Lipid peroxidation in human proteinuric disease

Citation
Ml. Solin et al., Lipid peroxidation in human proteinuric disease, KIDNEY INT, 59(2), 2001, pp. 481-487
Citations number
37
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
KIDNEY INTERNATIONAL
ISSN journal
00852538 → ACNP
Volume
59
Issue
2
Year of publication
2001
Pages
481 - 487
Database
ISI
SICI code
0085-2538(200102)59:2<481:LPIHPD>2.0.ZU;2-F
Abstract
Background. While metabolically generated oxidants are produced locally in experimental glomerular diseases, little is still known of their significan ce and the respective scavenger systems in human glomerular diseases. Methods. Here we studied kidneys from patients with congenital nephrotic sy ndrome of the Finnish type (CNF). a human model disease of isolated protein uria. Expression of specific mRNAs for a major antioxidant system against l ipoperoxidation [phospholipid hydroperoxide glutathione peroxidase (PHGPx)] and for mitochondrial proteins were studied in Northern blotting together with analysis of PHGPx in semi-quantitative reverse transcription-polymeras e chain reaction (RT-PCR). The respective proteins and lipoperoxide (LPO) a dducts malonyldialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were analyzed i n immunohistochemistry. Results. PHGPx and the mitochondrially encoded subunits of cytochrome-c-oxi dase were distinctly down-regulated within the glomeruli of CNF kidneys. Th ese changes were confirmed in semiquantitative RT-PCR. Increases of lipoper oxidation products MDA and 4-HNE were constantly found in the glomeruli of CNF. In agreement with findings in CNF. similar results were obtained in bi opsies from other human glomerular diseases. Conclusions. These findings suggest that local mitochondrial damage initiat es LPO. which then causes deposition of the cytotoxic LPO products in glome ruli, as seen especially in CNF kidneys. Together with down-regulation of t he local antioxidant protection, these may be important pathophysiologic me chanisms in human glomerular disease.