活性气体分子硫化氢对RNASET2介导的黑素细胞损伤保护作用及机制研究

项目名称： 活性气体分子硫化氢对RNASET2介导的黑素细胞损伤保护作用及机制研究

项目编号： No.81502748

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王倩倩

作者单位： 复旦大学

项目金额： 18万元

中文摘要： 2010年我们通过全基因组关联研究首次报道了白癜风易感基因：分泌性核酸酶RNASET2。我们前期研究发现：应激介导下高表达的RNASET2 蛋白具有“氧化应激”和“促凋亡”的双重作用，同时，最新文献证实H2S可以通过抗“氧化应激”和 “抑制凋亡”作用对细胞起到保护作用。基于此，我们推断：（1）H2S通过其抗氧化应激、抗凋亡及抗炎等生物学效应对RNASET2介导的黑素细胞损伤起到保护作用；（2）H2S可能通过改变RNASET2物理结构中的TRAF2结构域，阻断RNASET2与TRAF2蛋白的直接结合，关闭凋亡通路的进一步激活，从而发挥其保护细胞的生物学活性。因此，我们拟应用体外细胞模型探讨H2S对RNASET2介导的黑素细胞损伤的保护作用及分子机制，为白癜风潜在的治疗措施提供转化医学科研基础。

中文关键词： 硫化氢；分泌性核酸酶T2；黑素细胞；凋亡；氧化应激

英文摘要： Our recent genome-wide association study identified a link between vitiligo and genetic variants in the ribonuclease T2 (RNASET2) gene in 2010.Our previous study found that: high expression of RNASET2 protein induced by stress conditions have the dual roles of oxidative stress and apoptosis; Based on the latest literature that H2S can protect the cells by inhibiting oxidative stress and apoptosis . Then, we speculate the possible role and mechanism that: (1) H2S may protect melanocytes injury mediated by RNASET2 overexpression through its biological effect of anti-oxidative stress, anti -apoptosis and anti-inflammation.; (2) H2S may exert its biological effect by changing the TRAF2 domain of the physical structure of RNASET2 , block the direct combination of protein RNASET2 and TRAF2 , and then turn off further activation of apoptotic pathways. Therefore, we plan to explore protective effects and mechanisms of H2S on RNASET2 induced human melanocytes dysfunction by application of in vitro cell model and provide evidence for potential treatment of vitiligo from bench to the bedside.

英文关键词： sodium hydrosulfide ;RNASET2;melanocyte;apoptosis;oxidative stress