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SHR Neuro Krebs Kardio Lipid

Malle, E; Furtmüller, PG; Sattler, W; Obinger, C.
Myeloperoxidase: a target for new drug development?
Br J Pharmacol. 2007; 152(6): 838-854. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Malle Ernst
Sattler Wolfgang
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Number of Figures: 6
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Abstract:
Myeloperoxidase (MPO), a member of the haem peroxidase-cyclooxygenase superfamily, is abundantly expressed in neutrophils and to a lesser extent in monocytes and certain type of macrophages. MPO participates in innate immune defence mechanism through formation of microbicidal reactive oxidants and diffusible radical species. A unique activity of MPO is its ability to use chloride as a cosubstrate with hydrogen peroxide to generate chlorinating oxidants such as hypochlorous acid, a potent antimicrobial agent. However, evidence has emerged that MPO-derived oxidants contribute to tissue damage and the initiation and propagation of acute and chronic vascular inflammatory disease. The fact that circulating levels of MPO have been shown to predict risks for major adverse cardiac events and that levels of MPO-derived chlorinated compounds are specific biomarkers for disease progression, has attracted considerable interest in the development of therapeutically useful MPO inhibitors. Today, detailed information on the structure of ferric MPO and its complexes with low- and high-spin ligands is available. This, together with a thorough understanding of reaction mechanisms including redox properties of intermediates, enables a rationale attempt in developing specific MPO inhibitors that still maintain MPO activity during host defence and bacterial killing but interfere with pathophysiologically persistent activation of MPO. The various approaches to inhibit enzyme activity of MPO and to ameliorate adverse effects of MPO-derived oxidants will be discussed. Emphasis will be put on mechanism-based inhibitors and high-throughput screening of compounds as well as the discussion of physiologically useful HOCl scavengers.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Chlorides - metabolism
Enzyme Inhibitors - pharmacology
Free Radical Scavengers - pharmacology
Humans - pharmacology
Hydrogen Peroxide - metabolism
Models, Molecular - metabolism
Oxidants - metabolism
Peroxidase - antagonists and inhibitors

Find related publications in this database (Keywords)
MPO-H2O2-halide system
hypochlorite
inflammation
neutrophils
atherosclerosis
lipid oxidation
protein oxidation
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