CYP35: Xenobiotically induced gene expression in the nematode Caenorhabditis elegans

Menzel, Ralph; Rödel, Matthias; Kulas, Jana; Steinberg, Christian E. W.

doi:10.1016/j.abb.2005.03.020

Cited by 100 publications

(85 citation statements)

References 48 publications

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“…The cyp-35-family is known to be inducible by xenobiotics (Menzel et al 2005a). The same is visible with several gst-genes, and one cdr-and ugt-gene each.…”

Section: Resultsmentioning

confidence: 99%

Organic carbon source in formulated sediments influences life traits and gene expression of Caenorhabditis elegans

et al. 2011

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River water quality is strongly influenced by their sediments and their associated pollutants. To assess the toxic potential of sediments, sediment toxicity tests require reliable control sediments, potentially including formulated control sediments as one major option. Although some standardization has been carried out, one critical issue still remains the quality of sediment organic matter (SOM). Organic carbon not only binds hydrophobic contaminants, but may be a source of mild toxicity, even if the SOM is essentially uncontaminated. We tested two different sources of organic carbon and the mixture of both (Sphagnum peat (P) and one commercial humic substances preparation-HuminFeed(®), HF) in terms of life trait variables and expression profiles of selected life performance and stress genes of the nematode Caenorhabditis elegans. In synchronous cultures, gene expression profiling was done after 6 and 48 h, respectively. The uncontaminated Sphagnum P reduced growth, but increased numbers of offspring, whereas HF did not significantly alter life trait variables. The 6 h expression profile showed most of the studied stress genes repressed, except for slight to strong induction in cyp-35B1 (all exposures), gst-38 (only mixture), and small hsp-16 genes (all exposures). After 48 h, the expression of almost all studied genes increased, particularly genes coding for antioxidative defense, multiple xenobiotic resistance, vitellogenin-like proteins, and genes regulating lifespan. Overall, even essentially uncontaminated SOM may induce several modes of action on the molecular level in C. elegans which may lead to false results if testing synthetic xenobiotics. This contribution is a plea for a strict standardization of the SOM quality in formulated sediments and to check for corresponding effects in other model sediment organisms, especially if using molecular toxicity endpoints.

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“…The cyp-35-family is known to be inducible by xenobiotics (Menzel et al 2005a). The same is visible with several gst-genes, and one cdr-and ugt-gene each.…”

Section: Resultsmentioning

confidence: 99%

Organic carbon source in formulated sediments influences life traits and gene expression of Caenorhabditis elegans

et al. 2011

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“…[22][23][24][25][26] The cytochrome p450 monooxygenases responsible for production of the EETs and EpOMEs are present in the genome, though few have been characterized. [27][28][29] Finally, C. elegans contain arachidonic acid and linoleic acid, the precursors of these signaling molecules. [30,31] The genome of C. elegans contains five enzymes which display significant sequence similarity to the mammalian sEH.…”

Section: Introductionmentioning

confidence: 99%

Identification of two epoxide hydrolases in Caenorhabditis elegans that metabolize mammalian lipid signaling molecules

Harris

Aronov

Jones

et al. 2008

Archives of Biochemistry and Biophysics

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We have identified two genes in the genomic database for C. elegans that code for proteins with significant sequence similarity to the mammalian soluble epoxide hydrolase (sEH). The respective transcripts were cloned from a mixed stage cDNA library from C. elegans. The corresponding proteins obtained after recombinant expression in insect cells hydrolyzed standard epoxide hydrolase substrates, including epoxyeicosatrienoic acids (EETs) and leukotoxins (EpOMEs). The enzyme activity was inhibited by urea-based compounds originally designed to inhibit the mammalian sEH. In vivo inhibition of the enzymes using the most potent of these compounds resulted in elevated levels of the EpOMEs in the nematode. These results suggest that the hydrolases are involved in the metabolism of possible lipid signaling molecules in C. elegans.

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“…Furthermore, an expansion in the CYP superfamily is present in insects and nematodes with 90 CYPs being predicted in Drosophila [4] and 83 in Caenorhabditis elegans [5]. Earlier studies have shown that some members of cellular metabolism gene families, particularly the CYPs, are highly inducible in C. elegans by a range of small organic molecules [6][7][8]. We have recently shown that members of the CYP family are also induced by thiabendazole [TBZ; 2-(4-thiazolyl)-1H-benzimidazole] in C. elegans and that the most inducible CYP with the highest expression and for the longest duration is regulated by nhr-176 [9].…”

Section: Introductionmentioning

confidence: 99%

NHR-176 regulates cyp-35d1 to control hydroxylation-dependent metabolism of thiabendazole in Caenorhabditis elegans

Jones

Flemming

Urwin

2015

Biochemical Journal

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Knowledge of how drugs are metabolized and excreted is an essential component of understanding their fate within and among target and non-target organisms. Thiabendazole (TBZ) was the first benzimidazole (BZ) to be commercially available and remains one of the most important anthelmintic drugs for medical and veterinary use. We have characterized how Caenorhabditis elegans metabolizes and excretes TBZ. We have shown that TBZ directly binds to the nuclear hormone receptor (NHR)-176 and that this receptor is required for the induction by TBZ of the cytochrome P450 (CYP) encoded by cyp-35d1. Further, RNAi inhibition of cyp-35d1 in animals exposed to TBZ causes a reduction in the quantity of a hydroxylated TBZ metabolite and its glucose conjugate that is detected in C. elegans tissue by HPLC. This final metabolite is unique to nematodes and we also identify two P-glycoproteins (PGPs) necessary for its excretion. Finally, we have shown that inhibiting the metabolism we describe increases the susceptibility of C. elegans to TBZ in wild-type and in resistant genetic backgrounds.

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CYP35: Xenobiotically induced gene expression in the nematode Caenorhabditis elegans

Cited by 100 publications

References 48 publications

Organic carbon source in formulated sediments influences life traits and gene expression of Caenorhabditis elegans

Organic carbon source in formulated sediments influences life traits and gene expression of Caenorhabditis elegans

Identification of two epoxide hydrolases in Caenorhabditis elegans that metabolize mammalian lipid signaling molecules

NHR-176 regulates cyp-35d1 to control hydroxylation-dependent metabolism of thiabendazole in Caenorhabditis elegans

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