Mechanisms Mediating Oxalate-Induced Alterations in Renal Cell Functions

Jonassen, Julie A.; Cao, L. C.; Honeyman, Thomas W.; Scheid, C. R.

doi:10.1615/critreveukaryotgeneexpr.v13.i1.50

Cited by 77 publications

(70 citation statements)

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“…Potential injury to this part of the nephron was not addressed in this study. These results suggest that transient exposure of the kidney to high levels of oxalate may not be overtly harmful, but we can not rule out that more chronic exposures may produce the renal damage reported by others in model systems [12][13][14].…”

Section: Discussioncontrasting

confidence: 58%

Intestinal and renal handling of oxalate loads in normal individuals and stone formers

2007

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The renal handling and intestinal absorption of dietary oxalate are believed to be risk factors for calcium oxalate stone formation. In this study, we have examined the time and dose effects of soluble oxalate loads on the intestinal absorption and renal handling of oxalate in six stone formers (SF) and six normal individuals (N) who consumed diets controlled in oxalate and other nutrients. Urinary and plasma oxalate changes were monitored over 24 h after ingestion of 0, 2, 4, and 8 mmole oxalate loads, containing a mixture of 12 C-and 13 C 2 -oxalate. There were significant time and dose dependent changes in urinary oxalate excretion and secretion after these loads. However, there were no significant differences between SF and N in both the intestinal absorption and the renal handling of oxalate loads, as measured by the urinary excretion of oxalate (P = 0.96) and the ratio of oxalate to creatinine clearance (P = 0.34). 13 C 2 -oxalate absorption studies showed three of the subjects, two SF and one N, had enhanced absorption with the 8 mmole load. A clear difference in absorption was demonstrated in these individuals during the 8-24 h interval, suggesting that in these individuals there was greater oxalate absorption in the large intestine as compared to the other subjects. This enhanced absorption of oxalate warrants further characterization.

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Section: Discussioncontrasting

confidence: 58%

Intestinal and renal handling of oxalate loads in normal individuals and stone formers

2007

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“…cPLA 2 preferentially hydrolyses arachidonoyl phospholipids generating a number of byproducts including arachidonic acid and lysophospolipids. Exposure of MDCK cells to oxalate produces a time and concentration dependent increase in cPLA 2 activity (16). Inhibition of cPLA 2 activity blocks the oxalateinduced upregulation of Egr-1, c-jun and c-myc genes.…”

Section: Discussionmentioning

confidence: 99%

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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“…Hypoxia leads to tissue damage via generation of ROS contributing significantly to the mitochondrial apoptotic pathway (35). Scavengers for ROS, H 2 O 2 , and superoxide have been shown to inhibit apoptosis induced by ischemia-reperfusion (36).…”

Section: Generation Of Ros Was Reduced In Upar-deficient Allograftsmentioning

confidence: 99%

Renal Urokinase-Type Plasminogen Activator (uPA) Receptor but not uPA Deficiency Strongly Attenuates Ischemia Reperfusion Injury and Acute Kidney Allograft Rejection

Gueler

Rong

Mengel

et al. 2008

The Journal of Immunology

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Central mechanisms leading to ischemia induced allograft rejection are apoptosis and inflammation, processes highly regulated by the urokinase-type plasminogen activator (uPA) and its specific receptor (uPAR). Recently, up-regulation of uPA and uPAR has been shown to correlate with allograft rejection in human biopsies. However, the causal connection of uPA/uPAR in mediating transplant rejection and underlying molecular mechanisms remain poorly understood. In this study, we evaluated the role of uPA/uPAR in a mice model for kidney ischemia reperfusion (IR) injury and for acute kidney allograft rejection. uPAR but not uPA deficiency protected from IR injury. In the allogenic kidney transplant model, uPAR but not uPA deficiency of the allograft caused superior recipient survival and strongly attenuated loss of renal function. uPAR-deficient allografts showed reduced generation of reactive oxygen species and apoptosis. Moreover, neutrophil and monocyte/macrophage infiltration was strongly attenuated and up-regulation of the adhesion molecule ICAM-1 was completely abrogated in uPAR-deficient allografts. Inadequate ICAM-1 up-regulation in uPAR−/− primary aortic endothelial cells after C5a and TNF-α stimulation was confirmed by in vitro experiments. Our results demonstrate that the local renal uPAR plays an important role in the apoptotic and inflammatory responses mediating IR-injury and transplant rejection.

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Mechanisms Mediating Oxalate-Induced Alterations in Renal Cell Functions

Cited by 77 publications

References 0 publications

Intestinal and renal handling of oxalate loads in normal individuals and stone formers

Intestinal and renal handling of oxalate loads in normal individuals and stone formers

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

Renal Urokinase-Type Plasminogen Activator (uPA) Receptor but not uPA Deficiency Strongly Attenuates Ischemia Reperfusion Injury and Acute Kidney Allograft Rejection

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