Title | Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Oliveira RP, Abate JPorter, Dilks K, Landis J, Ashraf J, Murphy CT, T Blackwell K |
Journal | Aging Cell |
Volume | 8 |
Issue | 5 |
Pagination | 524-41 |
Date Published | 2009 09 |
ISSN | 1474-9726 |
Keywords | Animals, Arsenites, Caenorhabditis elegans, Caenorhabditis elegans Proteins, DNA, Helminth, DNA-Binding Proteins, Down-Regulation, Gene Expression Regulation, Longevity, NF-E2-Related Factor 1, Oligonucleotide Array Sequence Analysis, Reactive Oxygen Species, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, RNA, Messenger, tert-Butylhydroperoxide, Transcription Factors, Transcription, Genetic |
Abstract | 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. |
DOI | 10.1111/j.1474-9726.2009.00501.x |
Alternate Journal | Aging Cell |
Full Text | |
PubMed ID | 19575768 |
PubMed Central ID | PMC2776707 |
Grant List | GM70088 / GM / NIGMS NIH HHS / United States DK07260 / DK / NIDDK NIH HHS / United States GM62891 / GM / NIGMS NIH HHS / United States T32 DK007260 / DK / NIDDK NIH HHS / United States F32 GM070088 / GM / NIGMS NIH HHS / United States R01 GM062891-09 / GM / NIGMS NIH HHS / United States R01 GM062891 / GM / NIGMS NIH HHS / United States |