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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1998-12-10
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pubmed:abstractText |
The role of proteases in renal cell death has received limited investigation. Calpains are non-lysosomal cysteine proteases that are Ca+2 activated. Calpain inhibitors that block the active site of calpains (calpain inhibitor 1 and 2) or the Ca+2 binding domain of calpains (PD150606) decreased calpain activity in rabbit renal proximal tubule (RPT) suspensions. The inhibition of calpain activity decreased cell death produced by the diverse toxicants antimycin A (mitochondrial inhibitor), tetrafluroethyl-L-cysteine (nephrotoxic halocarbon), bromohydroquinone (nephro-toxic quinone), t-butylhydroperoxide (model oxidant) and ionomycin (Ca+2 ionophore). In summary, calpains appear to play a common and critical role in cell injury produced by diverse toxicants with different mechanisms of action. The general cysteine protease inhibitor trans-epoxysuccinyl-L-leucylamido (4-guanidino)-butane (E-64) decreased antimycin A- and tetrafluoroethyl-L-cysteine-induced cell death but had no effect on bromohydroquinone- or t-butylhydroperoxide-induced cell death. Serine/cysteine protease inhibitors (antipain, leupeptin) were not cytoprotective to RPT exposed to any of the toxicants. The cytoprotection associated with E-64 correlated with inhibition of lysosomal cathepsins and E-64 was only cytoprotective after some cell death had occurred. Since some cell death occurred prior to the E-64 cytoprotective effect, lysosomal cathepsins may be released from dying cells and subsequently target the remaining viable cells.
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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 |
Sep
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pubmed:issn |
0886-022X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
679-86
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pubmed:dateRevised |
2008-5-21
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pubmed:meshHeading |
pubmed-meshheading:9768434-Animals,
pubmed-meshheading:9768434-Apoptosis,
pubmed-meshheading:9768434-Calpain,
pubmed-meshheading:9768434-Cells, Cultured,
pubmed-meshheading:9768434-Cytoprotection,
pubmed-meshheading:9768434-Enzyme Activation,
pubmed-meshheading:9768434-Enzyme Inhibitors,
pubmed-meshheading:9768434-Humans,
pubmed-meshheading:9768434-Kidney,
pubmed-meshheading:9768434-Lysosomes,
pubmed-meshheading:9768434-Rabbits
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pubmed:year |
1998
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pubmed:articleTitle |
Proteases in renal cell death: calpains mediate cell death produced by diverse toxicants.
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pubmed:affiliation |
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA. schnellmannrickyg@exchange.uams.edu
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pubmed:publicationType |
Journal Article,
Review,
Research Support, Non-U.S. Gov't
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