Location of Repository

Clinical Severity of β-thalassaemia/Hb E Disease Is Associated with Differential Activities of the Calpain-Calpastatin Proteolytic System

By Suriyan Sukati, Saovaros Svasti, Roberto Stifanese, Monica Averna, Nantika Panutdaporn, Tipparat Penglong, Edon Melloni, Suthat Fucharoen and Gerd Katzenmeier


Earlier observations in the literature suggest that proteolytic degradation of excess unmatched α-globin chains reduces their accumulation and precipitation in β-thalassaemia erythroid precursor cells and have linked this proteolytic degradation to the activity of calpain protease. The aim of this study was to correlate the activity of calpain and its inhibitor, calpastatin, with different degrees of disease severity in β-thalassaemia. CD34+ cells were enriched from peripheral blood of healthy individuals (control group) and patients with mild and severe clinical presentations of β0-thalassaemia/Hb E disease. By ex vivo cultivation promoting erythroid cell differentiation for 7 days, proerythroblasts, were employed for the functional characterization of the calpain-calpastatin proteolytic system. In comparison to the control group, enzymatic activity and protein amounts of μ-calpain were found to be more than 3-fold increased in proerythroblasts from patients with mild clinical symptoms, whereas no significant difference was observed in patients with severe clinical symptoms. Furthermore, a 1.6-fold decrease of calpastatin activity and 3.2-fold accumulation of a 34 kDa calpain-mediated degradation product of calpastatin were observed in patients with mild clinical symptoms. The increased activity of calpain may be involved in the removal of excess α-globin chains contributing to a lower degree of disease severity in patients with mild clinical symptoms

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:3353910
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles



    1. (2000). A correlation of erythrokinetics, ineffective erythropoiesis, and erythroid precursor apoptosis in thai patients with thalassemia.
    2. (1984). A dual role for the Ca2+-requiring proteinase in the degradation of hemoglobin by erythrocyte membrane proteinases.
    3. (2010). A genome-wide association identified the common genetic variants influence disease severity in beta(0)-thalassemia/hemoglobin E.
    4. (2008). A scoring system for the classification of beta-thalassemia/Hb E disease severity.
    5. (2010). Adaptive modifications in the calpain/calpastatin system in brain cells after persistent alteration in Ca2+ homeostasis.
    6. (1998). Alpha- and beta-thalassemia in Thailand.
    7. (1988). An endogenous activator of the Ca2+-dependent proteinase of human neutrophils that increases its affinity for Ca2+. Proc Natl Acad Sci
    8. (2006). Association of calpastatin with inactive calpain: a novel mechanism to control the activation of the protease?
    9. (2006). Calpain and synaptic function.
    10. (1994). Calpastatin in erythrocytes of young and old individuals.
    11. (1991). Calpastatins: biochemical and molecular biological studies.
    12. (1999). Changes in intracellular localization of calpastatin during calpain activation.
    13. (1984). Characterization of the single peptide generated from the amino-terminus end of alpha- and beta-hemoglobin chains by the Ca2+-dependent neutral proteinase.
    14. (1987). Determination of variable severity of anemia in thalassemia: erythrocyte proteolytic activity.
    15. (2000). Differential degradation of calpastatin by m- and m-calpain in Ca 2+-enriched human neuroblastoma LAN-5 cells.
    16. (1987). Differential expression of erythrocyte calpain and calpastatin activities in beta 0-thalassemia/Hb E disease.
    17. (2009). Evolution of spectrin function in cytoskeletal and membrane networks.
    18. (2003). Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway.
    19. (2004). Genetic insights into the clinical diversity of b thalassaemia.
    20. Genetic modifiers of Hb E/beta0 thalassemia identified by a two-stage genome-wide association study.
    21. (1975). Globin synthesis in fractionated Normoblasts of beta-thalassemia heterozygotes.
    22. (1972). Haemoglobin synthesis during erythroid maturation in -thalassaemia.
    23. (2010). HbE/beta-thalassemia: basis of marked clinical diversity.
    24. (1991). Identification of two calpastatin forms in rat skeletal muscle and their susceptibility to digestion by homologous calpains.
    25. (2009). Increased erythropoiesis of beta-thalassaemia/Hb E proerythroblasts is mediated by high basal levels of ERK1/2 activation.
    26. (2000). Interferon gamma delays apoptosis of mature erythroid progenitor cells in the absence of erythropoietin.
    27. (1997). Modulation of rat brain calpastatin efficiency by post-translational modifications.
    28. (1994). Modulation of the intracellular Ca(2+)-dependent proteolytic system is critically correlated with the kinetics of differentiation of murine erythroleukemia cells.
    29. (1993). Molecular diversity of calpastatin in human erythroid cells.
    30. (2000). Properties and intracellular localization of calpain activator protein.
    31. (1980). Proteolysis in thalassemia: studies with protease inhibitors.
    32. (2000). Purification of mu-calpain, m-calpain, and calpastatin from animal tissues.
    33. (2007). Regulation of calpain activity in rat brain with altered Ca2+ homeostasis.
    34. (2000). Simplified multiplexPCR diagnosis of common southeast asian deletional determinants of alphathalassemia.
    35. (2012). Spectrin-based skeleton as an actor in cell signaling.
    36. (1985). Thalassemia in southeast Asia: determination of different degrees of severity of anemia in thalassemia.
    37. (1983). The appearance of a 34,000-dalton inhibitor of calpain (Ca2+-dependent cysteine proteinase) in rat liver after the administration of phenylhydrazine.
    38. (2003). The calpain system.
    39. (1981). The cytosol of human erythrocytes contains a highly Ca2+-sensitive thiol protease (calpain I) and its specific inhibitor protein (calpastatin).
    40. (2006). TNF-alpha-mediated cardiomyocyte apoptosis involves caspase-12 and calpain.
    41. (1997). Ubiquitin aldehyde increases adenosine triphosphate-dependent proteolysis of hemoglobin alpha-subunits in betathalassemic hemolysates.
    42. (2002). v-Srcinduced modulation of the calpain-calpastatin proteolytic system regulates transformation.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.