PCSK9-D374Y通过下调游离胆固醇外排率和细胞外信号调节激酶活性抑制肝细胞迁移。

IF 2.6 4区 医学 Q3 CELL BIOLOGY
Lei Huang, Ying Cheng, Yulian Mu, Kui Li
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引用次数: 0

摘要

9型蛋白转化酶可介导肝细胞内低密度脂蛋白受体蛋白的胞内溶酶体降解,降低肝脏清除循环中低密度脂蛋白胆固醇的能力,导致循环系统胆固醇水平升高。目前的研究主要集中在PCSK9与血脂代谢的关系上;然而,PCSK9在肝细胞中的生物学功能很少被提及。在这项研究中,我们评估了其对人肝癌细胞株HepG2的影响,包括增殖、迁移和游离胆固醇运输。PCSK9-D374Y是一种功能获得突变,不影响这些细胞的增殖,但显著抑制这些细胞的迁移和胆固醇外排能力。抑制细胞内游离胆固醇的跨膜流出调节小G蛋白和抑制细胞外信号调节激酶。总之,PCSK9-D374Y影响肝细胞特征,包括它们的迁移和游离胆固醇运输能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

<i>PCSK9-</i>D374Y Suppresses Hepatocyte Migration through Downregulating Free Cholesterol Efflux Rate and Activity of Extracellular Signal-Regulated Kinase.

<i>PCSK9-</i>D374Y Suppresses Hepatocyte Migration through Downregulating Free Cholesterol Efflux Rate and Activity of Extracellular Signal-Regulated Kinase.

<i>PCSK9-</i>D374Y Suppresses Hepatocyte Migration through Downregulating Free Cholesterol Efflux Rate and Activity of Extracellular Signal-Regulated Kinase.

PCSK9-D374Y Suppresses Hepatocyte Migration through Downregulating Free Cholesterol Efflux Rate and Activity of Extracellular Signal-Regulated Kinase.

Proprotein convertase subtilisin/kexin type 9 can mediate the intracellular lysosomal degradation of the low-density lipoprotein receptor protein in hepatocytes and decrease the liver's ability to scavenge low-density lipoprotein cholesterol from circulation, resulting in high levels of cholesterol in the circulatory system. Current studies have primarily focused on the relationship between PCSK9 and blood lipid metabolism; however, the biological function of PCSK9 in hepatocytes is rarely addressed. In this study, we evaluate its effects in the human hepatoma carcinoma cell line HepG2, including proliferation, migration, and free cholesterol transport. PCSK9-D374Y is a gain-of-function mutation that does not affect proliferation but significantly suppresses the migration and cholesterol efflux capacity of these cells. The suppression of the transmembrane outflow of intracellular-free cholesterol regulates small G proteins and the suppression of extracellular signal-regulated kinase. In summary, PCSK9-D374Y affects hepatocyte features, including their migration and free cholesterol transport capabilities.

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来源期刊
Analytical Cellular Pathology
Analytical Cellular Pathology ONCOLOGY-CELL BIOLOGY
CiteScore
4.90
自引率
3.10%
发文量
70
审稿时长
16 weeks
期刊介绍: Analytical Cellular Pathology is a peer-reviewed, Open Access journal that provides a forum for scientists, medical practitioners and pathologists working in the area of cellular pathology. The journal publishes original research articles, review articles, and clinical studies related to cytology, carcinogenesis, cell receptors, biomarkers, diagnostic pathology, immunopathology, and hematology.
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