Effects of extracellular matrix on the expression of peroxisomes in primary rat hepatocyte cultures

Background/Aims: Peroxisomes in wild-type cells vary between tissues and de velopmental stages. In the liver of some peroxisomal deficiency disorder pa tients, rare parenchymal cells express normal peroxisomes (mosaics); the me chanism is unknown. Our aim was to find factors regulating peroxisome expre ssion, Methods: Liver-specific as well as peroxisome characteristics were studied in three types of primary rat hepatocyte cultures, Results: Total glutathione e-transferase activity and albumin secretion bot h increased in the collagen I sandwich and immobilization gel cultures, In contrast, in monolayers cultured on plastic, total glutathione S-transferas e activity decreased and albumin secretion was only 30-40% compared to the collagen cultures, Glycogen rosettes typical of liver parenchymal cells wer e always abundant. Laminin and collagen IV-producing stellate cells were nu merous in the monolayer but almost absent in the sandwich cultures, In 6-da y-monolayer cultures, the number of liver-specific peroxisomes had decrease d while atypical small or elongated peroxisomes appeared. Immunolabeling de nsity for catalase and three beta-oxidation enzymes was decreased compared to adult rat liver; catalase specific activity in homogenates had dropped t o 15% and 4% in the sandwich and monolayer cultures, respectively. In 17-da y-sandwich cultures, some peroxisomes showed a very weak catalase reaction; total activity was 5%, Supplementation of the collagen type I cultures wit h several extracellular matrix factors could not prevent peroxisome dediffe rentiation, Conclusion: The presence of these extracellular matrix components is not su fficient for normal peroxisome expression. It is suggested that hepatocyte- specific and peroxisomal features are regulated differently. The sandwich p reserves hepatocyte differentiation better than the monolayer.