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 Lipop roteins 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 th e possible involvement of phospholipids in the oxidative interaction o f LDL with hemoglobin (Hb), using brain extract phospholipid liposomes as a model. The relative binding affinity and oxidative interaction o f three hemoglobin variants (intact Hb A and isolated beta- and alpha- chains) with LDL and liposome were compared. Studies carried out at lo w pH/ionic strength and under physiological conditions revealed that a ssociation of hemoglobin variants with the phosopholipid liposomes is driven by electrostatic forces but their binding is not a prerequisite for oxidative interaction. Unlike phospholipid liposomes, LDL underwe nt only a negligible association with the Hb variants under all pH/ion ic strength conditions. Nevertheless, LDL induced oxidation of Hb vari ants, mostly alpha-chains. The dissimilar behavior of the liposomes an d LDL indicated that LDL protein apo B rather than phospholipids is th e actual LDL surface component which interacts with the hemoglobin var iants. This agrees with the finding that apo B protein underwent oxida tive 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 reacti vity toward LDL. The results of the present study indicate that the mo dified LDL particles observed in beta-thalassemia may reflect lipoprot ein oxidation by alpha-chains in circulation. (C) 1997 Academic Press.