USP37稳定SREBP1a促进胆固醇摄取和脂质沉积
USP37 Promotes Cholesterol Uptake and Lipid Deposition by Stabilizing SREBP1a
王曼 1丁虎1
作者信息
- 1. 华中科技大学同济医学院附属同济医院心血管内科,武汉 430030
- 折叠
摘要
目的 筛选影响胆固醇调节元件结合蛋白1a(cholesterol regulatory element binding protein,SREBP1a)蛋白稳定性的去泛素化酶,并探索其调控机制.方法 通过去泛素化酶库筛选显著影响SREBP1a表达的去泛素化酶,免疫蛋白印记实验和实时荧光定量PCR(qRT-PCR)评估去泛素化酶对SREBP1a以及升脂基因表达的影响;通过红色荧光蛋白标记人源低密度脂蛋白(human Dil-low density lipoprotein,Human Dil-LDL)摄取和油红O染色等实验技术检测细胞摄取低密度脂蛋白(LDL)和脂质沉积情况.结果 去泛素化酶库筛选发现泛素特异肽酶37(ubiquitin specific pepti-dase 37,USP37)可显著增加肝细胞SREBP1a蛋白表达水平,促进胆固醇摄取及脂质沉积.USP37基因敲除可显著降低SREBP1a蛋白表达水平,抑制升脂基因表达及脂质沉积.结论 去泛素化酶USP37通过稳定SREBP1a蛋白表达,促进胆固醇摄取及脂质沉积,揭示了 SREBP1a翻译后调控的新模式.
Abstract
Objective To explore the role of deubiquitination enzymes in the post-translational regulation of cholesterol regulatory element binding protein 1a(SREBP1a)and the corresponding mechanisms.Methods The effects of deubiquitination enzyme on the ex-pression of SREBP1a and lipid-raising gene were investigated by immunoprotein imprinting and real-time fluorescent quantitative PCR(qRT-PCR).The ubiquitization level of SREBP1a was evaluated by immunoprecipitation.LDL uptake and lipid deposition were detected by human Dil-low density lipoprotein(Dil-LDL)uptake and oil red O staining.Results SREBP1a promoted cholesterol uptake and lipid deposition.Ubiquitin specific peptidase 37(USP37)could increase the protein expression level of SREBP1a and promote cholesterol up-take and lipid deposition.USP37 gene knockout could inhibit the expression of lipid-raising gene and lipid deposition.Conclusion Deu-biquitination enzyme USP37 promotes cholesterol uptake and cellular lipid deposition by stabilizing SREBP1a protein expression,revea-ling the post-translational regulation mode of SREBP1a gene expression.
关键词
去泛素化/脂质沉积/低密度脂蛋白摄取/USP37/SREBP1aKey words
deubiquitination/lipid deposition/low density lipid uptake/USP37/SREBP1a引用本文复制引用
基金项目
国家自然科学基金面上项目(81974047)
出版年
2024
NETL
NSTL
万方数据