| First Author | Calkins MJ | Year | 2005 |
| Journal | Proc Natl Acad Sci U S A | Volume | 102 |
| Issue | 1 | Pages | 244-9 |
| PubMed ID | 15611470 | Mgi Jnum | J:95887 |
| Mgi Id | MGI:3527925 | Doi | 10.1073/pnas.0408487101 |
| Citation | Calkins MJ, et al. (2005) Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription. Proc Natl Acad Sci U S A 102(1):244-9 |
| abstractText | Complex II inhibitors 3-nitropropionic acid (3NP) and malonate cause striatal damage reminiscent of Huntington's disease and have been shown to involve oxidative stress in their pathogenesis. Because nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent transcriptional activation by means of the antioxidant response element is known to coordinate the up-regulation of cytoprotective genes involved in combating oxidative stress, we investigated the significance of Nrf2 in complex II-induced toxicity. We found that Nrf2-deficient cells and Nrf2 knockout mice are significantly more vulnerable to malonate and 3NP and demonstrate increased antioxidant response element (ARE)-regulated transcription mediated by astrocytes. Furthermore, ARE preactivation by means of intrastriatal transplantation of Nrf2-overexpressing astrocytes before lesioning conferred dramatic protection against complex II inhibition. These observations implicate Nrf2 as an essential inducible factor in the protection against complex II inhibitor-mediated neurotoxicity. These data also introduce Nrf2-mediated ARE transcription as a potential target of preventative therapy in neurodegenerative disorders such as Huntington's disease. |
