Condition-adapted stress and longevity gene regulation byCaenorhabditis elegansSKN-1/Nrf
| Autor: | Riva de Paula Oliveira, Jessica N. Landis, Jess Porter Abate, Coleen T. Murphy, T. Keith Blackwell, Jasmine Ashraf, Kieran Dilks |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Aging
Transcription Genetic GeneralLiterature_INTRODUCTORYANDSURVEY Arsenites Longevity NF-E2-Related Factor 1 Down-Regulation Biology DNA-binding protein Article tert-Butylhydroperoxide RNA interference Animals RNA Messenger Caenorhabditis elegans Caenorhabditis elegans Proteins GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) Gene Transcription factor Oligonucleotide Array Sequence Analysis Genetics Regulation of gene expression Reverse Transcriptase Polymerase Chain Reaction Promoter Cell Biology DNA Helminth biology.organism_classification Cell biology DNA-Binding Proteins Gene expression profiling Gene Expression Regulation RNA Interference Reactive Oxygen Species Transcription Factors |
| Zdroj: | Aging Cell. 8:524-541 |
| ISSN: | 1474-9726 1474-9718 |
| DOI: | 10.1111/j.1474-9726.2009.00501.x |
| Popis: | Studies in model organisms have identified regulatory processes that profoundly influence aging, many of which modulate resistance against environmental or metabolic stresses. In Caenorhabditis elegans, the transcription regulator SKN-1 is important for oxidative stress resistance and acts in multiple longevity pathways. SKN-1 is the ortholog of mammalian Nrf proteins, which induce Phase 2 detoxification genes in response to stress. Phase 2 enzymes defend against oxygen radicals and conjugate electrophiles that are produced by Phase 1 detoxification enzymes, which metabolize lipophilic compounds. Here, we have used expression profiling to identify genes and processes that are regulated by SKN-1 under normal and stress-response conditions. Under nonstressed conditions SKN-1 upregulates numerous genes involved in detoxification, cellular repair, and other functions, and downregulates a set of genes that reduce stress resistance and lifespan. Many of these genes appear to be direct SKN-1 targets, based upon presence of predicted SKN-binding sites in their promoters. The metalloid sodium arsenite induces skn-1-dependent activation of certain detoxification gene groups, including some that were not SKN-1-upregulated under normal conditions. An organic peroxide also triggers induction of a discrete Phase 2 gene set, but additionally stimulates a broad SKN-1-independent response. We conclude that under normal conditions SKN-1 has a wide range of functions in detoxification and other processes, including modulating mechanisms that reduce lifespan. In response to stress, SKN-1 and other regulators tailor transcription programs to meet the challenge at hand. Our findings reveal striking complexity in SKN-1 functions and the regulation of systemic detoxification defenses. |
| Databáze: | OpenAIRE |
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