Oxidative instability of hemoglobin E (β26 Glu→Lys) is increased in the presence of free α subunits and reversed by α-hemoglobin stabilizing protein (AHSP): Relevance to HbE/β-thalassemia.

ABSTRACT: When adding peroxide (H2O2), β subunits of hemoglobin (Hb) bear the burden of oxidative changes due in part to the direct oxidation of its Cys93. The presence of unpaired α subunits within red cells and/or co-inheritance of another β subunit mutant, HbE (β26 Glu→Lys) have been implicated in the pathogenesis and severity of β thalassemia. We have found that although both HbA and HbE autoxidize at initially comparable rates, HbE loses heme at a rate almost 2 fold higher than HbA due to unfolding of the protein. Using mass spectrometry and the spin trap, DMPO, we were able to quantify irreversible oxidization of βCys93 to reflect oxidative instability of β subunits. In the presence of free α subunits and H2O2, both HbA and HbE showed βCys93 oxidation which increased with higher H2O2 concentra

SUBMITTER: Strader MB 

PROVIDER: S-EPMC4804395 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature