Lipid peroxidation acrolein

Flaenen GRMM, Bermeulen NPE, Taai Tin Tsoi JNL, et al. 1988. Activation of the microsomal glutathione-S-transferase and reduction of the gultathione dependent protection against lipid peroxidation by acrolein. Biochem Pharmacol 37 1933-1938. 

Jaeschke H, Kleinwaechter C, Wendel A. 1987. The role of acrolein in allyl alcohol-induced lipid peroxidation and liver cell damage in mice. Biochem Pharmacol 36 51-58. 

Figure 22.7. The major DNA lesions of the lipid peroxidation products. (A) DNA lesions produced by malondialdehyde. Mi denotes the monomeric form of malondialdehyde. Malo-ndialdehyde can polymerize to form dimers and trimers that can also react with DNA. The resulting lesions are designated as M2 and M3, respectively (c.g., M2G). These lesions, however, may not be significant in cells as polymerization of malondialdehyde is relatively slow at neutral pH. (B) The l,7V2-propano-dG DNA adducts produced by acrolein, crotonaldehyde, and 4-hydroxy-2-nonenal (HNE). Stereochemistry is not shown. The l.A -acrolcin-dG consists of three isomers. The 1, AAcrotonaldchyde-dG consists of two isomers. The FAAlINF-dGconsistsof four isomers. (C)EthenoDNAadductsproduced by 2,3-epoxy-4-hydroxynonenal. Further oxidation of 4-hydroxynonenal produces 2,3-epoxy-4-hydroxynonenal, which reacts with DNA to form the exocyclic etheno adducts.

Williams TI, Lynn BC, Markesbery WR, Lovell MA (2005) Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in Mild Cognitive Impairment and early Alzheimer s disease. Neurobiol Aging 27(8) 1094—1099 WUquet V, De Strooper B (2004) Amyloid-beta precursor protein processing in neurodegeneration. Curr Opin Neurobiol 14 582-588... 

Allyl alcohol is inactive per se and its toxic effect is mediated by its ADH oxidation to form acrolein, which is responsible for the hepatotoxic action. The toxicity of the alcohol (or its metabolite acrolein) is dependent on the concentration of glutathione (GSH). After severe depletion of GSH, the reactive metabolite of allyl alcohol can bind to essential sulfhydryl groups in the cellular macromolecules, leading to structural and functional changes in cellular molecules, which can be responsible for cell death. In this case, the appearance of lipid peroxidation could be merely the consequence of cell death. 

MDA is an abundant product of lipid peroxidation and one of the first products identified to arise from the oxidation of lipids [31-33]. MDA is a bifunctional electrophile with pH-dependent reactivity, which exists as the P-hydroxyacrolein tautomer in polar solvents and forms an enolate at physiological pH (pJC, = 4.46) [34, 35]. The structurally related base propenals are P-substituted acroleins that are similar to P-hydroxyacrolein in their reactivity with nucleophiles, but they are not ionizable at physiological pH. 

Dogterom, P., G. J. Mulder, and J. F. NageUcerke. 1988. Allyl alcohol and acrolein toxicity in isolated rat hepatocytes is independent of lipid peroxidation. Arcl . Toxicol. Suppl. 12 269-73 cited in Chem. Abstr. CA 110(1) 52457p. 

Cras et al, 1995). Lipid peroxidation is indicated by the high concentrations of the thiobarbituric acid reactive substances malondialdehyde, 4-HNE, acrolein, isopros-tanes, and altered phospholipid composition (Markesbery and Lovell, 1998 Butterfield et al., 2001). Many different proteins involved in AD are oxidatively modified (see Butterfield et al., 2006 for review Sultana et al., 2006). All these modifications are usually linked to a functional loss of proteins leading to their degradation or aggregation, as observed in AD. 

Gomez-Ramos, A., Diaz-Nido, J., Smith, M.A., Perry, G. and Avila, J. 2003. Effect of the lipid peroxidation product acrolein on tau phosphorylation in neural cells. J. Neurosci. Res. 71 863-870... 

Maeshima, T., Honda, K., Chikazawa, M., Shibata, T., Kawai, Y., Akagawa, M., and Uchida, K. Quantitative analysis of acrolein-specific adducts generated during lipid peroxidation modification of proteins in vitro Identification of Nt-formylethylhistidine as the major adduct. Chem. Res. Toxicol. 25 2012 1384—1392. 

Castegna, A., C. M. Landerback, H. Mohmmad-Abdul et al. Modulation of phospholipid asymmetry in synaptosomal membranes by the lipid peroxidation products, 4-hydroxynonenal and acrolein Imphcations for Alzheimer s disease. 1004(1-2), 2004 193-7. 

Lovell, M. A., C. Xie, andW. R. Markesbery. Acrolein, a product of lipid peroxidation, inhibits glucose and glutamate uptake in primary neuronal cultures. 29(8),... 

Lipid peroxidation of polyunsaturated fatty acids yields a group of reactive unsaturated aldehydic compounds (enals) such as 2-alkenals (acrolein [Acr], crotonaldehyde [Cro], 2-hexenal), 4-hydroxy-2-alkenals (4-hydroxy-2-nonenal [HNE], 4-hydroxy-2-hexenal [HHE]), and ketoaldehydes (malondialdehyde [MDA], glyoxal, 4-oxo-2-nonenal [ONE]) (Uchida 2003) (Eigure 18.1). 

The use of SPH strategy to enrich carbonylated species prior to mass spectrometric analysis is advantageous compared with direct immunoaffinity approaches. While the SPH method has the potential to enrich carbonylated peptides modified by a wide array of lipid peroxidation end products such as MDA, HNE, HHE, and acrolein, for example, an immunoaffinity approach requires separate antibodies against each kind of carbonyl adducts. Derivatization of peptide carbonyls with, for example, 2,4-dinitrophenylhydrazine (DNPH), and then, performing immunoaffinity-based enrichment with immobilized antidinitrophenyl antibodies, may preclude the need for separate antibodies [27]. However, these derivatives may form at low yields and, in addition, according to our experience, they tend to detach the DNPH tags with each processing step because of their instability. 

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