Williams Joshua D, Bermudez Yira, Park Sophia L, Stratton Steven P, Uchida Koji, Hurst Craig A, Wondrak Georg T
The University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA; Department of Biomedical Engineering, College of Engineering, University of Arizona, Tucson, AZ, USA.
The University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA; Department of Medicine, University of Arizona, Tucson, AZ, USA.
J Photochem Photobiol B. 2014 Mar 5;132:56-65. doi: 10.1016/j.jphotobiol.2014.01.019. Epub 2014 Feb 12.
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 threefold 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.
皮肤暴露于太阳紫外线辐射（UVR）是光老化和光致癌作用的一个致病因素。在人体皮肤中，氧化应激被广泛认为是急性和慢性UVR暴露产生有害影响的关键机制。脂质过氧化产物丙二醛（MDA）在氧化应激增加的情况下会在组织中积累，最近在人体皮肤中已证实存在包括二氢吡啶 - 赖氨酸（DHP）在内的MDA衍生蛋白表位。在此，我们首次证明，急性暴露于亚凋亡剂量的太阳模拟紫外线（SSL）会导致培养的人HaCaT角质形成细胞和健康人体皮肤中游离MDA和与蛋白结合的MDA衍生表位的形成。免疫组织化学染色显示，急性暴露于SSL足以使人体皮肤中总的MDA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在产生游离MDA和MDA衍生表位方面更有效。随后的组织微阵列（TMA）分析揭示了非黑色素瘤皮肤癌（NMSC）中MDA和DHP表位的普遍性。在鳞状细胞癌组织中，与相邻正常组织相比，MDA和DHP表位均增加了三倍多。综上所述，这些数据证明了在暴露于太阳UVR的健康人体皮肤和NMSC TMA组织中均存在MDA衍生表位；然而，这些表位作为皮肤光损伤新生物标志物的潜在用途以及在皮肤光致癌过程中的功能作用仍有待探索。
