Lipid peroxidation in human proteinuric disease.

Abstract:

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 semiquantitative 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.

journal_name

Kidney Int

journal_title

Kidney international

authors

Solin ML,Ahola H,Haltia A,Ursini F,Montine T,Roveri A,Kerjaschki D,Holthöfer H

doi

10.1046/j.1523-1755.2001.059002481.x

subject

Has Abstract

pub_date

2001-02-01 00:00:00

pages

481-7

issue

2

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)47498-8

journal_volume

59

pub_type

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