Increased IRP1 and IRP2 RNA binding activity accompanies a reduction of the labile iron pool in HFE-expressing cells

C. N. Roy, K. P. Blemings, K. M. Deck, Paige Davies, E. L. Anderson, R. S. Eisenstein, Caroline Enns

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Iron regulatory proteins (IRPs), the cytosolic proteins involved in the maintenance of cellular iron homeostasis, bind to stem loop structures found in the mRNA of key proteins involved iron uptake, storage, and metabolism and regulate the expression of these proteins in response to changes in cellular iron needs. We have shown previously that HFE-expressing fWTHFE/tTA HeLa cells have slightly increased transferrin receptor levels and dramatically reduced ferritin levels when compared to the same clonal cell line without HFE (Gross et al., 1998, J Biol Chem 273:22068-22074). While HFE does not alter transferrin receptor trafficking or non-transferrin mediated iron uptake, it does specifically reduce 55Fe uptake from transferrin (Roy et al., 1999, J Biol Chem 274:9022-9028). In this report, we show that IRP RNA binding activity is increased by up to 5-fold in HFE-expressing cells through the activation of both IRP isoforms. Calcein measurements show a 45% decrease in the intracellular labile iron pool in HFE-expressing cells, which is in keeping with the IRP activation. These results all point to the direct effect of the interaction of HFE with transferrin receptor in lowering the intracellular labile iron pool and establishing a new set point for iron regulation within the cell.

Original languageEnglish (US)
Pages (from-to)218-226
Number of pages9
JournalJournal of Cellular Physiology
Volume190
Issue number2
DOIs
StatePublished - 2002

Fingerprint

Iron-Regulatory Proteins
Iron
RNA
Transferrin Receptors
Chemical activation
Proteins
Transferrin
Ferritins
HeLa Cells
Protein Binding
Metabolism
Protein Isoforms
Homeostasis
Cells
Maintenance
Cell Line
Messenger RNA

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Increased IRP1 and IRP2 RNA binding activity accompanies a reduction of the labile iron pool in HFE-expressing cells. / Roy, C. N.; Blemings, K. P.; Deck, K. M.; Davies, Paige; Anderson, E. L.; Eisenstein, R. S.; Enns, Caroline.

In: Journal of Cellular Physiology, Vol. 190, No. 2, 2002, p. 218-226.

Research output: Contribution to journalArticle

Roy, C. N. ; Blemings, K. P. ; Deck, K. M. ; Davies, Paige ; Anderson, E. L. ; Eisenstein, R. S. ; Enns, Caroline. / Increased IRP1 and IRP2 RNA binding activity accompanies a reduction of the labile iron pool in HFE-expressing cells. In: Journal of Cellular Physiology. 2002 ; Vol. 190, No. 2. pp. 218-226.
@article{cb7f3c26929f4eefa025a6a1313b1e1b,
title = "Increased IRP1 and IRP2 RNA binding activity accompanies a reduction of the labile iron pool in HFE-expressing cells",
abstract = "Iron regulatory proteins (IRPs), the cytosolic proteins involved in the maintenance of cellular iron homeostasis, bind to stem loop structures found in the mRNA of key proteins involved iron uptake, storage, and metabolism and regulate the expression of these proteins in response to changes in cellular iron needs. We have shown previously that HFE-expressing fWTHFE/tTA HeLa cells have slightly increased transferrin receptor levels and dramatically reduced ferritin levels when compared to the same clonal cell line without HFE (Gross et al., 1998, J Biol Chem 273:22068-22074). While HFE does not alter transferrin receptor trafficking or non-transferrin mediated iron uptake, it does specifically reduce 55Fe uptake from transferrin (Roy et al., 1999, J Biol Chem 274:9022-9028). In this report, we show that IRP RNA binding activity is increased by up to 5-fold in HFE-expressing cells through the activation of both IRP isoforms. Calcein measurements show a 45{\%} decrease in the intracellular labile iron pool in HFE-expressing cells, which is in keeping with the IRP activation. These results all point to the direct effect of the interaction of HFE with transferrin receptor in lowering the intracellular labile iron pool and establishing a new set point for iron regulation within the cell.",
author = "Roy, {C. N.} and Blemings, {K. P.} and Deck, {K. M.} and Paige Davies and Anderson, {E. L.} and Eisenstein, {R. S.} and Caroline Enns",
year = "2002",
doi = "10.1002/jcp.10056",
language = "English (US)",
volume = "190",
pages = "218--226",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Increased IRP1 and IRP2 RNA binding activity accompanies a reduction of the labile iron pool in HFE-expressing cells

AU - Roy, C. N.

AU - Blemings, K. P.

AU - Deck, K. M.

AU - Davies, Paige

AU - Anderson, E. L.

AU - Eisenstein, R. S.

AU - Enns, Caroline

PY - 2002

Y1 - 2002

N2 - Iron regulatory proteins (IRPs), the cytosolic proteins involved in the maintenance of cellular iron homeostasis, bind to stem loop structures found in the mRNA of key proteins involved iron uptake, storage, and metabolism and regulate the expression of these proteins in response to changes in cellular iron needs. We have shown previously that HFE-expressing fWTHFE/tTA HeLa cells have slightly increased transferrin receptor levels and dramatically reduced ferritin levels when compared to the same clonal cell line without HFE (Gross et al., 1998, J Biol Chem 273:22068-22074). While HFE does not alter transferrin receptor trafficking or non-transferrin mediated iron uptake, it does specifically reduce 55Fe uptake from transferrin (Roy et al., 1999, J Biol Chem 274:9022-9028). In this report, we show that IRP RNA binding activity is increased by up to 5-fold in HFE-expressing cells through the activation of both IRP isoforms. Calcein measurements show a 45% decrease in the intracellular labile iron pool in HFE-expressing cells, which is in keeping with the IRP activation. These results all point to the direct effect of the interaction of HFE with transferrin receptor in lowering the intracellular labile iron pool and establishing a new set point for iron regulation within the cell.

AB - Iron regulatory proteins (IRPs), the cytosolic proteins involved in the maintenance of cellular iron homeostasis, bind to stem loop structures found in the mRNA of key proteins involved iron uptake, storage, and metabolism and regulate the expression of these proteins in response to changes in cellular iron needs. We have shown previously that HFE-expressing fWTHFE/tTA HeLa cells have slightly increased transferrin receptor levels and dramatically reduced ferritin levels when compared to the same clonal cell line without HFE (Gross et al., 1998, J Biol Chem 273:22068-22074). While HFE does not alter transferrin receptor trafficking or non-transferrin mediated iron uptake, it does specifically reduce 55Fe uptake from transferrin (Roy et al., 1999, J Biol Chem 274:9022-9028). In this report, we show that IRP RNA binding activity is increased by up to 5-fold in HFE-expressing cells through the activation of both IRP isoforms. Calcein measurements show a 45% decrease in the intracellular labile iron pool in HFE-expressing cells, which is in keeping with the IRP activation. These results all point to the direct effect of the interaction of HFE with transferrin receptor in lowering the intracellular labile iron pool and establishing a new set point for iron regulation within the cell.

UR - http://www.scopus.com/inward/record.url?scp=0036135887&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036135887&partnerID=8YFLogxK

U2 - 10.1002/jcp.10056

DO - 10.1002/jcp.10056

M3 - Article

VL - 190

SP - 218

EP - 226

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 2

ER -