Different signalling pathways are used in the commitment of murine erythroleukemia cells (TSA8) to differentiate, and in the erythropoietin action on progenitor cells.
The murine erythroleukemia (MEL) cell line, TSA8, becomes responsive to erythropoietin after induction with dimethyl sulfoxide (DMSO). We examined the signalling pathways involved in the commitment of TSA8 cells to become the erythroid progenitor cells responsive to erythropoietin, comparing them with the pathway used in an erythropoietin-induced change of the progenitor cells. Amiloride, an inhibitor of the Na+/H+ antiporter, completely blocked the commitment of TSA8 cells to become responsive to erythropoietin at a concentration that did not affect cell proliferation, while it showed no effect on the differentiation or proliferation of the erythroid progenitor cells derived from TSA8 cells by erythropoietin. Ethyleneglycol-bis (beta-aminoethyl ether) N,N,N',N'-tetra acetic acid (EGTA) inhibited the commitment of TSA8 cells to CFU-E-like cells without affecting colony formation. In contrast, EGTA did not inhibit erythropoietin-induced differentiation of the progenitor cells, but did inhibit their proliferation. These results indicate that erythropoietin uses different signalling pathways from those used in the induction of the commitment of TSA8 cells.
Fukumoto
H
H
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Matsui
Y
Y
Obinata
M
M
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003513:Cycloheximide / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D004921:Erythropoietin; D004533:Egtazic Acid; D000584:Amiloride; D003513:Cycloheximide