Oxalate exposure promotes reinitiation of the DNA synthesis and apoptosis of HK-2 cells, a line of human renal epithelial cells

Oxalate, a metabolic end product, is a major constituent of kidney stones. Previously, we and others have demonstrated that oxalate is toxic to renal epithelial cells. In the present study, we characterized oxalate-induced cell death in HK2 cells, a line of renal epithelial cells from the human kidney. For these studies, HK2 cells were exposed to oxalate for various time points. Cells were examined for nuclear morphology, DNA fragmentation, and expression of various apoptosis-related proteins. Apoptotic mode of cell death was also confirmed by TUNEL assay. Results from these studies revealed that oxalate exposure resulted in time-dependent increase in DNA fragmentation. Maximum DNA fragmentation was observed at 2-24 hours following oxalate exposure. Results from Western blot analysis demonstrated an increased expression of the FAS ligand. Taken together, these data reveal that oxalate-associated nephrotoxicity results from oxalate-induced apoptosis of renal epithelial cells.