Myeloperoxidase scavenges peroxynitrite: A novel anti-inflammatory action of the heme enzyme.
Peroxynitrite, a potent pro-inflammatory and cytotoxic species, interacts with a variety of heme containing proteins. We addressed the question whether (i) the interaction of myeloperoxidase (MPO, an enzyme generating hypochlorous acid from hydrogen peroxide and chloride ions) with peroxynitrite affects the clearance of peroxynitrite, and (ii) if peroxynitrite could modulate the chlorinating activity of MPO. Our results show that this interaction promotes the decomposition of the highly reactive pro-inflammatory oxidant, whereby MPO Compound II (but not Compound I) is formed. The efficiency of MPO to remove peroxynitrite was enhanced by L-tyrosine, nitrite and (-)-epicatechin, substances known to reduce Compound II with high reaction rate. Next, peroxynitrite (added as reagent) diminished the chlorinating activity of MPO in the presence of hydrogen peroxide. Alternatively, SIN-1, a peroxynitrite donor, reduced hypochlorous acid formation by MPO, as measured by aminophenyl fluorescein oxidation (time kinetics) and taurine chloramine formation (end point measurement). At inflammatory loci, scavenging of peroxynitrite by MPO may overcome the uncontrolled peroxynitrite decomposition and formation of reactive species, which lead to cell/tissue damage.
Institute of Molecular Biology and Biochemistry, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria.
Chintan N
CN
Koyani
Translational Centre for Regenerative Medicine Leipzig, University of Leipzig, Philipp-Rosenthal-Straße 55, 04103 Leipzig, Germany; Institute for Medical Physics and Biophysics, Medical Faculty, University of Leipzig, Haertelstraße 16-18, 04107 Leipzig, Germany.
Joerg
J
Flemmig
Institute of Molecular Biology and Biochemistry, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria.
Ernst
E
Malle
Translational Centre for Regenerative Medicine Leipzig, University of Leipzig, Philipp-Rosenthal-Straße 55, 04103 Leipzig, Germany; Institute for Medical Physics and Biophysics, Medical Faculty, University of Leipzig, Haertelstraße 16-18, 04107 Leipzig, Germany. Electronic address: juergen.arnhold@medizin.uni-leipzig.de.
Juergen
J
Arnhold
D000814:Aniline Compounds / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D002392:Catechin / Q000737:chemistry; D005452:Fluoresceins / Q000737:chemistry; D054879:Halogenation; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008981:Molsidomine / Q000031:analogs & derivatives / Q000737:chemistry; D009573:Nitrites / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000737:chemistry*; D030421:Peroxynitrous Acid / Q000737:chemistry*; D014443:Tyrosine / Q000737:chemistry
D000814:Aniline Compounds; D000893:Anti-Inflammatory Agents; D005452:Fluoresceins; D009573:Nitrites; D016877:Oxidants; C508569:aminophenyl fluorescein; D030421:Peroxynitrous Acid; D014443:Tyrosine; C002385:linsidomine; D002392:Catechin; D006861:Hydrogen Peroxide; D008981:Molsidomine; D009195:Peroxidase
APF; Flavonoids; Hypochlorite; MPO–H(2)O(2)–Cl(−) system; Nitric oxide; Superoxide