槲皮素-3-葡萄糖苷可增加低密度脂蛋白受体（LDLR）的表达，减弱前蛋白转化酶枯草溶菌素/kexin 9（PCSK9）的分泌，并刺激培养的Huh7人肝细胞摄取低密度脂蛋白。

Quercetin-3-glucoside increases low-density lipoprotein receptor (LDLR) expression, attenuates proprotein convertase subtilisin/kexin 9 (PCSK9) secretion, and stimulates LDL uptake by Huh7 human hepatocytes in culture.

作者信息

Mbikay Majambu, Sirois Francine, Simoes Sonia, Mayne Janice, Chrétien Michel

机构信息

Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada ; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada ; Laboratory of Functional Endoproteolysis, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.

Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada ; Laboratory of Functional Endoproteolysis, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.

出版信息

FEBS Open Bio. 2014 Sep 2;4:755-62. doi: 10.1016/j.fob.2014.08.003. eCollection 2014.

DOI:10.1016/j.fob.2014.08.003

PMID:25349780

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4208090/

Abstract

Low-density lipoprotein receptor (LDLR) mediates hepatic clearance of plasma cholesterol; proprotein convertase subtilisin/kexin 9 (PCSK9) opposes this clearance by promoting LDLR degradation. The plant flavonoid quercetin-3-β-d-glucoside (Q3G) has been shown to reduce hypercholesterolemia in experimental animals. Here, we examined how it affects LDLR and PCSK9 expression as well as LDL uptake by human Huh7 hepatocytes. At low micromolar concentrations, Q3G increased LDLR expression, reduced PCSK9 secretion, and stimulated LDL uptake. It also diminished intracellular sortilin, a sorting receptor known to facilitate PCSK9 secretion. Thus, as an LDLR inducer and a PCSK9 anti-secretagogue, Q3G may represent an effective anti-cholesterolemic agent.

摘要

低密度脂蛋白受体（LDLR）介导肝脏对血浆胆固醇的清除；前蛋白转化酶枯草杆菌蛋白酶/kexin 9型（PCSK9）通过促进LDLR降解来对抗这种清除。植物类黄酮槲皮素-3-β-d-葡萄糖苷（Q3G）已被证明可降低实验动物的高胆固醇血症。在此，我们研究了它如何影响人Huh7肝细胞中LDLR和PCSK9的表达以及LDL摄取。在低微摩尔浓度下，Q3G增加LDLR表达，减少PCSK9分泌，并刺激LDL摄取。它还减少了细胞内的sortilin，一种已知有助于PCSK9分泌的分拣受体。因此，作为一种LDLR诱导剂和PCSK9抗分泌剂，Q3G可能是一种有效的抗胆固醇药物。