
通讯作者：
Di Mascio, Paolo
DOI：
10.1016/j.jphotobiol.2010.07.010
发表时间：
2010-12-02
影响因子：
5.4
作者：
Lamore, Sarah D.;Azimian, Sara;Wondrak, Georg T.
通讯作者：
Wondrak, Georg T.
影响因子：
10.3
作者：
Dissemond, J;Schneider, LA;Scharffetter-Kochanek, K
通讯作者：
Scharffetter-Kochanek, K
影响因子：
3.5
作者：
Bhawal, UK;Ozaki, Y;Kato, Y
通讯作者：
Kato, Y
影响因子：
3.5
作者：
Lizama-Manibusan B;McLaughlin B
通讯作者：
McLaughlin B