Chemotherapy drugs induce pyroptosis through caspase-3-dependent cleavage of GSDME
文献类型：期刊论文
| 作者 | Zhang, Xixi; Zhang, Haibing; , |
| 刊名 | SCIENCE CHINA-LIFE SCIENCES
 |
| 出版日期 | 2018 |
| 卷号 | 61期号:6页码:739-740 |
| 关键词 | Low-density lipoprotein cholesterol LDLR PCSK9 Endosome Protein degradation |
| ISSN号 | 1674-7305 |
| DOI | 10.1007/s11427-017-9158-x |
| 文献子类 | Editorial Material |
| 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 | Life Sciences & Biomedicine - Other Topics |
| WOS关键词 | CELL-DEATH ; GASDERMIN ; CANCER |
| 语种 | 英语 |
| WOS记录号 | WOS:000435974800017 |
| 出版者 | SCIENCE PRESS |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/639]  |
| 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 | Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai 200031, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Zhang, Xixi,Zhang, Haibing,,. Chemotherapy drugs induce pyroptosis through caspase-3-dependent cleavage of GSDME[J]. SCIENCE CHINA-LIFE SCIENCES,2018,61(6):739-740. |
| APA | Zhang, Xixi,Zhang, Haibing,&,.(2018).Chemotherapy drugs induce pyroptosis through caspase-3-dependent cleavage of GSDME.SCIENCE CHINA-LIFE SCIENCES,61(6),739-740. |
| MLA | Zhang, Xixi,et al."Chemotherapy drugs induce pyroptosis through caspase-3-dependent cleavage of GSDME".SCIENCE CHINA-LIFE SCIENCES 61.6(2018):739-740. |
入库方式： OAI收割
来源：上海营养与健康研究所
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