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.
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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
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Acknowledgements
We are grateful to Luisa Rossi and Laura Scarino for helpful discussion, to Cecile Bouton and Cedric Fosset for supplying the IRE plasmid pSPT-fer and for help in establishing the band-shift assay protocol and to Neil R. Cashman for the gift of the original NSC34 cell line. We are indebted to Evamaria Görz for invaluable technical support. This work was supported by Telethon (GGP030066 to M.T.C.), by Deutsche Forschungsgemeinschaft (grant DA 559/2-1 to R.D.), by GIF (German–Israeli Foundation for Scientific Research and Development; grant no. 2066-1212.2/2002 to R.D.), Min. Salute (RF Malattie Neurodegenerative to M.T.C.), and a National Institutes of Health grant DK46828 to J.S.V.
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Danzeisen, R., Achsel, T., Bederke, U. et al. Superoxide dismutase 1 modulates expression of transferrin receptor. J Biol Inorg Chem 11, 489–498 (2006). https://doi.org/10.1007/s00775-006-0099-4
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DOI: https://doi.org/10.1007/s00775-006-0099-4