Clinical severity of β-thalassaemia/Hb E disease is associated with differential activities of the calpain-calpastatin proteolytic system.
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 s...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3353910?pdf=render |
| _version_ | 1811259727777103872 |
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| author | Suriyan Sukati Saovaros Svasti Roberto Stifanese Monica Averna Nantika Panutdaporn Tipparat Penglong Edon Melloni Suthat Fucharoen Gerd Katzenmeier |
| author_facet | Suriyan Sukati Saovaros Svasti Roberto Stifanese Monica Averna Nantika Panutdaporn Tipparat Penglong Edon Melloni Suthat Fucharoen Gerd Katzenmeier |
| author_sort | Suriyan Sukati |
| collection | DOAJ |
| description | 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 β(0)-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. |
| first_indexed | 2024-04-12T18:36:05Z |
| format | Article |
| id | doaj.art-9d925ad1f70f4412b4a00bc9feb01b74 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T18:36:05Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-9d925ad1f70f4412b4a00bc9feb01b742022-12-22T03:20:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3713310.1371/journal.pone.0037133Clinical severity of β-thalassaemia/Hb E disease is associated with differential activities of the calpain-calpastatin proteolytic system.Suriyan SukatiSaovaros SvastiRoberto StifaneseMonica AvernaNantika PanutdapornTipparat PenglongEdon MelloniSuthat FucharoenGerd KatzenmeierEarlier 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 β(0)-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.http://europepmc.org/articles/PMC3353910?pdf=render |
| spellingShingle | Suriyan Sukati Saovaros Svasti Roberto Stifanese Monica Averna Nantika Panutdaporn Tipparat Penglong Edon Melloni Suthat Fucharoen Gerd Katzenmeier Clinical severity of β-thalassaemia/Hb E disease is associated with differential activities of the calpain-calpastatin proteolytic system. PLoS ONE |
| title | Clinical severity of β-thalassaemia/Hb E disease is associated with differential activities of the calpain-calpastatin proteolytic system. |
| title_full | Clinical severity of β-thalassaemia/Hb E disease is associated with differential activities of the calpain-calpastatin proteolytic system. |
| title_fullStr | Clinical severity of β-thalassaemia/Hb E disease is associated with differential activities of the calpain-calpastatin proteolytic system. |
| title_full_unstemmed | Clinical severity of β-thalassaemia/Hb E disease is associated with differential activities of the calpain-calpastatin proteolytic system. |
| title_short | Clinical severity of β-thalassaemia/Hb E disease is associated with differential activities of the calpain-calpastatin proteolytic system. |
| title_sort | clinical severity of β thalassaemia hb e disease is associated with differential activities of the calpain calpastatin proteolytic system |
| url | http://europepmc.org/articles/PMC3353910?pdf=render |
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