Evaluation of human embryonic stem cell-derived hepatocyte-like cells for detection of CYP1A inducers.
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.
Department of Pharmacy, Shinshu University Hospital, Matsumoto, Japan.
Hiroyuki
H
Tsuchiya
Tamihide
T
Matsunaga
Kaori
K
Aikawa
Noboru
N
Kamada
Katsunori
K
Nakamura
Hinako
H
Ichikawa
Katsunori
K
Sasaki
Shigeru
S
Ohmori
D000328:Adult; D000418:Albumins / Q000378:metabolism; D000818:Animals; D001711:Biotransformation / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D055808:Drug Discovery; D053595:Embryonic Stem Cells / Q000737:chemistry* / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000737:chemistry* / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008875:Middle Aged; D009853:Omeprazole / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D000509:alpha-Fetoproteins / Q000235:genetics / Q000378:metabolism; D000099148:UGT1A1 Enzyme
D000418:Albumins; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D008748:Methylcholanthrene; D009853:Omeprazole; D012333:RNA, Messenger; D000509:alpha-Fetoproteins; D000099148:UGT1A1 Enzyme