Autor: |
Callus, Bernard, Tilbrook, Peta A., Busfield, Samatha J., Cull, Vanessa S., Bittorf, Thomas, Klinken, S.Peter |
Zdroj: |
Experimental Cell Research; July 1995, Vol. 219 Issue: 1 p39-46, 8p |
Abstrakt: |
The J2E erythroid cell line proliferates and differentiates in response to erythropoietin (epo). Here we demonstrate that the diuretic amiloride can suppress normal and hormone-induced cell division in a dose-dependent manner. In the presence of amiloride, cell numbers did not increase, [3H]thymidine incorporation decreased, and fewer cells were observed in the S, G2, and M phases of the cell cycle. In addition, the levels of proliferating cell nuclear antigen, a subunit of DNA polymerase δ, fell. In marked contrast, epoinitiated differentiation was potentiated when J2E cells were cultured with the drug: the number of benzidine-positive cells increased, hemoglobin content per cell rose, and more morphologically mature cells were produced. Immunoblotting with anti-phosphotyrosine antibodies revealed that amiloride reduced the number of phosphorylated proteins in epo-stimulated cells. Moreover, the protein content of p42 and p44 MAP kinases was noticeably downregulated in amiloridetreated cultures. These data indicate that amiloride may interfere with epo-induced signaling cascades within J2E cells which result in restricted cell division and promotion of maturation. |
Databáze: |
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