Crystals cause acute necrotic cell death in renal proximal tubule cells, but not in collecting tubule cells

Schepers, Marieke S.J.; Ballegooijen, Eddy S. Van; Bangma, Chris H.; Verkoelen, Carl F.

doi:10.1111/j.1523-1755.2005.00566.x

Cited by 100 publications

(79 citation statements)

References 35 publications

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“…A variety of renal epithelial cells including LLC-PK 1 , MDCK, HK-2 (human kidney), NRK (normal rat kidney) and RPTEC (human renal proximal tubular epithelial cells), when exposed to high levels of oxalate, or brushite or CaOx crystals, show signs of membrane damage, and release LDH and enzymes such as γ-glutamyl trasnspeptidase, and N-acetyl-β-glucoseaminidase (4,6,12,13).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore we also examined the production of hydrogen peroxide (H 2 O 2 ), one of the reactive oxygen species (ROS), and 8-isoprostane (8-IP), a marker for oxidative stress. Since renal epithelial cells exposed to CaOx crystals produce significant amounts of inflammatory mediators, monocyte chemoattractant protein-1 (MCP-1) (4) and prostaglandin-E2 (PGE2) (5,12) by the exposed cells we also investigated their production. As mentioned above, Randall's plaques start in the basement membrane and renal interstitium resulting in the tubular epithelial exposure from the basal side.…”

Section: Introductionmentioning

confidence: 99%

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Apatite Induced Renal Epithelial Injury: Insight Into the Pathogenesis of Kidney Stones

et al. 2008

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Purpose-Kidney stone formation is associated with the deposition of hydroxyapatite (HA) either as sub-epithelial plaques or tubular deposits in the renal papillae. We investigated the effect of renal epithelial exposure to HA crystals in vitro to develop an insight into the pathogenesis of kidney stones.Materials and methods-NRK52E cells were exposed to 67 μg/cm 2 or 133 μg/cm 2 of HA or calcium oxalate monohydrate crystals. In some studies cells were also exposed to crystals from the basal side. After exposure of 3 or 6 hours media were analyzed for, lactate dehydrogenase (LDH), 8-isoprostane (8-IP) and hydrogen peroxide (H 2 O 2 ). Media collected after cells' exposure on the apical side was also analyzed for the production of monocyte chemoattractant-1 (MCP-1) and prostaglandin E2 (PGE2). Cells were stained with DAPI to determine apoptotic activity and examined by SEM to observe crystal-cell interaction.Results-Cell exposure to HA resulted in the production of H 2 O 2 and 8-IP as well as release of LDH. Apical exposure appeared more provocative and injurious than the basal exposure. An exposure to HA for 6 hours, resulted in increased apoptotic activity. Apical exposure also resulted in increased production of MCP-1 and PGE2.Conclusion-Cell exposure to HA crystals induces oxidative stress, lipid peroxidation, and caused upregulation of mediators of inflammation that may be responsible for the inflammation in kidneys of stone patients associated with tubular deposition of HA. They may also play a role in eruption of subepithelial Randall's plaques to the papillary surface.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Apatite Induced Renal Epithelial Injury: Insight Into the Pathogenesis of Kidney Stones

et al. 2008

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“…8 COM crystals could modify the membrane structure and function, activate ROS, cause oxidant/antioxidant imbalance, lead to mitochondrial dysfunction, and increase lipid peroxidation, 19 which induces apoptotic or necrotic cell death in renal epithelial cells. 9,[47][48][49] COD is the second most common component of CaOx renal stones, although existing studies on the toxic effect of COD crystals on renal epithelial cells are inadequate. Our previous study reported that nano-COD induced higher toxicity on Vero cells compared with the micro-sized crystals.…”

Section: Discussionmentioning

confidence: 99%

Reinjury risk of nano-calcium oxalate monohydrate and calcium oxalate dihydrate crystals on injured renal epithelial cells: aggravation of crystal adhesion and aggregation

Gan¹,

Sun²,

Bhadja³

et al. 2016

IJN

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Background Renal epithelial cell injury facilitates crystal adhesion to cell surface and serves as a key step in renal stone formation. However, the effects of cell injury on the adhesion of nano-calcium oxalate crystals and the nano-crystal-induced reinjury risk of injured cells remain unclear. Methods African green monkey renal epithelial (Vero) cells were injured with H 2 O 2 to establish a cell injury model. Cell viability, superoxide dismutase (SOD) activity, malonaldehyde (MDA) content, propidium iodide staining, hematoxylin–eosin staining, reactive oxygen species production, and mitochondrial membrane potential (Δψm) were determined to examine cell injury during adhesion. Changes in the surface structure of H 2 O 2 -injured cells were assessed through atomic force microscopy. The altered expression of hyaluronan during adhesion was examined through laser scanning confocal microscopy. The adhesion of nano-calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) crystals to Vero cells was observed through scanning electron microscopy. Nano-COM and COD binding was quantitatively determined through inductively coupled plasma emission spectrometry. Results The expression of hyaluronan on the cell surface was increased during wound healing because of Vero cell injury. The structure and function of the cell membrane were also altered by cell injury; thus, nano-crystal adhesion occurred. The ability of nano-COM to adhere to the injured Vero cells was higher than that of nano-COD crystals. The cell viability, SOD activity, and Δψm decreased when nano-crystals attached to the cell surface. By contrast, the MDA content, reactive oxygen species production, and cell death rate increased. Conclusion Cell injury contributes to crystal adhesion to Vero cell surface. The attached nano-COM and COD crystals can aggravate Vero cell injury. As a consequence, crystal adhesion and aggregation are enhanced. These findings provide further insights into kidney stone formation.

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“…COM crystal-cell interaction leads to production of reactive oxygen species (ROS), for example, superoxide (O 2 ?À ) 24 and H 2 O 2 . 25 These ROS products can mediate proinflammatory cytokines, for example, monocyte chemoattractant protein-1, leading to inflammation, epithelial cell injury and ultimately necrotic cell death. 26,27 Nevertheless, pathogenic mechanisms underlying kidney stone formation remain unclear.…”

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confidence: 99%

Effects of calcium oxalate monohydrate crystals on expression and function of tight junction of renal tubular epithelial cells

Peerapen

Thongboonkerd

2011

Laboratory Investigation

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Crystals cause acute necrotic cell death in renal proximal tubule cells, but not in collecting tubule cells

Cited by 100 publications

References 35 publications

Apatite Induced Renal Epithelial Injury: Insight Into the Pathogenesis of Kidney Stones

Apatite Induced Renal Epithelial Injury: Insight Into the Pathogenesis of Kidney Stones

Reinjury risk of nano-calcium oxalate monohydrate and calcium oxalate dihydrate crystals on injured renal epithelial cells: aggravation of crystal adhesion and aggregation

Effects of calcium oxalate monohydrate crystals on expression and function of tight junction of renal tubular epithelial cells

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