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Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells

Background: Dyslipidaemias, particularly elevated plasma low-density lipoprotein cholesterol (LDL-C) levels, are major risk factors for cardiovascular disease (CVD). Besides pharmacological approaches, a nutritional strategy for CVD prevention has gained increasing attention. Among functional foods,...

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Autores principales: Macchi, Chiara, Greco, Maria Francesca, Ferri, Nicola, Magni, Paolo, Arnoldi, Anna, Corsini, Alberto, Sirtori, Cesare R., Ruscica, Massimiliano, Lammi, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747205/
https://www.ncbi.nlm.nih.gov/pubmed/35011066
http://dx.doi.org/10.3390/nu14010193
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author Macchi, Chiara
Greco, Maria Francesca
Ferri, Nicola
Magni, Paolo
Arnoldi, Anna
Corsini, Alberto
Sirtori, Cesare R.
Ruscica, Massimiliano
Lammi, Carmen
author_facet Macchi, Chiara
Greco, Maria Francesca
Ferri, Nicola
Magni, Paolo
Arnoldi, Anna
Corsini, Alberto
Sirtori, Cesare R.
Ruscica, Massimiliano
Lammi, Carmen
author_sort Macchi, Chiara
collection PubMed
description Background: Dyslipidaemias, particularly elevated plasma low-density lipoprotein cholesterol (LDL-C) levels, are major risk factors for cardiovascular disease (CVD). Besides pharmacological approaches, a nutritional strategy for CVD prevention has gained increasing attention. Among functional foods, the hypocholesterolemic properties of soy are driven by a stimulation of LDL-receptor (LDL-R) activity. Aim: To characterize the effect of two soy peptides, namely, β-conglycinin-derived YVVNPDNDEN and YVVNPDNNEN on the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key-regulators of the LDL-R. Methods: PCSK9 promoter activity (luciferase assay), PCSK9 protein expression (WB) and secretion (ELISA), PCSK9 interaction with LDL-R (binding assay) and human HepG2 cells were the objects of this investigation. Results: Treatment with YVVNPDNNEN peptide has led to a rise in PCSK9 gene expression (90.8%) and transcriptional activity (86.4%), and to a decrement in PCSK9 intracellular and secreted protein (−42.9%) levels. YVVNPDNNEN peptide reduced the protein expression of transcriptional factor HNF1α. Most changes driven by YVVNPDNDEN peptide were not statistically significant. Neither peptide inhibited the PCSK9–LDLR interaction. Conclusions: Although sharing a common effect on LDL-R levels through the inhibition of 3-hydroxy-3-methylglutaryl CoA reductase activity, only the YVVNPDNNEN peptide has an additional mechanism via the downregulation of PCSK9 protein levels.
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spelling pubmed-87472052022-01-11 Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells Macchi, Chiara Greco, Maria Francesca Ferri, Nicola Magni, Paolo Arnoldi, Anna Corsini, Alberto Sirtori, Cesare R. Ruscica, Massimiliano Lammi, Carmen Nutrients Article Background: Dyslipidaemias, particularly elevated plasma low-density lipoprotein cholesterol (LDL-C) levels, are major risk factors for cardiovascular disease (CVD). Besides pharmacological approaches, a nutritional strategy for CVD prevention has gained increasing attention. Among functional foods, the hypocholesterolemic properties of soy are driven by a stimulation of LDL-receptor (LDL-R) activity. Aim: To characterize the effect of two soy peptides, namely, β-conglycinin-derived YVVNPDNDEN and YVVNPDNNEN on the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key-regulators of the LDL-R. Methods: PCSK9 promoter activity (luciferase assay), PCSK9 protein expression (WB) and secretion (ELISA), PCSK9 interaction with LDL-R (binding assay) and human HepG2 cells were the objects of this investigation. Results: Treatment with YVVNPDNNEN peptide has led to a rise in PCSK9 gene expression (90.8%) and transcriptional activity (86.4%), and to a decrement in PCSK9 intracellular and secreted protein (−42.9%) levels. YVVNPDNNEN peptide reduced the protein expression of transcriptional factor HNF1α. Most changes driven by YVVNPDNDEN peptide were not statistically significant. Neither peptide inhibited the PCSK9–LDLR interaction. Conclusions: Although sharing a common effect on LDL-R levels through the inhibition of 3-hydroxy-3-methylglutaryl CoA reductase activity, only the YVVNPDNNEN peptide has an additional mechanism via the downregulation of PCSK9 protein levels. MDPI 2021-12-31 /pmc/articles/PMC8747205/ /pubmed/35011066 http://dx.doi.org/10.3390/nu14010193 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Macchi, Chiara
Greco, Maria Francesca
Ferri, Nicola
Magni, Paolo
Arnoldi, Anna
Corsini, Alberto
Sirtori, Cesare R.
Ruscica, Massimiliano
Lammi, Carmen
Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells
title Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells
title_full Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells
title_fullStr Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells
title_full_unstemmed Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells
title_short Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells
title_sort impact of soy β-conglycinin peptides on pcsk9 protein expression in hepg2 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747205/
https://www.ncbi.nlm.nih.gov/pubmed/35011066
http://dx.doi.org/10.3390/nu14010193
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