論文 - 詳細
| RRC ID | 45762 |
|---|---|
| 著者 | Jones LM, Flemming AJ, Urwin PE. |
| タイトル | NHR-176 regulates cyp-35d1 to control hydroxylation-dependent metabolism of thiabendazole in Caenorhabditis elegans. |
| ジャーナル | Biochem J |
| Abstract |
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. |
| 巻・号 | 466(1) |
| ページ | 37-44 |
| 公開日 | 2015-2-15 |
| DOI | 10.1042/BJ20141296 |
| PII | BJ20141296 |
| PMID | 25406993 |
| MeSH | ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism* Animals Anthelmintics / metabolism* Anthelmintics / pharmacology Biotransformation Caenorhabditis elegans / drug effects Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cytochrome P-450 Enzyme System / genetics Cytochrome P-450 Enzyme System / metabolism* Gene Expression Profiling Gene Expression Regulation Glucose / metabolism Hydroxylation Protein Isoforms / genetics Protein Isoforms / metabolism Receptors, Cytoplasmic and Nuclear / genetics Receptors, Cytoplasmic and Nuclear / metabolism* Thiabendazole / metabolism* Thiabendazole / pharmacology |
| IF | 4.097 |
| 引用数 | 14 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm0830 tm0333 |