Hydrogen peroxide inhibits lung neutral endopeptidase.
Oxidants have been implicated in the pathogenesis of many inflammatory airway diseases. Neutral endopeptidase (also called enkephalinase, EC 3.4.24.11) is a peptidase that is involved in the degradation of several proinflammatory peptides, such as tachykinins and kinins. Indirect evidence suggests that airway neutral endopeptidase is inactivated by oxidants. To determine whether hydrogen peroxide inactivates neutral endopeptidase, we studied the activity of this peptidase in washed crude preparations of membranes from guinea pig lungs. Washed crude membrane preparations were exposed to increasing concentrations of hydrogen peroxide (1.25-25 mM) in the presence or absence of two different concentrations of catalase (300 and 700 U/mL). Neutral endopeptidase activity was inhibited by hydrogen peroxide in a concentration-dependent fashion (p = .0001). Addition of catalase prevented, in a concentration-dependent fashion, the inhibition of neutral endopeptidase induced by hydrogen peroxide (p = .0001). Mannitol (40 mM) and L-methionine (20 mM) did not prevent inhibition of neutral endopeptidase induced by hydrogen peroxide (2.5 mM). It can be concluded that neutral endopeptidase is inactivated by hydrogen peroxide, an effect that is prevented by catalase. Hydrogen peroxide-induced inactivation of neutral endopeptidase is not mediated by spontaneous generation of either hydroxyl radical or hypochlorous acid in the membrane preparation. Our results suggest that neutral endopeptidase inactivation may occur in airway diseases associated with exposure to or production of oxidants.
Roisman
G L
GL
Service de Pneumologie, U.F.R. Cochin-Port-Royal, Université René Descartes, Paris, France.
Dusser
D J
DJ
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D004790:Enzyme Induction; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism; D008168:Lung / Q000201:enzymology*; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D017665:Hydroxyl Radical; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D015260:Neprilysin