4-Hydroperoxy-2-nonenal is not just an intermediate but a reactive molecule that covalently modifies proteins to generate unique intramolecular oxidation products.
ABSTRACT α,β-Unsaturated aldehydes generated during lipid peroxidation, such as 4-oxoalkenals and 4-hydroxyalkenals, can give rise to protein degeneration in a variety of pathological states. Although the covalent modification of proteins by these end products has been well studied, the reactivity of unstable intermediates possessing a hydroperoxy group, such as 4-hydroperoxy-2-nonenal (HPNE), with protein has received little attention. We have now established a unique protein modification in which the 4-hydroperoxy group of HPNE is involved in the formation of structurally unusual lysine adducts. In addition, we showed that one of the HPNE-specific lysine adducts constitutes the epitope of a monoclonal antibody raised against the HPNE-modified protein. Upon incubation with bovine serum albumin, HPNE preferentially reacted with the lysine residues. By employing N(α)-benzoylglycyl-lysine, we detected two major products containing one HPNE molecule per peptide. Based on the chemical and spectroscopic evidence, the products were identified to be the N(α)-benzoylglycyl derivatives of N(ε)-4-hydroxynonanoic acid-lysine and N(ε)-4-hydroxy-(2Z)-nonenoyllysine, both of which are suggested to be formed through mechanisms in which the initial HPNE-lysine adducts undergo Baeyer-Villiger-like reactions proceeding through an intramolecular oxidation catalyzed by the hydroperoxy group. On the other hand, using an HPNE-modified protein as the immunogen, we raised a monoclonal antibody against the HPNE-modified protein and identified one of the HPNE-specific lysine adducts, N(ε)-4-hydroxynonanoic acid-lysine, as an intrinsic epitope of the monoclonal antibody. Furthermore, we demonstrated that the HPNE-specific epitopes were produced not only in the oxidized low density lipoprotein in vitro but also in the atherosclerotic lesions. These results indicated that HPNE is not just an intermediate but also a reactive molecule that could covalently modify proteins in biological systems.
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ABSTRACT: Lipid peroxides and their reactive aldehyde derivatives (LPPs) have been linked to obesity-related pathologies, but whether they have a causal role has remained unclear. Glutathione peroxidase 4 (GPx4) is a selenoenzyme that selectively neutralizes lipid hydroperoxides, and human gpx4 gene variants have been associated with obesity and cardiovascular disease in epidemiological studies. This study tested the hypothesis that LPPs underlie cardio-metabolic derangements in obesity using a high fat, high sucrose (HFHS) diet in gpx4 haploinsufficient mice (GPx4+/-) and in samples of human myocardium.04/2015; 384(6). DOI:10.1016/j.molmet.2015.04.001
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ABSTRACT: Oxidative stress is a dysfunctional state of living cells, caused by the disturbance of the pro-/antioxidative equilibrium. This dynamic equilibrium, constitutive for all aerobic organisms, is an inevitable necessity of maintaining the level of oxidative factors on non-destructive value to the cell. Among these factors reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the best known molecules. This review article shows the current state of knowledge on the chemical specificity, relative reactivity and main sources of ROS and RNS in biological systems. As a Part 1 to the report about the role of oxidative stress in psychiatric disorders (see Smaga et al., Pharmacological Reports, this issue), special emphasis is placed on biochemical determinants in nervous tissue, which predisposed it to oxidative damage. Oxidative stress can be identified based on the analysis of various biochemical indicators showing the status of antioxidant barrier or size of the damage. In our article, we have compiled the most commonly used biomarkers of oxidative stress described in the literature with special regard to potentially effective in the early diagnosis of neurodegenerative processes. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.Pharmacological reports: PR 01/2015; 67(3). DOI:10.1016/j.pharep.2014.12.014 · 2.17 Impact Factor
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ABSTRACT: Solid Phase Microextraction (SPME) followed by Gas Chromatography/Mass Spectrometry (GC/MS) was employed to study the headspace composition of corn oil (maize oil) samples stored at room temperature in closed receptacles with limited amounts of air for different periods of time. Samples with a high oxidation level showed the presence of typical secondary volatile oxidation compounds such as alkanals, 2-alkenals, 2,4-alkadienals, acids, alcohols, ketones, alkylfurans and lactones. Aldehydes were the most numerous group; however, acids, which were fewer in number, showed the highest abundances. The high number of lactones detected is also noteworthy. In agreement with corn oil composition, those volatiles derived from linoleic acyl groups appeared in the highest abundances. The detection of two groups of toxic compounds, whose rise in concentration corresponded with the oxidation level of the samples, was remarkable. There were, on the one hand, alkylbenzenes and mono- and poly-cyclic aromatic hydrocarbons (PAHs) of low molecular weight, such as toluene, naphthalene and fluorene. On the other hand, there were oxygenated alpha,beta-unsaturated aldehydes like 4-hydroxy-2-nonenal, 4-oxo-2-nonenal and 4,5-epoxy-2-decenal brought about by the oxidation of omega-6 polyunsaturated acyl groups (linoleic), and, in much lower proportions, 4-hydroxy-2-hexenal and 4,5-epoxy-2-heptenal coming from omega-3 ones (linolenic).Practical applications: The identification and quantification of such a great number of volatile compounds coming from corn oil can be very helpful for other researchers who study the degradation of this vegetable oil or other kinds with similar proportions of acyl groups.European Journal of Lipid Science and Technology 04/2014; 116(4). DOI:10.1002/ejlt.201300244 · 2.03 Impact Factor