Toxicological assessment of chemicals using <i>Caenorhabditis elegans</i> and optical oxygen respirometry

Schouest, Katherine; Zitova, Alice; Spillane, Charles; Papkovsky, Dmitri B.

doi:10.1897/08-083.1

Cited by 26 publications

(13 citation statements)

References 38 publications

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“…C. elegans is a model organism for research in the fields of developmental biology, molecular biology, neurobiology and toxicology [38-40]. Here, we showed that C. elegans can also be used as a model organism for hypoxia studies.…”

Section: Discussionmentioning

confidence: 88%

A proteomic view of Caenorhabditis elegans caused by short-term hypoxic stress

Ren

Shi

et al. 2010

Proteome Sci

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BackgroundThe nematode Caenorhabditis elegans is both sensitive and tolerant to hypoxic stress, particularly when the evolutionarily conserved hypoxia response pathway HIF-1/EGL-9/VHL is involved. Hypoxia-induced changes in the expression of a number of genes have been analyzed using whole genome microarrays in C. elegans, but the changes at the protein level in response to hypoxic stress still remain unclear.ResultsHere, we utilized a quantitative proteomic approach to evaluate changes in the expression patterns of proteins during the early response to hypoxia in C. elegans. Two-dimensional difference gel electrophoresis (2D-DIGE) was used to compare the proteomic maps of wild type C. elegans strain N2 under a 4-h hypoxia treatment (0.2% oxygen) and under normoxia (control). A subsequent analysis by MALDI-TOF-TOF-MS revealed nineteen protein spots that were differentially expressed. Nine of the protein spots were significantly upregulated, and ten were downregulated upon hypoxic stress. Three of the upregulated proteins were involved in cytoskeletal function (LEV-11, MLC-1, ACT-4), while another three upregulated (ATP-2, ATP-5, VHA-8) were ATP synthases functionally related to energy metabolism. Four ribosomal proteins (RPL-7, RPL-8, RPL-21, RPS-8) were downregulated, indicating a decrease in the level of protein translation upon hypoxic stress. The overexpression of tropomyosin (LEV-11) was further validated by Western blot. In addition, the mutant strain of lev-11(x12) also showed a hypoxia-sensitive phenotype in subsequent analyses, confirming the proteomic findings.ConclusionsTaken together, our data suggest that altered protein expression, structural protein remodeling, and the reduction of translation might play important roles in the early response to oxygen deprivation in C. elegans, and this information will help broaden our knowledge on the mechanism of hypoxia response.

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Section: Discussionmentioning

confidence: 88%

A proteomic view of Caenorhabditis elegans caused by short-term hypoxic stress

Ren

Shi

et al. 2010

Proteome Sci

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“…Lethality was evaluated as the percent survival of the population based on a previously described method [32]. Fifty L1 larvae stage C. elegans were treated with different concentrations of HAEIBS for 48 hours.…”

Section: Methodsmentioning

confidence: 99%

Adverse Effects of Hydroalcoholic Extracts and the Major Components in the Stems of Impatiens balsamina L. on Caenorhabditis elegans

Hongfang

Zhuang

Hou³

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Impatiens balsamina L. (Balsaminaceae), an annual herb found throughout China, has been extensively used in traditional Chinese medicine (TCM). However, our knowledge regarding the adverse effects of I. balsamina in vivo is very limited. In this present study, the nematode Caenorhabditis elegans model was employed to fully assess the adverse effects of hydroalcoholic (EtOH 55%) extracts of I. balsamina stems (HAEIBS) in vivo. After exposure to 10 mg/mL HAEIBS, the major organism-level endpoints of C. elegans of percent survival, frequency of head thrash and body bends, and reproduction had decreased by 24%, 30%, and 25%, respectively. The lifespan of C. elegans was also greatly reduced after HAEIBS exposure compared to the controls. The active compounds in HAEIBS were separated using high speed countercurrent chromatograph (HSCCC) and characterized by high performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Two compounds, lawsone and 2-methoxy-1,4-naphthoquinone (MNQ), and their adverse effects were then more thoroughly detailed in this study. It was found that lawsone is the major toxin in HAEIBS with a higher toxicity than MNQ in terms of negative impact on C. elegans mortality, locomotion, reproduction, and lifespan. Our data also suggests that the C. elegans model may be useful for assessing the possible toxicity of other Chinese medicines, plant extracts, and/or compounds.

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“…While the majority of applications of optical O 2 micro-respirometry and OCR measurement are cell-based, the method has also been adapted for the monitoring of small aquatic organisms including Daphnia magna, Artemia salina, copepod Tigriopus, zebrafish Danio rerio [3,4]. These model organisms can be used to perform rapid, high-throughput biological testing of potentially hazardous chemicals and environmental samples, as well as basic biological and physiological studies.…”

Section: Respiration Of Small Organisms and Model Animalsmentioning

confidence: 99%

“…This invertebrate organism easily maintained under laboratory conditions is an attractive model for toxicology studies as it is sensitive to a wide range of toxicants, including heavy metals, organic phosphates and pesticides. Such studies have established C. elegans as a powerful model for rapid testing of the toxicity of soil and water samples as well as pharmaceutical compounds [53].…”

Section: Respiration Of Small Organisms and Model Animalsmentioning

confidence: 99%

“…Measurements are typically performed on adherent or suspension cell populations in microplate format. The method can also be applied to other specimens including aquatic organisms and model animals (such as C. elegans, Artemia, Zebrafish, Daphnia) [3,4], and on more specialised measurement formats such as customised microplates [5], capillary cuvettes [6] or fluidic biochips [7].…”

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confidence: 99%

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O2 Analysis on a Fluorescence Spectrometer or Plate Reader

Zhdanov

Hynes

Dmitriev

2012

Phosphorescent Oxygen-Sensitive Probes

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In this chapter, the use of Pt-porphyrin-based extracellular and intracellular O 2 sensing probes (ecO 2 and icO 2 ) on a TR-F plate reader format is described and critically assessed. The principles underpinning extracellular measurement are outlined and the assessment of biological oxygen consumption in prokaryotic cells, eukaryotic cells and small organisms is outlined along with a description of how such measurements can contribute to the development of a detailed picture of cell metabolism. The use of a mathematical model describing the distribution of local O 2 gradients within biological samples is also described. Finally, the principles of icO 2 sensing are discussed and some short case studies are provided for demonstrating the utility of icO 2 probes for the monitoring of cellular function and metabolic perturbations and how such measurements can be allied to other bioenergetic markers to generate a more complete picture of metabolic status.

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Toxicological assessment of chemicals using Caenorhabditis elegans and optical oxygen respirometry

Cited by 26 publications

References 38 publications

A proteomic view of Caenorhabditis elegans caused by short-term hypoxic stress

A proteomic view of Caenorhabditis elegans caused by short-term hypoxic stress

Adverse Effects of Hydroalcoholic Extracts and the Major Components in the Stems of Impatiens balsamina L. on Caenorhabditis elegans

O2 Analysis on a Fluorescence Spectrometer or Plate Reader

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