RIP1-Mediated Necroptosis Facilitates Oxidative Stress-Induced Melanocyte Death, Offering Insight into Vitiligo
RIP1-Mediated Necroptosis Facilitates Oxidative Stress-Induced Melanocyte Death, Offering Insight into Vitiligo
复制标题
RIP1介导的坏死下垂促进氧化应激诱导的黑素细胞死亡，为白癜风提供了洞察力
DOI：
10.1016/j.jid.2020.06.042
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发表时间：
2021-11-18
影响因子：
6.5
通讯作者：
Liu, Ling
中科院分区：
文献类型：
--
作者：
Li, Bowei;Yi, Xiuli;Liu, Ling
白癜风是一种常见的以黑素细胞死亡为特征的色素脱失性疾病，这种疾病可归因于多种机制，如细胞凋亡和自身免疫破坏。然而，作为一种新发现的细胞死亡方式，坏死下垂是否在白癜风的发病机制中起关键作用尚不清楚，也没有得到很好的研究。在本研究中，我们发现白癜风病变周围皮肤黑素细胞中坏死下垂标志物（包括磷酸化RIP3和磷酸化mlkl）呈阳性，支持白癜风存在坏死下垂。此外，过氧化氢处理的黑色素细胞中RIP1的表达显著上调。因此，RIP1干预抑制和MLKL缺乏可显著增强黑素细胞对过氧化氢诱导的坏死下垂的抵抗力。在机制上，我们证实了RIP1和RIP3可以在氧化应激下形成坏死体，并进一步触发磷酸化的MLKL易位到细胞膜，从而导致黑素细胞的破坏。最后，我们发现rip1介导的线粒体ROS的生成有助于黑素细胞中坏死体的形成。总之，我们的研究证实，坏死下垂通过RIP1信号通路显著促进氧化应激诱导的黑素细胞死亡，为白癜风的研究提供了新的思路。皮肤病学杂志（2021）141,2921e2931；doi: 10.1016 / j.jid.2020.06.042
Vitiligo is a common depigmentation disease characterized by melanocyte death, which is attributed to various mechanisms such as apoptosis and autoimmune destruction. However, whether necroptosis, a newly discovered way of cell death, plays a key role in the pathogenesis of vitiligo is still elusive and has not been well studied. In this study, we found that necroptosis markers, including phosphorylated RIP3 and phosphorylated-MLKL, were positive in melanocytes from vitiligo perilesional skin, which supported the existence of necroptosis in vitiligo. Furthermore, the expression of RIP1 was remarkably upregulated in melanocytes treated with hydrogen peroxide. Then, RIP1 intervention suppression and MLKL deficiency could significantly enhance the resistance of melanocytes to hydrogen peroxide-induced necroptosis. Mechanistically, we confirmed that RIP1 and RIP3 could form necrosomes under oxidative stress and further trigger phosphorylated MLKL translocation to the cell membrane, which led to the destruction of melanocytes. Finally, we showed that RIP1-mediated generation of mitochondrial ROS contributed to necrosome formation in melanocytes. Collectively, our study confirms that necroptosis significantly facilitates oxidative stress-induced melanocyte death through the RIP1 signaling pathway, offering insight into vitiligo. Journal of Investigative Dermatology (2021) 141, 2921e2931; doi:10.1016/j.jid.2020.06.042