title: The antimicrobial peptide parabutoporin competes with p47(phox) as a PKC-substrate and inhibits NADPH oxidase in human neutrophils.
abstract: We investigated parabutoporin (PP), an antimicrobial scorpion peptide, to understand its inhibition on NADPH oxidase in human PMN. We show that PP is a good substrate for all PKC-isotypes, implicated in the activation of NADPH oxidase, and acts as a potent competitive inhibitor of in vitro p47(phox)-phosphorylation by PKC-alpha, -betaI, -betaII and -delta, but not PKC-zeta. In PMN, PP also inhibits the PMA-stimulated phosphorylation of p47(phox) and its subsequent translocation. In contrast, PP affects the PKC-independent activation to a much lesser degree. This indicates that PP inhibits the activation of NADPH oxidase at submicromolar concentrations in a strongly PKC-dependent manner.
authors.affiliation: Laboratory of Biochemistry, IRC, KULAK, B8500 Kortrijk, Belgium.
authors.forename: Quinten F M
authors.initials: QF
authors.lastname: Remijsen
authors.forename: Alexandre
authors.initials: A
authors.lastname: Fontayne
authors.forename: Fons
authors.initials: F
authors.lastname: Verdonck
authors.forename: Elke
authors.initials: E
authors.lastname: Clynen
authors.forename: Liliane
authors.initials: L
authors.lastname: Schoofs
authors.forename: Jean
authors.initials: J
authors.lastname: Willems
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D006801:Humans; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects*; D010766:Phosphorylation; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism*; D012604:Scorpion Venoms / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D023181:Antimicrobial Cationic Peptides; D020033:Protein Isoforms; D012604:Scorpion Venoms; C496148:parabutoporin, Parabuthus schlechteri; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D011493:Protein Kinase C