Histone deacetylase inhibitors: opening a new field of research in the development of alternative methods ?

Vera Rogiers, Mathieu Vinken, Sarah Snykers, Tom Henkens, Joanna Fraczek, Evelien De Rop, Joery De Kock, Yordanova Doktorova Tatyana, Aneta Lukaszuk, Dirk Tourwé, Tamara Vanhaecke

Research output: Contribution to journalArticle

Abstract

In the present study, the ability of the hydroxamate histone deacetylase (HDAC) inhibitor 4-Me2N-BAVAH (5-(4-dimethylaminobenzoyl)-aminovaleric acid hydroxamate) to prevent dedifferentiation in cultures of primary hepatocytes is investigated. To this end, rat hepatocytes were isolated in the presence of 50uM 4-Me2N-BAVAH and exposure was subsequently continued for 7 days in monolayer culture (0.05% v/v ethanol-exposed cultures served as vehicle controls). It was found that in the continuous presence of 4-Me2NBAVAH, albumin secretion into the culture medium was 2.9- and 5.3-fold higher when compared to the control results after 4 and 7 days of cultivation, respectively. CYP1A1 was re-expressed after 4 days culture, but declined again thereafter, whilst CYP2B1 protein levels were maintained throughout the culture time in 4-Me2N-BAVAH-treated cells. In addition, pro-caspase-3 cleavage was significantly reduced after 7 days, pointing to decreased apoptosis and thus improved survival in the 4-Me2N-BAVAH-exposed hepatocytes. These findings provide additional evidence that HDAC inhibitors could play a major role in the preservation of the differentiated hepatic phenotype in vitro.
Original languageEnglish
Pages (from-to)613-617
Number of pages5
JournalAATEX
Issue number14
Publication statusPublished - 31 Mar 2008

Keywords

  • histone deacetylase inhibitor
  • primary hepatocyte
  • long-term culture
  • dedifferentiation
  • in vitro methods
  • alternative methods

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