Iron deficiency upregulates Egr1 expression

Seung-Min Lee, Sun Bok Lee, Ron Prywes, Christopher D. Vulpe

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Iron-deficient anemia is a prevalent disease among humans. We searched for genes regulated by iron deficiency and its regulated mechanism. cDNA microarrays were performed using Hepa1c1c7 cells treated with 100 μM desferrioxamine (DFO), an iron chelator. Early growth response 1 (Egr1) was upregulated with at least 20-fold increase within 4 h and lasted for 24 h, which was confirmed by qRT-PCR. This activation was not seen by ferric ammonium citrate (FAC). DFO increased the transcriptional activity of Egr1-luc (−604 to +160) and serum response element (SRE)-luc reporters by 2.7-folds. In addition, cycloheximide lowered DFO-induced Egr1 mRNA levels. The upregulation of Egr1 by DFO was accompanied by sustained ERK signals along with phosphorylation of Elk-1. The ERK inhibitor (PD98059) prevented the DFO-induced Egr1 mRNAs. Overexpression of Elk-1 mutant (pElk-1S383A) decreased Egr1 reporter activity. DFO lowered reactive oxygen species (ROS) production and increased caspase 3/7 activity and cell death. DFO-induced iron deficiency upregulates Egr1 in part through transcriptional activation via ERK and Elk-1 signals, which may be important in the regulation of cell death in hepatoma cells. Our study demonstrated that iron depletion controlled the expression of Egr1, which might contribute to decisions about cellular fate in response to iron deficiency.

Original languageEnglish
Article number3
JournalGenes and Nutrition
Volume10
Issue number4
DOIs
Publication statusPublished - 2015 Jul 22

Fingerprint

Deferoxamine
Up-Regulation
Iron
Growth
Cell Death
Serum Response Element
Caspase 7
Messenger RNA
Cycloheximide
Chelating Agents
Oligonucleotide Array Sequence Analysis
Caspase 3
Transcriptional Activation
Anemia
Hepatocellular Carcinoma
Reactive Oxygen Species
Phosphorylation
Polymerase Chain Reaction
Genes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Genetics

Cite this

Lee, Seung-Min ; Lee, Sun Bok ; Prywes, Ron ; Vulpe, Christopher D. / Iron deficiency upregulates Egr1 expression. In: Genes and Nutrition. 2015 ; Vol. 10, No. 4.
@article{e4d4dda9669f492fb2020946e8e44ff1,
title = "Iron deficiency upregulates Egr1 expression",
abstract = "Iron-deficient anemia is a prevalent disease among humans. We searched for genes regulated by iron deficiency and its regulated mechanism. cDNA microarrays were performed using Hepa1c1c7 cells treated with 100 μM desferrioxamine (DFO), an iron chelator. Early growth response 1 (Egr1) was upregulated with at least 20-fold increase within 4 h and lasted for 24 h, which was confirmed by qRT-PCR. This activation was not seen by ferric ammonium citrate (FAC). DFO increased the transcriptional activity of Egr1-luc (−604 to +160) and serum response element (SRE)-luc reporters by 2.7-folds. In addition, cycloheximide lowered DFO-induced Egr1 mRNA levels. The upregulation of Egr1 by DFO was accompanied by sustained ERK signals along with phosphorylation of Elk-1. The ERK inhibitor (PD98059) prevented the DFO-induced Egr1 mRNAs. Overexpression of Elk-1 mutant (pElk-1S383A) decreased Egr1 reporter activity. DFO lowered reactive oxygen species (ROS) production and increased caspase 3/7 activity and cell death. DFO-induced iron deficiency upregulates Egr1 in part through transcriptional activation via ERK and Elk-1 signals, which may be important in the regulation of cell death in hepatoma cells. Our study demonstrated that iron depletion controlled the expression of Egr1, which might contribute to decisions about cellular fate in response to iron deficiency.",
author = "Seung-Min Lee and Lee, {Sun Bok} and Ron Prywes and Vulpe, {Christopher D.}",
year = "2015",
month = "7",
day = "22",
doi = "10.1007/s12263-015-0468-0",
language = "English",
volume = "10",
journal = "Genes and Nutrition",
issn = "1555-8932",
publisher = "Springer Verlag",
number = "4",

}

Iron deficiency upregulates Egr1 expression. / Lee, Seung-Min; Lee, Sun Bok; Prywes, Ron; Vulpe, Christopher D.

In: Genes and Nutrition, Vol. 10, No. 4, 3, 22.07.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Iron deficiency upregulates Egr1 expression

AU - Lee, Seung-Min

AU - Lee, Sun Bok

AU - Prywes, Ron

AU - Vulpe, Christopher D.

PY - 2015/7/22

Y1 - 2015/7/22

N2 - Iron-deficient anemia is a prevalent disease among humans. We searched for genes regulated by iron deficiency and its regulated mechanism. cDNA microarrays were performed using Hepa1c1c7 cells treated with 100 μM desferrioxamine (DFO), an iron chelator. Early growth response 1 (Egr1) was upregulated with at least 20-fold increase within 4 h and lasted for 24 h, which was confirmed by qRT-PCR. This activation was not seen by ferric ammonium citrate (FAC). DFO increased the transcriptional activity of Egr1-luc (−604 to +160) and serum response element (SRE)-luc reporters by 2.7-folds. In addition, cycloheximide lowered DFO-induced Egr1 mRNA levels. The upregulation of Egr1 by DFO was accompanied by sustained ERK signals along with phosphorylation of Elk-1. The ERK inhibitor (PD98059) prevented the DFO-induced Egr1 mRNAs. Overexpression of Elk-1 mutant (pElk-1S383A) decreased Egr1 reporter activity. DFO lowered reactive oxygen species (ROS) production and increased caspase 3/7 activity and cell death. DFO-induced iron deficiency upregulates Egr1 in part through transcriptional activation via ERK and Elk-1 signals, which may be important in the regulation of cell death in hepatoma cells. Our study demonstrated that iron depletion controlled the expression of Egr1, which might contribute to decisions about cellular fate in response to iron deficiency.

AB - Iron-deficient anemia is a prevalent disease among humans. We searched for genes regulated by iron deficiency and its regulated mechanism. cDNA microarrays were performed using Hepa1c1c7 cells treated with 100 μM desferrioxamine (DFO), an iron chelator. Early growth response 1 (Egr1) was upregulated with at least 20-fold increase within 4 h and lasted for 24 h, which was confirmed by qRT-PCR. This activation was not seen by ferric ammonium citrate (FAC). DFO increased the transcriptional activity of Egr1-luc (−604 to +160) and serum response element (SRE)-luc reporters by 2.7-folds. In addition, cycloheximide lowered DFO-induced Egr1 mRNA levels. The upregulation of Egr1 by DFO was accompanied by sustained ERK signals along with phosphorylation of Elk-1. The ERK inhibitor (PD98059) prevented the DFO-induced Egr1 mRNAs. Overexpression of Elk-1 mutant (pElk-1S383A) decreased Egr1 reporter activity. DFO lowered reactive oxygen species (ROS) production and increased caspase 3/7 activity and cell death. DFO-induced iron deficiency upregulates Egr1 in part through transcriptional activation via ERK and Elk-1 signals, which may be important in the regulation of cell death in hepatoma cells. Our study demonstrated that iron depletion controlled the expression of Egr1, which might contribute to decisions about cellular fate in response to iron deficiency.

UR - http://www.scopus.com/inward/record.url?scp=84929460489&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929460489&partnerID=8YFLogxK

U2 - 10.1007/s12263-015-0468-0

DO - 10.1007/s12263-015-0468-0

M3 - Article

VL - 10

JO - Genes and Nutrition

JF - Genes and Nutrition

SN - 1555-8932

IS - 4

M1 - 3

ER -