Dissemond J, Schneider L A, Brenneisen P, Briviba K, Wenk J, Wlaschek M, Scharffetter-Kochanek K
Department of Dermatology, University of Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
Br J Dermatol. 2003 Aug;149(2):341-9. doi: 10.1046/j.1365-2133.2003.05457.x.
Lipid peroxidation (LPO) is one major effector mechanism by which ultraviolet (UV) A contributes to photoageing and the promotion of skin cancer. It is a fingerprint of photo-oxidative stress within the skin, and is initiated by several pathways, with different reactive oxygen species (ROS) and iron ions being involved.
To elucidate factors involved in UVA1-induced LPO in human dermal fibroblasts and mouse dermis, and the role of antioxidant enzymes in protecting cells against LPO.
Using a highly sensitive high-performance liquid chromatography procedure, we measured malondialdehyde (MDA), a specific metabolic tracer molecule for LPO, to determine the overall LPO produced by a given UVA1 dose in vitro and in vivo. By using the iron chelator desferrioxamine (DFO), the hydroxyl radical scavenger dimethylsulphoxide (DMSO) and fibroblasts that specifically overexpress single antioxidant enzymes, we further indirectly assessed the protective effect of manganese superoxide dismutase (MnSOD), catalase and phospholipid hydroperoxide glutathione peroxidase (PHGPx) as well as the relative importance of different ROS and the role of transitional iron for the total amount of LPO induced by a distinct UVA dose.
UVA1 irradiation resulted in a time- and dose-dependent increase in MDA levels in vitro, and the in vitro results were shown to have in vivo relevance. Fibroblasts incubated with DFO or DMSO produced lower levels of MDA than controls, as did fibroblasts overexpressing MnSOD, catalase or PHGPx.
The cellular iron pool and hydroxyl radicals were the most important determining factors for the total amount of MDA produced after a given UVA1 dose, and PHGPx overexpression had the greatest protective effect against LPO.
脂质过氧化（LPO）是紫外线A（UVA）导致光老化和促进皮肤癌的一种主要效应机制。它是皮肤内光氧化应激的标志，由多种途径引发，涉及不同的活性氧（ROS）和铁离子。
阐明人真皮成纤维细胞和小鼠真皮中UVA1诱导LPO所涉及的因素，以及抗氧化酶在保护细胞免受LPO影响中的作用。
我们使用一种高度灵敏的高效液相色谱法，测量丙二醛（MDA），一种LPO的特定代谢示踪分子，以确定给定UVA1剂量在体外和体内产生的总LPO。通过使用铁螯合剂去铁胺（DFO）、羟基自由基清除剂二甲基亚砜（DMSO）以及特异性过表达单一抗氧化酶的成纤维细胞，我们进一步间接评估了锰超氧化物歧化酶（MnSOD）、过氧化氢酶和磷脂氢过氧化物谷胱甘肽过氧化物酶（PHGPx）的保护作用，以及不同ROS的相对重要性和过渡铁在特定UVA剂量诱导的总LPO中的作用。
UVA1照射导致体外MDA水平呈时间和剂量依赖性增加，且体外结果显示具有体内相关性。与DFO或DMSO孵育的成纤维细胞产生的MDA水平低于对照组，过表达MnSOD、过氧化氢酶或PHGPx的成纤维细胞也是如此。
细胞铁池和羟基自由基是给定UVA1剂量后产生的MDA总量的最重要决定因素，过表达PHGPx对LPO具有最大的保护作用。
