scholarly journals 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 ◽  
Vol 4 (1) ◽  
pp. 755-762 ◽  
Author(s):  
Majambu Mbikay ◽  
Francine Sirois ◽  
Sonia Simoes ◽  
Janice Mayne ◽  
Michel Chrétien
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Human Hepatocytes ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Proprotein Convertase ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor ◽  
Ldl Uptake

scholarly journals Ascorbic acid enhances low-density lipoprotein receptor expression by suppressing proprotein convertase subtilisin/kexin 9 expression

2020 ◽  
Vol 295 (47) ◽  
pp. 15870-15882
Author(s):  
Dandan Wang ◽  
Xiaoxiao Yang ◽  
Yuanli Chen ◽  
Ke Gong ◽  
Maoyun Yu ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Proprotein Convertase ◽  
Acid Supplementation ◽  
Density Lipoprotein Receptor ◽  
Ldl Uptake ◽  
Ascorbic Acid Supplementation

Ascorbic acid, a water-soluble antioxidant, regulates various biological processes and is thought to influence cholesterol. However, little is known about the mechanisms underpinning ascorbic acid-mediated cholesterol metabolism. Here, we determined if ascorbic acid can regulate expression of proprotein convertase subtilisin/kexin 9 (PCSK9), which binds low-density lipoprotein receptor (LDLR) leading to its intracellular degradation, to influence low-density lipoprotein (LDL) metabolism. At cellular levels, ascorbic acid inhibited PCSK9 expression in HepG2 and Huh7 cell lines. Consequently, LDLR expression and cellular LDL uptake were enhanced. Similar effects of ascorbic acid on PCSK9 and LDLR expression were observed in mouse primary hepatocytes. Mechanistically, ascorbic acid suppressed PCSK9 expression in a forkhead box O3-dependent manner. In addition, ascorbic acid increased LDLR transcription by regulating sterol regulatory element-binding protein 2. In vivo, administration of ascorbic acid reduced serum PCSK9 levels and enhanced liver LDLR expression in C57BL/6J mice. Reciprocally, lack of ascorbic acid supplementation in L-gulono-γ-lactone oxidase deficient (Gulo−/−) mice increased circulating PCSK9 and LDL levels, and decreased liver LDLR expression, whereas ascorbic acid supplementation decreased PCSK9 and increased LDLR expression, ameliorating LDL levels in Gulo−/− mice fed a high fat diet. Moreover, ascorbic acid levels were negatively correlated to PCSK9, total and LDL levels in human serum samples. Taken together, these findings suggest that ascorbic acid reduces PCSK9 expression, leading to increased LDLR expression and cellular LDL uptake. Thus, supplementation of ascorbic acid may ameliorate lipid profiles in ascorbic acid-deficient species.

scholarly journals The Proprotein Convertase Subtilisin/Kexin Type 9-resistant R410S Low Density Lipoprotein Receptor Mutation

2016 ◽  
Vol 292 (5) ◽  
pp. 1573-1590 ◽  
Author(s):  
Delia Susan-Resiga ◽  
Emmanuelle Girard ◽  
Robert Scott Kiss ◽  
Rachid Essalmani ◽  
Josée Hamelin ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Proprotein Convertase ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor
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