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Ridefelt P, Larsson R, Nygren P, Larsson E, Nilsson K: Modulation of calcium signalling and proliferation in monoblastoid U-937 cells. Anticancer Res. 1996 Jul-Aug;16(4A):1643-50. The effects of TPA (12-0-tetradecanoylphorbol-13-acetate) and G-protein modulators on the concentration of cytoplasmic Ca2+ ([Ca2+] i), cytoplasmic pH and cell growth were investigated in monoblastoid U-937 cells. The G-protein activator NaF causes a dose-dependent increase of [Ca2+] i, that is partially sensitive to inhibition by pertussis toxin. The [Ca2+] i rise appears to come mainly from extracellular sources, and the Ca2+ influx is mediated by channels insensitive to the Ca2+ blocker verapamil. The Ca2+ ionophore ionomycin causes a biphasic rise of [Ca2+] i, reaching steady state levels slightly higher than those attained with NaF. TPA per se has no effect on [Ca2+] i, but potently reverses the NaF or ionomycin induced [Ca2+] i rise. Also, TPA partially counteracted the acidification induced by NaF. Both NaF and ionomycin per se had no effect on cell growth but partially counteracted TPA induced growth inhibition. Interferon-gamma and tumor necrosis factor-alpha did not affect [Ca2+] i by themselves but lowered the [Ca2+] i of NaF stimulated cells. The cytokines had no effect on cytoplasmic pH. This study indicates that elevations of [Ca2+] i in themselves does not trigger proliferation, but alterations of [Ca2+] i modulates the regulation of U937-cell growth. |
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