Melatonin and its metabolites protect human melanocytes against UVB-induced damage: Involvement of NRF2-mediated pathways.
Melatonin and its metabolites protect human melanocytes against UVB-induced damage: Involvement of NRF2-mediated pathways.
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DOI：
10.1038/s41598-017-01305-2
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发表时间：
2017-04-28
影响因子：
4.6
通讯作者：
Slominski AT
中科院分区：
文献类型：
--
作者：
Janjetovic Z;Jarrett SG;Lee EF;Duprey C;Reiter RJ;Slominski AT
紫外线（UV）是皮肤活性氧（ROS）以及6-4光产物和环丁烷嘧啶二聚体（CPD）的诱导剂，进一步对皮肤细胞造成损伤。用UVB照射培养的人黑色素细胞可刺激ROS的产生，而褪黑素或其代谢物：6-羟基褪黑素（6-OHM）、n1 -乙酰- n2 -甲酰基-5-甲氧基氨基（AFMK）、n -乙酰-5-羟色胺（NAS）和5-甲氧基色胺（5-MT）处理的细胞ROS的产生减少。褪黑素及其衍生物还能刺激NRF2（核因子-红细胞2 [NF-E2]相关因子2）及其靶酶和蛋白的表达，这些靶酶和蛋白在包括UVB在内的不同损伤因子对细胞的保护中发挥重要作用。使用siRNA沉默NRF2会降低褪黑激素的保护作用，而膜褪黑激素受体（MT1或MT2）不会改变褪黑激素或其衍生物的活性。褪黑素及其代谢物增强了暴露于UVB的黑色素细胞的DNA修复，并刺激了Ser-15位点磷酸化的p53的表达。综上所述，褪黑激素及其代谢物通过激活nrf2依赖通路保护黑素细胞免受uvb诱导的DNA损伤和氧化应激；这些作用独立于对经典膜褪黑激素受体的影响。因此，褪黑素及其衍生物可以作为黑色素细胞对抗uvb诱导病理的极好保护剂。
Ultraviolet light (UV) is an inducer of reactive oxygen species (ROS) as well as 6-4-photoproducts and cyclobutane pyrimidine dimers (CPD) in the skin, which further cause damage to the skin cells. Irradiation of cultured human melanocytes with UVB stimulated ROS production, which was reduced in cells treated with melatonin or its metabolites: 6-hydroxymelatonin (6-OHM), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), N-acetylserotonin (NAS), and 5-methoxytryptamine (5-MT). Melatonin and its derivatives also stimulated the expression of NRF2 (nuclear factor erythroid 2 [NF-E2]-related factor 2) and its target enzymes and proteins that play an important role in cell protection from different damaging factors including UVB. Silencing of NRF2 using siRNA diminished the protective effects of melatonin, while the membrane melatonin receptors (MT1 or MT2) did not change the activities of either melatonin or its derivatives. Melatonin and its metabolites enhanced the DNA repair in melanocytes exposed to UVB and stimulated expression of p53 phosphorylated at Ser-15. In conclusion, melatonin and its metabolites protect melanocytes from UVB-induced DNA damage and oxidative stress through activation of NRF2-dependent pathways; these actions are independent of an effect on the classic membrane melatonin receptors. Thus, melatonin and its derivatives can serve as excellent protectors of melanocytes against UVB-induced pathology.