Lovastatin inhibits receptor-stimulated Ca(2+)-influx in retinoic acid differentiated U937 and HL-60 cells.
Lovastatin was used to study the role of isoprenylated proteins on stimulus-induced increase of cytosolic Ca2+ in retinoic acid-differentiated U937 and HL-60 cells. Preincubation of the cells with lovastatin for 11-24 h reduced the Ca(2+)-influx induced by PAF of FMLP. The maximal decrease was 60% in U937 cells and 40% in HL-60 cells. The ID50s of lovastatin in U937 and HL-60 cells were 5 microM and 15 microM, respectively. Lovastatin did not inhibit Ca(2+)-discharge from intracellular stores. Addition of mevalonate to lovastatin-treated cells completely reversed the inhibition of PAF- and FMLP-stimulated Ca(2+)-mobilization. Immunoreactivity of ras-like proteins was decreased in membranes and increased in the cytosol of U937 cells by 1 day treatment with lovastatin. We conclude that isoprenylated proteins are involved in the regulation of receptor-stimulated Ca(2+)-entry of differentiated HL-60 and U937 cells.
Haag
H
H
Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Universität München, Germany.
Grünberg
B
B
Weber
C
C
Vauti
F
F
Aepfelbacher
M
M
Siess
W
W
D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008148:Lovastatin / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*; D018631:ras Proteins / Q000378:metabolism
D014212:Tretinoin; D008148:Lovastatin; D018631:ras Proteins; D002118:Calcium