title: An intracellular calcium store regulates protein synthesis in HeLa cells, but it is not the hormone-sensitive store.
abstract: There is considerable evidence, reviewed by Brostrom and Brostrom [1], that Ca2+ stores are involved in the regulation of protein synthesis. We provide evidence in HeLa cells that is consistent with their findings that depletion of Ca2+ stores and not changes in cytosolic free Ca2+ ([Ca2+]i) inhibit protein synthesis, but we also show that the mechanism leading to depletion is critical. Specifically, depletion of stores by the Ca(2+)-mobilizing hormone histamine does not inhibit protein synthesis. In assessing the role of Ca2+ stores in protein synthesis, experiments in certain cell types have been complicated by the use of Ca2+ ionophores, which simultaneously elevate [Ca2+]i and deplete Ca2+ stores. We have measured total cell Ca2+, [Ca2+]i and protein synthesis in HeLa cells under conditions that allowed evaluation of the separate contributions of stores and [Ca2+]i. Using 1,2-bis(2-aminophenoxyethane)-N,N,N'N'-tetraacetic acid (BAPTA) as an intracellular Ca2+, chelator and thapsigargin, which inhibits the membrane Ca(2+)-ATPase of storage vesicles, total cell Ca2+ can be depleted and this depletion is enhanced by extracellular EGTA which blocks Ca2+ influx; [Ca2+]i is actually lowered by BAPTA under these conditions. Protein synthesis is inhibited by BAPTA in the presence of EGTA and by thapsigargin with or without EGTA. However, histamine which with EGTA, affects an equal degree of Ca2+ depletion does not inhibit protein synthesis. Thus, it is suggested that Ca2+ stores are not homogeneous, and that the hormone-sensitive store specifically does not play a role in the regulation of protein synthesis. In this respect, the hormone-sensitive and insensitive stores do not functionally communicate and may be separately regulated.
authors.affiliation: Department of Physiology, University of Connecticut Health Center, Farmington.
authors.forename: S F
authors.initials: SF
authors.lastname: Preston
authors.forename: R D
authors.initials: RD
authors.lastname: Berlin
mesh_terms: D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006367:HeLa Cells; D006632:Histamine / Q000502:physiology*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D014176:Protein Biosynthesis; D011506:Proteins / Q000187:drug effects; D011969:Receptors, Histamine H1 / Q000502:physiology; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
chemical_list: D011506:Proteins; D011969:Receptors, Histamine H1; D013729:Terpenes; D004533:Egtazic Acid; D019284:Thapsigargin; D006632:Histamine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium