Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1998-12-10
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0886-022X
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
679-86
pubmed:dateRevised
2008-5-21
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Proteases in renal cell death: calpains mediate cell death produced by diverse toxicants.
pubmed:affiliation
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA. schnellmannrickyg@exchange.uams.edu
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't