Linked Life Data

19575768

Source:http://linkedlifedata.com/resource/pubmed/id/19575768

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-9-25
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1474-9726
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
524-41
pubmed:dateRevised
2010-9-2
pubmed:meshHeading
pubmed-meshheading:19575768-Animals, pubmed-meshheading:19575768-Arsenites, pubmed-meshheading:19575768-Caenorhabditis elegans, pubmed-meshheading:19575768-Caenorhabditis elegans Proteins, pubmed-meshheading:19575768-DNA, Helminth, pubmed-meshheading:19575768-DNA-Binding Proteins, pubmed-meshheading:19575768-Down-Regulation, pubmed-meshheading:19575768-Gene Expression Regulation, pubmed-meshheading:19575768-Longevity, pubmed-meshheading:19575768-NF-E2-Related Factor 1, pubmed-meshheading:19575768-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:19575768-RNA, Messenger, pubmed-meshheading:19575768-RNA Interference, pubmed-meshheading:19575768-Reactive Oxygen Species, pubmed-meshheading:19575768-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19575768-Transcription, Genetic, pubmed-meshheading:19575768-Transcription Factors, pubmed-meshheading:19575768-tert-Butylhydroperoxide
pubmed:year
2009
pubmed:articleTitle
Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf.
pubmed:affiliation
Section on Developmental and Stem Cell Biology, Joslin Diabetes Center, Department of Pathology, Harvard Medical School, Harvard Stem Cell Institute, One Joslin Place, Boston, MA 02215, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural