Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1389183 (autodigestion)
 317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nutritional factors, especially the protein and fat content of the diet, may alter the likelihood of pancreatic injury after a number of insults, including chronic ethanol intake. This issue was studied experimentally by match-feeding rats liquid diets of varying protein content with and without ethanol. Protein synthesis and enzyme secretion were investigated, because these parameters are believed to increase the capacity for pancreatic autodigestion. Protein synthesis was assessed by determining the incorporation of tritiated phenylalanine into trichloroacetic acid precipitated protein 10 minutes after IP injection and then corrected for the size of the precursor pool. Enzyme secretion was studied using pancreatic acini, which were prepared using clostripain-poor collagenase. Chronic ethanol feeding stimulated protein synthesis and lipase secretion and content in rats receiving adequate amounts of protein. These stimulatory effects of ethanol were markedly attenuated in rats administered protein poor diets. Protein deficiency per se significantly decreased the weight, protein, and enzyme content of the rat pancreas as well as increased the percentage release of lipase from acini. Although extrapolation from animal studies may be tenuous, the present findings may explain the link between nutrition and the occurrence of alcoholic pancreatitis.
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PMID:Interactive effects of dietary protein and ethanol on rat pancreas. Protein synthesis and enzyme secretion. 198 46

Intrapancreatic activation of proteases is believed to play a major role in the pathogenesis of acute necrotizing pancreatitis. Several authors have questioned, however, the central role of trypsin in autodigestion of the pancreas. To clarify the direct effects of pancreatic enzymes and other related factors on acinar cells, we used the model of isolated pancreatic acini. Acini were prepared from male Wistar rats by collagenase digestion. Protein synthesis was measured by incubation of acini with [35S]methionine. Acini were resuspended thereafter in fresh buffer and further incubated for 30-90 min under various conditions [e.g., with pancreatic homogenates, ascites (from rats with pancreatitis induced by sodium taurocholate), pure pancreatic enzymes, and other factors]. The percentage of release of newly synthesized proteins into the culture medium was regarded as a biochemical parameter of cellular integrity. A morphologic score of cellular integrity was obtained via light microscopic evaluation of acini at the end of the various incubations by measuring the degree of cell lysis, loss of cell granules, ballooning, formation of vacuoles, and karyopyknosis. When normal [35S]methionine-labeled pancreatic acini were incubated with various factors, the percentage of release of labeled proteins into the medium was as follows: incubation with HEPES/Ringer's buffer, 1.8%; hemorrhagic pancreatic ascites, 3.8%; pancreatic homogenates, 2.0%; lipase, 1.8%; phospholipase A2, 3.0%; phospholipase A2 + lecithin, 3.2%; trypsin, 2.5%; 5% olive oil, 1.8%; ascites + olive oil, 78.3%; ascites + homogenized epididymal fat, 79.9%; lipase + olive oil, 32.0%; pancreatic homogenates + olive oil, 28.0%; diolein, 2.65%; and oleic acid, 62.9%. The cellular release of radiolabeled proteins showed an inverse correlation with cellular integrity as shown by light microscopy. We postulate that interstitial release of degradation products from triglycerides by lipase causes cellular disruption. Whereas phospholipase A2 and proteases do not seem to be very harmful in the early phases of cellular damage, lipase may play a major role in acute necrotizing pancreatitis.
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PMID:Role of pancreatic enzymes and their substrates in autodigestion of the pancreas. In vitro studies with isolated rat pancreatic acini. 291 45

Canine pancreases were excised, minced, mechanically chopped, and incubated with collagenase in a manner similar to that used routinely in the preparation of mixed-cell pancreatic autografts. The resultant pancreatic fragments were studied by light and electron microscopy after various periods of collagenase incubation. As a control, pancreatic tissue was studied immediately after organ excision, immediately before addition of collagenase, and after various periods of incubation in balanced salt solution without collagenase. The mincing and chopping procedures alone induced a large population of highly aberrant, severely vacuolated acinar cells within the fragments. This vacuolation was caused by massive dilation of the cisternae of the rough endoplasmic reticulum. Subsequent incubation in collagenase solution, which appeared to destroy the aberrant cells in a selective manner, led to a remnant population with much improved acinar cell morphology. Incubation in balanced salt solution without collagenase resulted in a progressive increase in vacuolated cell incidence until abnormal pancreatic acinar cells dominated the tissue. The findings suggest that collagenase treatment may facilitate mixed-cell pancreatic transplantation by culling degenerative acinar cells from the grafted cell population, thereby reducing the likelihood of autodigestion at the transplant site. The extensive acinar cell destruction mediated by the collagenase may also be responsible for the release of a previously described hypotensive factor (pancreatic shock factor) into the graft infusion.
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PMID:Morphological changes in pancreatic fragments prepared for transplantation by collagenase treatment. 608 89

During the past decade, strains of Bacteroides fragilis that produce an enterotoxin have been implicated in diarrheal disease in animals and humans. The extracellular enterotoxin has been purified and characterized as a single polypeptide (M(r), approximately 20,000). Single specific primer-PCR was used to clone a portion of the B. fragilis enterotoxin gene. The recombinant protein expressed by the cloned gene fragment reacted with monospecific antibodies to B. fragilis enterotoxin by enzyme-linked immunosorbent assay and immunoblot analysis. The deduced amino acid sequence revealed a signature zinc-binding consensus motif (HEXXHXXGXXH/Met-turn) characteristic of metalloproteases termed metzincins. Sequence comparisons showed close identity to matrix metalloproteases (e.g., human fibroblast collagenase) within the zinc-binding and Met-turn region. Purified enterotoxin contained 1 g-atom of Zn2+ per molecule and hydrolyzed gelatin, azocoll, actin, tropomyosin, and fibrinogen. The enterotoxin also underwent autodigestion. The N-terminal amino acid sequences of two autodigestion products were identical to the deduced amino acid sequence of the recombinant enterotoxin and revealed cleavage at Cys-Leu and Ser-Leu peptide bonds. Gelatinase (type IV collagenase) activity comigrated with the toxin when analyzed by gel fractionation and zymography, indicating that protease activity is due to the enterotoxin and not to a contaminating protease(s). Optimal proteolytic activity occurred at 37 degrees C and pH 6.5. Primary proteolytic cleavage sites in actin were identified, revealing cleavage at Gly-Met and Thr-Leu peptide bonds. Enzymatic activity was inhibited by metal chelators but not by inhibitors of other classes of proteases. Additionally, cytotoxic activity of the enterotoxin on human carcinoma HT-29 cells was inhibited by acetoxymethyl ester EDTA. The metalloprotease activity of the enterotoxin suggests a possible mechanism for enterotoxicity and may have additional implications in the study of disease caused by B. fragilis.
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PMID:The enterotoxin of Bacteroides fragilis is a metalloprotease. 780 55

Two different endopeptidases which digest the chromogenic substrate Azocoll were found in soybean leaves. Azocollase A has a molecular weight of 17,500 and a pI of 6.0. Azocollase B has a molecular weight of 52,000 and a pI of 9.0. Both digest Azocoll optimally at pH 9.0. Azocollase A is inhibited by 3 millimolar ethylenediamine tetraacetate (EDTA) and azocollase B by 100 micromolar parachloromercuribenzoate. Studies on whole plants grown in the greenhouse and in the field show that total azocollase activity gradually increased during leaf maturation when leaf protein and chlorophyll increased, and then declined again during leaf senescence. Young leaves which are still expanding contain mostly azocollase B and little azocollase A. Leaf maturation was associated with a dramatic increase in azocollase A (40- to 50-fold), while azocollase B activity increased more slowly. This increase in azocollase A occurred in the 2- to 3-week period following leaf expansion. Azocollase A, separated from other proteinases by gel filtration on Sephadex G-100, digested denatured leaf protein and casein, resulting in the release of free alpha-amino groups. Break-down of leaf proteins by autodigestion of extracts at pH 9.0 resulted in the release of free alpha-amino groups and endopeptidic cleavage of polypeptides. However, polypeptide cleavage was not inhibited by parachloromercuribenzoate or EDTA indicating that the azocollases do not play a major role in the hydrolysis of leaf proteins in crude extracts.
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PMID:Azocoll-digesting Proteinases in Soybean Leaves: Characteristics and Changes during Leaf Maturation and Senescence. 1666 Oct 69