Document Detail


Evaluation of human embryonic stem cell-derived hepatocyte-like cells for detection of CYP1A inducers.
MedLine Citation:
PMID:  22673034     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There is a great deal of interest in differentiation of human embryonic stem cells (hESCs) into hepatocyte-like cells for application in pharmaceutical screening. Cytochrome P450 (CYP) 1A is involved in the metabolic activation of procarcinogenic compounds as well as in detoxification of drugs. We differentiated hESCs into hepatocyte-like cells (hESC-derived hepatocyte-like cells) and examined whether CYP1A was induced in these cells by typical inducers of CYP1A. hESC-derived hepatocyte-like cells expressed albumin, α-fetoprotein, CYP3A4, CYP3A7, CYP1A1, CYP1A2, and UDP-glucuronyl transferase (UGT) 1A1 mRNA. The levels of CYP1A1, CYP1A2, and UGT1A1 mRNA expression were increased by omeprazole and 3-methylcholanthrene. Furthermore, the enzyme activity of CYP1A was also increased by these compounds. In conclusion, hESC-derived hepatocyte-like cells are available for the detection of CYP1A inducers.
Authors:
Hiroyuki Tsuchiya; Tamihide Matsunaga; Kaori Aikawa; Noboru Kamada; Katsunori Nakamura; Hinako Ichikawa; Katsunori Sasaki; Shigeru Ohmori
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-29
Journal Detail:
Title:  Drug metabolism and pharmacokinetics     Volume:  27     ISSN:  1880-0920     ISO Abbreviation:  Drug Metab. Pharmacokinet.     Publication Date:  2012  
Date Detail:
Created Date:  2012-12-27     Completed Date:  2013-09-03     Revised Date:  2014-03-28    
Medline Journal Info:
Nlm Unique ID:  101164773     Medline TA:  Drug Metab Pharmacokinet     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  598-604     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Albumins / metabolism
Animals
Biotransformation / drug effects,  genetics
Cell Differentiation / drug effects,  genetics
Cell Line
Cytochrome P-450 CYP1A1 / biosynthesis*,  genetics,  metabolism
Cytochrome P-450 CYP1A2 / genetics,  metabolism
Cytochrome P-450 CYP3A / genetics,  metabolism
Cytochrome P-450 Enzyme System / metabolism
Drug Discovery
Embryonic Stem Cells / chemistry*,  cytology*,  drug effects,  enzymology
Enzyme Induction / drug effects
Glucuronosyltransferase / genetics,  metabolism
Hepatocytes / chemistry*,  cytology*,  drug effects,  enzymology
Humans
Male
Metabolic Detoxication, Drug
Methylcholanthrene / pharmacology
Mice
Middle Aged
Omeprazole / pharmacology
RNA, Messenger / genetics
alpha-Fetoproteins / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Albumins; 0/RNA, Messenger; 0/alpha-Fetoproteins; 56-49-5/Methylcholanthrene; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.1/Cytochrome P-450 CYP1A1; EC 1.14.14.1/Cytochrome P-450 CYP1A2; EC 1.14.14.1/Cytochrome P-450 CYP3A; EC 2.4.1.-/UGT1A1 enzyme; EC 2.4.1.17/Glucuronosyltransferase; KG60484QX9/Omeprazole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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