Crocetin exerts hypocholesterolemic effect by inducing LDLR and inhibiting PCSK9 and Sortilin in HepG2 cells
| Autor: | Asha Martin, A Aisha Siddiq |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Nutrition and Dietetics
Endocrinology Diabetes and Metabolism PCSK9 Crocetin Hep G2 Cells Proprotein convertase Carotenoids Sterol regulatory element-binding protein Cell biology chemistry.chemical_compound Adaptor Proteins Vesicular Transport Endocrinology chemistry Receptors LDL LDL receptor Kexin Humans lipids (amino acids peptides and proteins) Proprotein Convertase 9 Receptor Vitamin A Lipoprotein |
| Zdroj: | Nutrition research (New York, N.Y.). 98 |
| ISSN: | 1879-0739 |
| Popis: | Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important post- transcriptional regulator of plasma levels of low- density lipoprotein cholesterol (LDL-C). Inhibition of PCSK9 has emerged as an attractive strategy in recent years to combat hypercholesterolemia stimulating the search for PCSK9 inhibitors. The carotenoid crocetin exhibits hypocholesterolemic effect. However, it is unknown whether the beneficial effect is mediated through PCSK9 modulation. We hypothesized that crocetin inhibits PCSK9 and therefore, in our quest for natural and safe PCSK9 inhibitors, we investigated the effect of crocetin on PCSK9 expression and other key molecular targets involved in hepatic cholesterol metabolism using the human hepatoma cell line HepG2 as a model system. We demonstrate for the first time that crocetin treatment significantly decreases PCSK9 and Sterol regulatory element binding proteins (SREBP) expression in a dose dependent manner, accompanied by a concomitant increase in the hepatic Low-Density lipoprotein receptor (LDLR) expression. Additionally, crocetin significantly downregulates the levels of both mRNA and protein expression of sortilin, a key sorting receptor that facilitates PCSK9 transport in the trans Golgi network in a dose dependent manner. Overall, our results suggest that crocetin is a LDLR inducer, and an inhibitor of PCSK9, sortilin and SREBPs making it an effective natural anti-cholesterol agent. |
| Databáze: | OpenAIRE |
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