CHARACTERIZATION OF CYTOCHROME P450 EXPRESSION IN MURINE EMBRYONIC STEM CELL-DERIVED HEPATIC TISSUE SYSTEM
| Autor: | Eisuke Tomioka, Junji Kuroda, Nobuo Shibata, Yoh-ichi Tagawa, Yoichi Inada, Masahiko Nishiyama, Makoto Murakami, Shinichi Miyagawa, Yasuhiko Hashikura, Tomoyuki Kishida, Masaru Tsutsui, Satoru Tanaka, Shinichiro Ogawa, Fumiyasu Satoh, Akiko Kamiyoshi |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Pluripotent Stem Cells
Time Factors genetic structures Liver cytology Cellular differentiation Pharmaceutical Science Hydroxylation Cell Line Mice Cytochrome P-450 Enzyme System Animals Testosterone RNA Messenger Induced pluripotent stem cell Pharmacology biology Cytochrome P450 Cell Differentiation Embryo Mammalian Embryonic stem cell eye diseases Cell biology Isoenzymes Liver Biochemistry Cell culture Phenobarbital Hepatocytes biology.protein Stem cell Drug metabolism |
| Zdroj: | Drug Metabolism and Disposition. 34:696-701 |
| ISSN: | 1521-009X 0090-9556 |
| Popis: | An in vitro system for liver organogenesis from murine embryonic stem (ES) cells has been recently established. This system is expected to be applied to the development of a new drug metabolism assay system that uses ES cells as a substitute for animal experiments. The objective of this study was to elucidate the drug metabolism profiles of the murine ES cell-derived hepatic tissue system compared with those of primary cultures of murine adult and fetal hepatocytes. The expression of the genes of the cytochrome P450 (P450) family, such as Cyp2a5, Cyp2b10, Cyp2c29, Cyp2d9, Cyp3a11, and Cyp7a1, was observed in the murine ES cell-derived hepatic tissue system at 16 days and 18 days after plating (A16 and A18). To investigate the activities of these P450 family enzymes in the murine ES cell-derived hepatic tissue system at A16 and A18, testosterone metabolism in this system was analyzed. Testosterone was hydroxylated to 6beta-hydroxytestosterone (6beta-OHT), 16alpha-OHT, 2alpha-OHT, and 2beta-OHT in this system, and was not hydroxylated to 15alpha-OHT, 7alpha-OHT, and 16beta-OHT. This metabolism profile was similar to that of fetal hepatocytes and different from that of adult hepatocytes. Furthermore, pretreatment with phenobarbital resulted in a 2.5- and 2.6-fold increase in the production of 6beta-OHT and 16beta-OHT. Thus, evidence for drug metabolic activities in relation to P450s has been demonstrated in this system. These results in this system would be a stepping stone of the research on the development and differentiation to adult liver. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|