Ceruloplasmin as protector against oxidative injury – ‘Antioxidant Ceruloplasmin Is Expressed by Glomerular Parietal Epithelial Cells and Secreted into Urine in Association with Glomerular Aging and High-Calorie Diet’
“... Cp functions as an important antioxidant mechanism. It serves as a ferroxidase that converts toxic ferrous iron to nontoxic ferric iron, which thereby becomes available for binding to and transport by transferrin (1). At the same time, Cp serves as an antioxidant by removing the free ferrous iron, which acts as a major producer of oxidants (superoxide and hydroxyl radical) (33). Cp also serves as a general antioxidant by catalyzing the destruction of oxygen radicals (2,3,34) and can bind to and inhibit neutrophil myeloperoxidase oxidant activity (4). Oxidative damage is thought to be of major importance in tissue aging, including lipid peroxidation and damage to DNA and proteins (3,14,15). Increased levels of lipid peroxidation products as well as oxidant-induced DNA damage have been shown to be associated with aging and with accelerated aging states such as diabetes and chronic kidney disease (14–22). Decreased levels of available antioxidants also have been associated with frailty and chronic disease states (21). ....For example, De Tata et al. (36) reported that aldehydes that are generated by lipid peroxidation are present in urine and that levels of aldehyde excretion are affected by both age and diet. Cp that is present on the surface of and secreted by parietal epithelial cells could detoxify filtered ferrous iron and other oxidants and thereby reduce oxidant injury in Bowman’s space and in the downstream nephron....
Conclusion
We speculate that we have uncovered part of a novel function of the parietal epithelial cell as a protective mechanism situated immediately downstream of the glomerular filter. Cp may be one part of a more complex repertoire of this cell, which functions to protect the glomerular podocytes in Bowman’s space and the downstream nephron from oxidant injury. The finding that this antioxidant mechanism was clearly increased with age and was enhanced by a process that is known to accelerate oxidant injury and the aging process (a high-calorie diet) raises the question of whether this could be one part of a mechanism that protects the aging kidney. On the basis of these results, evaluation of other antioxidant processes in older kidneys also is warranted, because conclusions that are drawn on the basis of younger kidneys may not be applicable to old kidneys. This report shows that, at least with respect to Cp, an old kidney is not the same as a young kidney. This is important when one considers that ESRD is a disease of older age. Reduced capacity of the kidney to produce Cp such as may occur in chronic renal diseases also could render the kidney less able to detoxify the large amounts of iron that commonly are administered to these patients for treatment of anemia.”
Read more/full paper: http://m.jasn.asnjournals.org/content/17/5/1382.fullDiscussion