Caenorhabditis elegans
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PROVIDER: PRJNA102949 | ENA |
REPOSITORIES: ENA
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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
2007-11-01 | GSE9301 | GEO
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
2016-04-01 | E-GEOD-77976 | biostudies-arrayexpress
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.
2016-04-01 | GSE77976 | GEO
Project description:Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that generates free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. Mammalian NF-E2-related factor 2 (Nrf2) and its C. elegans ortholog SKN-1, mediate protective responses to oxidative stress by promoting target gene expression via antioxidant response elements (ARE). Genetic analyses showed that skn-1 mediates plumbagin’s lifespan-extending effect in C. elegans. Further screening of a series of plumbagin analogs identified three additional naphthoquinones that could induce SKN-1 targets in C. elegans. Naphthazarin showed skn-1-dependent lifespan extension, over an extended dose range compared to plumbagin, while the other naphthoquinones, oxoline and menadione, had differing effects on C. elegans survival and failed to activate ARE reporter expression in cultured mammalian cells. Our findings reveal the potential for low doses of naturally occurring naphthoquinones to extend lifespan by engaging a specific adaptive cellular stress response pathway.
2012-03-21 | GSE28301 | GEO
Project description:Reactive Oxygen Species increase gradually with aging and Steadily diminish the cell's ability to maintain homeostasis. Nuclear Factor-like 2 and its C elegans ortholog, SKN-1 are transcription factors that play a pivotal role in oxidative stress response, cellular homeostasis and lifespan. But like other defence systems, Nrf2-mediated stress response is compromised in aging and neurodegenerative diseases. In this study we provide evidence that this FDA-approved drug is a bona fide activator of Nrf2/SKN-1 pathway.
2016-12-21 | MSV000080435 | MassIVE
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. Experiment Overall Design: TJ1060 was grown at 16 ï°C. Eggs were collected by hypochlorite, hatched overnight at 20 ï°C (Emmons, 1979 #52) and first-stage larvae (L1âs) were placed onto 2 % peptone plates (1.7 % agar, 20 g/l peptone, 25 mM NaCl, 50 mM KH2PO4 pH 6.0, 5 µg/ml cholesterol, 1 mM CaCl2, 1 mM MgSO4) at 25 ï°C. Sterile 3 day old young adult animals on peptone plates were treated with 99 % O2 at 40 PSI for 6 hours at 20 ï°C in a hyperbaric O2 chamber. Half of the worms were untreated and served as a control population. A small plate of strain CL2166 [dvIs19 pAF15(gst-4::GFP::NLS)] was used as an indicator strain and checked for GFP induction in both control and experimental conditions. Worms were harvested by washing off plates with S-basal and quick frozen in liquid nitrogen. Total RNA was prepared using TRIZOL reagent and standard protocols and cleaned up on Qiagen RNeasy columns. The Affymetrix labeling kit was used to prepare labeled cRNA as a target for the Affymetrix GeneChip® C.elegans Genome Array. Gene chip hybridization and scanning were done at Genome Explorations (Memphis, MN) and the University of Colorado at Boulder Gene Chip Core Facility (Boulder, CO).
2008-06-16 | E-GEOD-9301 | biostudies-arrayexpress
Project description:While screening our in-house 1,072 marketed drugs for their ability to extend the lifespan using Caenorhabditis elegans (C. elegans) as an animal model, crotamiton (N-ethyl-o-crotonotoluidide) showed anti-aging activity and was selected for further structural optimization. After replacing the ortho-methyl of crotamiton with ortho-fluoro, crotamiton derivative JM03 was obtained and showed better activity in terms of lifespan-extension and stress resistance than crotamiton. It was further explored that JM03 extended the lifespan of C. elegans through osmotic avoidance abnormal-9 (OSM-9). Besides, JM03 improves the ability of nematode to resist oxidative stress and hypertonic stress through OSM-9, but not osm-9/capsaicin receptor related-2 (OCR-2). Then the inhibition of OSM-9 by JM03 reduces the aggregation of Q35 in C. elegans via upregulating the genes associated with proteostasis. SKN-1 signaling was also found to be activated after JM03 treatment, which might contribute to proteostasis, stress resistance and lifespan extension. In summary, this study explored a new small molecule derived from crotamiton, which has efficient anti-oxidative, anti-hypertonic and anti-aging effects, and could further lead to promising application prospects.
2022-04-10 | GSE200459 | GEO
Project description:HIF-1 and SKN-1 Coordinate the Transcriptional Response to Hydrogen Sulfide in C. elegans
| PRJNA134311 | ENA
Project description:While screening our in-house 1,072 marketed drugs for their ability to extend the lifespan using Caenorhabditis elegans (C. elegans) as an animal model, crotamiton (N-ethyl-o-crotonotoluidide) showed anti-aging activity and was selected for further structural optimization. After replacing the ortho-methyl of crotamiton with ortho-fluoro, crotamiton derivative JM03 was obtained and showed better activity in terms of lifespan-extension and stress resistance than crotamiton. It was further explored that JM03 extended the lifespan of C. elegans through osmotic avoidance abnormal-9 (OSM-9). Besides, JM03 improves the ability of nematode to resist oxidative stress and hypertonic stress through OSM-9, but not osm-9/capsaicin receptor related-2 (OCR-2). Then the inhibition of OSM-9 by JM03 reduces the aggregation of Q35 in C. elegans via upregulating the genes associated with proteostasis. SKN-1 signaling was also found to be activated after JM03 treatment, which might contribute to proteostasis, stress resistance and lifespan extension. In summary, this study explored a new small molecule derived from crotamiton, which has efficient anti-oxidative, anti-hypertonic and anti-aging effects, and could further lead to promising application prospects.
2021-09-17 | GSE184076 | GEO
Project description:The WDR-23 protein regulates the transcription factor SKN-1 directly. C. elegans wdr-23 mutants have highly active SKN-1 and are stress resistant, long-lived, small, and reproduce poorly. We used microarrays to measure global gene expression in wdr-23 mutants and to indentify genes regulated by SKN-1.
2020-09-01 | GSE73101 | GEO