TY - JOUR
T1 - Depletion of endoplasmic reticulum calcium stores protects against hypoxia- and mitochondrial inhibitor-induced cellular injury and death
AU - Waters, Shayla L.
AU - Wong, Jeremy K.
AU - Schnellmann, Rick G.
PY - 1997/11/7
Y1 - 1997/11/7
N2 - 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.
AB - 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.
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U2 - 10.1006/bbrc.1997.7606
DO - 10.1006/bbrc.1997.7606
M3 - Article
C2 - 9367881
AN - SCOPUS:0031558813
SN - 0006-291X
VL - 240
SP - 57
EP - 60
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -