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Trichostatin A Enhances Gap Junctional Intercellular Communication in Primary Cultures of Adult Rat Hepatocytes

Vinken, Mathieu ; Henkens, Tom ; Vanhaecke, Tamara ; Papeleu, Peggy ; Geerts, Albert ; Van Rossen, Elke ; Chipman, James Kevin ; Meda, Paolo ; Rogiers, Vera

In: Toxicological Sciences, 2006, vol. 91, no. 2, p. 484-492

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    Title
    • Trichostatin A Enhances Gap Junctional Intercellular Communication in Primary Cultures of Adult Rat Hepatocytes
    Author
    • Vinken, Mathieu. Department of Toxicology, Vrije Universiteit Brussel, B-1090 Brussels, Belgium
    • Henkens, Tom. Department of Toxicology, Vrije Universiteit Brussel, B-1090 Brussels, Belgium
    • Vanhaecke, Tamara. Department of Toxicology, Vrije Universiteit Brussel, B-1090 Brussels, Belgium
    • Papeleu, Peggy. Department of Toxicology, Vrije Universiteit Brussel, B-1090 Brussels, Belgium
    • Geerts, Albert. Department of Cell Biology, Vrije Universiteit Brussel, B-1090 Brussels, Belgium
    • Van Rossen, Elke. Department of Cell Biology, Vrije Universiteit Brussel, B-1090 Brussels, Belgium
    • Chipman, James Kevin. School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom; and
    • Meda, Paolo. Department of Cell Physiology and Metabolism, CMU Université de Genève, CH-1211 Genève 4, Switzerland
    • Rogiers, Vera. Department of Toxicology, Vrije Universiteit Brussel, B-1090 Brussels, Belgium
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Toxicological Sciences, 2006, vol. 91, no. 2, p. 484-492. Oxford University Press
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:296643
    Summary
    The effects of histone deacetylase inhibitor Trichostatin A (TSA) on connexin (Cx) expression and gap junctional intercellular communication (GJIC) were investigated in primary cultures of adult rat hepatocytes. GJIC was monitored by using the scrape-loading/dye transfer method. Immunoblotting and immunocytochemistry were used to investigate Cx protein levels and localization. Cx gene expression was studied by means of quantitative reverse transcriptase-polymerase chain reaction. TSA increased Cx32 protein levels and affected negatively the Cx26 protein levels. The latter was preferentially located in the cytosol of cultured cells. TSA also promoted the appearance of Cx43 in the nuclear compartment of primary cultured hepatocytes. Overall, this resulted in enhanced GJIC activity. It is important to note that the time of onset of TSA treatment was crucial for the extent of its outcome and that the effects of TSA on Cx protein levels occurred independently of transcriptional changes. TSA differentially affects Cx proteins in primary rat hepatocyte cultures, suggesting distinct regulation and/or distinct roles of the different Cx species in the control of hepatic homeostasis. TSA enhances GJIC between primary cultured rat hepatocytes, an interesting finding supporting its use to further optimize liver-based in vitro models for pharmacotoxicological purposes