Regulation of dual oxidase hydrogen peroxide synthesis results in an epithelial respiratory burst

Abstract

Redox status is a central determinant of cellular activities and redox imbalance is correlated with numerous diseases. NADPH oxidase activity results in formation of H₂O₂, that, in turn, sets cellular redox status, a key regulator of cellular homeostasis and responses to external stimuli. Hydrogen peroxide metabolism regulates cell redox status by driving changes in protein cysteine oxidation often via cycling of thioredoxin/peroxiredoxin and glutathione; however, regulation of enzymes controlling synthesis and utilization of H₂O₂ is not understood beyond broad outlines. The data presented here show that calcium-stimulated epithelial Duox H₂O₂ synthesis is transient, independent of intracellular calcium renormalization, H₂O₂ scavenging by antioxidant enzymes, or substrate depletion. The data support existence of a separate mechanism that restricts epithelial H₂O₂ synthesis to a burst and prevents harmful changes in redox tone following continuous stimulation. Elucidation of this H₂O₂ synthesis tempering mechanism is key to understanding cellular redox regulation and control of downstream effectors, and this observation provides a starting point for investigation of the mechanism that controls H₂O₂-mediated increases in redox tone.

Keywords: Cell redox status; Duox; Hydrogen peroxide; NADPH oxidase.