The antimicrobial peptide parabutoporin competes with p47(phox) as a PKC-substrate and inhibits NADPH oxidase in human neutrophils.
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.
Remijsen
Quinten F M
QF
Laboratory of Biochemistry, IRC, KULAK, B8500 Kortrijk, Belgium.
Fontayne
Alexandre
A
Verdonck
Fons
F
Clynen
Elke
E
Schoofs
Liliane
L
Willems
Jean
J
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
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