title: Differentiation of HL-60 promyelocytic leukemia cells is accompanied by a modification of magnesium homeostasis.
abstract: Magnesium homeostasis in HL-60 promyelocytic leukemia cells was compared to that in neutrophyl-like HL-60 cells obtained by 1.3% DMSO treatment. Magnesium homeostasis was studied by the characterization of magnesium efflux, the identification of intracellular magnesium pools, and the regulation of intracellular ionized Mg2+. In both undifferentiated and neutrophyl-like HL-60 cells, magnesium efflux occurred via the Na-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 ineffective in undifferentiated HL-60 cells but induced 60-70% increase of magnesium efflux in neutrophyl-like HL-60 cells. Selective membrane permeabilization by the cation ionophore A23187 induced a large magnesium release when cells were treated with rotenone. In both cell populations, the addition of glucose to rotenone-treated cells restored magnesium 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 neutrophyl-like HL-60 cells, respectively. Stimuli that triggered magnesium efflux, such as db cAMP in undifferentiated and IFN-alpha in neutrophyl-like HL-60 cells, induced a slow but consistent increase of [Mg2+]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 cells. Stimulation of magnesium efflux is paralleled by an increase of [Mg2+]i which reflects a release of magnesium from the bound cation pool.
authors.affiliation: Institute of General Pathology and Giovanni XXIII Cancer Research Center, Catholic University of Sacred Heart, Roma, Italy. ibipg@rm.unicatt.it
authors.forename: F I
authors.initials: FI
authors.lastname: Wolf
authors.forename: V
authors.initials: V
authors.lastname: Covacci
authors.forename: N
authors.initials: N
authors.lastname: Bruzzese
authors.forename: A
authors.initials: A
authors.lastname: Di Francesco
authors.forename: A
authors.initials: A
authors.lastname: Sacchetti
authors.forename: D
authors.initials: D
authors.lastname: Corda
authors.forename: A
authors.initials: A
authors.lastname: Cittadini
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D017920:Antiporters / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D016718:Arachidonic Acid / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002794:Choline / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004072:Digitonin / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D018922:HL-60 Cells; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology
chemical_list: D017920:Antiporters; D016898:Interferon-alpha; C046250:sodium-magnesium antiporter; D012402:Rotenone; D005576:Colforsin; D016718:Arachidonic Acid; D000001:Calcimycin; D003994:Bucladesine; D000255:Adenosine Triphosphate; D000527:Alprostadil; D008274:Magnesium; D004072:Digitonin; D002794:Choline; D007099:Imipramine; D002118:Calcium; D004121:Dimethyl Sulfoxide