Cytosolic Ca2+ elevation and calpain inhibitors in HgCl2 injury to rat kidney proximal tubule epithelial cells.
This study assessed HgCl2 injury to proximal tubule epithelial cells as it relates to the concentration of ionized cytosolic Ca2+ ([Ca2+]i) elevation and activation of calpains. Experiments in high and low extracellular Ca2+ concentration ([Ca2+]e) were performed using the calpain inhibitors antipain and leupeptin, and also trypsin inhibitor, methylamine, chloroquine, and ryanodine. Cell killing was time/dose dependent and greater with high [Ca2+]e. After 30 min treatment with 25 microM HgCl2, 19% of cells in low [Ca2+]e were dead while 72% died in high [Ca2+]e. Morphologic changes such as cytoplasmic blebbing were also greater in high [Ca2+]e. Antipain and leupeptin diminished toxicity. Leupeptin did not block Ca2+ entry into cells. Results show that HgCl2 toxicity is correlated with increased [Ca2+]i, and that calpains may mediate the resultant pathological changes.
Elliget
K A
KA
Department of Pathology, University of Maryland School of Medicine, Baltimore 21201, USA.
Phelps
P C
PC
Trump
B F
BF
D000818:Animals; D000976:Antipain / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003593:Cytoplasm / Q000648:ultrastructure; D003600:Cytosol / Q000737:chemistry; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007976:Leupeptins / Q000494:pharmacology*; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D051381:Rats
D007976:Leupeptins; D000976:Antipain; D008627:Mercuric Chloride; D002154:Calpain; C032854:leupeptin; D002118:Calcium