Abstract
Acrolein, an unpleasant and troublesome by-product of overheated organic matter, occurs as a ubiquitous pollutant in the enviroment, e.g., incomplete combustion of plastic materials, cigarette smoking, and overheating frying oils. In this review, the process of discovery that the most toxic aldehyde acrolein is not just a pollutant but also a lipid peroxidation product that could be ubiquitously generated in biological systems is introduced. During incubation with protein, acrolein preferentially reacted with lysine residues to generate the novel acrolein-lysine adduct, Nε- (3-formyl-3, 4-dehydropiperidino) lysine (FDP-lysine). Acid hydrolysis of the adduct led to derivative detectable with amino acid analysis. During incubation of LDL with acrolein, lysine residues that had disappeared were partially recovered by FDP-lysine. The same derivative was detected in the oxidatively modified LDL with Cu2+. To confirm the presence of protein-bound acrolein in vivo, the monoclonal antibody (mAb5F6) against acrolein-modified protein was raised. The acrolein-lysine adduct, FDP-lysine, was found to be an epitope of the antibody. Enzyme-linked immunosorbent assay (ELISA) for measuring free acrolein indicated a considerable acrolein to be released from Cu2+-oxidized LDL. That (i) oxidative modification of low-density lipoprotein (LDL) with Cu2+ generated acrolein-LDL adducts and (ii), during long-term incubation of protein with glucose, ascorbate, or arachidonate in vitro, arachidonate was the only source of antigenic material suggest polyunsaturated fatty acids to possibly be sources of acrolein that cause the production of protein-bound acrolein. Immunohistochemical analysis of atherosclerotic lesions from a human aorta demonstrated antigenic materials recognized by mAb5F6 to actually be present in the lesions and this to clearly be related to macrophages.
