Abstract:
:The ability of cells to control the balance between the generation and quenching of reactive oxygen species is important in combating potentially damaging effects of oxidative stress. One mechanism that cells use to maintain redox homeostasis is the antioxidant response pathway. Antioxidant response elements (AREs) are cis-acting elements located in regulatory regions of antioxidant and phase II detoxification genes. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is a member of the Cap 'n' Collar family of transcription factors that binds to the ARE and regulates the transcription of specific ARE-containing genes such as NAD(P)H:quinone oxidoreductase 1, glutamylcysteine synthetase and heme oxygenase. Activation of Nrf2 results in release from its negative repressor, Kelch-like ECH-associated protein 1 (Keap1), and allows Nrf2 to translocate into the nucleus to induce gene expression. In this study, we demonstrate that increasing Nrf2 activity by various methods, including chemical induction, Nrf2 overexpression or Keap1 siRNA knockdown, protects cells against specific types of oxidative damage. Cells were protected against 6-hydroxydopamine- and 3-morpholinosydnonimine-mediated toxicity but not against 1-methyl-1-4-phenylpyridinium toxicity. As oxidative stress is a hallmark of several neurodegenerative disorders, including Parkinson's disease, pharmacological agents that selectively target the Keap1-Nrf2 pathway may provide a novel neuroprotective strategy for the treatment of these diseases.
journal_name
J Neurochemjournal_title
Journal of neurochemistryauthors
Cao TT,Ma L,Kandpal G,Warren L,Hess JF,Seabrook GRdoi
10.1111/j.1471-4159.2005.03377.xkeywords:
subject
Has Abstractpub_date
2005-10-01 00:00:00pages
406-17issue
2eissn
0022-3042issn
1471-4159pii
JNC3377journal_volume
95pub_type
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