title: Acute changes in cellular zinc alters zinc uptake rates prior to zinc transporter gene expression in Jurkat cells.
abstract: A coordinated network of zinc transporters and binding proteins tightly regulate cellular zinc levels. Canonical responses to zinc availability are thought to be mediated by changes in gene expression of key zinc transporters. We investigated the temporal relationships of actual zinc uptake with patterns of gene expression in membrane-bound zinc transporters in the human immortalized T lymphocyte Jurkat cell line. Cellular zinc levels were elevated or reduced with exogenous zinc sulfate or N,N,N',N-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), respectively. Excess zinc resulted in a rapid 44 % decrease in the rate of zinc uptake within 10 min. After 120 min, the expression of metallothionein (positive control) increased, as well as the zinc exporter, ZnT1; however, the expression of zinc importers did not change during this time period. Zinc chelation with TPEN resulted in a rapid twofold increase in the rate of zinc uptake within 10 min. After 120 min, the expression of ZnT1 decreased, while again the expression of zinc importers did not change. Overall, zinc transporter gene expression kinetics did not match actual changes in cellular zinc uptake with exogenous zinc or TPEN treatments. This suggests zinc transporter regulation may be the initial response to changes in zinc within Jurkat cells.
authors.affiliation: Nutrition & Metabolism Center, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA, 94609, USA.
authors.forename: Tai C
authors.initials: TC
authors.lastname: Holland
authors.affiliation: Nutrition & Metabolism Center, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA, 94609, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Killilea
authors.affiliation: Nutrition & Metabolism Center, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA, 94609, USA.
authors.forename: Swapna V
authors.initials: SV
authors.lastname: Shenvi
authors.affiliation: Nutrition & Metabolism Center, Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA, 94609, USA. jking@chori.org.
authors.forename: Janet C
authors.initials: JC
authors.lastname: King
mesh_terms: D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D002413:Cations, Divalent; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005021:Ethylamines / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D017136:Ion Transport; D019169:Jurkat Cells; D008668:Metallothionein / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism*; D019287:Zinc Sulfate / Q000494:pharmacology*
chemical_list: D027682:Cation Transport Proteins; D002413:Cations, Divalent; D002614:Chelating Agents; D005021:Ethylamines; C491053:MT2A protein, human; C511824:N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine; D020033:Protein Isoforms; D011725:Pyridines; C498299:SLC30A1 protein, human; C403517:SLC39A1 protein, human; D019287:Zinc Sulfate; D008668:Metallothionein; D015032:Zinc
keywords: Biomarkers; Lymphocyte; Metal chelator; Metallothionein