Oxidative interaction of unpaired hemoglobin chains with lipids and proteins: A key for modified serum lipoproteins in thalassemia

Svetlana M. Altamentova, Esther Marva, Nurith Shaklai

Research output: Contribution to journalArticlepeer-review

Abstract

We searched for a biochemical explanation to the modification of lipoproteins like low-density lipoproteins (LDL) observed in patients with the severe hemolytic anemia β-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 β- and α-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 inter-action. Unlike phospholipid liposomes, LDL under-went only a negligible association with the Hb variants under all pH/ionic strength conditions. Nevertheless, LDL induced oxidation of Hb variants, mostly α-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 α-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 β-thalassemia may reflect lipoprotein oxidation by α-chains in circulation.

Original languageEnglish
Pages (from-to)39-46
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume345
Issue number1
DOIs
StatePublished - 1 Sep 1997

Keywords

  • Hemoglobin chains
  • Liposomes
  • Low-density lipoprotein
  • Peroxidation
  • Phospholipids
  • Thalassemia

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