Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the effects of acute pancreatitis on hepatic function and hepatic cellular and subcellular organellar fragility, we studied 1) the hepatic secretion of lysosomal enzymes (beta-glucuronidase, beta-galactosidase, and N-acetyl-beta-glucosaminidase) into bile in the isolated perfused rat liver model; 2) the aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and lysosomal enzyme levels in the effluent in an isolated liver model; 3) hepatic lysosomal fragility in an in vitro incubation study; and 4) protective effects of a new low molecular weight synthetic protease inhibitor, ONO 3307, against hepatic injury in doses of 2 and 5 mg/kg.h in acute pancreatitis induced by a supramaximal dose of cerulein in rats. Decreased hepatic secretion of lysosomal enzymes into bile and accelerated hepatic lysosomal fragility were observed in acute pancreatitis induced by cerulein. ONO 3307 showed a significant protective effect against this hepatic injury in acute pancreatitis, the dose of 5 mg/kg.h showing a more potent effect than the dose of 2 mg/kg.h. These results suggest that the impaired hepatic function, including depressed hepatic secretion of lysosomal enzymes, seems to be closely related to accelerated hepatic fragility and that some unknown protease, which is present in pancreatitis and is susceptible to inhibition by ONO 3307, plays a crucial pathologic role in the development of this liver injury during acute pancreatitis.
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PMID:Effects of acute pancreatitis on hepatic secretion of lysosomal enzymes into bile and hepatic lysosomal fragility: protective effects of a new synthetic protease inhibitor, ONO 3307. 150 86

Transforming growth factor-beta (TGF-beta) is an important cytokine in the fibrogenesis in many organs, including the pancreas. Using an adenoviral vector expressing the entire extracellular domain of type II human TGF-beta receptor (AdTbeta-ExR), we investigated whether inhibition of TGF-beta action is effective against persistent pancreatic fibrosis, and whether it exerts a beneficial effect on the pancreas in the process of chronic injury. To induce chronic pancreatic injury and pancreatic fibrosis, mice were subjected to three episodes of acute pancreatitis induced by six intraperitoneal injections of 50 microg/kg body weight cerulein at hourly intervals, per week for 3 consecutive weeks. Mice were infected once with AdTbeta-ExR, or with a control adenoviral vector expressing bacterial beta-galactosidase (AdLacZ). Pancreatic fibrosis was evaluated by histology and hydroxyproline content. Activation of pancreatic stellate cells (PSCs) was assessed by immunostaining for alpha-smooth muscle actin. Apoptosis and proliferation of acinar cells were assessed by immunostaining of ssDNA and Ki-67, respectively. Three-week cerulein injection induced pancreatic fibrosis and pancreatic atrophy with proliferation of activated PSCs. In AdTbeta-ExR-injected mice, but not AdLacZ-injected mice, pancreatic fibrosis was significantly attenuated. This finding was accompanied by a reduction of activated PSCs. AdTbeta-ExR, but not AdLacZ, significantly increased pancreas weight after chronic pancreatic injury. AdTbeta-ExR did not change the proportion of proliferating acinar cells, whereas it reduced the number of apoptotic acinar cells. Our results demonstrate that inhibition of TGF-beta action not only decreases pancreatic fibrosis but also protects the pancreas against chronic injury by preventing acinar cell apoptosis.
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PMID:Inhibition of transforming growth factor beta decreases pancreatic fibrosis and protects the pancreas against chronic injury in mice. 1550 60