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The Antioxidant Defense System Keap1-Nrf2 Comprises a Multiple Sensing Mechanism for Responding to a Wide Range of Chemical Compounds▿ †
- Publication Year :
- 2008
- Publisher :
- American Society for Microbiology (ASM), 2008.
-
Abstract
- application/pdf<br />Animals have evolved defense systems for surviving in a chemically diverse environment. Such systems should demonstrate plasticity, such as adaptive immunity, enabling a response to even unknown chemicals. The antioxidant transcription factor Nrf2 is activated in response to various electrophiles and induces cytoprotective enzymes that detoxify them. We report here the discovery of a multiple sensing mechanism for Nrf2 activation using zebrafish and 11 Nrf2-activating compounds. First, we showed that six of the compounds tested specifically target Cys-151 in Keap1, the ubiquitin ligase for Nrf2, while two compounds target Cys-273. Second, in addition to Nrf2 and Keap1, a third factor was deemed necessary for responding to three of the compounds. Finally, we isolated a zebrafish mutant defective in its response to seven compounds but not in response to the remaining four. These results led us to categorize Nrf2 activators into six classes and hypothesize that multiple sensing allows enhanced plasticity in the system.
- Subjects :
- Transcriptional Activation
Embryo, Nonmammalian
NF-E2-Related Factor 2
Mutant
Response Elements
digestive system
environment and public health
Antioxidants
Animals
Cysteine
Molecular Biology
Zebrafish
Transcription factor
Regulation of gene expression
biology
Mechanism (biology)
Prostaglandin D2
Maleates
Cell Biology
Articles
Hydrogen Peroxide
respiratory system
Zebrafish Proteins
Acquired immune system
biology.organism_classification
KEAP1
Ubiquitin ligase
Oxidative Stress
Biochemistry
Gene Expression Regulation
Glutathione S-Transferase pi
Mutation
biology.protein
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING
Carrier Proteins
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....0363e66bf91d10c38abe4e20916bca79