Xenobiotic metabolism and transport in <i>Caenorhabditis elegans</i>

Hartman, Jessica H.; Widmayer, Samuel J.; Bergemann, Christina M.; King, Dillon E.; Morton, Katherine; Romersi, Riccardo F.; Jameson, Laura E.; Leung, Maxwell C.K.; Andersen, Erik C.; Taubert, Stefan; Meyer, Joel N.

doi:10.1080/10937404.2021.1884921

Cited by 65 publications

(71 citation statements)

References 349 publications

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“…All showed robust induction, validating our RNAseq data (Figure 1D-J). XME induction was consistently observed in the intestine, in line with previous reports of detoxification functions in this tissue (Hartman et al, 2021). XME induction was also observed in other tissues, and most consistently in AMsh glial cells, which are components of the major sensory organ in the head of the animal (Singhvi and Shaham, 2019).…”

Section: Penicillium Brevicompactum Exposure Induces Expression Of Stress Response Genes Including Xenobiotic Metabolizing Enzymessupporting

confidence: 90%

“…XMEs in C. elegans have primarily been studied in the intestine (Hartman et al, 2021). In this study we have demonstrated that XMEs are also induced in AMsh glia following P. brevicompactum or Serratia marcescens exposure.…”

Section: Discussionmentioning

confidence: 60%

“…Xenobiotic metabolizing enzymes (XMEs) are major detoxification proteins encoded by cytochrome P450 (cyp), UDP-glucoronosyltransferase (ugt), and glutathione-s-transferase (gst) gene families (Hartman et al, 2021). 18 of the P. brevicompactum-induced genes encode XMEs (Figure 1C).…”

Section: Penicillium Brevicompactum Exposure Induces Expression Of Stress Response Genes Including Xenobiotic Metabolizing Enzymesmentioning

confidence: 99%

“…Xenobiotic metabolizing enzymes (XMEs) are key detoxification proteins that include phase I enzymes of the cytochrome P450 (cyp) family, and phase II enzymes of the UDPglucoronosyltransferase (ugt) and glutathione-s-transferase (gst) families (Hartman et al, 2021). XME functions have been extensively explored in the mammalian liver, where they play a major role in detoxification.…”

Section: Introductionmentioning

confidence: 99%

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Nuclear hormone receptors promote gut and glia detoxifying enzyme induction and protect C. elegans from the mold P. brevicompactum

Wallace

Lizzappi

Liang

et al. 2021

Preprint

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Animals encounter microorganisms in their habitats, adapting physiology and behavior accordingly. The nematode Caenorhabditis elegans is found in microbe-rich environments; however, its responses to fungi are not extensively studied. Here we describe interactions of C. elegans and Penicillium brevicompactum, an ecologically-relevant mold. Transcriptome studies reveal that co-culture upregulates stress-response genes, including xenobiotic metabolizing enzymes (XMEs), in C. elegans intestine and AMsh glial cells. The nuclear hormone receptors (NHR) NHR-45 and NHR-156 are key induction regulators, and mutants that cannot induce XMEs in the intestine when exposed to P. brevicompactum experience mitochondrial stress and exhibit developmental defects. Different C. elegans wild isolates harbor sequence polymorphisms in nhr-156, resulting in phenotypic diversity in AMsh glia responses to microbe exposure. We propose that P. brevicompactum mitochondria-targeting mycotoxins are deactivated by intestinal detoxification, allowing tolerance to moldy environments. Our studies support the idea that C. elegans NHR gene expansion/diversification underlies adaptation to microbial environments.

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Section: Penicillium Brevicompactum Exposure Induces Expression Of Stress Response Genes Including Xenobiotic Metabolizing Enzymessupporting

confidence: 90%

Section: Discussionmentioning

confidence: 60%

Section: Penicillium Brevicompactum Exposure Induces Expression Of Stress Response Genes Including Xenobiotic Metabolizing Enzymesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nuclear hormone receptors promote gut and glia detoxifying enzyme induction and protect C. elegans from the mold P. brevicompactum

Wallace

Lizzappi

Liang

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…For example, cytochrome P450 requires a heme cofactor and the coenzyme cytochrome P450 reductase. While emb-8 is the worm´s homolog to the human P450 reductase, worms are not able to synthesize heme and need to scavenge this component from their diet (Hartman et al 2021). Another metabolic difference can be found in the bioactivation of BaP, which causes the production of ROS and DNA adducts.…”

Section: Limitations Opportunities and Future Directionsmentioning

confidence: 99%

A fast and reliable method for monitoring genomic instability in the model organism Caenorhabditis elegans

et al. 2021

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The identification of genotoxic agents and their potential for genotoxic alterations in an organism is crucial for risk assessment and approval procedures of the chemical and pharmaceutical industry. Classically, testing strategies for DNA or chromosomal damage focus on in vitro and in vivo (mainly rodent) investigations. In cell culture systems, the alkaline unwinding (AU) assay is one of the well-established methods for detecting the percentage of double-stranded DNA (dsDNA). By establishing a reliable lysis protocol, and further optimization of the AU assay for the model organism Caenorhabditis elegans (C. elegans), we provided a new tool for genotoxicity testing in the niche between in vitro and rodent experiments. The method is intended to complement existing testing strategies by a multicellular organism, which allows higher predictability of genotoxic potential compared to in vitro cell line or bacterial investigations, before utilizing in vivo (rodent) investigations. This also allows working within the 3R concept (reduction, refinement, and replacement of animal experiments), by reducing and possibly replacing animal testing. Validation with known genotoxic agents (bleomycin (BLM) and tert-butyl hydroperoxide (tBOOH)) proved the method to be meaningful, reproducible, and feasible for high-throughput genotoxicity testing, and especially preliminary screening.

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The worm Adult Activity Test (wAAT): A de novo mathematical model for detecting acute chemical effects in Caenorhabditis elegans

Hunt

Welch

Camacho

et al. 2023

J of Applied Toxicology

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We have adapted a semiautomated method for tracking Caenorhabditis elegans spontaneous locomotor activity into a quantifiable assay by developing a sophisticated method for analyzing the time course of measured activity. The 16‐h worm Adult Activity Test (wAAT) can be used to measure C. elegans activity levels for efficient screening for pharmacological and toxicity‐induced effects. As with any apical endpoint assay, the wAAT is mode of action agnostic, allowing for detection of effects from a broad spectrum of response pathways. With caffeine as a model mild stimulant, the wAAT showed transient hyperactivity followed by reversion to baseline. Mercury chloride (HgCl2) produced an early dose–response hyperactivity phase followed by pronounced hypoactivity, a behavior pattern we have termed a toxicant “escape response.” Methylmercury chloride (meHgCl) produced a similar pattern to HgCl2, but at much lower concentrations, a weaker hyperactivity response, and more pronounced hypoactivity. Sodium arsenite (NaAsO2) and dimethylarsinic acid (DMA) induced hypoactivity at high concentrations. Acute toxicity, as measured by hypoactivity in C. elegans adults, was ranked: meHgCl > HgCl2 > NaAsO2 = DMA. Caffeine was not toxic with the wAAT at tested concentrations. Methods for conducting the wAAT are described, along with instructions for preparing C. elegans Habitation Medium, a liquid nutrient medium that allows for developmental timing equivalent to that found with C. elegans grown on agar with OP50 Escherichia coli feeder cultures. A de novo mathematical parametric model for adult C. elegans activity and the application of this model in ranking exposure toxicity are presented.

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Xenobiotic metabolism and transport in Caenorhabditis elegans

Cited by 65 publications

References 349 publications

Nuclear hormone receptors promote gut and glia detoxifying enzyme induction and protect C. elegans from the mold P. brevicompactum

Nuclear hormone receptors promote gut and glia detoxifying enzyme induction and protect C. elegans from the mold P. brevicompactum

A fast and reliable method for monitoring genomic instability in the model organism Caenorhabditis elegans

The worm Adult Activity Test (wAAT): A de novo mathematical model for detecting acute chemical effects in Caenorhabditis elegans

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