title: Peroxidases inhibit nitric oxide (NO) dependent bronchodilation: development of a model describing NO-peroxidase interactions.
abstract: Recent studies demonstrate that nitric oxide (NO) serves as a physiological substrate for mammalian peroxidases [(2000) J. Biol. Chem. 275, 37524]. We now show that eosinophil peroxidase (EPO) and lactoperoxidase (LPO), peroxidases known to be enriched in airways of asthmatic subjects, function as a catalytic sink for NO, modulating its bioavailability and function. Using NO-selective electrodes and direct spectroscopic and rapid kinetic methods, we examined the interactions of NO with EPO and LPO compounds I and II and ferric forms and compared the results to those reported for myeloperoxidase. A unified kinetic model for NO interactions with intermediates of mammalian peroxidases during steady-state catalysis is presented that accommodates unique features observed with each member of the mammalian peroxidase superfamily. Potential functional consequences of peroxidase-NO interactions in asthma are investigated by utilizing organ chamber studies with tracheal rings. In the presence of pathophysiologically relevant levels of peroxidases and H(2)O(2), NO-dependent bronchodilation of preconstricted tracheal rings was reversibly inhibited. Thus, NO interaction with mammalian peroxidases may serve as a potential mechanism for modulating their catalytic activities, influencing the regulation of local inflammatory and infectious events in vivo.
authors.affiliation: Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. abusouh@ccf.org
authors.forename: H M
authors.initials: HM
authors.lastname: Abu-Soud
authors.forename: M Y
authors.initials: MY
authors.lastname: Khassawneh
authors.forename: J T
authors.initials: JT
authors.lastname: Sohn
authors.forename: P
authors.initials: P
authors.lastname: Murray
authors.forename: M A
authors.initials: MA
authors.lastname: Haxhiu
authors.forename: S L
authors.initials: SL
authors.lastname: Hazen
mesh_terms: D000818:Animals; D001249:Asthma / Q000201:enzymology / Q000503:physiopathology; D001980:Bronchi / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D002384:Catalysis; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009126:Muscle Relaxation / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D010544:Peroxidases / Q000378:metabolism*; D013552:Swine; D014132:Trachea / Q000201:enzymology / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D010544:Peroxidases