Defective calcium influx in rat myelomonocytic leukemia cells which are resistant to differentiation-inducing effects of lipid A.
We compared the calcium mobilization in parent lipid A-sensitive leukemia cells (P2) and lipid A-resistant cells (LR) after treating them with lipid A in order to clarify the signal transduction involved in the differentiation induced by lipid A. Lipid A induced differentiation in P2 cells; however, LR cells were completely resistant to it. A dramatic elevation of intracellular free calcium ion concentration ([Ca2+]i) occurred in P2 cells, but only a slight elevation of [Ca2+]i in LR cells. Calcium ionophore in combination with lipid A induced differentiation in LR cells. An elevation of [Ca2+]i observed in P2 cells was abrogated by an addition of EGTA, which partially inhibited the differentiation of P2 cells stimulated by lipid A. Altogether, these data indicate that calcium influx is essential for the differentiation of P2 cells stimulated by lipid A and that defective calcium influx is responsible for the resistance to lipid A in LR cells.
Shinobu
N
N
Laboratory of Pathology, Hokkaido University School of Medicine, Sapporo, 060, Japan.
Kobayashi
M
M
Wang
J
J
Li
Y Q
YQ
Imai
K
K
Matsuno
K
K
Hosokawa
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016257:Fura-2; D007476:Ionophores / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D007942:Leukemia, Experimental; D015479:Leukemia, Myelomonocytic, Acute / Q000139:chemically induced; D008050:Lipid A / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000096:biosynthesis; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007476:Ionophores; D007529:Isoflavones; D008050:Lipid A; D009281:Naphthalenes; D011971:Receptors, Immunologic; D013449:Sulfonamides; D014665:Vasodilator Agents; D004533:Egtazic Acid; C017967:W 7; C055439:psi-tectorigenin; C058819:calphostin C; D002118:Calcium; D016257:Fura-2