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  • The myeloperoxidase product hypochlorous acid generates irreversible high-density lipoprotein receptor inhibitors.

The myeloperoxidase product hypochlorous acid generates irreversible high-density lipoprotein receptor inhibitors.

Arteriosclerosis, thrombosis, and vascular biology (2013-03-16)
Veronika Binder, Senka Ljubojevic, Johannes Haybaeck, Michael Holzer, Dalia El-Gamal, Rudolf Schicho, Burkert Pieske, Akos Heinemann, Gunther Marsche
ABSTRACT

Elevated levels of advanced oxidation protein products have been described in several chronic inflammatory diseases, like chronic renal insufficiency, rheumatoid arthritis, and atherosclerosis. Recent findings revealed that advanced oxidation protein products are inhibitors of the major high-density lipoprotein receptor, scavenger receptor class B, type 1 (SR-BI). Here, we investigated which oxidation-induced structural alterations convert plasma albumin into a high-density lipoprotein-receptor inhibitor. Exposure of albumin to the physiological oxidant, hypochlorous acid, generated high-affinity SR-BI ligands. Protection of albumin-lysine residues before exposure to hypochlorous acid as well as regeneration of N-chloramines after oxidation of albumin completely prevented binding of oxidized albumin to SR-BI, indicating that modification of albumin-lysine residues is required to generate SR-BI ligands. Of particular interest, N-chloramines within oxidized albumin promoted irreversible binding to SR-BI, resulting in permanent receptor blockade. We observed that the SR-BI inhibitory activity of albumin isolated from chronic kidney disease patients correlated with the content of the myeloperoxidase-specific oxidation product 3-chlorotyrosine and was associated with alterations in the composition of high-density lipoprotein. Given that several potential atheroprotective activities of high-density lipoprotein are mediated by SR-BI, the present results raise the possibility that oxidized plasma albumin, through permanent SR-BI blockade, contributes to the pathophysiology of cardiovascular disease.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Peroxidase from horseradish, Highly stabilized, essentially salt-free, lyophilized powder, 200-300 units/mg solid (using pyrogallol)
Sigma-Aldrich
Peroxidase from horseradish, Type II, essentially salt-free, lyophilized powder, 150-250 units/mg solid (using pyrogallol)
Sigma-Aldrich
Peroxidase from horseradish, Type XII, essentially salt-free, lyophilized powder, ≥250 units/mg solid (using pyrogallol)
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Peroxidase from horseradish, Type VI, essentially salt-free, lyophilized powder, ≥250 units/mg solid (using pyrogallol)
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Peroxidase from horseradish, Type X, ammonium sulfate suspension
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Peroxidase from horseradish, Type VI-A, essentially salt-free, lyophilized powder, ≥250 units/mg solid (using pyrogallol), 950-2000 units/mg solid (using ABTS)
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Lactoperoxidase from bovine milk, lyophilized powder (essentially salt-free), ≥200 units/mg protein
Sigma-Aldrich
Peroxidase from horseradish, Type I, essentially salt-free, lyophilized powder, ≥50 units/mg solid (using pyrogallol)
Sigma-Aldrich
Peroxidase from horseradish, lyophilized, powder, ~150 U/mg
Sigma-Aldrich
Lactoperoxidase from bovine milk, lyophilized, powder, ≥150 U/mg
Sigma-Aldrich
Myeloperoxidase from human leukocytes, lyophilized powder, ≥50 units/mg protein