Aldehydes protein adducts

Aldehyde-protein adducts and hydroxyl radicals also stimulate immunological responses directed against the specific modifications of proteins. High antibody titres have been observed from patients with severe alcoholic liver disease, particularly IgA and IgG autoantibodies. Such antibodies have considerable specificity towards aldehyde-lysine residues. Alcohol consumption markedly increases the hepatic output of very low-density lipoprotein (VLDL), but decreases the low-density lipoprotein (LDL) levels and apolipoprotein B. Ethylation of apo-B-lysine renders LDL immunogenic and accelerates its clearance. Alcoholics have been shown to develop acetaldehyde adducts in apo-B-containing lipoproteins, particularly VLDL. 

O. Niemela. 1999. Aldehyde-protein adducts in the liver as a result of ethanol-induced oxidative stress Front. Biosci. 1 ... 

Formation of protein adducts with reactive aldehydic products may provide a general basis for observed pathogenesis. 

Among the various end products of the oxidative breakdown of biomembrane polyunsaturated fatty acids, aldehydes have been well characterized for their potential contribution to free radical pathobiology. The group of aldehydes that displays the greatest number of biochemical activities is the 4-hydroxyalkenals. Quantitatively, the most representative hydroxyalkenal in animal tissues is 4-hydroxy-23-nonenal (4-HNE). This aldehyde derives from the oxidation of arachidonic add, as well as linoleic acid. s Monoclonal antibodies against 4-HNE protein adducts have positively identified this molecule in human chronic diseases, and several reports pointed to the potential effect of increased levels of 4-HNE on different cell functions. 

This chapter snmmarized protein lipoxidation, mainly focusing on protein adduction chemistry with reactive aldehydes generated from the peroxidation of polyunsaturated fatty acids. On the basis of a large number of reports concerning the chemical and immunochemical detection of lipoxidation products in vivo, there may be no... 

Ichihashi, K., Osawa, T., Toyokuni, S., and Uchida, K. Endogenous formation of protein adducts with carcinogenic aldehydes Implication for oxidative stress. J. Biol. Chem. 276 2001 23903-23913. 

Hydroxynonenal is one of the major aldehyde products of lipid peroxidation and has been reported to be the most toxic aldehyde formed (Bene-detti et al. 1979, 1980, Benedetti and Comporti 1987). Li et al. (1996) found a formation of protein adducts in alveolar macrophages from C3H/HeJ and C57BL/6J mice in a dose-dependent manner. Alveolar macrophages from both strains had extensive apoptosis at 100 [iM 4-hydroxyonenal. 

Ethanol and Acetaldehyde. - Alcohol dehydrogenase (ADH) and cytochrome P4502E1 (CYP2E1) oxidise ethanol to acetaldehyde, which is further oxidised to acetate by aldehyde dehydrogenase (ADH). Acetaldehyde has been considered to play a key role in the toxicity of ethanol, primarily through its formation of covalent adducts (Schiff bases) with proteins, thereby provoking an immunotoxic response. More recently, attention has focussed on the role of the a-hydroxyethyl radical, which also forms protein adducts that elicit im-munotoxicity. ... 

Burcham, P. C. and Pyke, S. M. (2006). Hydralazine inhibits rapid acrolein-induced protein oligomerization Role of aldehyde scavengers and adduct trapping in cross-link blocking and cytoprotection. Mol. Pharm. 69,1056-1065. 

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. 

Pentosidine is determined by HPLC with spectrofluorimetric detection (excitation and emission wavelengths of 335 and 385 nm, respectively) (S14), although immunochemical and ELISA assays for determination of various protein oxidative modification products have become increasingly popular (08). Protein-aldehyde adducts can be estimated using adduct-specific antibodies (U2, Wl). Another approach requires stabilization of adducts, producing derivatives resistant to conditions used in protein acid hydrolysis and quantification of hydrolysis products by gas chromatography-mass spectrometry (R7). 

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