Publication: Alpha-hemoglobin stabilizing protein: Molecular function and clinical correlation
Issued Date
2010-01-01
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ISSN
10939946
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2-s2.0-77951212077
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Mahidol University
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SCOPUS
Bibliographic Citation
Frontiers in Bioscience. Vol.15, No.1 (2010), 1-11
Suggested Citation
Chairat Turbpaiboon, Prapon Wilairat Alpha-hemoglobin stabilizing protein: Molecular function and clinical correlation. Frontiers in Bioscience. Vol.15, No.1 (2010), 1-11. doi:10.2741/3601 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/28807
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Title
Alpha-hemoglobin stabilizing protein: Molecular function and clinical correlation
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Abstract
The discovery of alpha-hemoglobin stabilizing protein (AHSP), a chaperone for free alpha-hemoglobin (alpha-Hb), has provided a satisfactory solution to the perplexing problem of balanced globin levels for Hb production in erythroid cells in the face of a two-fold excess of alpha-globin to beta-globin gene dosage. Unmatched alpha-Hb is unstable and precipitates onto membranes, where the released heme exerts oxidative damages resulting in ineffective erythropoiesis and hemolytic anemia, the underlying causes of pathology in the hereditary anemia of beta-thalassemia. The interaction of alpha-Hb with AHSP involves surfaces normally employed in binding to beta-Hb. However, a conformational change to the AHSP-bound alpha-Hb results in an oxidized heme, but in a pocket that is now less exposed to the outside environment, thereby protecting against both peroxide-induced heme loss and iron-induced redox reaction. Studies in both mice and humans indicate that reduction in AHSP can result in hematological pathology. Conversely, alpha-Hb variants that are compromised in their ability to bind with AHSP produce beta-thalassemia-like symptoms. Disease conditions like some forms of thalassemia that are directly associated with AHSP structural and/or functional defects can now be included within the category of chaperonopathies.