Superoxide dismutase 1 modulates expression of transferrin receptor |
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| Authors: | 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 |
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| Affiliation: | (1) Department of Neurology, University of Ulm, Ulm, Germany;(2) Fondazione Santa Lucia IRCCS, Rome, Italy;(3) DiFBC, University of Sassari, Sassari, Italy;(4) Department of Psychobiology and Psychopharmacology, CNR Institute for Neuroscience, Rome, Italy;(5) Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095-1569, USA;(6) Department of Biology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00133 Rome, Italy |
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| 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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| Keywords: | Ferritin Iron regulatory protein Iron metabolism Oxidative stress Superoxide dismutase Transferrin receptor |
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