DIFFERENTIATION OF HL-60 PROMYELOCYTIC LEUKEMIA-CELLS IS ACCOMPANIED BY A MODIFICATION OF MAGNESIUM HOMEOSTASIS

Magnesium homeostasis in HL-60 promyelocytic leukemia cells was compar ed to that in neutrophyl-like HL-60 cells obtained by 1.3% DMSO treatm ent. Magnesium homeostasis was studied by the characterization of magn esium efflux, the identification of intracellular magnesium pools, and the regulation of intracellular ionized Mg2+. In both undifferentiate d and neutrophyl-like HL-60 cells, magnesium efflux occurred via the N a-Mg antiporter which was inhibited by imipramine and stimulated by db cAMP and forskolin. Receptor-mediated signals such as ATP, IFN-alpha, or PGE1, which can trigger cAMP-dependent magnesium efflux,were ineff ective in undifferentiated HL-60 cells but induced 60-70% increase of magnesium efflux in neutrophyl-like HL-60 cells. Selective membrane pe rmeabilization by the cation ionophore A23187 induced a large magnesiu m release when cells were treated with rotenone. In both cell populati ons, the addition of glucose to rotenone-treated cells restored magnes ium release to the control level. Permeabilization by 0.005% digitonin provoked the release of 90% cell total magnesium in both cell types. Intracellular [Mg2+](i) was 0.15 and 0.26 mM in undifferentiated and n eutrophyl-like HL-60 cells, respectively. Stimuli that triggered magne sium efflux, such as db cAMP in undifferentiated and IFN-alpha in neut rophyl-like HL-60 cells, induced a slow but consistent increase of [Mg 2+](i) which was independent from Ca2+ movements. Overall, these data indicate that magnesium homeostasis is regulated by receptor-mediated magnesium efflux which was modified during differentiation of HL-60 ce lls. Stimulation of magnesium efflux is paralleled by an increase of [ Mg2+](i) which reflects a release of magnesium from the bound cation p ool. J. Cell. Biochem. 71:441-448, 1998. (C) 1998 Wiley-Liss, Inc.