Allyl Isothiocyanate that Induces GST and UGT Expression Confers Oxidative Stress Resistance on C. elegans, as Demonstrated by Nematode Biosensor

Hasegawa, Koichi; Miwa, Satsuki; Tsutsumiuchi, Kaname; Miwa, Johji

doi:10.1371/journal.pone.0009267

Cited by 47 publications

(34 citation statements)

References 46 publications

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“…elegans with life span extension often show enhanced resistance to thermal and oxidative stress [10], suggesting that worms fed the GD1 diet would also demonstrate stress resistance. Juglone is a quinone that imposes both oxidative and electrophilic stress [27,28]. Juglone penetrates the worm cuticle and has been used to select for oxidative stress-resistant mutants [29].…”

Section: Resultsmentioning

confidence: 99%

Delayed accumulation of intestinal coliform bacteria enhances life span and stress resistance in Caenorhabditis elegans fed respiratory deficient E. coli

et al. 2012

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BackgroundStudies with the nematode model Caenorhabditis elegans have identified conserved biochemical pathways that act to modulate life span. Life span can also be influenced by the composition of the intestinal microbiome, and C. elegans life span can be dramatically influenced by its diet of Escherichia coli. Although C. elegans is typically fed the standard OP50 strain of E. coli, nematodes fed E. coli strains rendered respiratory deficient, either due to a lack coenzyme Q or the absence of ATP synthase, show significant life span extension. Here we explore the mechanisms accounting for the enhanced nematode life span in response to these diets.ResultsThe intestinal load of E. coli was monitored by determination of worm-associated colony forming units (cfu/worm or coliform counts) as a function of age. The presence of GFP-expressing E. coli in the worm intestine was also monitored by fluorescence microscopy. Worms fed the standard OP50 E. coli strain have high cfu and GFP-labeled bacteria in their guts at the L4 larval stage, and show saturated coliform counts by day five of adulthood. In contrast, nematodes fed diets of respiratory deficient E. coli lacking coenzyme Q lived significantly longer and failed to accumulate bacteria within the lumen at early ages. Animals fed bacteria deficient in complex V showed intermediate coliform numbers and were not quite as long-lived. The results indicate that respiratory deficient Q-less E. coli are effectively degraded in the early adult worm, either at the pharynx or within the intestine, and do not accumulate in the intestinal tract until day ten of adulthood.ConclusionsThe findings of this study suggest that the nematodes fed the respiratory deficient E. coli diet live longer because the delay in bacterial colonization of the gut subjects the worms to less stress compared to worms fed the OP50 E. coli diet. This work suggests that bacterial respiration can act as a virulence factor, influencing the ability of bacteria to colonize and subsequently harm the animal host. Respiratory deficient bacteria may pose a useful model for probing probiotic relationships within the gut microbiome in higher organisms.

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Section: Resultsmentioning

confidence: 99%

Delayed accumulation of intestinal coliform bacteria enhances life span and stress resistance in Caenorhabditis elegans fed respiratory deficient E. coli

et al. 2012

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“…The only enriched "Molecular Function" (MF) GO term found for this compartment was "transferase activity, transferring hexosyl groups" (GO:0016758; p ϭ 1.5 ϫ 10 Ϫ5 ; Table II), an activity common among genes highly or exclusively expressed in the nematode intestine, for a variety of purposes including maintaining bacterial flora, producing mucin and modulating fat storage (4). Interpro domain enrichment testing showed that "UDP-glucuronosyl/UDP-glucosyltransferase" domains were the most significantly enriched among IIM proteins (IPR002213; p ϭ 3.3 ϫ 10 Ϫ4 ; Table III); UDP-glycosyltransferases are found in all living organisms, and in C. elegans they are primarily responsible for the detoxification of foreign compounds (65,66). The IIM proteins were also enriched for many ABC transporter domain-containing proteins (Table III) that affect the absorption, distribution, and elimination of xenobiotics, including known anthelmintic drugs (67,68).…”

Section: Functional Enrichment Analyses Reveal Known and Novel Functimentioning

confidence: 99%

Functional and Phylogenetic Characterization of Proteins Detected in Various Nematode Intestinal Compartments*

Rosa

Townsend

Jasmer

et al. 2015

Molecular & Cellular Proteomics

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The parasitic nematode intestine is responsible for nutrient digestion and absorption, and many other processes essential for reproduction and survival, making it a valuable target for anthelmintic drug treatment. However, nematodes display extreme biological diversity (including occupying distinct trophic habitats), resulting in limited knowledge of intestinal cell/protein functions of fundamental or adaptive significance. We developed a perfusion model for isolating intestinal proteins in Ascaris suum (a parasite of humans and swine), allowing for the identification of over 1000 intestinal A. suum proteins (using mass spectrometry), which were assigned to several different intestinal cell compartments (intestinal tissue, the integral and peripheral intestinal membranes, and the intestinal lumen). A multi-omics analysis approach identified a large diversity of biological functions across intestinal compartments, based on both functional enrichment analysis (identifying terms related to detoxification, proteolysis, and host-parasite interactions) and regulatory binding sequence analysis to identify putatively active compartment-specific transcription factors (identifying many related to intestinal sex differentiation or lifespan regulation). Orthologs of A. suum proteins in 15 other nematodes species, five host species, and two outgroups were identified and analyzed. Different cellular compartments demonstrated markedly different levels of protein conservation; e.g. integral intestinal membrane proteins were the most conserved among nematodes (up to 96% conservation), whereas intestinal lumen proteins were the most diverse (only 6% conservation across all nematodes, and 71% with no host orthologs). Finally, this integrated multi-omics analysis identified conserved nematode-specific intestinal proteins likely performing essential functions (including V-type ATPases and ABC transporters), which may serve as promising anthelmintic drug or vaccine targets in future research. Collectively, the findings provide valuable new insights on conserved and adaptive features of nematode intestinal cells, membranes and the intestinal lumen, and potential targets for parasite treatment and control. Molecular & Cellular

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“…Differential interference contrast and high-magnification fluorescent images were taken of worms with an Olympus BX60 microscope. Fluorescence was quantified from the photomicrographs with a nematode image analyzer FL (v1.0.0.1) as described previously (http://www.vision .cs.chubu.ac.jp/fl1001/ [33]). …”

Section: Yeast Assaysmentioning

confidence: 99%

Direct Interaction between the WD40 Repeat Protein WDR-23 and SKN-1/Nrf Inhibits Binding to Target DNA

Leung

Hasegawa

Wang

et al. 2014

Molecular and Cellular Biology

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c SKN-1/Nrf transcription factors activate cytoprotective genes in response to reactive small molecules and strongly influence stress resistance, longevity, and development. The molecular mechanisms of SKN-1/Nrf regulation are poorly defined. We previously identified the WD40 repeat protein WDR-23 as a repressor of Caenorhabditis elegans SKN-1 that functions with a ubiquitin ligase to presumably target the factor for degradation. However, SKN-1 activity and nuclear accumulation are not always correlated, suggesting that there could be additional regulatory mechanisms. Here, we integrate forward genetics and biochemistry to gain insights into how WDR-23 interacts with and regulates SKN-1. We provide evidence that WDR-23 preferentially regulates one of three SKN-1 variants through a direct interaction that is required for normal stress resistance and development. Homology modeling predicts that WDR-23 folds into a ␤-propeller, and we identify the top of this structure and four motifs at the termini of SKN-1c as essential for the interaction. Two of these SKN-1 motifs are highly conserved in human Nrf1 and Nrf2 and two directly interact with target DNA. Lastly, we demonstrate that WDR-23 can block the ability of SKN-1c to interact with DNA sequences of target promoters identifying a new mechanism of regulation that is independent of the ubiquitin proteasome system, which can become occupied with damaged proteins during stress.

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Allyl Isothiocyanate that Induces GST and UGT Expression Confers Oxidative Stress Resistance on C. elegans, as Demonstrated by Nematode Biosensor

Cited by 47 publications

References 46 publications

Delayed accumulation of intestinal coliform bacteria enhances life span and stress resistance in Caenorhabditis elegans fed respiratory deficient E. coli

Delayed accumulation of intestinal coliform bacteria enhances life span and stress resistance in Caenorhabditis elegans fed respiratory deficient E. coli

Functional and Phylogenetic Characterization of Proteins Detected in Various Nematode Intestinal Compartments*

Direct Interaction between the WD40 Repeat Protein WDR-23 and SKN-1/Nrf Inhibits Binding to Target DNA

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