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Arch Biochem Biophys. 2015 Apr 1;571:1-9. doi: 10.1016/j.abb.2015.02.028. Epub 2015 Feb 27.

Myeloperoxidase scavenges peroxynitrite: A novel anti-inflammatory action of the heme enzyme.

Author information

1
Institute of Molecular Biology and Biochemistry, Medical University of Graz, Harrachgasse 21, 8010 Graz, Austria.
2
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.
3
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.

Abstract

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.

KEYWORDS:

APF; Flavonoids; Hypochlorite; MPO–H(2)O(2)–Cl(−) system; Nitric oxide; Superoxide

PMID:
25731855
PMCID:
PMC4388333
DOI:
10.1016/j.abb.2015.02.028
[Indexed for MEDLINE]
Free PMC Article

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