Proteases in renal cell death: Calpains mediate cell death produced by diverse toxicants

Rick G. Schnellmann, Shayla Waters Williams

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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 (Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)679-686
Number of pages8
JournalRenal Failure
Volume20
Issue number5
DOIs
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Nephrology

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