Project description:The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins TRX-2 and TRX-3 do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, SKN-1 transcriptional activity remains largely unaffected. Interestingly, RNA-Seq revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport and localization being most prevalent. However, one prominent lipase-related gene, lips-6, is highly up regulated upon loss of trx-1 in a skn-1-dependent manner. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism. Four samples were analyzed: Two nematode strains were analyzed, each under non-stressed and stressed (10mM NaAs) conditions
Project description:The Caenorhabditis elegans oxidative stress response transcription factor, SKN-1, is essential for the maintenance of redox homeostasis and is a functional ortholog of the Nrf family of transcription factors. The numerous levels of regulation that govern these transcription factors underscore their importance. Here, we add a thioredoxin, encoded by trx-1, to the expansive list of SKN-1 regulators. We report that loss of trx-1 promotes nuclear localization of intestinal SKN-1 in a redox-independent, cell non-autonomous fashion from the ASJ neurons. Furthermore, this regulation is not general to the thioredoxin family, as two other C. elegans thioredoxins TRX-2 and TRX-3 do not play a role in this process. Moreover, TRX-1-dependent regulation requires signaling from the p38 MAPK signaling pathway. However, while TRX-1 regulates SKN-1 nuclear localization, SKN-1 transcriptional activity remains largely unaffected. Interestingly, RNA-Seq revealed that loss of trx-1 elicits a general, organism-wide down-regulation of several classes of genes; those encoding for collagens and lipid transport and localization being most prevalent. However, one prominent lipase-related gene, lips-6, is highly up regulated upon loss of trx-1 in a skn-1-dependent manner. Together, these results uncover a novel role for a thioredoxin in regulating intestinal SKN-1 nuclear localization in a cell non-autonomous manner, thereby contributing to the understanding of the processes involved in maintaining redox homeostasis throughout an organism.
Project description:Oxidative stress may play a role in normal aging. SKN-1 is a transcription factor necessary for intestine development in Caenorhabditis elegans, which also regulates the response to oxidative stress post-embryonically. Using DNA microarrays, we found that oxidative stress induces the antioxidant response, the heat shock response, and detoxification genes, while the expression of genes involved in homeostasis, development, and reproduction were decreased. Both up-regulated and down-regulated genes can be wholly, partially, or not at all dependent on SKN-1 action. However, induction of the heat shock response by oxidative stress was not affected by SKN-1 removal. Keywords: stress response