Involvement of the essential metal transporter Zip14 in hepatic Cd accumulation during inflammation.
Upregulation of Zip14 contributes to hepatic zinc (Zn) and non-transferrin-bound iron (Fe) uptake during infection and inflammation. We investigated whether this essential metal transporter is also involved in hepatic cadmium (Cd) uptake under these conditions. An injection of lipopolysaccharide (LPS), turpentine oil (Tur) and n-hexane (Hex) resulted in an decrease in plasma Zn and Fe concentrations to 25-50% and an increase in hepatic concentrations of both metals to 150-200% of control mice. LPS significantly increased plasma interleukin (IL)-6 levels more rapidly than Tur or Hex. Tur or Hex significantly increased hepatic Zip14 mRNA expression and decreased ferroportin 1 mRNA expression following continuous increase of IL-6 level. Hepatic Cd and Zn concentrations increased significantly after repeated injections of Cd in Tur- or Hex-treated mice fed a control diet. Treatment with Tur or Hex additionally increased hepatic Cd accumulation in Zn-deficient mice, unlike in Fe-deficient mice. These results suggest that Zn transporters, such as Zip14, may be involved in hepatic Cd uptake during inflammation.
Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-Kita, Tondabayashi, Osaka 584-8540, Japan. minkyon@osaka-ohtani.ac.jp
Kyong-Son
KS
Min
Masaoki
M
Takano
Katsumi
K
Amako
Hidenori
H
Ueda
Keiichi
K
Tanaka
D000210:Acute-Phase Reaction / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D002104:Cadmium / Q000378:metabolism; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000493:pharmacokinetics*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism*; D003677:Deficiency Diseases / Q000150:complications / Q000378:metabolism; D004032:Diet; D004927:Escherichia coli Infections / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006586:Hexanes / Q000633:toxicity; D054884:Host-Pathogen Interactions; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000097:blood; D007501:Iron / Q000378:metabolism; D000090463:Iron Deficiencies; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism; D014425:Turpentine / Q000633:toxicity; D015032:Zinc / Q000172:deficiency / Q000378:metabolism; D000098742:Ferroportin
D027682:Cation Transport Proteins; D006586:Hexanes; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C500556:SLC39A14 protein, mouse; D000098742:Ferroportin; D002104:Cadmium; C026385:n-hexane; D007501:Iron; D015032:Zinc; D019256:Cadmium Chloride; D014425:Turpentine