机构：[1]Department of Atherosclerosis, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Anzhen Hospital Affiliated with Capital Medical University, Beijing, China临床科室动脉硬化门诊首都医科大学附属安贞医院[2]Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Qiaokou District, Wuhan 430030, China[3]Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, China科研平台职能科室临床流行病与循证医学中心儿科研究所首都医科大学附属北京儿童医院[4]Department of Cardiology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China[5]University of South China, Hengyang 421001, China[6]The Affiliated Hospital of North China University of Science and Technology, North China University of Science and Technology, Tangshan 063000, Hebei Province, China
Objectives: Familial hypercholesterolemia (FH) is an autosomal dominant disorder of cholesterol metabolism. Three recognized genes (LDLR, APOB and PCSK9) present in only 20-30% of patients with possible FH cases. Additional FH-causing genes need to be explored. The present study found an isolated gene change, sEH R287Q, in a core family of FH. In this study, we aimed to investigate the roles of R287Q on sEH expression and on LDLR expression, LDL binding to LDLR and LDL internalization. Materials and methods: 167 lipid-related genes of a core FH family were sequenced using a gene-capture chip. Through carrier dependent protein expression, the expression level (western blot), hydrolase activity (fluorescent chemistry) and intracellular localization (immunofluorescence and Confocal Laser Scanning Microscope) of recombinant sEH R287Q in cultured BEL-7402 cells were conducted. The effect of wild type and R287Q of sEH on LDLR expression, LDL binding to LDLR and LDL internalization were also conducted through Flow Cytometry. Results: sEH R287Q was the only gene changes among 167 lipid-related genes in the FH core family. Both expression level and hydrolase activity of recombinant sEH R287Q in cultured cells were significantly declined compared with that of the wild type sEH. sEH R287Q also decreased the binding of LDL to LDLR and LDL internalization and had no effect on cell-surface LDLR protein level. Conclusion: Our results suggest that sEH R287Q may have a role in the elevation of blood LDL in FH. The exactly role of sEH R287Q on FH deserves further study.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81471098, 81670811]; Capital Medical University Basic-Clinical Cooperation Research Fund of China [15JL71]
第一作者机构：[1]Department of Atherosclerosis, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Anzhen Hospital Affiliated with Capital Medical University, Beijing, China[2]Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Qiaokou District, Wuhan 430030, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Atherosclerosis, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Anzhen Hospital Affiliated with Capital Medical University, Beijing, China
推荐引用方式(GB/T 7714)：
Tang Ling,Wang Guoliang,Jiang Long,et al.Role of sEH R287Q in LDLR expression, LDL binding to LDLR and LDL internalization in BEL-7402 cells[J].GENE.2018,667:95-100.doi:10.1016/j.gene.2018.04.038.
APA：
Tang, Ling,Wang, Guoliang,Jiang, Long,Chen, Panpan,Wang, Wei...&Wang, Luya.(2018).Role of sEH R287Q in LDLR expression, LDL binding to LDLR and LDL internalization in BEL-7402 cells.GENE,667,
MLA：
Tang, Ling,et al."Role of sEH R287Q in LDLR expression, LDL binding to LDLR and LDL internalization in BEL-7402 cells".GENE 667.(2018):95-100
