ArticleBiochemical and biophysical research communications2008
Iron regulatory proteins increase neuronal vulnerability to hydrogen peroxide.
Article in Biochemical and biophysical research communications, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 14 citations in OpenAlex.
- Deferoxamine deconditioning increases neuronal vulnerability to hemoglobin.Experimental cell research · 2020Article
- Brain Iron Metabolism Dysfunction in Parkinson's Disease.Molecular neurobiology · 2017Review
- Oxidative stress increases HO-1 expression in ARPE-19 cells, but melanosomes suppress the increase when light is the stressor.Investigative ophthalmology & visual science · 2013Article
- Iron regulatory protein-2 knockout increases perihematomal ferritin expression and cell viability after intracerebral hemorrhage.Brain research · 2010Article
- Minocycline attenuates iron neurotoxicity in cortical cell cultures.Biochemical and biophysical research communications · 2009Article
- Cysteine oxidation regulates the RNA-binding activity of iron regulatory protein 2.Molecular and cellular biology · 2009Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Iron regulatory protein (IRP)-1 and IRP2 inhibit ferritin synthesis by binding to an iron responsive element in the 5'-untranslated region of its mRNA. The present study tested the hypothesis that neurons lacking these proteins would be resistant to hydrogen peroxide (H(2)O(2)) toxicity. Wild-type cortical cultures treated with 100-300microM H(2)O(2) sustained widespread neuronal death, as measured by lactate dehydrogenase assay, and a significant increase in malondialdehyde. Both endpoints were reduced by over 85% in IRP2 knockout cultures. IRP1 gene deletion had a weaker and variable effect, with approximately 20% reduction in cell death at 300microM H(2)O(2). Ferritin expression after H(2)O(2) treatment was increased 1.9- and 6.7-fold in IRP1 and IRP2 knockout cultures, respectively, compared with wild-type. These results suggest that iron regulatory proteins, particularly IRP2, increase neuronal vulnerability to oxidative injury. Therapies targeting IRP2 binding to ferritin mRNA may attenuate neuronal loss due to oxidative stress.
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Registered trials
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