論文 - 詳細
| RRC ID | 53353 |
|---|---|
| 著者 | Papaluca A, Ramotar D. |
| タイトル | A novel approach using C. elegans DNA damage-induced apoptosis to characterize the dynamics of uptake transporters for therapeutic drug discoveries. |
| ジャーナル | Sci Rep |
| Abstract |
Organic cation transporter (OCT) function is critical for cellular homeostasis. C. elegans lacking OCT-1 displays a shortened lifespan and increased susceptibility to oxidative stress. We show that these phenotypes can be rescued by downregulating the OCT-1 paralogue, OCT-2. Herein, we delineate a biochemical pathway in C. elegans where uptake of genotoxic chemotherapeutics such as doxorubicin and cisplatin, and subsequent DNA damage-induced apoptosis of germ cells, are dependent exclusively upon OCT-2. We characterized OCT-2 as the main uptake transporter for doxorubicin, as well as a number of other therapeutic agents and chemical compounds, some identified through ligand-protein docking analyses. We provide insights into the conserved features of the structure and function and gene regulation of oct-1 and oct-2 in distinct tissues of C. elegans. Importantly, our innovative approach of exploiting C. elegans uptake transporters in combination with defective DNA repair pathways will have broad applications in medicinal chemistry. |
| 巻・号 | 6 |
| ページ | 36026 |
| 公開日 | 2016-10-27 |
| DOI | 10.1038/srep36026 |
| PII | srep36026 |
| PMID | 27786254 |
| PMC | PMC5081529 |
| MeSH | Animals Apoptosis* Caenorhabditis elegans / drug effects* Caenorhabditis elegans Proteins DNA Damage* Drug Discovery / methods* Membrane Transport Proteins / deficiency* Mutagens / metabolism* Organic Cation Transporter 2 / metabolism* |
| IF | 3.998 |
| 引用数 | 9 |
| 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 | 2 |
| 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 | tm6691 |