Increased Antioxidant Response Research Articles

Protection from mitochondrial complex II inhibitionin vitroandin vivoby Nrf2-mediated transcription

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.

Antioxidant response modulated by copper in healthy or parasitized carp ( Cyprinus carpio L.) by Ptychobothrium sp. (Cestoda)

An increased antioxidant response (catalase, glutathione S-transferase (GST) and glutathione reductase (GRd) activities in liver and GST activity in head kidney) was observed in carp parasitized by Ptychobothrium sp. compared to healthy fish. In case of a copper contamination of these fish, the decrease in enzymatic activities observed was less pronounced in parasitized than in healthy carp.