|
| Am J Nephrol. 2004 Nov 10;24(5):557-568 [Epub ahead of print] Related Articles,
Links
Molecular Mechanism of Oxalate-Induced Free Radical Production and Glutathione
Redox Imbalance in Renal Epithelial Cells: Effect of Antioxidants.
Rashed T, Menon M, Thamilselvan S.
Department of Urology, Vattikuti Urology Institute and Henry Ford Health
Sciences Center, Detroit, Mich., USA.
Background: Peroxidation of renal cells is a critical event in the nucleation
and formation of calcium oxalate crystals under hyperoxaluric conditions. We
previously demonstrated that oxalate-induced peroxidative injury is one of the
major mechanisms in promoting crystal attachment to renal epithelial cells.
Methods: In this study we have demonstrated that the mechanism of
oxalate-induced peroxidative injury is through the induction of TGF-beta(1) and
glutathione (GSH) redox imbalance in LLC-PK(1) cells. Results: LLC-PK(1), renal
epithelial cells exposed to oxalate had significantly higher reactive oxygen
species (ROS) production; higher TGF-beta(1) levels, as measured by ELISA (1.89
+/- 0.035 fold increase) or Western blot (1.65 +/- 0.01 fold increase);
increased malondialdehyde formation; increased LDH release, and loss of cell
viability. In addition, oxalate exposure significantly decreased GSH content,
glutathione reductase, glucose-6-phosphate dehydrogenase activities, and
increased oxidized GSH content. Treatment with vitamin E, neutralizing
anti-TGF-beta antibody, or diphenylene iodium, an inhibitor of NAD(P)H oxidase,
significantly inhibited oxalate-induced ROS production and prevented
peroxidative injury and cytolysis. Vitamin E, catalase, or desferoxamine
treatment also significantly restored the oxalate-induced cellular GSH redox
status toward the control level, and vitamin E treatment significantly
attenuated the oxalate-mediated increase in TGF-beta(1) protein in cultured
LLC-PK(1) cells. Conclusions: This is the first study to demonstrate that the
mechanism of oxalate-induced free radical production in renal tubular
epithelial cells is through the activation of NAD(P)H oxidase via cytokine
TGF-beta(1) induction. These results also provide direct evidence that
antioxidant therapy might prevent calcium oxalate nucleation and kidney stone
formation by preventing oxalate-mediated peroxidative injury and GSH redox
imbalance. Copyright (c) 2004 S. Karger AG, Basel.
PMID: 15539792 [PubMed - as supplied by publisher]
--------------------------------------------------------------------------
------
Who loves ya.
Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore
DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking
|
|