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Hepatocyte Polarity and the Peroxisomal Compartment: A Comparative Study

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Abstract

In search of factors that regulate the phenotype of the peroxisomal compartment in wild-type liver parenchymal cells, we compared hepatocyte polarity to peroxisome differentiation, using adult liver as the standard. Differentiation parameters were evaluated in a three-dimensional culture model (spheroid), in 'sandwich' and monolayer primary hepatocyte cultures, and in 15.5 and 18.5-day-old foetal rat liver.

Peroxisomes, studied by immunohistochemistry, enzyme histochemistry, and catalase specific activity, were better differentiated depending on foetal age (day 18.5 > day 15.5) and culture type (spheroid > sandwich > monolayer). The hepatocyte polarity markers ATP-, ADP-, and AMP-hydrolysing activities were, in all models, mislocalized at the lateral plasma membrane, whereas in contrast the multidrug resistance-associated protein 2 (mrp2) antigen was always correctly immunolocalized at the apical membrane domain. In cultures, the correct secretion of fluorescein (mrp2-mediated) into bile canaliculi was observed. Bile canaliculi (branching, ultrastructure and immunolocalization of the tight-junction associated protein ZO-1), were better differentiated in 18.5 than in 15.5-day-old foetal liver and in spheroid > sandwich > monolayer cultures.

Our results show a parallelism between changes of the peroxisomal compartment and bile canalicular structure together with mrp2-mediated secretory function. Distinct polarization characteristics do not necessarily change simultaneously, suggesting different regulatory mechanisms.

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Authors and Affiliations

  1. Department of Human Anatomy, Embryology, Histology, and Medical Physics, Ghent University, Godshuizenlaan 4, B-9000, Gent, Belgium

    Marianne Depreter, Ingrid Kerckaert & Frank Roels

  2. GlaxoSmithKline, Cellular and Biochemical Toxicology, In Vitro Models, Park Road B2, Ware, SG12 0DP, UK

    Tracy Walker

  3. Department of Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090, Brussel, Belgium

    Karen De Smet, Sonja Beken & Vera Rogiers

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  1. Marianne Depreter
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Depreter, M., Walker, T., De Smet, K. et al. Hepatocyte Polarity and the Peroxisomal Compartment: A Comparative Study. Histochem J 34, 139–151 (2002). https://doi.org/10.1023/A:1020990414190

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