The proteomic study of sodium butyrate antiproliferative/cytodifferentiation effects on K562 cells
- 作者：Dana Grebeň ; ová ; Kateř ; ina Kuž ; elová ; Michaela Pluskalová ; Gabriela Peš ; lová ; Petr Halada ; Zbyně ; k Hrkal
- 关键词：K562 ; Cell cycle ; Hemoglobin synthesis ; BCR-ABL ; Proteome analysis ; HSP90 ; p23 ; CYP-A ; prefoldin2
- 刊名：Blood Cells ; Molecules ; and Diseases
- 出版年：2006
- 期刊代码：277_10799796
- 类别：med
- 出版时间：November-December 2006
- 卷：37
- 期：3
- 页码：210-217
- 文件大小：533 K
摘要
Employing methods of cell biology and proteome analysis tools, we examined effects of an inhibitor of histone deacetylases, sodium butyrate (SB), on the proliferation/differentiation characteristics of chronic myelogenous leukemia (CML)-derived cells K562. SB suppressed proliferation of K562 cells by inducing cell cycle arrest in G1 phase, which was followed by their transition to G0 phase (decrease of Ki-67 antigen-positive cells) and erythroid differentiation (increased glycophorin A expression and synthesis of hemoglobins). Neither terminal apoptosis (low counts of TUNEL-positive cells) nor necrosis (moderate counts of propidium iodide-positive cells) occurred. Importantly, SB attenuated protein expression of CML-related chimeric kinase BCR-ABL that is responsible for the deregulated proliferation of CML cells. The proteomic analysis (2-D electrophoresis combined with MALDI-TOF mass spectrometry and/or Western blotting) revealed several proteins that were differentially expressed or their mobility was altered due to butyrate treatment, namely, HSP90, HSP70, p23, cyclophilin A (CYPA), prefoldin2 (PFD2) and α-, γ-, ε-human globin chains. Perturbation of HSP90 multichaperone complex of which BCR-ABL is the client protein is presumably a cause of BCR-ABL suppression. Changes in other proteins with chaperonic functions, CYPA and PFD2, may reflect SB antiproliferative and cytodifferentiation effects.