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.
The catalytic activities of 4 glycosidases (hyaluronate-4-glycanohydrolase (EC 3.2.1.35), beta-N-acetyl-D-glucosaminidase (EC 3.2.1.30), beta-glucuronidase (EC 3.2.1.31), alpha-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 thioacetamide-induced rat liver fibrosis (22 weeks). In non-parenchymal liver cells the catalytic activities of beta-N-acetyl-D-glucosaminidase, beta-glucuronidase, alpha-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 application 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 beta-glucuronidase, beta-N-acetyl-D-glucosaminidase, arylsulphatases A and B, and cathepsin D but only slightly increased activities of hyaluronate-4-glycanohydrolase and alpha-L-iduronidase, respectively. In the serum of liver-damaged rats the activity of alpha-L-iduronidase was strongly elevated, while that of N-acetyl-beta-D-glucosaminidase was only slightly increased. The activities of beta-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.
D000818:Animals; D001192:Arylsulfatases / Q000378:metabolism*; D002402:Cathepsin D; D002403:Cathepsins / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology* / Q000473:pathology; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D011509:Proteoglycans / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013429:Sulfatases / Q000378:metabolism*; D013853:Thioacetamide / Q000633:toxicity
D011509:Proteoglycans; D013853:Thioacetamide; D013429:Sulfatases; D001192:Arylsulfatases; D006026:Glycoside Hydrolases; D002403:Cathepsins; D002402:Cathepsin D