The proteomic study of sodium butyrate antiproliferative/cytodifferentiation effects on K562 cells.
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 alpha-, gamma-, epsilon-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.
Grebenová
Dana
D
Department of Cellular Biochemistry, Institute of Hematology and Blood Transfusion, U Nemocnice l, 128 20 Prague-2, Czech Republic.
Kuzelová
Katerina
K
Pluskalová
Michaela
M
Peslová
Gabriela
G
Halada
Petr
P
Hrkal
Zbynek
Z
D002087:Butyrates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D016193:G1 Phase / Q000187:drug effects; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D020543:Proteome / Q000096:biosynthesis*; D040901:Proteomics
D002087:Butyrates; D020543:Proteome