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

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

doi:10.1016/j.fob.2014.08.003

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

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

Authors

Majambu Mbikay¹, Francine Sirois², Sonia Simoes³, Janice Mayne⁴, Michel Chrétien¹

Affiliations

¹ 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.
² Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada ; Laboratory of Functional Endoproteolysis, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.
³ Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
⁴ Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

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.

Keywords: ABCA1, ATP-binding cassette transporter A1; ApoB, apolipoprotein B; Cholesterol; HMGCoAR, 3-hydroxy-3-methylglutaryl-CoA reductase; Hepatocytes; LDL-C, low-density lipoprotein-cholesterol; LDLR, low-density lipoprotein receptor; Low-density lipoprotein receptor; PCSK9, proprotein convertase subtilisin/kexin 9; Proprotein convertase; Q3G, quercetin-3-β-d-glucoside; Quercetin; SREBP-2, sterol regulatory element-binding protein 2; Sortilin; TGN, trans Golgi network.