The malondialdehyde-derived fluorophore DHP-lysine is a potent sensitizer of UVA-induced photooxidative stress in human skin cells
The malondialdehyde-derived fluorophore DHP-lysine is a potent sensitizer of UVA-induced photooxidative stress in human skin cells
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DOI：
10.1016/j.jphotobiol.2010.07.010
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发表时间：
2010-12-02
影响因子：
5.4
通讯作者：
Wondrak, Georg T.
中科院分区：
文献类型：
--
作者：
Lamore, Sarah D.;Azimian, Sara;Wondrak, Georg T.
光驱动的电子和能量转移涉及非DNA皮肤发色团作为内源性光敏剂诱导UVA暴露的人皮肤的氧化应激，这一过程与光老化和光致癌相关。丙二醛是来自膜脂质过氧化的亲电二羰基物质。人皮肤细胞的光敏剂免疫组织化学分析揭示了在人皮肤中存在大量的丙二酰二亚胺衍生的和DHP-赖氨酸表位。（3，5-二甲酰基-4-甲基-4H-吡啶-1-基）-己酸-叔丁酯作为肽结合的DHP的模型。在暴露于UVA和DHP-赖氨酸DHP-的联合作用的人皮肤Hs 27成纤维细胞以及原代和HaCaT角质形成细胞中观察到赖氨酸光动力抑制增殖和诱导细胞死亡。赖氨酸光敏化诱导细胞内氧化应激p38 MAPK激酶激活和血红素加氧酶-1表达上调与UVA驱动的DHP-1活性氧形成一致。在化学测定中检测到超氧化物、过氧化氢和单线态氧的赖氨酸形成，但在细胞光敏化期间使用SOD或过氧化氢酶几乎没有保护作用。相反，NaN 3的包含完全消除了DHP-光敏化。赖氨酸，并支持这一假设，即丙二醛衍生的蛋白质表位可能作为人体皮肤中UVA诱导的氧化应激的内源性敏化剂（C）2010 Elsevier B V保留所有权利
Light-driven electron and energy transfer involving non-DNA skin chromophores as endogenous photosensitizers induces oxidative stress in UVA-exposed human skin a process relevant to photoaging and photocarcinogenesis Malondialdehyde is an electrophilic dicarbonyl-species derived from membrane lipid peroxidation Here we present experimental evidence suggesting that the malondialdehyde-derived protein epitope dihydropyridine (DHP)-lysine is a potent endogenous UVA-photosensitizer of human skin cells Immunohistochemical analysis revealed the abundant occurrence of malondialdehyde-derived and DHP-lysine epitopes in human skin Using the chemically protected dihydropyridine-derivative (2S)-Boc-2-amino-6-(3 5-diformyl-4-methyl-4H-pyridin-1-yl)-hexanoic acid-t-butylester as a model of peptide-bound DHP-lysine photodynamic inhibition of proliferation and induction of cell death were observed in human skin Hs27 fibroblasts as well as primary and HaCaT keratinocytes exposed to the combined action of UVA and DHP-lysine DHP-lysine photosensitization induced intracellular oxidative stress p38 MAPkinase activation and upregulation of heme oxygenase-1 expression Consistent with UVA-driven ROS formation from DHP-lysine formation of superoxide hydrogen peroxide and singlet oxygen was detected in chemical assays but little protection was achieved using SOD or catalase during cellular photosensitization In contrast inclusion of NaN3 completely abolished DHP-photosensitization Taken together these data demonstrate photodynamic activity of DHP-lysine and support the hypothesis that malondialdehyde-derived protein-epitopes may function as endogenous sensitizers of UVA-induced oxidative stress in human skin (C) 2010 Elsevier B V All rights reserved