Proton channel blockers inhibit Duox activity independent of Hv1 effects.

ABSTRACT: The NADPH oxidase reaction produces protons. In the case of the NADPH oxidase, NOX2, activity depends on secretion of these protons and is inhibited by blockade of the voltage-gated proton channel (Hv1). Duox1 and Duox2 activities similarly produce intracellular protons but synthesize hydrogen peroxide directly instead of superoxide. Hv1 contributes to acid secretion in some epithelia that express Duox. To test the hypothesis that Duox activity is also sensitive to Hv1 channel blockers, Duox was assayed in the presence of either Zn²⁺ or 5-chloro-2-guanidinobenzimidazole (ClGBI). Both compounds inhibited Duox activity in normal human bronchial epithelial cells but with an IC50 over 10-fold higher than that reported for Hv1 (IC50 Zn²⁺ = 0.68 mM; IC50 ClGBI = 0.07-0.14 m

SUBMITTER: Gattas MV 

PROVIDER: S-EPMC6920136 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature