Zhao Yan, Xiong Renxue, Jin Shiyu, Li Yujie, Dong Tingru, Wang Wei, Song Xiuzu, Guan Cuiping
Department of Dermatology, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310009, China.
Department of Dermatology, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310009, China; Department of Dermatology, Hangzhou Third People's Hospital, Hangzhou 310009, China.
Biochem Pharmacol. 2025 Apr;234:116811. doi: 10.1016/j.bcp.2025.116811. Epub 2025 Feb 18.
Oxidative stress plays a critical role in the pathogenesis of vitiligo by damaging keratinocytes, which disrupts their biological functions and influences the progression of the disease. MitoQ, a mitochondria-specific antioxidant, has the potential to prevent disorders associated with oxidative stress and to exert protective effects specifically on mitochondria. This study investigated the protective effects of MitoQ against oxidative stress in keratinocytes. We observed downregulated expression levels of Nrf2, PINK1, Parkin, and LC3 in vitiligo patients. HaCaT cells were treated with 900 μM HO and/or 50 nM MitoQ, revealing that MitoQ mitigated the downregulation of Nrf2, PINK1, and Parkin; reduced the nuclear translocation of Nrf2; and decreased the level of mitophagy induced by HO. Following the knockdown of NFE2L2 or PINK1 in HaCaT cells, we noted an increase in intracellular reactive oxygen species, changes in mitochondrial morphology, a dramatic decrease in the mitochondrial membrane potential, and a significant rise in cell death levels. In comparison to the group without NFE2L2 or PINK1 knockdown, MitoQ treatment failed to alleviate these conditions. These results suggest that MitoQ may regulate the PINK1/Parkin signaling pathway via Nrf2 to counteract mitochondrial oxidative stress induced by HO and protect cells from damage. Therefore, our study offers experimental evidence and insights that may inform the development of therapeutic interventions for vitiligo.
氧化应激通过损伤角质形成细胞在白癜风发病机制中起关键作用，这会破坏其生物学功能并影响疾病进展。MitoQ是一种线粒体特异性抗氧化剂，有预防与氧化应激相关疾病的潜力，并能对线粒体发挥特异性保护作用。本研究调查了MitoQ对角质形成细胞氧化应激的保护作用。我们观察到白癜风患者中Nrf2、PINK1、Parkin和LC3的表达水平下调。用900μM HO和/或50 nM MitoQ处理HaCaT细胞，结果显示MitoQ减轻了Nrf2、PINK1和Parkin的下调；减少了Nrf2的核转位；并降低了HO诱导的线粒体自噬水平。在HaCaT细胞中敲低NFE2L2或PINK1后，我们注意到细胞内活性氧增加、线粒体形态改变以及线粒体膜电位显著降低，细胞死亡水平显著上升。与未敲低NFE2L2或PINK1的组相比，MitoQ处理未能缓解这些情况。这些结果表明，MitoQ可能通过Nrf2调节PINK1/Parkin信号通路，以对抗HO诱导的线粒体氧化应激并保护细胞免受损伤。因此，我们的研究提供了实验证据和见解，可能为白癜风治疗干预措施的开发提供参考。
