细胞色素P450（CYP）4F2是20-HETE合酶，我们通过人群关联研究、现代生物学研究及CYP4F2转基因小鼠研究，阐述了20-HETE的增加导致高血压。最近，我们在对高盐饲养CYP4F2转基因小鼠的研究中发现，20-HETE与高盐交互作用影响泛素-蛋白酶体系统，提示蛋白泛素化可能与盐敏感性高血压有关。因此，本项目拟利用高通量的串联质谱技术，开展Dahl盐敏感性大鼠和Dahl盐抵抗性大鼠的肾脏泛素化组学研究，围绕大鼠模型的20-HETE水平不同对高盐反应的敏感性不同这一推断，筛查20-HETE调控的泛素化靶蛋白；同时辅助细胞模型，鉴定泛素化蛋白的特异性泛素连接酶E3，阐明20-HETE调节的泛素化蛋白对盐敏感性高血压的作用机制，为治疗盐敏感性高血压提供潜在的药物靶点。

Cytochrome P450 4F2 (CYP4F2) is a synthase of 20-HETE. We have reported that the increase of 20-HETE is involved in hypertension through the studies in population association, modern biology and CYP4F2 transgenic mice. Recently, we fed CYP4F2 transgenic mice with high salt diet, and found that interaction of 20-HETE with high salt affected ubiquitin-proteasome system, suggesting that ubiquitinated proteins probably link to salt-sensitive hypertension. Therefore, in this project, we are carrying out renal ubiquitylomics study in Dahl Salt-Sensitive rats and Dahl Salt-Resistive rats by tandem mass spectrometry, since we suppose that different levels of 20-HETE result in various responses to high salt. We will screen the ubiquitinated protein modulated by 20-HETE from the kidney of rat models. Furthermore, we will use rat model combined with cell model to identify the specific ubiquitin ligase E3 to the ubiquitinated protein, and elucidate the mechanism of 20-HETE in modulation of ubiquitination and the role of renal ubiquitinated protein in pathogenesis of salt-sensitive hypertension. This achievement will provide a potential target for the therapy of salt-sensitive hypertension.