Differential thermal stability and oxidative vulnerability of the hemoglobin variants, HbA2 and HbE.
Apart from few early biophysical studies, the relative thermal instability of HbE has been only shown by clinical investigations. We have compared in vitro thermal stability of HbE with HbA2 and HbA using optical spectroscopy. From absorption measurements in the soret region, synchronous fluorescence spectroscopy and dynamic light scattering experiments, we have found thermal stability of the three hemoglobin variants following the order HbE<HbA<HbA2 in terms of structural unfolding and aggregation pattern. We have found formation of intermolecular dityrosine fluorophores with characteristic fluorescence signature, at pH >11.0 in all the three variants. Under oxidative stress conditions in presence of hydrogen peroxide, HbE has been found to be more vulnerable to aggregation compared to HbA and HbA2. Taken together, these studies have shown thermal and oxidative instability of HbE and points towards the role of HbE in the upregulation of redox regulators and chaperone proteins in erythrocyte proteome of patients suffering from HbEbeta thalassemia.
Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Bidhannagar, Kolkata, India.
Abhijit
A
Chakrabarti
Dipankar
D
Bhattacharya
Sanghamitra
S
Deb
Madhumita
M
Chakraborty
D006441:Hemoglobin A / Q000737:chemistry* / Q000378:metabolism*; D006446:Hemoglobin E / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010084:Oxidation-Reduction; D017510:Protein Folding; D055550:Protein Stability
D006441:Hemoglobin A; D006446:Hemoglobin E