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UTSUGISAWA Taiju
Department School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine Position Associate Professor |
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| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | Ribosomal protein S19 deficiency leads to reduced proliferation and increased apoptosis but does not affect terminal erythroid differentiation in a cell line model of Diamond-Blackfan anemia. |
| Journal | Formal name：Stem cells (Dayton, Ohio) Abbreviation：Stem Cells ISSN code：15494918/10665099 |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | 26(2),pp.323-9 |
| Author and coauthor | Miyake Koich, Utsugisawa Taiju, Flygare Johan, Kiefer Thomas, Hamaguchi Isao, Richter Johan, Karlsson Stefan |
| Authorship | 2nd author |
| Publication date | 2008/02 |
| Summary | Diamond-Blackfan anemia (DBA) is a congenital red-cell aplasia in which 25% of the patients have a mutation in the ribosomal protein (RP) S19 gene. It is not known how the RPS19 deficiency impairs erythropoiesis and proliferation of hematopoietic progenitors. To elucidate molecular mechanisms in RPS19-deficient DBA, we analyzed the effects of RPS19 deficiency on erythropoietin (EPO)-induced signal transduction, cell cycle, and apoptosis in RPS19-deficient TF-1 cells. We did not find any abnormality in EPO-induced signal transduction. However, RPS19-deficient TF-1 cells showed G0/G1 arrest (82% vs. 58%; p < .05) together with accumulation of p21 and p27. The fraction of apoptotic cells detected by Annexin V analysis also increased compared with control cells (13% vs. 3.1%; p < .05). Western blot analysis of apoptosis-related proteins showed that the level of bcl-2 and Bad was decreased and Bax was increased in RPS19-deficient TF-1 cells. Moreover, primary CD34-positive cells from DBA patients detected by Annexin V analysis also generated a higher number of apoptotic cells compared with normal CD34-positive cells during in vitro culture (38% vs. 8.9%; n = 5; p < .001). Finally, we show that although RPS19 silencing reduces EPO-induced development of erythroid progenitors expressing glycophorin A (GPA), RPS19 silencing in cells already expressing GPA does not affect GPA expression. These findings indicate that RPS19 deficiency causes apoptosis and accelerated loss of erythroid progenitors in RPS19-deficient DBA. |
| DOI | 10.1634/stemcells.2007-0569 |
| PMID | 17962699 |