Oxalate toxicity in renal epithelial cells

Characteristics of apoptosis and necrosis

Caroline Miller, Lori Kennington, Rachel Cooney, Yasuo Kohjimoto, Lu Cheng Cao, Thomas Honeyman, James M. Pullman, Julie Jonassen, Cheryl Scheid

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)132-141
Number of pages10
JournalToxicology and Applied Pharmacology
Volume162
Issue number2
DOIs
StatePublished - Jan 15 2000
Externally publishedYes

Fingerprint

Oxalates
Toxicity
Necrosis
Cell death
Epithelial Cells
Apoptosis
Kidney
Cell Death
Ceramides
Genes
Cells
Tissue
Poisons
DNA
Cytotoxins
LLC-PK1 Cells
Metabolites
Cell Line
Oxidants
DNA Cleavage

Keywords

  • Cellular toxicity
  • LLC-PK1
  • Necrosis
  • NRK
  • Renal epithelial cells

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Miller, C., Kennington, L., Cooney, R., Kohjimoto, Y., Cao, L. C., Honeyman, T., ... Scheid, C. (2000). Oxalate toxicity in renal epithelial cells: Characteristics of apoptosis and necrosis. Toxicology and Applied Pharmacology, 162(2), 132-141. https://doi.org/10.1006/taap.1999.8835

Oxalate toxicity in renal epithelial cells : Characteristics of apoptosis and necrosis. / Miller, Caroline; Kennington, Lori; Cooney, Rachel; Kohjimoto, Yasuo; Cao, Lu Cheng; Honeyman, Thomas; Pullman, James M.; Jonassen, Julie; Scheid, Cheryl.

In: Toxicology and Applied Pharmacology, Vol. 162, No. 2, 15.01.2000, p. 132-141.

Research output: Contribution to journalArticle

Miller, C, Kennington, L, Cooney, R, Kohjimoto, Y, Cao, LC, Honeyman, T, Pullman, JM, Jonassen, J & Scheid, C 2000, 'Oxalate toxicity in renal epithelial cells: Characteristics of apoptosis and necrosis', Toxicology and Applied Pharmacology, vol. 162, no. 2, pp. 132-141. https://doi.org/10.1006/taap.1999.8835
Miller, Caroline ; Kennington, Lori ; Cooney, Rachel ; Kohjimoto, Yasuo ; Cao, Lu Cheng ; Honeyman, Thomas ; Pullman, James M. ; Jonassen, Julie ; Scheid, Cheryl. / Oxalate toxicity in renal epithelial cells : Characteristics of apoptosis and necrosis. In: Toxicology and Applied Pharmacology. 2000 ; Vol. 162, No. 2. pp. 132-141.
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