Oxidative crosslinking of LDL protein induced by hemin: involvement of tyrosines.
This study investigated free hemin induced modifications in low density lipoprotein (LDL). By use of fluorescent probes hemin was found to associate with LDL thereby inducing peroxidation of both lipids and protein. Upon LDL peroxidation, covalent crosslinking of apolipoprotein B (Apo B) occurred as judged by SDS-PAGE. Concomitantly, a multifluorophore emission developed, which included contribution of bityrosines. The simultaneous formation of protein aggregates and bityrosines was interpreted as the involvement of intermolecular bityrosines in the hemin induced crosslinking of Apo B. Since LDL protein aggregation relates to conversion of macrophages into foam cells, hemin should be considered as an endogenous trigger of atherosclerosis.
Miller
Y I
YI
Sackler Institute of Molecular Medicine, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Shaklai
N
N
D001055:Apolipoproteins B / Q000737:chemistry / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology; D003300:Copper / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000378:metabolism* / Q000633:toxicity; D006427:Hemin / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*
D001055:Apolipoproteins B; D003432:Cross-Linking Reagents; D008077:Lipoproteins, LDL; D010545:Peroxides; D014443:Tyrosine; D006427:Hemin; D003300:Copper; C007543:dityrosine