Oxidation of low-density lipoprotein by hemoglobin-hemichrome.
Hemoglobin and myoglobin are inducers of low-density lipoprotein oxidation in the presence of H(2)O(2). The reaction of these hemoproteins with H(2)O(2) result in a mixture of protein products known as hemichromes. The oxygen-binding hemoproteins function as peroxidases but as compared to classic heme-peroxidases have a much lower activity on small sized and a higher one on large sized substrates. A heme-globin covalent adduct, a component identified in myoglobin-hemichrome, was reported to be the cause of myoglobin peroxidase activity on low-density lipoprotein. In this study, we analyzed the function of hemoglobin-hemichrome in low-density lipoprotein oxidation. Oxidation of lipids was analyzed by formation of conjugated diene and malondialdehyde; and oxidation of Apo-B protein was analyzed by development of bityrosine fluorescence and covalently cross-linked protein. Hemoglobin-hemichrome has indeed triggered oxidation of both lipids and protein, but unlike myoglobin, hemichrome has required the presence of H(2)O(2). In correlation to this, we found that unlike myoglobin, hemichrome formed by hemoglobin/H(2)O(2) does not contain a globin-heme covalent adduct. Nevertheless, hemoglobin-hemichrome remains oxidatively active towards LDL, indicating that other components of the oxidatively denatured hemoglobin should be considered responsible for its hazardous activity in vascular pathology.
Bamm
Vladimir Varlen
VV
Sackler Institute of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.
Tsemakhovich
Vladimir Abraham
VA
Shaklai
Nurith
N
D004591:Electrophoresis, Polyacrylamide Gel; D006420:Hemeproteins / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008706:Methemoglobin / Q000378:metabolism; D009211:Myoglobin / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D013053:Spectrophotometry; D017392:Thiobarbituric Acid Reactive Substances; D013997:Time Factors
D006420:Hemeproteins; D006454:Hemoglobins; D008077:Lipoproteins, LDL; D009211:Myoglobin; D017392:Thiobarbituric Acid Reactive Substances; C001332:hemichrome; D008706:Methemoglobin; D006861:Hydrogen Peroxide; D010100:Oxygen