Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of lysosomotropic agent--sodium aurothiomalate on liver damage and lysosomal changes during acute toxic hepatitis was studied. Combined administration of sodium aurothiomalete led to less extensive necrosis and to widening dystrophic areas in the hepatic parenchyma. Solubilization of the acid RNA-ase activity was decreased, and nonsedimentable activities of beta-galactosidase, cathepsin D were the same as in acute CCl4-hepatitis.
 ...
PMID:[Effect of sodium aurothiomalate in acute toxic hepatitis]. 40 45

Physical and chemical properties of the rat liver lysosomes with single Triton WR 1339 overloading were studied during the administration of a detergent to intact rats and those with acute toxic hepatitis. Administration of the latter to intact animals was accompanied by a reduction of the floating density of the particles, solubilization of the lysosome enzymes and by increased fragility of the particles in the hypotonic medium. Lysosomes of the hepatocytes in rats with toxic hepatitis also displayed signs of overloading of the vacuolar apparatus with the preparation administered. The most pronounced solubilization of the lysosomal enzymes beta-galactosidase, acid RNA-ase, cathepsin D--was noted in case of combined action of CCl4 and Triton WR 1339 24, 48, 72 hours and 7 days after the CCl4 poisoning. Possible consequences of overloading of the vacuolar apparatus of the rat hepatocytes are discussed.
 ...
PMID:[Role of vacuolar apparatus overload in lysosomal changes in liver cells in acute toxic hepatitis]. 42 73

Structural and functional changes in the dog liver and regional lymph nodes lysosomes were studied during toxic hepatitis induced by CCl4 administration (single and repeated). Total activity of lysosomal enzymes (acid RNA-ase and beta-galactosidase) was higher in the regional lymph nodes than in the liver, reflecting the barrier, protective function of the organ. During acute toxic hepatitis the specific activities of acid RNA-ase and cathepsin D displayed a sharp rise. No normalization of the indices under study occurred during the observation period (from 8 to 30 days). At the same time there was a rise of the regional lymph node weight and an elevation of the relative macrophage and neutrophil content in the sinuses. The increased activity of the lysosome enzymes in the regional lymph nodes in injury of the liver was connected with greater functional load on the lymph nodes effecting hydrolysis of biopolymeres which penetrated into the regional lymphatic node with the lymph.
 ...
PMID:[Structuro-functional changes in dog liver and regional lymph node lysosomes in toxic hepatitis]. 70 70

The distribution of cathepsin D in liver with CCl4 induced cirrhosis and its involution in rats was investigated by ultrastructural cytochemistry. Besides intracellular, it was revealed the extracellular activity of cathepsin D. The reaction product was on collagen fibers near the hepatocytes and connective tissue cells as well as on the hepatocytes microvilli and on the outside part of cellular membrane of connective tissue cells (macrophage, fibroblast, Ito cells). Hence the source of extracellular cathepsin D in liver are the parenchymatous as well as nonparenchymal cell elements. The results testify that under the cirrhosis and its involution, the cathepsin D takes part in intracellular proteolysis and is secreted by hepatocytes and connective tissue cells in the intracellular space; it also takes part in extracellular catabolism of connective tissue.
 ...
PMID:[Intracellular and extracellular activity of cathepsin D in the liver in cirrhosis and its involution]. 233 65

Serum from patients with chronic liver diseases (chronic hepatitis, cirrhosis, and hepatomas) contained greater concentrations of calciferin (total 1.7-fold, free 3.3-fold) than that from normal subjects. There were also decreases in the concentration and affinity of the calciferin-binding protein(s) in the patients' sera, but the amount of cathepsin D (EC 3.4.23.5)-like acid protease (total and free) was within normal limits. In addition, rats with acute liver injuries (partial hepatectomy or CCl4 administration) showed increases in calciferin and acid protease in their serum. Rats subjected to continuous feeding of 3'-methyl-4-dimethylaminoazobenzene (a potent hepatocarcinogen) also showed an increase of both analytes in the earlier stages (two to eight weeks; acute phase). Later (13 weeks or more; chronic phase), however, only acid protease appeared to return to normal values.
 ...
PMID:Calciferin and cathepsin D-like acid protease in serum in acute and chronic liver injuries in rats and humans. 258 17

Changes in activities of a new proteinase cathepsin T as well as some other lysosomal acid proteinases and hydrolases were examined in liver homogenate from rats treated with a single hepatotoxic dose of carbon tetrachloride. The most striking changes were several-fold increases of liver cathepsin T and D activities over their levels in untreated rats 3 days after administration of the agent to rats. Increase of cathepsin T was greater than that of cathepsin D at all doses of the hepatotoxin examined. The activities of N alpha-benzoyl-DL-arginine 2-naphthylamide hydrolase, acid phosphatase, beta-galactosidase and beta-glucuronidase in poisoned rat liver were unchanged or only slightly increased. Cathepsin T and D activities were less enhanced in mitochondrial lysosomal fractions than in the homogenate, and were greatly elevated in the supernatant fractions of liver from the treated rats. As judged from the molecular weights, the elevated activities of cathepsins T and D in the treated rat liver could be attributable to the two cathepsins themselves and not to other proteinases. Administration to rats of other hepatotoxic agents, thioacetamide and dimethylnitrosamine, also induced the elevation of the two cathepsin activities in liver, but on partial hepatectomy the activities of liver cathepsins T and D did not show such marked increases. Nonparenchymal liver cell fractions were responsible for almost all the increased activities of liver cathepsins T and D. It is possible that cathepsins T and D play a role in the heterolytic breakdown of hepatocyte molecules following CCl4 poisoning.
 ...
PMID:Increased activities of liver cathepsins T and D in carbon tetrachloride-treated rats. 649 24

Liver tissue cirrhosis, developed in rats after long-term administration of CCl4, led to distinct increase in activities of acid phosphatase, acid DNAase, cathepsin D, beta-galactosidase and beta-glucosidase. When the treatment with the hepatotropic toxins was stopped activity of lysosomal enzymes decreased slightly but was maintained at the high level. Within a day after a single administration of choriogonine distinct decrease as compared with the controls in activity of all the acid hydrolases studied was found. Within subsequent periods the lysosomal enzymes activity continued to decrease and within 2 months after the choriogonine treatment it was distinctly lower as compared with control animals.
 ...
PMID:[Effect of choriogonine on the enzymatic activity of lysosomes in the cirrhotic liver in the rat]. 681 64

In rats with CCl4-induced liver cirrhosis, a twofold decrease of blood clearance rate and a fourfold reduction in number of Kupffer cells taking up colloidal carbon particles has been demonstrated. Zymosan stimulation does not lead to granuloma-like structures in the liver of CCl4-cirrhotic rats. In cirrhotic rats, unlike controls, the cathepsin D activity of liver tissue is very little increased by zymosan treatment and there is virtually no increase in collagenolytic activity. The increase in PGE content in cirrhotic rat liver after prodigiosan stimulation was 2.5 times less than in stimulated control animals. In cirrhotic rats, the IL-1 producing capacity of blood monocytes in vitro in response to lipopolysaccharide drops almost fivefold. The total count of bone marrow-derived myeloid colonies in cirrhotic zymosan-stimulated animals was reduced by 1.5-fold whereas in control animals zymosan induced a 1.8-fold increase in the number of myeloid colonies. The number, uptake and nitroblue tetrazolium-reducing capacities of lung, spleen, peritoneal and bone marrow macrophages in animals with liver cirrhosis were only slightly increased in response to zymosan as compared to control animals. The low response of extrahepatic macrophages to stimuli in cirrhotic animals is thought to be due to their premobilization during the development of cirrhosis.
 ...
PMID:Mononuclear phagocyte system responsiveness in CCl4-induced liver cirrhosis. 833 74

Autophagy is a regulatory pathway in liver fibrosis. We investigated the roles of autophagy in human cirrhotic livers. Cirrhotic and noncirrhotic liver tissues were obtained from patients with hepatocellular carcinoma, and liver tissues from live donors served as control. Patients with cirrhotic livers had significantly increased levels of various essential autophagy-related genes compared with noncirrhotic livers. In addition, colocalization of autophagy marker microtubule-associated protein 1 light chain 3B (LC3B) with lysosome-associated membrane protein-1, increased levels of lysosome-associated membrane protein-2, and increased maturation of lysosomal cathepsin D were observed in cirrhotic livers. By using dual-immunofluorescence staining, we demonstrated that increased LC3B was located mainly in the cytokeratin 19-labeled ductular reaction (DR) in human cirrhotic livers and in an experimental cirrhosis induced by 2-acetylaminofluorene (AAF) with carbon tetrachloride (CCl4), indicating a conserved response to chronic liver damage. Furthermore, an AAF/CCl4-mediated increase in DR and fibrosis were attenuated after chloroquine treatment, suggesting that the autophagy-lysosome pathway was essential for AAF/CCl4-induced DR-fibrosis. In conclusion, we demonstrated that increased autophagy marker positively correlated with DR during the development of cirrhosis. Therefore, targeting autophagy may hold therapeutic value for liver cirrhosis.
...
PMID:Increased Autophagy Markers Are Associated with Ductular Reaction during the Development of Cirrhosis. 2615 32