Oxidative interaction of unpaired hemoglobin chains with lipids and proteins: a key for modified serum lipoproteins in thalassemia.
We searched for a biochemical explanation to the modification of lipoproteins like low-density lipoproteins (LDL) observed in patients with the severe hemolytic anemia beta-thalassemia. Because a large fraction of the LDL surface is composed of phospholipids, we first explored the possible involvement of phospholipids in the oxidative interaction of LDL with hemoglobin (Hb), using brain extract phospholipid liposomes as a model. The relative binding affinity and oxidative interaction of three hemoglobin variants (intact Hb A and isolated beta- and alpha-chains) with LDL and liposome were compared. Studies carried out at low pH/ionic strength and under physiological conditions revealed that association of hemoglobin variants with the phospholipid liposomes is driven by electrostatic forces but their binding is not a prerequisite for oxidative interaction. Unlike phospholipid liposomes, LDL underwent only a negligible association with the Hb variants under all pH/ionic strength conditions. Nevertheless, LDL induced oxidation of Hb variants, mostly alpha-chains. The dissimilar behavior of the liposomes and LDL indicated that LDL protein apo B rather than phospholipids is the actual LDL surface component which interacts with the hemoglobin variants. This agrees with the finding that apo B protein underwent oxidative crosslinking by the hemoglobin variants among which alpha-chains were most active. We concluded from these results that the ability of hemoglobin to undergo autooxidation is the key to its oxidative reactivity toward LDL. The results of the present study indicate that the modified LDL particles observed in beta-thalassemia may reflect lipoprotein oxidation by alpha-chains in circulation.
Altamentova
S M
SM
Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 698887, Israel.
Marva
E
E
Shaklai
N
N
D001923:Brain Chemistry; D005914:Globins / Q000378:metabolism; D006441:Hemoglobin A / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D015227:Lipid Peroxidation; D008074:Lipoproteins / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008081:Liposomes / Q000378:metabolism; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D017086:beta-Thalassemia / Q000097:blood*
D006454:Hemoglobins; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008081:Liposomes; D010743:Phospholipids; D005914:Globins; D006441:Hemoglobin A