Superoxide dismutase 1 modulates expression of transferrin receptor

  • Ruth Danzeisen
  • Tilmann Achsel
  • Ulrich Bederke
  • Mauro Cozzolino
  • Claudia Crosio
  • Alberto Ferri
  • Malte Frenzel
  • Edith Butler Gralla
  • Lea Huber
  • Albert Ludolph
  • Monica Nencini
  • Giuseppe Rotilio
  • Joan Selverstone Valentine
  • Maria Teresa Carrì
Original Paper

DOI: 10.1007/s00775-006-0099-4

Cite this article as:
Danzeisen, R., Achsel, T., Bederke, U. et al. J Biol Inorg Chem (2006) 11: 489. doi:10.1007/s00775-006-0099-4

Abstract

Copper–zinc superoxide dismutase (SOD1) plays a protective role against the toxicity of superoxide, and studies in Saccharomyces cerevisiae and in Drosophila have suggested an additional role for SOD1 in iron metabolism. We have studied the effect of the modulation of SOD1 levels on iron metabolism in a cultured human glial cell line and in a mouse motoneuronal cell line. We observed that levels of the transferrin receptor and the iron regulatory protein 1 were modulated in response to altered intracellular levels of superoxide dismutase activity, carried either by wild-type SOD1 or by an SOD-active amyotrophic lateral sclerosis (ALS) mutant enzyme, G93A-SOD1, but not by a superoxide dismutase inactive ALS mutant, H46R-SOD1. Ferritin expression was also increased by wild-type SOD1 overexpression, but not by mutant SOD1s. We propose that changes in superoxide levels due to alteration of SOD1 activity affect iron metabolism in glial and neuronal cells from higher eukaryotes and that this may be relevant to diseases of the nervous system.

Keywords

FerritinIron regulatory proteinIron metabolismOxidative stressSuperoxide dismutaseTransferrin receptor

Abbreviations

ALS

Amyotrophic lateral sclerosis

FALS

Familial amyotrophic lateral sclerosis

HEPES

N′-(2-Hydroxyethyl)piperazine-N′-ethanesulfonic acid

IRE

Iron responsive element

IRP

Iron regulatory protein

mRNA

Messenger RNA

mRNP

Messenger ribonucleoprotein

ROS

Reactive oxygen species

SDS

Sodium dodecyl sulfate

SOD

Superoxide dismutase

SOD1

Cu,Zn superoxide dismutase

SOD2

Exclusively mitochondrial, Mn-containing enzyme

SOD3

Extracellular Cu,Zn protein

TfR

Transferrin receptor

Tris

Tris(hydroxymethyl)aminomethane

Copyright information

© SBIC 2006

Authors and Affiliations

  • Ruth Danzeisen
    • 1
  • Tilmann Achsel
    • 2
  • Ulrich Bederke
    • 1
  • Mauro Cozzolino
    • 2
  • Claudia Crosio
    • 2
    • 3
  • Alberto Ferri
    • 2
    • 4
  • Malte Frenzel
    • 1
  • Edith Butler Gralla
    • 5
  • Lea Huber
    • 1
  • Albert Ludolph
    • 1
  • Monica Nencini
    • 2
  • Giuseppe Rotilio
    • 6
  • Joan Selverstone Valentine
    • 5
  • Maria Teresa Carrì
    • 2
    • 6
  1. 1.Department of NeurologyUniversity of UlmUlmGermany
  2. 2.Fondazione Santa Lucia IRCCSRomeItaly
  3. 3.DiFBCUniversity of SassariSassariItaly
  4. 4.Department of Psychobiology and PsychopharmacologyCNR Institute for NeuroscienceRomeItaly
  5. 5.Department of Chemistry and BiochemistryUCLALos AngelesUSA
  6. 6.Department of BiologyUniversity of Rome “Tor Vergata”RomeItaly