Aspirin induces Nrf2-mediated transcriptional activation of haem oxygenase-1 in protection of human melanocytes from H2 O2 -induced oxidative stress.
Aspirin induces Nrf2-mediated transcriptional activation of haem oxygenase-1 in protection of human melanocytes from H2 O2 -induced oxidative stress.
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阿司匹林诱导 Nrf2 介导的血红素加氧酶 1 转录激活，保护人类黑素细胞免受 H2O2 诱导的氧化应激
DOI：
10.1111/jcmm.12812
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发表时间：
2016-07
影响因子：
5.3
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Jian Z;Tang L;Yi X;Liu B;Zhang Q;Zhu G;Wang G;Gao T;Li C
通过抗氧化剂去除过氧化氢（H2 O2）已被证明对白癜风患者有益。阿司匹林（乙酰水杨酸，阿萨）具有抗氧化活性，在许多氧化应激相关疾病中具有很好的预防和治疗作用。阿萨是否能保护人类黑素细胞免受氧化应激的影响还有待进一步研究。在这里，我们研究了阿萨对H2 O2诱导的人黑素细胞氧化损伤的潜在保护作用和机制。用不同浓度的阿萨预处理人黑素细胞，然后暴露于1.0 mM H2 O2。通过流式细胞术评价细胞凋亡、细胞内活性氧（ROS）水平，并通过细胞计数试剂盒-8测定法测定细胞活力。在有或没有Nrf 2-siRNA转染的情况下，测定总NRF 2表达和磷酸化NRF 2表达、NRF 2核转位和抗氧化反应元件（ARE）转录活性，以研究可能的分子机制。在活力增加的同时，10 - 90 μmol/l阿萨预处理导致原代人黑素细胞中凋亡细胞率、乳酸脱氢酶释放和细胞内ROS水平降低。此外，我们发现阿萨显著诱导NRF 2核转位，增强ARE-荧光素酶活性，增加p-NRF 2和总NRF 2水平，并诱导人黑素细胞中血红素加氧酶-1（HO-1）的表达。此外，Nrf 2表达的敲低或HO-1的药理学抑制消除了阿萨对黑素细胞对抗H2 O2诱导的细胞毒性和细胞凋亡的保护作用。这些结果表明，阿萨通过Nrf 2驱动的HO-1转录激活保护人类黑素细胞免受H2 O2诱导的氧化应激。
The removal of hydrogen peroxide (H2O2) by antioxidants has been proven to be beneficial to patients with vitiligo. Aspirin (acetylsalicylic acid, ASA) has antioxidant activity and has great preventive and therapeutical effect in many oxidative stress‐relevant diseases. Whether ASA can protect human melanocytes against oxidative stress needs to be further studied. Here, we investigated the potential protective effect and mechanisms of ASA against H2O2‐induced oxidative injury in human melanocytes. Human melanocytes were pre‐treated with different concentrations of ASA, followed by exposure to 1.0 mM H2O2. Cell apoptosis, intracellular reactive oxygen species (ROS) levels were evaluated by flow cytometry, and cell viability was determined by an Cell Counting Kit‐8 assay. Total and phosphorylated NRF2 expression, NRF2 nuclear translocation and antioxidant response element (ARE) transcriptional activity were assayed with or without Nrf2‐siRNA transfection to investigate the possible molecular mechanisms. Concomitant with an increase in viability, pre‐treatment of 10‐90 μmol/l ASA resulted in decreased rate of apoptotic cells, lactate dehydrogenase release and intracellular ROS levels in primary human melanocytes. Furthermore, we found ASA dramatically induced NRF2 nuclear translocation, enhanced ARE‐luciferase activity, increased both p‐ NRF2 and total NRF2 levels, and induced the expression of haem oxygenase‐1 (HO‐1) in human melanocytes. In addition, knockdown of Nrf2 expression or pharmacological inhibition of HO‐1 abrogated the protective action of ASA on melanocytes against H2O2‐induced cytotoxicity and apoptosis. These results suggest that ASA protects human melanocytes against H2O2‐induced oxidative stress via Nrf2‐driven transcriptional activation of HO‐1.