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Titolo:
Expression and induction of a large set of drug-metabolizing enzymes by the highly differentiated human hepatoma cell line BC2
Autore:
Gomez-Lechon, MJ; Donato, T; Jover, R; Rodriguez, C; Ponsoda, X; Glaise, D; Castell, JV; Guguen-Guillouzo, C;
Indirizzi:
Hosp U La Fe, Ctr Invest, Unidad Hepatol Expt, Valencia 46009, Spain Hosp U La Fe Valencia Spain 46009 ad Hepatol Expt, Valencia 46009, Spain Fac Biol, Dept Parasitol & Biol Celular, Burjassot, Spain Fac Biol Burjassot Spain ept Parasitol & Biol Celular, Burjassot, Spain Hop Pontchaillou, INSERM, U522, Rennes, France Hop Pontchaillou Rennes France ntchaillou, INSERM, U522, Rennes, France
Titolo Testata:
EUROPEAN JOURNAL OF BIOCHEMISTRY
fascicolo: 5, volume: 268, anno: 2001,
pagine: 1448 - 1459
SICI:
0014-2956(200103)268:5<1448:EAIOAL>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT HEPATOCYTES; HUMAN-LIVER; IN-VITRO; CYCLE PROGRESSION; NUCLEAR FACTOR-4; GENE-EXPRESSION; PRIMARY CULTURE; GROWTH-FACTOR; HEPG2 CELLS; CYTOCHROME-P450;
Keywords:
conjugating enzymes; cytochrome P-450; differentiation; hepatoma cell line; transcription factors;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
67
Recensione:
Indirizzi per estratti:
Indirizzo: Gomez-Lechon, MJ Hosp U La Fe, Ctr Invest, Unidad Hepatol Expt, Avda Campanar 21, Valencia 46009, Spain Hosp U La Fe Avda Campanar 21 Valencia Spain46009 Spain
Citazione:
M.J. Gomez-Lechon et al., "Expression and induction of a large set of drug-metabolizing enzymes by the highly differentiated human hepatoma cell line BC2", EUR J BIOCH, 268(5), 2001, pp. 1448-1459

Abstract

The BC2 cell line derived from the human hepatocarcinoma, HGB, undergoes aspontaneous sharp differentiation process in culture as it becomes confluent, remains stably differentiated for several weeks, and may return to proliferation thereafter under appropriate density conditions. The relevance ofthe line as an hepatic model has been evaluated. Cells synthesize a large number of plasma proteins, and rates of glycogen and urea synthesis increase with time of confluency and become sensitive to insulin, reflecting the process of differentiation. Differentiated BC2 cells express the most relevant cytochrome P-450 (CYP) isozyme activities (CYP1A1/2, 2A6, 2B6, 2C9, 2E1,and 3A4) and conjugating enzymes (glutathione S-transferase and UDP-glucuronyltransferase) and also respond to model inducers. Methylcholanthrene induced an increase in CYP1A1/2 enzyme activity (eightfold), phenobarbital induced CYP2B6 activity (1.7-fold), and dexamethasone induced CYP3A4 activity (fivefold). In parallel, expression of the most relevant liver-enriched transcription factors, HNF-4, HNF-1, C/EBP-alpha and C/EBP-beta mRNAs, was significantly increased in differentiated cultures. This increase was largest in HNF-1 and HNF-4, which supports the idea that a redifferentiation process towards the hepatic phenotype takes place. BC2 is an hepatic cell line that is able to express most hepatic functions, especially the drug-biotransformation function, far more efficiently than any previously described humanhepatoma cell line.

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Documento generato il 29/03/20 alle ore 03:02:31