4-oxo-2-nonenal is both more neurotoxic and more protein reactive than 4-hydroxy-2-nonenal

摘要: Electrophilic aldehydes, generated from oxidation of polyunsaturated fatty acyl chains under conditions oxidative stress, bind to proteins and polynucleotides can lead cell death. 4-Hydroxy-2-nonenal (HNE) 4-oxo-2-nonenal (ONE) have been shown here be toxic human neuroblastoma cells in culture at low micromolar concentrations. ONE is 4-5 times more neurotoxic concentrations near the threshold lethality. The reactions these two aldehydes with model proteins, ribonuclease A beta-lactoglobulin, their Lys epsilon-dimethylamino derivatives, followed spectrophotometrically. On basis t(1/2) measurements for disappearance alpha,beta-unsaturated chromophore, 6-31 reactive proteins. fastest reaction involves Schiff base formation epsilon-amino groups, whereas not spectroscopically apparent HNE. Detailed kinetic studies initial HNE carried out amino acids acid surrogates. Whereas imidazole thiol nucleophiles involve straightforward Michael adduct formation, kinetics analyses reveal reversibility both adduction amines amines. Although than toward conjugate addition nucleophiles, it less Lys/amine adduction. greater neurotoxicity could reflect part different reactivity characteristics as compared