| First Author | Regan RF | Year | 2008 |
| Journal | Biochem Biophys Res Commun | Volume | 375 |
| Issue | 1 | Pages | 6-10 |
| PubMed ID | 18655771 | Mgi Jnum | J:139003 |
| Mgi Id | MGI:3807098 | Doi | 10.1016/j.bbrc.2008.07.061 |
| Citation | Regan RF, et al. (2008) Iron regulatory proteins increase neuronal vulnerability to hydrogen peroxide. Biochem Biophys Res Commun 375(1):6-10 |
| abstractText | 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. |
