Melatonin protects skin keratinocyte from hydrogen peroxide-mediated cell death via the SIRT1 pathway.
Melatonin protects skin keratinocyte from hydrogen peroxide-mediated cell death via the SIRT1 pathway.
复制标题
DOI：
10.18632/oncotarget.7679
复制
发表时间：
2016-03-15
期刊：
影响因子：
--
通讯作者：
Park SY
中科院分区：
文献类型：
--
作者：
Lee JH;Moon JH;Nazim UM;Lee YJ;Seol JW;Eo SK;Lee JH;Park SY
褪黑激素（N-乙酰基-5-甲氧基色胺）主要在松果体中合成并分泌，在多种细胞的细胞增殖以及细胞转移和细胞存活的调节中发挥着关键作用。本研究的目的是探讨褪黑素对H2O2诱导的细胞损伤的保护作用以及褪黑素对人角质形成细胞的作用机制。过氧化氢剂量依赖性地诱导人角质形成细胞的细胞损伤，并且褪黑激素的共同处理可以保护角质形成细胞免受H2O2诱导的细胞损伤。褪黑激素治疗激活了自噬通量信号，该信号通过 p62 蛋白水平的降低来识别。通过自噬抑制剂和 ATG5 siRNA 技术抑制自噬通量，阻断了褪黑激素对 H2O2 诱导的人角质形成细胞细胞死亡的保护作用。我们发现使用 Sirtinol 和 Sirt1 siRNA 抑制 Sirt1 可以逆转褪黑激素的保护作用，并诱导 H2O2 处理的细胞中的自噬过程。这是第一份证明褪黑激素激活的自噬通量通过 Sirt1 途径保护人类角质形成细胞免受过氧化氢诱导的损伤的报告。这项研究还表明，褪黑激素有可能用作皮肤病的治疗剂。
Melatonin (N-acetyl-5-methoxytryptamine), which is primarily synthesized in and secreted from the pineal gland, plays a pivotal role in cell proliferation as well as in the regulation of cell metastasis and cell survival in a diverse range of cells. The aim of this study is to investigate protection effect of melatonin on H2O2-induced cell damage and the mechanisms of melatonin in human keratinocytes. Hydrogen peroxide dose-dependently induced cell damages in human keratinocytes and co-treatment of melatonin protected the keratinocytes against H2O2-induced cell damage. Melatonin treatment activated the autophagy flux signals, which were identified by the decreased levels of p62 protein. Inhibition of autophagy flux via an autophagy inhibitor and ATG5 siRNA technique blocked the protective effects of melatonin against H2O2-induced cell death in human keratinocytes. And we found the inhibition of sirt1 using sirtinol and sirt1 siRNA reversed the protective effects of melatonin and induces the autophagy process in H2O2-treated cells. This is the first report demonstrating that autophagy flux activated by melatonin protects human keratinocytes through sirt1 pathway against hydrogen peroxide-induced damages. And this study also suggest that melatonin could potentially be utilized as a therapeutic agent in skin disease.