title: Impaired glomerular and tubular antioxidative defense mechanisms in nephrotic syndrome.
abstract: The molecular mechanisms behind acquired nephrotic syndrome (NS) are still largely unknown. One possible explanation for the development of proteinuria is oxidative damage to the glomerular cells. Our hypothesis was that the oxidative defense is weakened in NS, and we focused on measurements of the oxidative-antioxidative status in the glomerular and tubular parts of the nephron. Gene expression was analyzed in renal biopsies from patients with NS. In addition, to compare the acute and chronic phases of the disease, we studied puromycin-treated rats. In the biopsy material, the expression of enzymes involved in the antioxidative defense was higher in the tubulointerstitial compartment than in the glomerular cells. Real-time PCR analysis revealed a decreased glomerular expression in nephrotic kidneys for the antioxidant enzymes catalase and glutathione peroxidase-3, and -4. The tubular gene expression was downregulated for catalase, glutathione peroxidase-3, and thioredoxin reductase-1 and -2. The altered gene expression was accompanied by increased lipid peroxidation in urine. In rats, serum concentrations of ascorbyl-free radicals, measured with electron spin resonance, were elevated in the acute phase of the disease, suggesting increased oxidative stress in the circulation. In addition, we saw an increase in the plasma antioxidant capacity combined with a decreased oxidation of proteins in sera from nephrotic rats, but not from humans. In conclusion, there is a marked downregulation of several antioxidative enzymes in nephrotic kidneys, especially in glomerular structures. Our data suggest that oxidative damage to glomerular cells may contribute significantly to the course and prognosis of nephrotic syndrome.
authors.affiliation: Institute of Medicine, Department of Molecular and Clinical Medicine (Nephrology), Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. anna.granqvist@wlab.gu.se
authors.forename: Anna
authors.initials: A
authors.lastname: Granqvist
authors.forename: Ulf A
authors.initials: UA
authors.lastname: Nilsson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ebefors
authors.forename: Börje
authors.initials: B
authors.lastname: Haraldsson
authors.forename: Jenny
authors.initials: J
authors.lastname: Nyström
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001706:Biopsy; D016022:Case-Control Studies; D002374:Catalase / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005919:Glomerular Filtration Rate; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D007684:Kidney Tubules / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D011692:Puromycin Aminonucleoside / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D011692:Puromycin Aminonucleoside; D002374:Catalase; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase