title: Zinc deprivation impairs growth factor-stimulated calcium influx into murine 3T3 cells associated with decreased cell proliferation.
abstract: Zinc plays a critical role in growth, a process that depends primarily on cell proliferation. Murine fibroblasts, Swiss 3T3 cells, were used to explore the hypothesis that a critical role of zinc in cell proliferation relates to its function in calcium influx. Cells were deprived of zinc by an impermeant chelator, diethylenetriaminepentaacetate (0.6 mmol/L), and low-calcium status was achieved by using a low- (<5 μmol/L) calcium medium. Cells were stimulated by a composite of growth factors (GF): platelet-derived GF, insulin-like GF-I, and epidermal GF. GF stimulation of cell proliferation was assessed by the incorporation of tritiated thymidine and calcium influx by the increase in fluorescence of cells loaded with Fluo-4. Proliferation was dependent on both zinc and calcium and they interacted in this process. GF stimulated an immediate sharp increase in intracellular calcium, indicative of internal calcium release, which peaked within 1 min and decreased to an elevated plateau, a pattern typical of a store-operated calcium channel. The sustained calcium influx of zinc-deprived cells was markedly lower than that of supplemented cells. Verapamil, a calcium channel blocker, also depressed both cell proliferation and calcium influx. In summary, zinc deficiency impaired GF-stimulated calcium influx into murine fibroblasts in association with decreased cell proliferation.
authors.affiliation: Department of Biochemistry and University of Missouri, Columbia, MO 65211, USA. odellb@missouri.edu
authors.forename: Boyd L
authors.initials: BL
authors.lastname: O'Dell
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Browning
mesh_terms: D000818:Animals; D000077214:Becaplermin; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D004369:Pentetic Acid / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins / Q000494:pharmacology; D041701:Swiss 3T3 Cells; D014700:Verapamil / Q000494:pharmacology; D015032:Zinc / Q000172:deficiency*
chemical_list: D002121:Calcium Channel Blockers; D002614:Chelating Agents; D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D004369:Pentetic Acid; D014700:Verapamil; D015032:Zinc