論文 - 詳細
| RRC ID | 63345 |
|---|---|
| 著者 | Lim PL, Tan W, Latchoumycandane C, Mok WC, Khoo YM, Lee HS, Sattabongkot J, Beerheide W, Lim SG, Tan TM, Boelsterli UA. |
| タイトル | Molecular and functional characterization of drug-metabolizing enzymes and transporter expression in the novel spontaneously immortalized human hepatocyte line HC-04. |
| ジャーナル | Toxicol In Vitro |
| Abstract |
In toxicological research, immortalized human hepatocytes provide a useful alternative to primary hepatocytes because interindividual variability in the expression of drug-metabolizing enzymes and drug transporters can largely be eliminated. However, it is essential that the cell line retain the original phenotype. The purpose of this study was to characterize a novel spontaneously immortalized human hepatocyte cell line, HC-04, with respect to the transcript and functional protein expression profile for the major drug-metabolizing enzymes and transmembrane transporters. HC-04 cells retained hepatocyte-specific function including albumin production and ornithine transcarbamoylase and glucose-6-phosphatase activity. Most of the major CYP forms were expressed at basal levels and responsive to inducing agents. In particular, CYP3A4 was expressed abundantly, and HC-04 cells were able to metabolize the CYP3A4 probe, midazolam, at a rate similar to primary human hepatocytes. Furthermore, the major human sulfotransferase and UDP-glucuronosyltransferase forms, as well as members of the ABC and SLC transporter superfamilies, nuclear receptors, and hepatic transcription factors were also expressed. HC-04 cells readily responded to standard hepatotoxicants that are dependent on CYP-mediated bioactivation, while another, tumor-derived cell line remained refractory to the drug challenge. Collectively, HC-04 cells provide a reliable, stable, and reproducible model for biomechanistic studies in drug toxicology. |
| 巻・号 | 21(8) |
| ページ | 1390-401 |
| 公開日 | 2007-12-1 |
| DOI | 10.1016/j.tiv.2007.05.003 |
| PII | S0887-2333(07)00156-7 |
| PMID | 17590308 |
| MeSH | Acetaminophen / metabolism Analgesics, Non-Narcotic / metabolism Anti-Inflammatory Agents, Non-Steroidal / metabolism Antifibrinolytic Agents / metabolism Biomarkers Carrier Proteins / genetics Carrier Proteins / metabolism* Cell Line Cytochrome P-450 Enzyme System / genetics Cytochrome P-450 Enzyme System / metabolism* Diclofenac / metabolism Gene Expression Profiling* Gene Expression Regulation* Hepatocytes / metabolism* Humans Vitamin K 3 / metabolism |
| IF | 2.959 |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 1 |
| 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 | |
| ヒト・動物細胞 | HuH-7(RCB1366) |