title: Two Peptides from Soy β-Conglycinin Induce a Hypocholesterolemic Effect in HepG2 Cells by a Statin-Like Mechanism: Comparative in Vitro and in Silico Modeling Studies.
abstract: Two peptides from soybean β-conglycinin, i.e., YVVNPDNDEN (peptide 2) and YVVNPDNNEN (peptide 3), are known to be absorbed by human enterocytes. The former is a fragment of LRVPAGTTFYVVNPDNDENLRMIA (peptide 1), previously shown to increase the low-density lipoprotein (LDL) uptake and degradation in hepatocytes. Research carried out in silico on their interactions with the catalytic site of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCoAR) demonstrated that they behave as competitive inhibitors of HMGCoAR activity with a statin-like mechanism, confirmed by direct inhibition experiments. Research in HepG2 cells aimed at investigating the effects of these peptides on cholesterol metabolism showed that compared to mock treatment peptide 2 at 350 μM up-regulates the mature SREBP2 protein level by 134.0 ± 10.5%, increases the LDLR protein level by 152.0 ± 20.0%, and enhances the HMGCoAR protein production by 171 ± 29.9%, whereas peptide 3 up-regulates the mature SREBP2 protein level by 158.0 ± 9.2%, increases the LDL level 164.0 ± 17.9%, and induces a HMGCoAR protein increase by 170 ± 50.0%.
authors: Department of Pharmaceutical Sciences, University of Milan , via Mangiagalli 25, Milan 20133, Italy.
authors: Carmen
authors: C
authors: Lammi
authors: Cardio-toraco-vascular Department, Niguarda Hospital , Milan 20162, Italy.
authors: Chiara
authors: C
authors: Zanoni
authors: Department of Pharmaceutical Sciences, University of Milan , via Mangiagalli 25, Milan 20133, Italy.
authors: Anna
authors: A
authors: Arnoldi
authors: Department of Pharmaceutical Sciences, University of Milan , via Mangiagalli 25, Milan 20133, Italy.
authors: Giulio
authors: G
authors: Vistoli
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology*; D052179:Antigens, Plant / Q000737:chemistry / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D003198:Computer Simulation; D005916:Globulins / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008958:Models, Molecular; D010455:Peptides / Q000494:pharmacology*; D055314:Seed Storage Proteins / Q000737:chemistry / Q000494:pharmacology*; D030262:Soybean Proteins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000924:Anticholesteremic Agents; D052179:Antigens, Plant; D005916:Globulins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010455:Peptides; D055314:Seed Storage Proteins; D030262:Soybean Proteins; C013894:beta-conglycinin protein, Glycine max; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases
keywords: HMGCoA reductase; HepG2 cell line; cholesterol regulation; plant protein; β-conglycinin