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Acrolein is known as a ubiquitous pollutant in the environment, for example,
incomplete combustion of plastic materials, cigarette smoking, and overheat-
ing frying oils. Acrolein is also a metabolite formed in the biotransformation
of allyl compounds and the widely used anticancer drug cyclophosphamide.
Its high reactivity indeed makes acrolein a dangerous substance for the living
cell. Among all
-unsaturated aldehydes, including 4-hydroxy-2-nonenal,
acrolein is by far the strongest electrophile and, therefore, shows the highest
reactivity with nucleophiles, such as the sulfhydryl group of cysteine, imidaz-
ole group of histidine, and amino group of lysine (357). Acrolein undergoes
nucleophilic addition at the double bond to form a secondary derivative with
retention of the aldehyde group, resulting in the formation of the Michael
addition-type acrolein-amino acid adducts. It has been shown that acrolein
modifies lysine and histidine residues of human serum albumin (358) and
proteinase (359). It was shown that this aldehyde is not just a pollutant, but
also a lipid peroxidation product that could be ubiquitously generated in bio-
logical systems (360). Upon incubation with BSA, acrolein was rapidly incor-
porated into the protein and generated the protein-linked carbonyl derivative.
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, N-
-(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 neointima of arterial walls. The observations that (i)
oxidative modification of LDL with Cu 2+ generated the acrolein-LDL adducts
and that (ii) the iron-catalyzed oxidation of arachidonate in the presence of
protein resulted in the formation of antigenic materials suggested that poly-
unsaturated fatty acids are sources of acrolein that cause the production of
protein-bound acrolein. The data suggest that the protein-bound acrolein rep-
resents potential markers of oxidative stress and long-term damage to proteins
in aging, atherosclerosis, and diabetes (360).
Metal toxicity, as mild congenital methylmercury toxicity, influences protein
turnover. To prove this, female rats were injected intravenously with 10 mg/kg
methylmercury chloride on the fourth day of impregnation. Controls received
saline. At postnatal days 1, 7, 14, and 21, pup brain slices were incubated
with either 3-hydroxy[3-14C]butyrate or [U-14C] glucose. The rate of oxida-
tion of 3-hydroxybutyrate was significantly reduced at days 14 and 21 in the
methylmercury-treated pups. There was a marked reduction in the incorpora-
tion of label from both substrates into total brain lipids during the most rapid
phase of myelination. Incorporation of 14C from [U-14C] glucose into proteins
was decreased at all ages. Since there was no decrease in the incorporation of
[1-14C]leucine into proteins in the methylmercury-treated pups, this decrease
could have resulted from changes in pool sizes of certain amino acids in the
brain (361).
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