Malondialdehyde adducts

Hadley, M. and Draper, H.H. (1990). Isolation of a guanine-malondialdehyde adduct from rat and human urine. Lipids 25, 82-85. 

Chen, J., Peterson, D., Schenker, S., and Henderson, G.I. (2000). Eormation of malondialdehyde adducts in fivers of rats exposed to ethanol Role in ethanol-mediated inhibition of cytochrome c oxidase. Alcoholism Clin. Exp. Res. 24(4) 544-552. 

The chemical adducts formed by reaction of aldehydes with lysine residues form highly immunogenic epitopes, and antibodies have been prepared specific for malondialdehyde- and 4-hydroxynonenal-conjugated LDL (Gonen et al., 1987 Yla-Herttuala et al., 1989 Jurgens et al., 1990). These antibodies cross-react with material in atherosclerotic lesions but not normal tissue, thus supporting the central role of lipid peroxidation in the patho nesis of atherosclerosis (Yla-Herttuala et al., 1989, 1991). 

Stone, K., Ksebati, M. and Marnett, L.J. (1990a). Identification of the adducts formed by reaction of malondialdehyde with adenosine. Chem. Res. Tox. 3, 33-38. 

DNA alkylation has the potential to yield a time-dependent spectrum of adducts, in which initially formed kinetically favored lesions give way to the thermodynamically favored adducts over time. Reversible alkylation has been observed at several of the nucleophilic sites in DNA, including N3A (CC-1065,7, Scheme 8.10, duocarmycin, 8)," " NIA (qui-none methide, 9)," N7G (leinamycin, Schane 8.11, aflatoxin Bj epoxide, 10 and quinone methide, 9),57.ii4.ii8 (quinone methide, 9)," and bPG (ecteinascidin 743,11)." The bidentate Nl/ISPG adduct of malondialdehyde also forms reversibly. ... 

Chaudhary, A.K., Nokubo, M., Reddy. G.R., Yeola, S.N., Morrow, J.D., Blair, LA. Marnett, L.J. (1994) Detection of endogenous malondialdehyde-deoxyguanosine adducts in human liver. Science, 265, 1580-1582... 

Agarwal, S. Draper, H.H., (1992) Isolation of a malondialdehyde-deoxyguanosine adduct from rat liver DNA. Free Rad. Biol. Med., 13, 695-699... 

L.H. (1994) Detection of endogenous malondialdehyde-deoxyguanosine adducts in human liver. Science, 265, 1580-1584... 

Wang, M., Dhingra, K., Hittelman, W.N., Liehr, J.G., de Andrade, M., and Donghui, L. 1996. Lipid peroxidation-induced putative malondialdehyde-DNA adducts in human breast tissues. Cancer Epidemiol. Biomarkers Prev. 5, 705—710. 

Inhibition of the formation of CML and pentosidine from various AGE precursors and BSA was more efficient with OPB-9195 than with AG.601 OPB-9195 also inhibited the formation of two ALEs (malondialdehyde-lysine and 4-hydroxynonenal-protein adduct) with an efficiency similar to that of AG. In glucose-based peritoneal dialysis fluid, OPB-9195 inhibited AGE formation, probably by trapping reactive carbonyls, such as GO, MGO, and 3-deoxyglucosone. 

Marnett LJ, Basu AK, O Hara SM. 1986. The role of cyclic nucleic acid adducts in the mutational specificity of malondialdehyde and beta-substituted acroleins in Salmonella. IARC Sci Publ... 

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.

Aldehydes, which are secondary products of lipid peroxidation, consist of other groups of agents involved in oxidative stress and modification of proteins structures. Protein cross-linking can occur in vitro employing the malondialdehyde (MDA) Schiff-base-type adducts produced by lysine residues. 

Formation of hybrid adducts with acetaldehyde and malondialdehyde (MAA adducts) has been shown to act in a synergistic manner and may be involved in the stabilisation of protein adducts in vivo. Malondialdehyde (HOCH=CH-CHO) is a highly reactive dialdehyde originating from the non-enzymatic lipid peroxidation of a variety of unsaturated fatty acids. 

Furthermore other free radical induced processes, e.g. lipid peroxidation, produce reactive intermediates that may be important. Examples of such other lesions are for example malondialdehyde induced DNA damage and exocyclic DNA adducts [22]. 

---