Erythroid differentiation of cultured murine erythroleukemia cells by the spermine analogue canavalmine |
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Authors: | Shinsuke Fujihara Toshikatsu Nakashima Yutaka Kurogochi |
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Affiliation: | Department of Pharmacology, Nara Medical University, Kashihara 634 Japan |
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Abstract: | Canavalmine, an analogue of spermine, induced erythroid differentiation of murine erythroleukemia cells 745A, as evidenced by benzidine staining and heme content of cultured cells. Benzidine-positive cells synthesizing hemoglobin appeared on day 4 after addition of 250 μM canavalmine. The canavalmine-induced cell differentiation was inhibited by the addition of agents which alter the structure of the cell membrane, such as local anesthetics (procainamide and lidocaine) or Ca2+ antagonists (nifedipine and verapamil) at dosages not toxic for the cell growth. Canavalmine did not significantly affect the levels of conjugated polyamines in the acid-insoluble fraction of the cells. In contrast, the level of free spermidine in the acid-soluble fraction greatly decreased during the 18 h after canavalmine treatment. Putrescine and spermidine, when added externally to the growth medium, showed dose-dependent inhibition of canavalmine-induced cell differentiation. Neither cadaverine nor spermine had any significant effect. These results suggest that not only structural change of cell membrane but alteration of the polyamine metabolism, especially a regulation of the cellular level of free spermidine, might have a key importance in erythroid differentiation of murine erythroleukemia cells induced by canavalmine. |
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Keywords: | Canavalmine Spermine analog Differentiation (Erythroleukemia cell) |
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