title: Lovastatin inhibits receptor-stimulated Ca(2+)-influx in retinoic acid differentiated U937 and HL-60 cells.
abstract: 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.
authors.affiliation: Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Universität München, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Haag
authors.forename: B
authors.initials: B
authors.lastname: Grünberg
authors.forename: C
authors.initials: C
authors.lastname: Weber
authors.forename: F
authors.initials: F
authors.lastname: Vauti
authors.forename: M
authors.initials: M
authors.lastname: Aepfelbacher
authors.forename: W
authors.initials: W
authors.lastname: Siess
mesh_terms: 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
chemical_list: D014212:Tretinoin; D008148:Lovastatin; D018631:ras Proteins; D002118:Calcium