Interaction of lipid peroxidation products with nuclear macromolecules.
The interaction of lipid peroxidation products with nuclear macromolecules was investigated in rat liver nuclei labelled with [3H]arachidonic acid. Lipid peroxidation reactions were driven both non-enzymatically and enzymatically by the addition of ascorbate-Fe2+ or NADPH-ADP-Fe3+, respectively, to the incubation mixtures. The extent of peroxidation was evaluated by the formation of thiobarbituric acid chromophore and of radioactive hydrophilic peroxidation products. The results obtained show that: (1) nuclear membrane lipid peroxidation products formed during incubation interact with DNA and total nuclear proteins; (2) non-enzymatic lipid peroxidation processes induced a 40% larger association of peroxidation products to DNA compared to processes driven enzymatically, whereas the corresponding interaction with total nuclear proteins was similar in both peroxidation systems; (3) the radioactivity associated with histones decreased during incubation in the presence of ascorbate-Fe2+ or NADPH-ADP-Fe3+, and increased in control samples (no additions); (4) inhibition of lipid peroxidation by the iron chelator Desferrioxamine B prevented the association of peroxidation products to nuclear macromolecules; (5) the levels of radioactivity found in DNA after 180 min of incubation would represent the formation of 0.6-1.0 adducts per 10(6) DNA bases. The results obtained provide evidence for an interaction between lipid peroxidation products and chromatin in the interior of the cell nucleus.
Vaca
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Department of Radiobiology, Arrhenius Laboratories for Natural Sciences, University of Stockholm, Sweden.
Harms-Ringdahl
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D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology; D046911:Macromolecular Substances; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D002843:Chromatin; D008054:Lipid Peroxides; D046911:Macromolecular Substances; D008563:Membrane Lipids; D004247:DNA; D003676:Deferoxamine