T. Buyn et al., A 5-LIPOXYGENASE INHIBITOR AT MICROMOLAR CONCENTRATION RAISES INTRACELLULAR CALCIUM IN U937 CELLS PRIOR TO THEIR PHYSIOLOGICAL CELL-DEATH, Prostaglandins, leukotrienes and essential fatty acids, 56(1), 1997, pp. 69-77
Micromolar MK886, a selective inhibitor of 5-lipoxygenase at nanomolar
concentration, induces physiologic cell death in U937 and chronic mye
logenous leukemia blast cells. When U937 cells were challenged with 10
mu M MK886, an acute, biphasic and sustained rise in intracellular Ca
2+ occurred, as determined with Fura-2. The initial increase was follo
wed by a transient decline and a larger rise due to an influx of exter
nal Ca2+. The first increase and part of the subsequent rise also deve
loped in Ca2+-free medium, identifying their origin from intracellular
stores. The intracellular Ca2+ concentration of U937 cells that remai
ned after culture for 24 or 48 h with 5 or 10 mu M MK886 was not relia
bly altered from the control values of 130 +/- 8.3 nM. Under similar c
onditions MK886 did not increase cytosol Ca2+ of a human prostate (PC3
) cell line examined in suspension. The increase in intracellular Ca2 in response to MK886 in calcium-containing medium was confirmed with
an ACAS laser spectrometer. U937 cytosol pH was measured with the fluo
rescent probe BCECF, but no persistent acute or chronic change was ind
uced by MK886. The rapid and sustained rise in Ca2+ induced by MK886 i
s an early event in U937 cells which subsequently undergo physiologic
cell death characterized in many by apoptosis.