Iron uptake by ZIP8 and ZIP14 in human proximal tubular epithelial cells

Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Sanne van RaaijRachel P L van Swelm

Abstract

In patients with iron overload disorders, increasing number of reports of renal dysfunction and renal iron deposition support an association between increased iron exposure and renal injury. In systemic iron overload, elevated circulating levels of transferrin-bound (TBI) and non-transferrin-bound iron (NTBI) are filtered to the renal proximal tubules, where they may cause injury. However, the mechanisms of tubular iron handling remain elusive. To unravel molecular renal proximal tubular NTBI and TBI handling, human conditionally immortalized proximal tubular epithelial cells (ciPTECs) were incubated with 55Fe as NTBI and fluorescently labeled holo-transferrin as TBI. Ferrous iron importers ZIP8 and ZIP14 were localized in the ciPTEC plasma membrane. Whereas silencing of either ZIP8 or ZIP14 alone did not affect 55Fe uptake, combined silencing significantly reduced 55Fe uptake compared to control (p < 0.05). Furthermore, transferrin receptor 1 (TfR1) and ZIP14, but not ZIP8, colocalized with early endosome antigen 1 (EEA1). TfR1 and ZIP14 also colocalized with uptake of fluorescently labeled transferrin. Furthermore, ZIP14 silencing decreased 55Fe uptake after 55Fe-Transferrin exposure (p < 0.05), suggesting ZIP14 could be invo...Continue Reading

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Citations

Jun 26, 2020·Metallomics : Integrated Biometal Science·Haoxuan DingJie Feng
Mar 9, 2021·Journal of Alzheimer's Disease : JAD·Najla JouiniSamir Belal
Oct 1, 2020·Pharmaceuticals·Ravneet ChhabraMeera Nanjundan
Apr 30, 2021·Frontiers in Medicine·Ewa WlazloYogesh Scindia
Aug 13, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sannette C HallDaren L Knoell
Nov 30, 2021·American Journal of Physiology. Renal Physiology·James A VotavaRichard S Eisenstein
Oct 23, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Qingli LiuMitchell D Knutson

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Methods Mentioned

BETA
FCS
transfection
scraping
PCR
biopsies

Software Mentioned

GraphPad Prism

Related Concepts

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