PROTEIN-BOUND ACROLEIN - POTENTIAL MARKERS FOR OXIDATIVE STRESS

Acrolein (CH2=CH-CHO) is known as a ubiquitous pollutant in the enviro nment. Here me show that this notorious aldehyde is not just a polluta nt, but also a lipid peroxidation product that could be ubiquitously g enerated in biological systems. Upon incubation with BSA, acrolein was rapidly incorporated into the protein and generated the protein-linke d carbonyl derivative, a putative marker of oxidatively modified prote ins under oxidative stress, To verify the presence of protein-bound ac rolein in vivo, the mAb (mAb5F6) against the acrolein-modified keyhole limpet hemocyanin was raised. It was found that the acrolein-lysine a dduct, N-epsilon-(3-formyl-3,4-dehydropiperidino) lysine, constitutes an epitope of the antibody. Immunohistochemical analysis of atheroscle rotic lesions from a human aorta demonstrated that antigenic materials recognized by mAb5FG indeed constituted the lesions, in which intense positivity was associated primarily with macrophage-derived foam cell s and the thickening neointima of arterial malls. The observations tha t (i) oxidative modification of low-density lipoprotein with Cu2+ gene rated the acrolein-low-density lipoprotein adducts and (ii) the iron-c atalyzed oxidation of arachidonate in the presence of protein resulted in the formation of antigenic materials suggested that polyunsaturate d fatty acids are sources of acrolein that cause the production of pro tein-bound acrolein. These data suggest that the protein-bound acrolei n represents potential markers of oxidative stress and long-term damag e to protein in aging, atherosclerosis, and diabetes.