Modulation of calcium signalling and proliferation in monoblastoid U-937 cells.
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.
Ridefelt
P
P
Department of Surgery, Uppsala University, Sweden.
Larsson
R
R
Nygren
P
P
Larsson
E
E
Nilsson
K
K
D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007371:Interferon-gamma / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D037342:Pertussis Toxin; D015398:Signal Transduction / Q000187:drug effects; D012969:Sodium Fluoride / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D010566:Virulence Factors, Bordetella; D015759:Ionomycin; D007371:Interferon-gamma; D012969:Sodium Fluoride; D014700:Verapamil; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium