title: Thiocyanate catalyzes myeloperoxidase-initiated lipid oxidation in LDL.
abstract: There is evidence that LDL oxidation may render the lipoprotein atherogenic. The myeloperoxidase-hydrogen peroxide (MPO/H2O2) system of activated phagocytes may be involved in this process. Chloride is supposed to be the major substrate for MPO, generating reactive hypochlorous acid (HOCl), modifying LDL. The pseudo-halide thiocyanate (SCN-) has been shown to be a suitable substrate for MPO, forming reactive HOSCN/SCN*. As relatively abundant levels of SCN- are found in plasma of smokers--a well-known risk group for cardiovascular disease--the ability of SCN- to act as a catalyst of LDL atherogenic modification by MPO/H2O2 was tested. Measurement of conjugated diene and lipid hydroperoxide formation in LDL preparations exposed to MPO/H2O2 revealed that SCN- catalyzed lipid oxidation in LDL. Chloride did not diminish the effect of SCN- on lipid oxidation. Surprisingly, SCN inhibited the HOCl-mediated apoprotein modification in LDL. Nitrite--recently found to be a substrate for MPO--showed some competing properties. MPO-mediated lipid oxidation was inhibited by heme poisons (azide, cyanide) and catalase. Ascorbic acid was the most effective compound in inhibiting the SCN- -catalyzed reaction. Bilirubin showed some action, whereas tocopherol was ineffective. When LDL oxidation was performed with activated human neutrophils, which employ the MPO pathway, SCN- catalyzed the cell-mediated LDL oxidation. The MPO/H2O2/SCN- system may have the potential to play a significant role in the oxidative modification of LDL--an observation further pointing to the link between the long-recognized risk factors of atherosclerosis: elevated levels of LDL and smoking.
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, A-1090, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Exner
authors.forename: Marcela
authors.initials: M
authors.lastname: Hermann
authors.forename: Roland
authors.initials: R
authors.lastname: Hofbauer
authors.forename: Beda
authors.initials: B
authors.lastname: Hartmann
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kapiotis
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gmeiner
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001059:Apoproteins / Q000737:chemistry; D001205:Ascorbic Acid / Q000737:chemistry; D001393:Azoles / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D002384:Catalysis; D002712:Chlorides / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005609:Free Radicals; D006418:Heme / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000494:pharmacology; D054833:Isoindoles; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008055:Lipids / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D009573:Nitrites / Q000737:chemistry / Q000494:pharmacology; D016566:Organoselenium Compounds / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D010586:Phagocytes / Q000378:metabolism; D010587:Phagocytosis; D012307:Risk Factors; D012907:Smoking; D013861:Thiocyanates / Q000494:pharmacology*; D013997:Time Factors; D014461:Ultracentrifugation
chemical_list: D000975:Antioxidants; D001059:Apoproteins; D001393:Azoles; D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D005609:Free Radicals; D054833:Isoindoles; D008055:Lipids; D008077:Lipoproteins, LDL; D009573:Nitrites; D016566:Organoselenium Compounds; D013861:Thiocyanates; C042986:ebselen; D006418:Heme; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D009195:Peroxidase; C031760:thiocyanate; D001205:Ascorbic Acid; D010100:Oxygen