Evidence map›Paper›PMID 22898811›Full record

ArticleThe Journal of biological chemistry2012

ZIP8 is an iron and zinc transporter whose cell-surface expression is up-regulated by cellular iron loading.

Chia-Yu Wang, Supak Jenkitkasemwong, Stephanie Duarte, Brian K Sparkman, Ali Shawki, Bryan Mackenzie, Mitchell D Knutson

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers.

0numbers the graph read from it
0cells of the map it votes in
237citing papers in PubMed
11.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

237 citing papers in PubMed, 365 citations in OpenAlex.

  1. Trial
  2. Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. iScience · 2026
    Article
  8. Review
  9. Overlaps in mammalian iron and manganese homeostasis: recent advances.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
    Review
  10. Review
  11. Molecular and therapeutic frontiers in anemia therapy.The Journal of clinical investigation · 2026
    Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Regulation of mitochondrial iron homeostasis in tumor cells.Molecular medicine (Cambridge, Mass.) · 2026
    Review
  18. Article
  19. Article
  20. Review

177 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Chia-Yu WangFood Science and Human Nutrition Department, University of Florida, Gainesville, Florida 32611, USA.
Supak Jenkitkasemwong
Stephanie Duarte
Brian K Sparkman
Ali Shawki
Bryan Mackenzie
Mitchell D Knutson
University of Florida · USUniversity of Cincinnati Medical Center · US

Funding

RESEARCH RESOURCE IN RADIONUCLIDE RESEARCHR24CA086307 · NCI · WASHINGTON UNIVERSITY · PI WELCH, MICHAEL J. · 1999 to 2009
$8.4M
ZIP Proteins and Iron MetabolismR01DK080706 · NIDDK · UNIVERSITY OF FLORIDA · PI KNUTSON, MITCHELL D · 2008 to 2022
$4.7M
Divalent metal-ion transporter DMT1 and its role in intestinal metal-ion uptakeR01DK080047 · NIDDK · UNIVERSITY OF CINCINNATI · PI MACKENZIE, BRYAN · 2008 to 2012
$1.5M
NCI NIH HHS R24 CA086307NIDDK NIH HHS R01 DK080047NIDDK NIH HHS R01 DK080706
6 · The paper itself

Abstract

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.

Indexed as

AnimalsCation Transport ProteinsCell Line, TumorCell MembraneHEK293 CellsHumansIon TransportIronOocytesOrgan SpecificityRatsUp-RegulationXenopus laevisCation Transport ProteinsIronSLC39A8 protein, humanSlc39a8 protein, rat

Identifiers

PMID22898811
PMCPMC3464513
OpenAlexW2032656951

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.