title: Cytosolic Ca2+ elevation and calpain inhibitors in HgCl2 injury to rat kidney proximal tubule epithelial cells.
abstract: 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.
authors.affiliation: Department of Pathology, University of Maryland School of Medicine, Baltimore 21201, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Elliget
authors.forename: P C
authors.initials: PC
authors.lastname: Phelps
authors.forename: B F
authors.initials: BF
authors.lastname: Trump
mesh_terms: 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
chemical_list: D007976:Leupeptins; D000976:Antipain; D008627:Mercuric Chloride; D002154:Calpain; C032854:leupeptin; D002118:Calcium