Depletion of endoplasmic reticulum calcium stores protects against hypoxia- and mitochondrial inhibitor-induced cellular injury and death

Shayla L. Waters, Jeremy K. Wong, Rick G. Schnellmann

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

We have shown previously that intracellular Ca+2 chelation and calpain inhibitors block the influx of extracellular Ca+2 and Cl- during the late phase of cell injury in renal proximal tubules (RPT) exposed to the mitochondrial inhibitor antimycin A. Since the endoplasmic reticulum (ER) is the major intracellular Ca+2 storage site, ER Ca+2 release/depletion may mediate the Ca+2 influx and cell death. Treatment of RPT suspensions with thapsigargin, an ER Ca+2-ATPase inhibitor, increased cytosolic free Ca+2 (Ca(f)+2) levels from 122 ± 7 to 322 ± 55 nM within 10 sec of addition followed by a return to control levels within 3 min. A 5-min pretreatment of RPT suspensions with thapsigargin blocked antimycin A- and hypoxia-induced influx of extracellular Ca+2 and Cl- and the resulting cell death/lysis. These data suggest that ER Ca+2 release/depletion during cell injury may trigger a signaling cascade that causes extracellular Ca+2 influx followed by Cl- influx, cell swelling, and ultimately cell death/lysis.

Original languageEnglish (US)
Pages (from-to)57-60
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume240
Issue number1
DOIs
StatePublished - Nov 7 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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