Kidney international · 2001
Lipid peroxidation in human proteinuric disease.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Solin M L, Ahola H, Haltia A, Ursini F, Montine T, Roveri A, Kerjaschki D, Holthöfer H
Аннотация
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.
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.
Предметные рубрики MeSH
AdolescentAldehydesBlotting, NorthernChildChild, PreschoolGlutathione PeroxidaseHumansImmunohistochemistryIsoenzymesKidneyLipid PeroxidesMalondialdehydeNephrotic SyndromePhospholipid Hydroperoxide Glutathione PeroxidaseProstaglandin-Endoperoxide SynthasesProteinuriaRNA, MessengerReverse Transcriptase Polymerase Chain Reaction