DJ-1蛋白对氧化应激下线粒体稳态的调控研究

Vitiligo is a depigmenting disorder caused by reduction or loss of melanocyte in the skin. Vitiligo is easy to diagnose, but difficult to treat, and it can cause negative impact on social life. The etiology of vitiligo is still unkown, oxidative damage has been recognized as an important pathogenesis. Mitochondria is very sensitive to oxidative stress, the break of mitochondrial homeostasis was the initiating factor to the whole cell damage against oxidative stress.The DJ-1 protein has been confirmed to have protective effect in dopaminergic neurons against oxidative damage, and it is an important protective factor in the pathogenesis of Parkinson's disease. But the role of DJ-1 protein in oxidative damage in vitiligo has not been studied. In this study, we will establish the melanocyte oxidative stress model, observe the subcellular location and translocation of DJ-1 protein in melanocyte. Using short hairpin RNA gene silencing and plasmid transfection to make DJ-1 gene silenced and overexpressed, observe the change of mitochondrial homeostasis(morphology, membrane permeability, fission/ fusion and mtDNA), intracellular ROS level and cell apoptosis. We hope that this research may provide new insight to vitiligo's pathogenesis and treatment.

白癜风是由于皮肤黑素细胞减少或丧失所致的色素脱失性疾病，易诊断，难治疗，对患者生活、社交造成严重影响。本病病因不清，目前认为氧化损伤是重要发病机制。线粒体是细胞内对氧化损伤最敏感的细胞器，线粒体稳态破坏是细胞整体氧化损伤发生的始动因素。DJ-1蛋白在多巴胺能神经元的氧化损伤中起到保护作用，是帕金森病发病机制中的重要保护因子，但其在白癜风氧化损伤中的作用尚未见深入研究。本研究通过建立黑素细胞的氧化应激模型，动态观察氧化应激下DJ-1蛋白在细胞内的移位；并采用小发卡RNA基因沉默和质粒转染技术上调或下调DJ-1的表达，观察氧化应激下DJ-1不同表达水平对线粒体稳态（形态、结构、膜通透性、分裂融合、线粒体DNA）、细胞内ROS水平、细胞凋亡的影响，探讨其发挥保护作用的机制，为完善白癜风发病机制、开发潜在的治疗手段提供科学的理论依据。