Simvastatin Protects Human Melanocytes from H2O2-Induced Oxidative Stress by Activating Nrf2
Simvastatin Protects Human Melanocytes from H2O2-Induced Oxidative Stress by Activating Nrf2
复制标题
辛伐他汀通过激活 Nrf2 保护人类黑素细胞免受 H2O2 诱导的氧化应激
DOI：
10.1016/j.jid.2017.01.020
复制
发表时间：
2017-06-01
影响因子：
6.5
通讯作者：
Li, Chunying
中科院分区：
文献类型：
--
作者：
Chang, Yuqian;Li, Shuli;Li, Chunying
预防过氧化氢（H2 O2）诱导的氧化应激已被证明是有益的白癜风患者。辛伐他汀具有抗氧化能力，对多种氧化应激相关疾病具有保护作用。然而，辛伐他汀是否可以保护人类黑素细胞免受氧化应激的影响还没有研究。在本研究中，我们初步发现，0.1 mmol/L至1.0 mmol/L的辛伐他汀预处理导致细胞活力增加，细胞凋亡的黑素细胞响应于H2 O2。此外，辛伐他汀能够增强抗氧化酶的活性，减少细胞内活性氧的积累。此外，我们发现，辛伐他汀促进核红细胞2相关因子（Nrf 2）的激活和Nrf 2的敲低取消了辛伐他汀对H2 O2诱导的氧化损伤的保护作用。更重要的是，丝裂原活化蛋白激酶途径和p62之间的相互增强有助于辛伐他汀诱导的黑素细胞中Nrf 2的激活。最后，辛伐他汀表现出更强的抗氧化能力和更好的保护作用比阿司匹林在过氧化氢处理的黑素细胞。总之，我们的研究结果表明，辛伐他汀保护人类黑素细胞从H2 O2诱导的氧化应激通过激活Nrf 2，从而支持辛伐他汀作为一个潜在的白癜风治疗剂。
The prevention of hydrogen peroxide (H2O2)-induced oxidative stress has proved to be beneficial to vitiligo patients. Simvastatin possesses antioxidative capacity and has shown protective effect in various oxidative stress-related diseases. However, whether simvastatin can protect human melanocytes against oxidative stress has not been investigated. In this study, we initially found that pretreatment with 0.1 mmol/L to 1.0 mmol/L simvastatin led to increased cell viability and decreased cell apoptosis of melanocytes in response to H2O2. In addition, simvastatin was able to potentiate the activity of antioxidant enzymes and lessen intracellular reactive oxygen species accumulation. Furthermore, we found that simvastatin promoted the activation of nuclear erythroid 2-related factor (Nrf2) and that knockdown of Nrf2 abolished the protective effect of simvastatin against H2O2-induced oxidative damage. More importantly, the mutual enhancement between mitogen-activated protein kinase pathways and p62 contributed to simvastatin-induced Nrf2 activation in melanocytes. Finally, simvastatin showed more antioxidative capacity and better protective effect than aspirin in H2O2-treated melanocytes. Taken together, our results show that simvastatin protects human melanocytes from H2O2-induced oxidative stress by activating Nrf2, thus supporting simvastatin as a potential therapeutic agent for vitiligo.