Protein-bound acrolein: Potential markers for oxidative stress

Koji Uchida, Masamichi Kanematsu, Kensuke Sakai, Tsukasa Matsuda, Nobutaka Hattori, Yoshikuni Mizuno, Daisuke Suzuki, Toshio Miyata, Noriko Noguchi, Etsuo Niki, Toshihiko Osawa

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567 Citations (Scopus)


Acrolein (CH2=CH-CHO) is known as a ubiquitous pollutant in the environment. Here we show that this notorious aldehyde is not just a pollutant, but also a lipid peroxidation product that could be ubiquitously generated in biological systems. Upon incubation with BSA, acrolein was rapidly incorporated into the protein and generated the protein-linked carbonyl derivative, a putative marker of oxidatively modified proteins under oxidative stress. To verify the presence of protein-bound acrolein in vivo, the mAb (mAb5F6) against the acrolein-modified keyhole limpet hemocyanin was raised. It was found that the acrolein-lysine adduct, Nε-(3-formyl-3,4- dehydropiperidino) lysine, constitutes an epitope of the antibody. Immunohistochemical analysis of atherosclerotic lesions from a human aorta demonstrated that antigenic materials recognized by mAb5F6 indeed constituted the lesions, in which intense positivity was associated primarily with macrophage-derived foam cells and the thickening neo-intima of arterial walls. The observations that (i) oxidative modification of low-density lipoprotein with Cu2+ generated the acrolein-low-density lipoprotein adducts and (ii) the iron-catalyzed oxidation of arachidonate in the presence of protein resulted in the formation of antigenic materials suggested that polyunsaturated fatty acids are sources of acrolein that cause the production of protein-bound acrolein. These data suggest that the protein-bound acrolein represents potential markers of oxidative stress and long-term damage to protein in aging, atherosclerosis, and diabetes.

Original languageEnglish
Pages (from-to)4882-4887
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
Publication statusPublished - 1998 Apr 28


  • Antibody
  • Atherosclerosis
  • Covalent modification of protein


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