Department of Dermatology, University of Münster, Von-Esmarch-Str. 58, 48149 Münster, Germany.
Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387 Kraków, Poland.
Int J Mol Sci. 2018 Nov 28;19(12):3786. doi: 10.3390/ijms19123786.
Melatonin (Mel) is the major biologically active molecule secreted by the pineal gland. Mel and its metabolites, 6-hydroxymelatonin (6(OH)Mel) and 5-methoxytryptamine (5-MT), possess a variety of functions, including the scavenging of free radicals and the induction of protective or reparative mechanisms in the cell. Their amphiphilic character allows them to cross cellular membranes and reach subcellular organelles, including the mitochondria. Herein, the action of Mel, 6(OH)Mel, and 5-MT in human MNT-1 melanoma cells against ultraviolet B (UVB) radiation was investigated. The dose of 50 mJ/cm² caused a significant reduction of cell viability up to 48%, while investigated compounds counteracted this deleterious effect. UVB exposure increased catalase activity and led to a simultaneous Ca influx (16%), while tested compounds prevented these disturbances. Additional analysis focused on mitochondrial respiration performed in isolated mitochondria from the liver of BALB/cJ mice where Mel, 6(OH)Mel, and 5-MT significantly enhanced the oxidative phosphorylation at the dose of 10 M with lower effects seen at 10 or 10 M. In conclusion, Mel, 6(OH)Mel and 5-MT protect MNT-1 cells, which express melatonin receptors (MT1 and MT2) against UVB-induced oxidative stress and mitochondrial dysfunction, including the uncoupling of oxidative phosphorylation.
褪黑素（Mel）是松果腺分泌的主要生物活性分子。Mel 及其代谢产物 6-羟褪黑素（6（OH）Mel）和 5-甲氧基色胺（5-MT）具有多种功能，包括清除自由基和诱导细胞内保护或修复机制。它们的两亲性特征允许它们穿过细胞膜并到达亚细胞细胞器，包括线粒体。在此，研究了 Mel、6（OH）Mel 和 5-MT 在人 MNT-1 黑素瘤细胞中对紫外线 B（UVB）辐射的作用。50mJ/cm²的剂量导致细胞活力显著降低，最高可达 48%，而研究的化合物则对抗了这种有害作用。UVB 暴露增加了过氧化氢酶的活性，并导致 Ca 流入（16%），而测试的化合物则阻止了这些干扰。进一步的分析集中在从 BALB/cJ 小鼠肝脏中分离的线粒体的线粒体呼吸上，在 10 M 的剂量下，Mel、6（OH）Mel 和 5-MT 显著增强了氧化磷酸化，而在 10 或 10 M 的剂量下则观察到较低的效果。总之，Mel、6（OH）Mel 和 5-MT 可保护表达褪黑素受体（MT1 和 MT2）的 MNT-1 细胞免受 UVB 诱导的氧化应激和线粒体功能障碍，包括氧化磷酸化解偶联。
