title: The involvement of low-density lipoprotein in hemin transport potentiates peroxidative damage.
abstract: Hemin binds to isolated low-density lipoprotein (LDL) and thereby triggers LDL oxidation. In this study we investigated whether hemin can get together with LDL under physiological conditions. The relative affinity of three blood components to free hemin was as follows: RBCM < LDL < albumin. At physiological molar ratio of LDL/albumin all the hemin was bound to albumin. In molar excess of albumin over hemin, existing even under pathological conditions, albumin served as an efficient antioxidant for the plasma hemin-induced LDL oxidation. RBCM-embedded hemin, unlike plasma hemin, affected LDL: the mobile hemin was transferred from RBCM to LDL in the absence of albumin, whereas in the presence of albumin most of the mobile hemin finally reached the albumin but partially via LDL. Thus, a transient hemin is built up in LDL. This transient hemin triggered LDL oxidation which was not inhibited but rather promoted by albumin. The involvement of albumin in this oxidation was explained by its acting as a pump thereby increasing the transient hemin in LDL. It is suggested that increased membrane hemin level as in hemoglobinopathies and/or excess LDL in dyslipidemia provide conditions for hemin-induced LDL oxidation.
authors.affiliation: Sackler Institute of Molecular Medicine, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Y I
authors.initials: YI
authors.lastname: Miller
authors.forename: Y
authors.initials: Y
authors.lastname: Felikman
authors.forename: N
authors.initials: N
authors.lastname: Shaklai
mesh_terms: D001692:Biological Transport; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006427:Hemin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: D008077:Lipoproteins, LDL; D012709:Serum Albumin; D006427:Hemin