The antimicrobial peptide parabutoporin competes with p47phox as a PKC-substrate and inhibits NADPH oxidase in human neutrophils

Quinten F.M. Remijsen; Alexandre Fontayne; Fons Verdonck; Elke Clynen; Liliane Schoofs; Jean Willems

doi:10.1016/j.febslet.2006.10.024

The antimicrobial peptide parabutoporin competes with p47phox as a PKC-substrate and inhibits NADPH oxidase in human neutrophils

Quinten F.M. Remijsen, Alexandre Fontayne, Fons Verdonck, Elke Clynen, Liliane Schoofs, Jean Willems

Source

FEBS Letters > 2006 > 580 > 26 > 6206-6210

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-α, -βI, -βII and -δ, but not PKC-ζ. 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.