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An immunosuppressive agent, FTY720, increases intracellular concentration of calcium ion and induces apoptosis in HL‐60
Author(s) -
SHINOMIYA T.,
LI X.K.,
AMEMIYA H.,
SUZUKI S.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.d01-2281.x
Subject(s) - intracellular , calcium in biology , apoptosis , calcium , chemistry , biophysics , pharmacology , microbiology and biotechnology , medicine , biology , biochemistry
We previously reported that FTY720 is an efficient inducer of apoptosis in lymphocytes and cultured cell lines. In the present study, HL‐60 human promyerocytoma cells also induced apoptosis through in vitro treatment with the drug, demonstrating extensive DNA fragmentation 6 hr after incubation. The major target of FTY720 was the common signalling pathway of apoptosis, since a rapid (<1 min) increase in the intracellular Ca 2+ concentration ([Ca 2+ ] i ) was found in the cells treated with the drug. Calcium chelation in the culture medium with EGTA did not affect the [Ca 2+ ] i mobilization. A phospholipase C inhibitor, U73122, inhibited the increase in [Ca 2+ ] i as well as the fragmentation of the nuclear DNA, whereas U73343, a non‐effective analogue of U73122, had little effect. These results suggest that FTY720‐induced apoptosis is mediated through an activation of phospholipase C and the subsequent release of Ca 2+ from intracellular calcium pools. In addition, the treatment of HL‐60 with pertussis toxin (PTX) did not inhibit Ca 2+ mobilization or apoptosis, suggesting that the activation of phospholipase C is independent of PTX‐sensitive G‐proteins.