Journal
KIDNEY INTERNATIONAL
Volume 59, Issue 2, Pages 481-487Publisher
ELSEVIER SCIENCE INC
DOI: 10.1046/j.1523-1755.2001.059002481.x
Keywords
nephrotic syndrome of the Finnish type; lipoperoxides; 4-hydroxynoneal; malonyldialdehyde; phospholipid hydroperoxide glutathione; peroxidase; glomerular disease
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Background. While metabolically generated oxidants are produced locally in experimental glomerular diseases, little is still known of their significance and the respective scavenger systems in human glomerular diseases. Methods. Here we studied kidneys from patients with congenital nephrotic syndrome of the Finnish type (CNF). a human model disease of isolated proteinuria. Expression of specific mRNAs for a major antioxidant system against lipoperoxidation [phospholipid hydroperoxide glutathione peroxidase (PHGPx)] and for mitochondrial proteins were studied in Northern blotting together with analysis of PHGPx in semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The respective proteins and lipoperoxide (LPO) adducts malonyldialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were analyzed in immunohistochemistry. Results. PHGPx and the mitochondrially encoded subunits of cytochrome-c-oxidase were distinctly down-regulated within the glomeruli of CNF kidneys. These changes were confirmed in semiquantitative RT-PCR. Increases of lipoperoxidation products MDA and 4-HNE were constantly found in the glomeruli of CNF. In agreement with findings in CNF. similar results were obtained in biopsies from other human glomerular diseases. Conclusions. These findings suggest that local mitochondrial damage initiates LPO. which then causes deposition of the cytotoxic LPO products in glomeruli, as seen especially in CNF kidneys. Together with down-regulation of the local antioxidant protection, these may be important pathophysiologic mechanisms in human glomerular disease.
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