Impact of peptide permeation enhancer on tight junctions opening cellular mechanisms

Article Article scientifique Article Impact of peptide permeation enhancer on tight junctions opening cellular mechanisms eng 2022-10-27 2022-12 author Brunner Joël School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland. 753026 author Schvartz Domitille Proteomics Core Facility, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 665782 Services communs de la faculté de médecine (SCMU) author Gouiller Aurélie School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland. 824671 Section des sciences pharmaceutiques (FARMA) author Hainard Alexandre 0009-0006-7403-3261 Proteomics Core Facility, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 635700 Services communs de la faculté de médecine (SCMU) author Borchard Gerrit 0000-0001-6268-2586 School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland. 635281 Section des sciences pharmaceutiques (FARMA) 101375 10.1016/j.bbrep.2022.101375 36324528 2405-5808 PMC9618981 https://www.sciencedirect.com/science/article/pii/S2405580822001753 The myristoylated pentapeptide, L-R5, contains an amino acid sequence of the zeta inhibitory peptide (ZIP) portion (pseudosubstrate) of protein kinase C zeta (PKC ζ). As PKC ζ is involved in the modulation of epithelial tight junctions (TJs) through the phosphorylation of TJ proteins, L-R5 was suggested to interact with the enzyme resulting in the enhancement of paracellular permeability. This study shows that L-R5 does not bind to the enzyme but interacts directly with TJ proteins. We show here that the binding of PKC ζ to occludin and its successive phosphorylation is prevented by L-R5, which leads to TJ disruption and enhanced epithelial permeability. Although L-R5 did not show any <i>in vitro</i> cytotoxicity, a proteomics study revealed that L-R5 interferes with other regulatory pathways, e.g., apoptosis and immune response. We suggest that structural modification of the peptide may increase the specificity TJ protein-peptide interaction. L-R5 peptide Occludin PKC zeta Protein interaction Tight junction Dewey 610 Dewey 615 3 Faculté de médecine 2 31 Section des sciences pharmaceutiques 17 false 879 Biopharmacie Biochemistry and biophysics reports 32 8026666e-0144-4b0b-adb9-bac7e9bf2c04 Article (Published version) Public 1-s2.0-S2405580822001753-main.pdf 8382282 application/pdf CC BY-NC-ND-4.0 72bf2721e347f0228886e588ec9178c4bfe50780b7dd4a582c874a4387370f80 openAccess Faculté de médecine Faculté des sciences / Section des sciences pharmaceutiques

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Impact of peptide permeation enhancer on tight junctions opening cellular mechanisms	Biochemistry and biophysics reports			2022	2	20

Archive ouverte UNIGE

Gouiller, Aurélie