TY - JOUR
T1 - Oxalate toxicity in renal epithelial cells
T2 - Characteristics of apoptosis and necrosis
AU - Miller, Caroline
AU - Kennington, Lori
AU - Cooney, Rachel
AU - Kohjimoto, Yasuo
AU - Cao, Lu Cheng
AU - Honeyman, Thomas
AU - Pullman, James
AU - Jonassen, Julie
AU - Scheid, Cheryl
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health: NIH RO1 ES07864 and DK 43184 and by a postdoctoral fellowship to C. Miller, 1F32DK09634–01. The bcl-2 vector and vector controls were graciously provided by Dr. Robert Woodland and Dr. Madeline Schmidt, UMASS Medical School. Dr. Isabelle Joris provided invaluable assistance in the preparation and analysis of morphological studies.
PY - 2000/1/15
Y1 - 2000/1/15
N2 - Studies in various tissues, including the kidney, have demonstrated that toxins elicit apoptosis under certain conditions and necrosis under others. The nature of the response has important consequences for the injured tissue in that necrotic cells elicit inflammatory responses, whereas apoptotic cells do not. Thus, there has been considerable interest in defining the mode of cell death elicited by known cytotoxins. The present studies examined the response of renal epithelial cells to oxalate, a metabolite excreted by the kidney that produces oxidant stress and death of renal cells at pathophysiological concentrations. These studies employed LLC-PK1 cells, a renal epithelial cell line from pig kidney and NRK-52E (NRK) cells, a line from normal rat kidney, and compared the effects of oxalate with those of known apoptotic agents. Changes in cellular and nuclear morphology, in nuclear size, in ceramide production, and in DNA integrity were assessed. The ability of bel-2, an anti-apoptotic gene product, to attenuate oxalate toxicity was also assessed. These studies indicated that oxalate-induced death of renal epithelial cells exhibits several features characteristic of apoptotic cell death, including increased production of ceramide, increased abundance of apoptotic bodies, and marked sensitivity to the level of expression of the antiapoptotic gene bel-2. Oxalate-induced cell death also exhibits several characteristics of necrotic cell death in that the majority of the cells exhibited cellular and nuclear swelling after oxalate treatment and showed little evidence of DNA cleavage by TUNEL assay. These results suggest that toxic concentrations of oxalate trigger both forms of cell death in renal epithelial cells. (C) 2000 Academic Press.
AB - Studies in various tissues, including the kidney, have demonstrated that toxins elicit apoptosis under certain conditions and necrosis under others. The nature of the response has important consequences for the injured tissue in that necrotic cells elicit inflammatory responses, whereas apoptotic cells do not. Thus, there has been considerable interest in defining the mode of cell death elicited by known cytotoxins. The present studies examined the response of renal epithelial cells to oxalate, a metabolite excreted by the kidney that produces oxidant stress and death of renal cells at pathophysiological concentrations. These studies employed LLC-PK1 cells, a renal epithelial cell line from pig kidney and NRK-52E (NRK) cells, a line from normal rat kidney, and compared the effects of oxalate with those of known apoptotic agents. Changes in cellular and nuclear morphology, in nuclear size, in ceramide production, and in DNA integrity were assessed. The ability of bel-2, an anti-apoptotic gene product, to attenuate oxalate toxicity was also assessed. These studies indicated that oxalate-induced death of renal epithelial cells exhibits several features characteristic of apoptotic cell death, including increased production of ceramide, increased abundance of apoptotic bodies, and marked sensitivity to the level of expression of the antiapoptotic gene bel-2. Oxalate-induced cell death also exhibits several characteristics of necrotic cell death in that the majority of the cells exhibited cellular and nuclear swelling after oxalate treatment and showed little evidence of DNA cleavage by TUNEL assay. These results suggest that toxic concentrations of oxalate trigger both forms of cell death in renal epithelial cells. (C) 2000 Academic Press.
KW - Cellular toxicity
KW - LLC-PK1
KW - NRK
KW - Necrosis
KW - Renal epithelial cells
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U2 - 10.1006/taap.1999.8835
DO - 10.1006/taap.1999.8835
M3 - Article
C2 - 10637137
AN - SCOPUS:0034650458
SN - 0041-008X
VL - 162
SP - 132
EP - 141
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 2
ER -