RRC ID 1961
著者 Tsutsui M, Ogawa S, Inada Y, Tomioka E, Kamiyoshi A, Tanaka S, Kishida T, Nishiyama M, Murakami M, Kuroda J, Hashikura Y, Miyagawa S, Satoh F, Shibata N, Tagawa Y.
タイトル Characterization of cytochrome P450 expression in murine embryonic stem cell-derived hepatic tissue system.
ジャーナル Drug Metab Dispos
Abstract 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.
巻・号 34(4)
ページ 696-701
公開日 2006-4-1
DOI 10.1124/dmd.105.007674
PII dmd.105.007674
PMID 16415121
MeSH Animals Cell Differentiation Cell Line Cytochrome P-450 Enzyme System / genetics Cytochrome P-450 Enzyme System / metabolism* Embryo, Mammalian Hepatocytes / cytology Hepatocytes / drug effects Hepatocytes / enzymology Hydroxylation Isoenzymes / genetics Isoenzymes / metabolism Liver / cytology Liver / drug effects Liver / enzymology* Mice Phenobarbital / pharmacology Pluripotent Stem Cells / cytology Pluripotent Stem Cells / drug effects Pluripotent Stem Cells / enzymology* RNA, Messenger / metabolism Testosterone / metabolism Time Factors
IF 3.231
引用数 20
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 STO(RCB0536)