학술논문
Trans-Epithelial Transport, Metabolism, and Biological Activity Assessment of the Multi-Target Lupin Peptide LILPKHSDAD (P5) and Its Metabolite LPKHSDAD (P5-Met).
Document Type
Academic Journal
Author
Lammi C; Department of Pharmaceutical Sciences, University of Milan, 20122 Milan, Italy.; Aiello G; Department of Pharmaceutical Sciences, University of Milan, 20122 Milan, Italy.; Department of Human Science and Quality of Life Promotion, Telematic University San Raffaele, 00166 Rome, Italy.; Bollati C; Department of Pharmaceutical Sciences, University of Milan, 20122 Milan, Italy.; Li J; Department of Pharmaceutical Sciences, University of Milan, 20122 Milan, Italy.; Bartolomei M; Department of Pharmaceutical Sciences, University of Milan, 20122 Milan, Italy.; Ranaldi G; Food and Nutrition Research Centre, CREA, 00178 Rome, Italy.; Ferruzza S; Food and Nutrition Research Centre, CREA, 00178 Rome, Italy.; Fassi EMA; Department of Pharmaceutical Sciences, University of Milan, 20122 Milan, Italy.; Grazioso G; Department of Pharmaceutical Sciences, University of Milan, 20122 Milan, Italy.; Sambuy Y; Food and Nutrition Research Centre, CREA, 00178 Rome, Italy.; Arnoldi A; Department of Pharmaceutical Sciences, University of Milan, 20122 Milan, Italy.
Source
Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE
Subject
Language
English
Abstract
P5 (LILPKHSDAD) is a hypocholesterolemic peptide from lupin protein with a multi-target activity, since it inhibits both 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) and proprotein convertase subtilisin/kexin type-9 (PCSK9). This work shows that, during epithelial transport experiments, the metabolic transformation mediated by intestinal peptidases produces two main detected peptides, ILPKHSDAD (P5-frag) and LPKHSDAD (P5-met), and that both P5 and P5-met are linearly absorbed by differentiated human intestinal Caco-2 cells. Extensive comparative structural, biochemical, and cellular characterizations of P5-met and the parent peptide P5 demonstrate that both peptides have unique characteristics and share the same mechanisms of action. In fact, they exert an intrinsically multi-target behavior being able to regulate cholesterol metabolism by modulating different pathways. The results of this study also highlight the dynamic nature of bioactive peptides that may be modulated by the biological systems they get in contact with.