Effects of intracellular calcium on cell survival and the MAPK pathway in a human hormone-dependent leukemia cell line (TF-1).
Changes in the cytoplasmic calcium concentration ([Ca(2+)](i)) regulate a wide variety of cellular processes. Here we demonstrate that increased [Ca(2+)](i) was able to induce hormone-independent survival and proliferation, as well as to evoke apoptosis in human myelo-erythroid GM-CSF/IL-3 dependent leukemia cells (TF-1). Cellular responses induced by elevated [Ca(2+)](i) depended on the duration and amplitude of the calcium-signal. Moderate or high, but transient, elevation of [Ca(2+)](i) caused a transient, biphasic activation of ERK1/2 and protected cells from hormone withdrawal-induced apoptosis.(1) In contrast, high and long-lasting elevation of [Ca(2+)](i) led to sustained activation of the ERK1/2 kinases and apoptosis of TF-1 cells. Our data suggest that a time-dependent action of the MAPK pathway works as a decision-point between cell proliferation and apoptosis.
Apáti
Agota
A
Membrane Research Group of the Hungarian Academy of Sciences, Nádor u. 7, H-1051 Budapest, Hungary. apati@biomembrane.hu
Jánossy
Judit
J
Brózik
Anna
A
Magócsi
Mária
M
D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007938:Leukemia; D020935:MAP Kinase Signaling System / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007211:Indoles; D000001:Calcimycin; D015759:Ionomycin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D000252:Calcium-Transporting ATPases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; C000543:cyclopiazonic acid