Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Bergt, C; Marsche, G; Panzenboeck, U; Heinecke, JW; Malle, E; Sattler, W.
Human neutrophils employ the myeloperoxidase/hydrogen peroxide/chloride system to oxidatively damage apolipoprotein A-I.
Eur J Biochem. 2001; 268(12):3523-3531
Doi: 10.1046%2Fj.1432-1327.2001.02253.x
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- Führende Autor*innen der Med Uni Graz
- Sattler Wolfgang
- Co-Autor*innen der Med Uni Graz
- Malle Ernst
- Marsche Gunther
- Panzenboeck Ute
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- Abstract:
- The structural integrity of apolipoprotein A-I (apo A-I) is critical to the physiological function of high-density lipoprotein (HDL). Oxidized lipoproteins are thought to be of central importance in atherogenesis, and oxidation products characteristic of myeloperoxidase, a heme protein secreted by activated phagocytes, have been detected in human atherosclerotic tissue. At plasma concentrations of halide ion, hypochlorous acid is a major product of the myeloperoxidase-hydrogen peroxide-chloride system. We therefore investigated the effects of activated human neutrophils, a potent source of myeloperoxidase and hydrogen peroxide, on the protein and lipid components of HDL. Both free and HDL-associated apo A-I exposed to activated human neutrophils underwent extensive degradation as monitored by RP-HPLC and Western blotting with a polyclonal antibody to apo A-I. Replacement of the neutrophils with reagent HOCl resulted in comparable damage (at molar oxidant : HDL subclass 3 ratio = 100) as observed in the presence of activated phagocytes. Apo A-I degradation by activated neutrophils was partially inhibited by the HOCl scavenger methionine, by the heme inhibitor azide, by chloride-free conditions, by the peroxide scavenger catalase, and by a combination of superoxide dismutase (SOD)/catalase, implicating HOCl in the cell-mediated reaction. The addition of a protease inhibitor (3,4-dichloroisocoumarin) further reduced the extent of apo A-I damage. In contrast to the protein moiety, there was little evidence for oxidation of unsaturated fatty acids or cholesterol in HDL3 exposed to activated neutrophils, suggesting that HOCl was selectively damaging apo A-I. Our observations indicate that HOCl generated by myeloperoxidase represents one pathway for protein degradation in HDL3 exposed to activated phagocytes.
- Find related publications in this database (using NLM MeSH Indexing)
- Blotting, Western -
- Catalase - metabolism
- Chlorides - metabolism
- Chromatography, High Pressure Liquid - metabolism
- Electrophoresis, Polyacrylamide Gel - metabolism
- Humans - metabolism
- Hydrogen Peroxide - metabolism
- Neutrophils - enzymology
- Peroxidase - metabolism
- Superoxide Dismutase - metabolism
- Find related publications in this database (Keywords)
- apolipoprotein fragmentation
- high-density lipoprotein
- hypochlorous acid
- peroxidase