Background: Dyslipidaemias, particularly elevated plasma low-density lipoprotein cho- lesterol (LDL-C) levels, are major risk factors for cardiovascular disease (CVD). Besides pharmaco- logical 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 con- vertase 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 investiga- tion. 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.

Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells / C. Macchi, M.F. Greco, N. Ferri, P. Magni, A. Arnoldi, A. Corsini, C.R. Sartori, M. Ruscica, C. Lammi. - In: NUTRIENTS. - ISSN 2072-6643. - 14:1(2022 Jan), pp. 193.1-193.10. [10.3390/nu14010193]

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

C. Macchi
Primo
;
M.F. Greco
Secondo
;
P. Magni;A. Arnoldi;A. Corsini;M. Ruscica
Penultimo
;
C. Lammi
Ultimo
2022

Abstract

Background: Dyslipidaemias, particularly elevated plasma low-density lipoprotein cho- lesterol (LDL-C) levels, are major risk factors for cardiovascular disease (CVD). Besides pharmaco- logical 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 con- vertase 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 investiga- tion. 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.
Settore CHIM/10 - Chimica degli Alimenti
31-dic-2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/893646
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