Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN.
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Date
2009
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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.
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Keywords
Aging, Caenorhabditis elegans, Insulin signaling, Detoxification
Citation
OLIVEIRA, R. de P. et al. Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN. Aging Cell, v. 8, p. 524-541, 2009. Disponível em: <http://onlinelibrary.wiley.com/doi/10.1111/j.1474-9726.2009.00501.x/abstract>. Acesso em: 20 de jul. 2017.