title: Myeloperoxidase-catalyzed oxidative inactivation of human kininogens: the impairment of kinin-precursor and prekallikrein-binding functions.
abstract: Bradykinin-related vasoactive peptides (kinins) are important mediators of local and systemic inflammatory reactions. However, at local inflammatory foci, the production of kinins from proteinaceous precursors (kininogens) can be affected by reactive oxygen species released by phagocyte cells. One of the predominant oxidants at these places is hypochlorous acid which is formed from hydrogen peroxide and chloride ions by neutrophil myeloperoxidase. In this study, inactivation of human kininogens after oxidation with the myeloperoxidase-H₂O₂-chloride system was observed and analyzed by protein chemistry methods. The kinin release from oxidized kininogens by major kinin-producing enzymes, plasma and tissue kallikreins, proceed with a very low rate. This effect was assigned to apparent inability of kallikreins to process the kinin N-terminus owing to the conversion of the adjacent Met-361 residue to methionine sulfoxide. Additionally, the oxidized high-molecular mass kininogen lost its natural ability to bind plasma prekallikrein. This effect was assigned to the oxidation of Trp-569 residue within the prekallikrein-binding region which is subsequently destructed owing to cleavage of the peptide bond after that residue. One possible pathophysiological consequence of the described effects on kininogens could be the impairment of the normal assembly and triggering of the kinin-forming system on defense cell surfaces.
authors.affiliation: Department of Analytical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Kraków, Poland. andrzej.kozik@uj.edu.pl
authors.forename: Andrzej
authors.initials: A
authors.lastname: Kozik
authors.forename: Anna
authors.initials: A
authors.lastname: Golda
authors.forename: Pawel
authors.initials: P
authors.lastname: Mak
authors.forename: Piotr
authors.initials: P
authors.lastname: Suder
authors.forename: Jerzy
authors.initials: J
authors.lastname: Silberring
authors.forename: Anna
authors.initials: A
authors.lastname: Barbasz
authors.forename: Maria
authors.initials: M
authors.lastname: Rapala-Kozik
mesh_terms: D000595:Amino Acid Sequence; D001920:Bradykinin / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007704:Kininogens / Q000378:metabolism*; D007705:Kinins / Q000378:metabolism*; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism; D008969:Molecular Sequence Data; D009195:Peroxidase / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism; D011288:Prekallikrein / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
chemical_list: D007704:Kininogens; D007705:Kinins; D017382:Reactive Oxygen Species; D014364:Tryptophan; D011288:Prekallikrein; D008715:Methionine; D009195:Peroxidase; D001920:Bradykinin; C013111:methionine sulfoxide