Source:http://linkedlifedata.com/resource/pubmed/id/11932257
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
24
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pubmed:dateCreated |
2002-6-10
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pubmed:abstractText |
The lysosomal cysteine protease cathepsin B is thought to play a central role in intrapancreatic trypsinogen activation and the onset of experimental pancreatitis. Recent in vitro studies have suggested that this mechanism might be of pathophysiological relevance in hereditary pancreatitis, a human inborn disorder associated with mutations in the cationic trypsinogen gene. In the present study evidence is presented that cathepsin B is abundantly present in the secretory compartment of the human exocrine pancreas, as judged by immunogold electron microscopy. Moreover, pro-cathepsin B and mature cathepsin B are both secreted together with trypsinogen and active trypsin into the pancreatic juice of patients with sporadic pancreatitis or hereditary pancreatitis. Finally, cathepsin B- catalyzed activation of recombinant human cationic trypsinogen with hereditary pancreatitis-associated mutations N29I, N29T, or R122H were characterized. In contrast to a previous report, cathepsin B-mediated activation of wild type and all three mutant trypsinogen forms was essentially identical under a wide range of experimental conditions. These observations confirm the presence of active cathepsin B in the human pancreatic secretory pathway and are consistent with the notion that cathepsin B-mediated trypsinogen activation might play a pathogenic role in human pancreatitis. On the other hand, the results clearly demonstrate that hereditary pancreatitis-associated mutations do not lead to increased or decreased trypsinogen activation by cathepsin B. Therefore, mutation-dependent alterations in cathepsin B-induced trypsinogen activation are not the cause of hereditary pancreatitis.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
21389-96
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11932257-Blotting, Western,
pubmed-meshheading:11932257-Cathepsin B,
pubmed-meshheading:11932257-Cations,
pubmed-meshheading:11932257-Dose-Response Relationship, Drug,
pubmed-meshheading:11932257-Humans,
pubmed-meshheading:11932257-Hydrogen-Ion Concentration,
pubmed-meshheading:11932257-Immunohistochemistry,
pubmed-meshheading:11932257-Mutagenesis, Site-Directed,
pubmed-meshheading:11932257-Mutation,
pubmed-meshheading:11932257-Pancreas,
pubmed-meshheading:11932257-Pancreatitis,
pubmed-meshheading:11932257-Plasmids,
pubmed-meshheading:11932257-Recombinant Proteins,
pubmed-meshheading:11932257-Time Factors,
pubmed-meshheading:11932257-Trypsinogen
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pubmed:year |
2002
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pubmed:articleTitle |
Presence of cathepsin B in the human pancreatic secretory pathway and its role in trypsinogen activation during hereditary pancreatitis.
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pubmed:affiliation |
Department of Physiology, University of California Los Angeles, Los Angeles, California 90095, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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