Changes in the Catalytic Activities of Proteoglycan-Degrading Lysosomal Enzymes in Parenchymal and Non-Parenchymal Liver Cells and in Serum During the Development of Experimental Liver Fibrosis

Abstract

Summary:The catalytic activities of 4 glycosidases (hyaluronate-4-glycanohydrolase (EC 3.2.1.35), ß-Nacetyl-D-glucosaminidase (EC 3.2.1.30), ß-glucuronidase (EC 3.2.1.31), -L-iduronidase (EC 3.2.1.76)), of the arylsulphatases A and B (EC 3.1.6.1) and of the protease cathepsin D (EC 3.4.23.5) were measured in extracts from hepatocytes and non-parenchymal cells and in serum during the development of thioacetamideinduced rat liver fibrosis (22 weeks). In non-parenchymal liver cells the catalytic activities of ß-N-acetyl-Dglucosaminidase, ß-glucuronidase, -L-iduronidase and cathepsin D were increased significantly during chronic liver damage, but that of hyaluronate-4-glycanohydrolase was reduced by 40 to 65% during the period of applicätion of thioacetamide. The catalytic activities of the arylsulphatases were lowered by 65% compared to control values in the 12th week but with advancing liver damage the catalytic activities returned to nearly normal values. Parenchymal cells of rats, which had been liver-damaged for 6 months, contained strongly elevated activities of ß-glucuronidase, ß-N-acetyl-D-glucosaminidase, arylsulphatases A and B, and cathepsin D but only slightly increased activities of hyaluronate-4-glycanohydrolase and -L-iduronidase, respectively. In the serum of liver-damaged rats the activity of -L-iduronidase was strongly elevated, while that of Nacetyl-ß-D-glucosaminidase was only slightly increased. The activities of ß-glucuronidase and of arylsulphatases A and B were decreased during the whole period of treatment. The catalytic functions of hyaluronate-4-glycanohydrolase and of cathepsin D, respectively, were decreased initially, but both enzyme activities were elevated during the more advanced stages of long term thioacetamide treatment. Aktivitätsänderungen Proteoglykan^abbauender^ lysosomaler Enzyme in Parenchym-und Nicht-Parenchymzellen der Leber sowie im Serum während der Entwicklung einer experimentellen LeberfibroseZusammenfassung: Die katalytischen Aktivitäten von vier Glykosidasen (Hyaluronat-4-glykanohydrolase (EC 3.2.1.35), ß-N-Acetyl-D-glucosaminidase (EC 3.2.1.30), ß-Glucuronidase (EC 3.2.1.31), cc-LIduronidase (EC 3.2,1.76)) sowie zweier Sulfatasen (Arylsulfatase A und B) (EC 3.1.6.1) und einer Protease /(Kathepsin D) (EC 3.4.23.5) wurden in den löslichen Extrakten von Hepatocyten und Nicht-Parenchymzellen der Leber und im Serum im Verlaufe einer Thioacetamid-induzierten Leberfibrose (22 Wochen) bestimmt. In Nicht-Parenchymzellen sind die katalytischen Aktivitäten der ß-N-Acetyl-£>-glucosaminidase, ß-Glucuronidase, -L-Idufonidase und Kathepsin D bei chronischer Leberschädigung signifikant erhöht, wohingegen die katalytische Aktivität der Hyaluronat-4-glykanohydrolase im gesamten Untersuchungszeitraum um 40 bis 65% vermindert ist. Die katalytischen Aktivitäten der Arylsulfatasen A und B waren in der 12. Woche der Schädigung um 65% erniedrigt (verglichen mit den Kontrollen), mit fortschreitender Leberschädigung wurden jedoch wieder Normalwerte erreicht. Parenchymzellen von Ratten, die 6...

Heterogenous Zonal Distribution of Lysosomal Enzymes in Rat Liver

“…The periportal [27], but the degradative enzymes are present both in parenchymal and nonparenchymal cells [28], Both proteoglycans and glycosaminoglycans have been suggested to have a role in the fibrotic transformation of the liver [28,29] and the relatively low activ ity of these glycosidases in the perivenous region (table 3) may contribute to the onset of fibrosis in this region. Although the activ ities of glycosidases may not be the rate lim iting step in glycosaminoglycan degradation, the activities change during development of fibrosis.…”