硒通过SECIS元件调控硒蛋白保护血管内皮细胞免于氧化损伤的作用机制

流行病学发现硒（Se）具有预防心血管疾病的功效，但作用机制尚不完全清楚。Se主要通过硒蛋白保护血管内皮细胞（VEC）免于氧化损伤。硒代半胱氨酸插入序列（SECIS）元件是合成硒蛋白的限速步骤。项目组前期发现，Se在保护VEC免于氧化损伤时，硒蛋白表达不一致，存在高表达的优势硒蛋白。Se是否通过SECIS元件调控优势硒蛋白保护VEC免于氧化损伤？尚未见报道。本项目研究氧化应激条件下，Se保护VEC的作用；采用RNA-seq和蛋白组学的方法，筛选优势硒蛋白；采用分子克隆技术构建含SECIS元件的荧光素酶UGA突变载体系统，在细胞水平和动物水平分析SECIS元件及重编码影响因子SBP2、rL30、EFsec和eIF4A3对优势硒蛋白表达的影响，验证Se通过SECIS元件及重编码影响因子调控优势硒蛋白的表达，进而起到保护VEC免于氧化损伤的作用，以期进一步阐明Se预防心血管疾病的分子机制。

Epidemiological studies indicated selenium (Se) has important role in preventing cardiovascular diseases, but its mechanism is not fully understood. Se protects vascular endothelial cells (VEC) from oxidative damage mainly through selenoproteins. Selenocysteine insertion sequence (SECIS) element is a rate-limiting step in the synthesis of selenoprotein. In our preliminary study, we found that Se protects VEC from oxidative damage, and the expression of selenium protein was inconsistent, and there was a dominant selenoprotein with high expression. Does Se protect VEC from oxidative damage by regulating dominant selenoproteins through SECIS elements? No report has yet been reported. In this project, we will study the protective effect of Se on VEC under oxidative stress, screen dominant selenoproteins by RNA-seq and proteomics, construct luciferase UGA mutation vector system containing SECIS elements, and analyze the effects of SECIS elements and recoding influencing factors SBP2, rL30, EFsec and eIF4A3 on the expression of dominant proteomics at the cellular and animal levels, and test Se regulates the expression of dominant selenoproteins protecting VEC from oxidative damage through SECIS elements and recoding influencing factors. Our purpose is to further elucidate the molecular mechanism of Se in preventing cardiovascular diseases.