| ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading. | |
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MedLine Citation:
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PMID: 22898811 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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ZIP8 (SLC39A8) belongs to the ZIP family of metal-ion transporters. Among the ZIP proteins, ZIP8 is most closely related to ZIP14, which can transport iron, zinc, manganese, and cadmium. Here we investigated the iron transport ability of ZIP8, its subcellular localization, pH dependence, and regulation by iron. Transfection of HEK 293T cells with ZIP8 cDNA enhanced the uptake of (59)Fe and (65)Zn by 200 and 40%, respectively, compared with controls. Excess iron inhibited the uptake of zinc and vice versa. In RNA-injected Xenopus oocytes, ZIP8-mediated (55)Fe(2+) transport was saturable (K(0.5) of ∼0.7 μm) and inhibited by zinc. ZIP8 also mediated the uptake of (109)Cd(2+), (57)Co(2+), (65)Zn(2+) > (54)Mn(2+), but not (64)Cu (I or II). By using immunofluorescence analysis, we found that ZIP8 expressed in HEK 293T cells localized to the plasma membrane and partially in early endosomes. Iron loading increased total and cell-surface levels of ZIP8 in H4IIE rat hepatoma cells. We also determined by using site-directed mutagenesis that asparagine residues 40, 88, and 96 of rat ZIP8 are glycosylated and that N-glycosylation is not required for iron or zinc transport. Analysis of 20 different human tissues revealed abundant ZIP8 expression in lung and placenta and showed that its expression profile differs markedly from ZIP14, suggesting nonredundant functions. Suppression of endogenous ZIP8 expression in BeWo cells, a placental cell line, reduced iron uptake by ∼40%, suggesting that ZIP8 participates in placental iron transport. Collectively, these data identify ZIP8 as an iron transport protein that may function in iron metabolism. |
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Authors:
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Chia-Yu Wang; Supak Jenkitkasemwong; Stephanie Duarte; Brian K Sparkman; Ali Shawki; Bryan Mackenzie; Mitchell D Knutson |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-08-16 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 287 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-08 Completed Date: 2012-12-31 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 34032-43 Citation Subset: IM |
Affiliation:
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Food Science and Human Nutrition Department, University of Florida, Gainesville, Florida 32611, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cation Transport Proteins / biosynthesis*, genetics Cell Line, Tumor Cell Membrane / genetics, metabolism* HEK293 Cells Humans Ion Transport / physiology Iron / metabolism* Oocytes Organ Specificity / physiology Rats Up-Regulation / physiology* Xenopus laevis |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK080047/DK/NIDDK NIH HHS; R01 DK080047/DK/NIDDK NIH HHS; R01 DK080706/DK/NIDDK NIH HHS; R24 CA086307/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cation Transport Proteins; 0/ZIP8 protein, rat; 0/Zip8 protein, human; 7439-89-6/Iron |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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