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Calcium oxalate toxicity in renal epithelial cells: the mediation of crystal size on cell death mode

View Article: PubMed Central - PubMed

ABSTRACT

The cytotoxicity of calcium oxalate (CaOx) in renal epithelial cells has been studied extensively, but the cell death mode induced by CaOx with different physical properties, such as crystal size and crystal phase, has not been studied in detail. In this study, we comparatively investigated the differences of cell death mode induced by nano-sized (50 nm) and micron-sized (10 μm) calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) to explore the cell death mechanism. The effect of the exposure of nano-/micron-sized COM and COD crystals toward the African green monkey renal epithelial (Vero) cells were investigated by detecting cell cytoskeleton changes, lysosomal integrity, mitochondrial membrane potential (Δψm), apoptosis and/or necrosis, osteopontin (OPN) expression, and malondialdehyde (MDA) release. Nano-/micron-sized COM and COD crystals could cause apoptosis and necrosis simultaneously. Nano-sized crystals primarily caused apoptotic cell death, leading to cell shrinkage, phosphatidylserine ectropion, and nuclear shrinkage, whereas micron-sized crystals primarily caused necrotic cell death, leading to cell swelling and cell membrane and lysosome rupture. Nano-sized COM and COD crystals induced much greater cell death (sum of apoptosis and necrosis) than micron-sized crystals, and COM crystals showed higher cytotoxicity than the same-sized COD crystals. Both apoptosis and necrosis could lead to mitochondria depolarization and elevate the expression of OPN and the generation of lipid peroxidation product MDA. The amount of expressed OPN and generated MDA was positively related to cell injury degree. The physicochemical properties of crystals could affect the cell death mode. The results of this study may provide a basis for future studies on cell death mechanisms.

No MeSH data available.


MDA release amount and OPN expression after treatment with 200 μg/ml nano-/micron-sized COM and COD crystals for 6 h. (a) MDA release amount in Vero cells after treatment by COM and COD crystals. (b) OPN expression observation by fluorescence staining.
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fig4: MDA release amount and OPN expression after treatment with 200 μg/ml nano-/micron-sized COM and COD crystals for 6 h. (a) MDA release amount in Vero cells after treatment by COM and COD crystals. (b) OPN expression observation by fluorescence staining.

Mentions: The changes in the generated MDA amount in Vero cells are shown in Figure 4a. The MDA content in the nano-sized crystal-treated groups was much greater than that in the micron-sized crystal-treated groups. COM crystals caused more serious injury to cells than the same-sized COD crystals. The released amount of MDA was consistent with the degree of Vero cell injury.


Calcium oxalate toxicity in renal epithelial cells: the mediation of crystal size on cell death mode
MDA release amount and OPN expression after treatment with 200 μg/ml nano-/micron-sized COM and COD crystals for 6 h. (a) MDA release amount in Vero cells after treatment by COM and COD crystals. (b) OPN expression observation by fluorescence staining.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4979418&req=5

fig4: MDA release amount and OPN expression after treatment with 200 μg/ml nano-/micron-sized COM and COD crystals for 6 h. (a) MDA release amount in Vero cells after treatment by COM and COD crystals. (b) OPN expression observation by fluorescence staining.
Mentions: The changes in the generated MDA amount in Vero cells are shown in Figure 4a. The MDA content in the nano-sized crystal-treated groups was much greater than that in the micron-sized crystal-treated groups. COM crystals caused more serious injury to cells than the same-sized COD crystals. The released amount of MDA was consistent with the degree of Vero cell injury.

View Article: PubMed Central - PubMed

ABSTRACT

The cytotoxicity of calcium oxalate (CaOx) in renal epithelial cells has been studied extensively, but the cell death mode induced by CaOx with different physical properties, such as crystal size and crystal phase, has not been studied in detail. In this study, we comparatively investigated the differences of cell death mode induced by nano-sized (50 nm) and micron-sized (10 μm) calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) to explore the cell death mechanism. The effect of the exposure of nano-/micron-sized COM and COD crystals toward the African green monkey renal epithelial (Vero) cells were investigated by detecting cell cytoskeleton changes, lysosomal integrity, mitochondrial membrane potential (Δψm), apoptosis and/or necrosis, osteopontin (OPN) expression, and malondialdehyde (MDA) release. Nano-/micron-sized COM and COD crystals could cause apoptosis and necrosis simultaneously. Nano-sized crystals primarily caused apoptotic cell death, leading to cell shrinkage, phosphatidylserine ectropion, and nuclear shrinkage, whereas micron-sized crystals primarily caused necrotic cell death, leading to cell swelling and cell membrane and lysosome rupture. Nano-sized COM and COD crystals induced much greater cell death (sum of apoptosis and necrosis) than micron-sized crystals, and COM crystals showed higher cytotoxicity than the same-sized COD crystals. Both apoptosis and necrosis could lead to mitochondria depolarization and elevate the expression of OPN and the generation of lipid peroxidation product MDA. The amount of expressed OPN and generated MDA was positively related to cell injury degree. The physicochemical properties of crystals could affect the cell death mode. The results of this study may provide a basis for future studies on cell death mechanisms.

No MeSH data available.