Department of Biochemistry, Faculty of Medicine, Dokuz Eylül University, Izmir, Turkey.
Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylül University, Izmir, Turkey.
Photodermatol Photoimmunol Photomed. 2019 Jul;35(4):221-231. doi: 10.1111/phpp.12456. Epub 2019 Mar 20.
People living in Mediterranean countries are mostly exposed to solar ultraviolet (UV) radiation that damages skin and results in photoaging which involves activation of epidermal growth factor receptor (EGFR) and downstream signal transduction through mitogen-activated protein kinases (MAPKs) in fibroblasts. Generation of reactive oxygen/nitrogen species by UV radiation is also critical for EGFR and MAPKs activation. MAPKs are responsible for activation of AP-1 subunits in the nucleus which induce matrix metalloproteinases. Melatonin, along with its metabolites, are known to be the most effective free radical scavenger and protective agent due to its ability to react with various radicals, lipophilic/hydrophilic structures.
In this study, we investigated the effects of melatonin on UVA-irradiated primary human dermal fibroblasts (HDFs) by following the alteration of molecules from cell membrane to the nucleus and oxidative/nitrosative damage status of the cells in a time-dependent manner which have not been clearly elucidated yet.
To mimic UVA dosage in Mediterranean countries, HDFs were exposed to UVA with sub-cytotoxic dosage (20 J/cm ) after pretreatment with melatonin (1 μmol/L) for 1 hour. Changes in the activation of the molecules and oxidative/nitrosative stress damage were analyzed at different time points.
Our results clearly show that melatonin decreases UVA-induced oxidative/nitrosative stress damage in HDFs. It also suppresses phosphorylation of EGFR, activation of MAPK/AP-1 signal transduction pathway and production of matrix metalloproteinases in a time-dependent manner.
Melatonin can be used as a protective agent for skin damage against intracellular detrimental effects of relatively high dosage of UVA irradiation.
生活在地中海国家的人大多会受到太阳紫外线（UV）辐射的伤害，这种辐射会导致皮肤光老化，涉及表皮生长因子受体（EGFR）的激活和成纤维细胞中丝裂原活化蛋白激酶（MAPKs）的下游信号转导。UV 辐射产生的活性氧/氮物种对于 EGFR 和 MAPKs 的激活也很关键。MAPKs 负责激活细胞核中 AP-1 亚基，诱导基质金属蛋白酶的产生。褪黑素及其代谢产物因其能够与各种自由基、亲脂性/亲水性结构反应的能力，被认为是最有效的自由基清除剂和保护剂。
在这项研究中，我们通过研究分子从细胞膜到细胞核的变化以及细胞的氧化/硝化损伤状态，来研究褪黑素对 UVA 照射的原代人真皮成纤维细胞（HDFs）的影响，这些变化在时间上的变化尚未得到明确阐明。
为了模拟地中海国家的 UVA 剂量，在用褪黑素（1 μmol/L）预处理 1 小时后，用亚细胞毒性剂量（20 J/cm ）照射 HDFs 以模拟 UVA 剂量。在不同时间点分析分子激活和氧化/硝化应激损伤的变化。
我们的结果清楚地表明，褪黑素可减少 UVA 诱导的 HDFs 氧化/硝化应激损伤。它还可以抑制 EGFR 的磷酸化、MAPK/AP-1 信号转导途径的激活和基质金属蛋白酶的产生，这是一个时间依赖性的过程。
褪黑素可用作皮肤损伤的保护剂，以防止相对高剂量 UVA 照射对细胞内有害影响。
