Ferryl heme and associated protein radicals with high redox potentials (~1.0 V) can induce a wide variety of oxidative reactions that affect the protein and nearby molecules [2].
First, addition of exogenous Hp both markedly inhibits heme loss and second, as a result of this inhibition, globin precipitation is prevented.
Hp bound metHb and prevented heme loss and hemopexin captures any free heme released from metHb during its denaturation.
For example, autooxidation of oxyhemoglobin (HbO2) or oxymyoglobin (MbO2) produces met-Hb or met-Mb, respectively, and superoxide radicals (O2•−, HO2•) via electron transfer [3,4].
This result is in accord with recent work, which showed that Hp binding to Hb prevents oxidative damage to the globin.
For example, Hp 2-2 has been associated with an increased susceptibility to diabetic cardiovascular disease; uptake of Hb-Hp(1-1) complexes by CD163 receptors is reportedly faster and its binding results in increased concentrations of anti-inflammatory mediators than Hb-Hp(2-2) complexes; and the angiogenic potency of Hp 2-2 is reportedly greater than that of Hp 1-1 [18].
Hemolysis and the transfusion of banked blood or Hb-based therapeutics can result in varying quantities of circulating acellular Hb which can induce life threatening radical generating reactions in patients with a compromised vascular system [60].
Third, exposure to extracellular Hb, in the form of oxygen therapeutics or when Hb is released from old red blood cells, have also been reported to induce oxidative toxicity in kidney and brain tissues [65].
In that study, heme was shown to specifically bind to endothelial Toll-like receptors (TLR4) and trigger a cascade of inflammatory responses, which could be attributed to oxidation and degradation of cell-free Hb [73].
These findings are consistent with a recent study which showed that both Hp and hemopexin (heme scavenger) were equally effective in preventing vasoocclusion in a sickle cell mouse model infused with Hb [73].
Haptoglobin (Hp) is an abundant and conserved plasma glycoprotein, which binds acellular adult hemoglobin (Hb) dimers with high affinity and facilitates their rapid clearance from circulation following hemolysis.
Haptoglobin (Hp) is a Hb-scavenging plasma glycoprotein which binds non-covalently to hemoglobin dimers that are generated by dissociation of acellular Hb tetramers after hemolysis [6].
Hp is the first-line scavenger that binds and accelerates the clearance of Hb in the circulation, although the macrophage CD163 receptor has also been the focus of several recent investigations [66– 68].
Probably the most important Hp-mediated abrogation of Hb toxicity is stabilization of heme within the central cavity of the Hb subunits, which almost completely prevents its dissociation and subsequent free heme-mediated oxidative reactions and inflammatory responses.
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.