Aspirin induces Nrf2-mediated transcriptional activation of haem oxygenase-1 in protection of human melanocytes from H2O2-induced oxidative stress

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• 作者：Zhe Jian ; Lingzhen Tang ; Xiuli Yi ; Bangmin Liu ; Qian Zhang ; Guannan Zhu ; Gang Wang ; Tianwen Gao and Chunying Li
• 刊名：Journal of Cellular and Molecular Medicine
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：20
• 期：7
• 页码：1307-1318
• 全文大小：2665K
• ISSN：1582-4934

文摘

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.