Folic Acid Protects Melanocytes from Oxidative Stress via Activation of Nrf2 and Inhibition of HMGB1.
Folic Acid Protects Melanocytes from Oxidative Stress via Activation of Nrf2 and Inhibition of HMGB1.
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DOI：
10.1155/2021/1608586
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发表时间：
2021
影响因子：
--
通讯作者：
Zhang W
中科院分区：
文献类型：
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作者：
Du P;Zhang S;Li S;Yang Y;Kang P;Chen J;Gao T;Li C;Zhang Q;Zhang W
白癜风是一种皮肤色素脱失性疾病，由于失去表皮黑素细胞。越来越多的证据表明，氧化应激通过直接破坏黑素细胞并引发炎症反应，最终破坏黑素细胞，在白癜风中起着至关重要的作用。叶酸（FA）是叶酸的氧化形式，具有高生物利用度，具有强大的抗氧化特性，并在多种氧化应激相关疾病中显示出治疗潜力。然而，FA是否保护黑素细胞免受氧化损伤仍然未知。在本研究中，我们首次发现FA减轻了H2O2诱导的黑素细胞的异常生长和凋亡。此外，FA增强抗氧化酶的活性，显着降低细胞内ROS水平在黑素细胞。随后，FA有效地激活核因子E2相关因子2（Nrf2）通路，Nrf2敲低阻断FA对H2O2处理的黑素细胞的保护作用。此外，FA抑制氧化应激下黑素细胞中促炎性HMGB1的产生。总之，我们的研究结果支持FA通过激活Nrf2和抑制HMGB1对人黑素细胞抗氧化损伤的保护作用，从而表明FA作为治疗白癜风的潜在治疗剂。
Vitiligo is a cutaneous depigmentation disease due to loss of epidermal melanocytes. Accumulating evidence has indicated that oxidative stress plays a vital role in vitiligo via directly destructing melanocytes and triggering inflammatory response that ultimately undermines melanocytes. Folic acid (FA), an oxidized form of folate with high bioavailability, exhibits potent antioxidant properties and shows therapeutic potential in multiple oxidative stress-related diseases. However, whether FA safeguards melanocytes from oxidative damages remains unknown. In this study, we first found that FA relieved melanocytes from H2O2-induced abnormal growth and apoptosis. Furthermore, FA enhanced the activity of antioxidative enzymes and remarkably reduced intracellular ROS levels in melanocytes. Subsequently, FA effectively activated nuclear factor E2-related factor 2 (Nrf2) pathway, and Nrf2 knockdown blocked the protective effects of FA on H2O2-treated melanocytes. Additionally, FA inhibited the production of proinflammatory HMGB1 in melanocytes under oxidative stress. Taken together, our findings support the protective effects of FA on human melanocytes against oxidative injury via the activation of Nrf2 and the inhibition of HMGB1, thus indicating FA as a potential therapeutic agent for the treatment of vitiligo.