PAQR3 modulates blood cholesterol level by facilitating interaction between LDLR and PCSK9
文献类型：期刊论文
| 作者 | Huang, Meiqin1; Zhao, Zilong1; Cao, Qianqian1; Wei, Siying1; Zhao, Jingyu1; Bai, Meijuan1; Chen, Yan1,2; You, Xue2; , |
| 刊名 | METABOLISM-CLINICAL AND EXPERIMENTAL
 |
| 出版日期 | 2019 |
| 卷号 | 94期号:-页码:88-95 |
| 关键词 | Low-density lipoprotein cholesterol LDLR PCSK9 Endosome Protein degradation |
| ISSN号 | 0026-0495 |
| DOI | 10.1016/j.metabol.2019.02.005 |
| 文献子类 | Article |
| 英文摘要 | Objective: Low-density lipoprotein cholesterol (LDL-C) is the hallmark of atherosclerotic cardiovascular diseases. The hepatic LDL receptor (LDLR) plays an important role in clearance of circulating LDL-C. PCSK9 facilitates degradation of LDLR in the lysosome and antagonizing PCSK9 has been successfully used in the clinic to reduce blood LDL-C level. Here we identify a new player that modulates LDLR interaction with PCSK9, thus controlling LDLR degradation and cholesterol homeostasis. Methods: The blood LDL-C and cholesterol levels were analyzed in mice with hepatic deletion of Paqr3 gene. The half-life of LDLR was analyzed in HepG2 cells. The interaction of PAQR3 with LDLR and PCSK9 was analyzed by co-immunoprecipitation and immunofluorescent staining. Results: The blood LDL-C and total cholesterol levels in the mice with hepatic deletion of Paqr3 gene were significantly lower than the control mice after feeding with high-fat diet (p < 0.001 and p < 0.05 respectively). The steady-state level of LDLR protein is elevated by Paqr3 knockdown/deletion and reduced by PAQR3 overexpression. The half-life of LDLR protein is increased by Paqr3 knockdown and accelerated by PAQR3 overexpression. PAQR3 interacts with the beta-sheet domain of LDLR and the P-domain of PCSK9 respectively. In addition, PAQR3 can be localized in early endosomes and colocalized with LDLR, PCSK9 and LDL. Mechanistically, PAQR3 enhances the interaction between LDLR and PCSK9. Conclusion: Our study reveals that PAQR3 plays a pivotal role in controlling hepatic LDLR degradation and blood LDL-C level via modulating LDLR-PCSK9 interaction. (C) 2019 Elsevier Inc. All rights reserved. |
| 学科主题 | Endocrinology & Metabolism |
| WOS关键词 | LOW-DENSITY-LIPOPROTEIN ; SUBTILISIN/KEXIN TYPE 9 ; HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA ; MONOCLONAL-ANTIBODY ; SERINE-PROTEASE ; PROPROTEIN ; RECEPTOR ; EFFICACY ; SAFETY ; TOLERABILITY |
| 语种 | 英语 |
| WOS记录号 | WOS:000470306600010 |
| 出版者 | W B SAUNDERS CO-ELSEVIER INC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1011]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Univ Chinese Acad Sci, Chinese Acad Sci, CAS Key Lab Nutr Metab & Food Safety, Shanghai Inst Nutr & Hlth,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China; 2.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Huang, Meiqin,Zhao, Zilong,Cao, Qianqian,et al. PAQR3 modulates blood cholesterol level by facilitating interaction between LDLR and PCSK9[J]. METABOLISM-CLINICAL AND EXPERIMENTAL,2019,94(-):88-95. |
| APA | Huang, Meiqin.,Zhao, Zilong.,Cao, Qianqian.,Wei, Siying.,Zhao, Jingyu.,...&,.(2019).PAQR3 modulates blood cholesterol level by facilitating interaction between LDLR and PCSK9.METABOLISM-CLINICAL AND EXPERIMENTAL,94(-),88-95. |
| MLA | Huang, Meiqin,et al."PAQR3 modulates blood cholesterol level by facilitating interaction between LDLR and PCSK9".METABOLISM-CLINICAL AND EXPERIMENTAL 94.-(2019):88-95. |
入库方式： OAI收割
来源：上海营养与健康研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。