Localization of 4-hydroxy-2-nonenal-modified proteins in kidney following iron overload
| Autor: | Luke I. Szweda, Richard Weindruch, Terry D. Oberley, Theodor A. Zainal |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Nitrilotriacetic Acid Free Radicals Protein Carbonyl Content Mitochondrion Protein oxidation Kidney Biochemistry Ferric Compounds Nephrotoxicity Lipid peroxidation Kidney Tubules Proximal chemistry.chemical_compound Mice Physiology (medical) Malondialdehyde Animals Rats Wistar Microscopy Immunoelectron Cell Nucleus Aldehydes Kidney metabolism Proteins Immunogold labelling Mitochondria Rats chemistry Lipid Peroxidation Oxidation-Reduction |
| Zdroj: | Free radical biologymedicine. 26(9-10) |
| ISSN: | 0891-5849 |
| Popis: | Intraperitoneal (IP) injection of ferric nitrilotriacetate (Fe-NTA) to rats and mice results in iron-induced free radical injury and cancer in kidneys. We sought to clarify the exact localization of acute oxidative damage in Fe-NTA-induced nephrotoxicity by performing immunogold light and electron microscopic (EM) techniques using an antibody against 4-hydroxy-2-nonenal (HNE)-modified proteins. Biochemical assays were done to provide complementary quantitative data. Renal accumulation of lipid peroxidation-derived aldehydes, such as malondialdehyde (MDA) and 4-hydroxy-2-alkenals (4-HDA), increased in parallel with protein carbonyl content, an indicator of protein oxidation, 30 min after administration of Fe-NTA. Immunogold light microscopy showed that HNE-modified proteins increased at 30 min with positivity localized to proximal tubular cells. Immunogold EM demonstrated that HNE-modified proteins were mainly in the mitochondria and nuclei of the proximal tubular epithelium. The intensity of labeling at both the light and EM levels increased together with levels of biochemically measured lipid peroxidation products and protein carbonyl content. Our data suggest that the mechanism of acute nephrotoxicity of Fe-NTA involves mitochondrial and nuclear oxidative damage, findings that may help to define the mechanisms of iron-induced cell injury. |
| Databáze: | OpenAIRE |
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