Calpains mediate acute renal cell death: Role of autolysis and translocation

Xiuli Liu, Juanita J. Rainey, Jay F. Harriman, Rick G. Schnellmann

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

The goals of this study were to determine 1) the expression of calpain isoforms in rabbit renal proximal tubules (RPT); 2) calpain autolysis and translocation, and calpastatin levels during RPT injury; and 3) the effect of a calpain inhibitor (PD-150606) on calpain levels, mitochondrial function, and ion transport during RPT injury. RT-PCR, immunoblot analysis, and FITC-casein zymography demonstrated the presence of only μ- and m-calpains in rabbit RPT. The mitochondrial inhibitor antimycin A decreased RPT μ- and m-calpain and calpastatin levels in conjunction with cell death and increased plasma membrane permeability. No increases in either μ- or m-calpain were observed in the membrane nor were increases observed in autolytic forms of either μ- or m-calpain in antimycin A-exposed RPT. PD-150606 blocked antimycin A-induced cell death, preserved calpain levels in antimycin A-exposed RPT, and promoted the recovery of mitochondrial function and active Na+ transport in RPT after hypoxia and reoxygenation. The present study suggests that calpains mediate RPT injury without undergoing autolysis or translocation, and ultimately they leak from cells subsequent to RPT injury/death. Furthermore, PD-150606 allows functional recovery after injury.

Original languageEnglish (US)
Pages (from-to)F728-F738
JournalAmerican Journal of Physiology - Renal Physiology
Volume281
Issue number4 50-4
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Active sodium transport
  • Calpastatin
  • Hypoxia/reoxygenation
  • Mitochondrial function
  • Mitochondrial inhibitor
  • Rabbit

ASJC Scopus subject areas

  • Physiology
  • Urology

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