Radical-induced protein peroxidation and its biological consequences

Full text: There is considerable interest in the actions of oxygen free radicals and related species on biological systems. All such systems are constantly exposed to internal and external sources of these reactive species, and all have made significant commitments towards the development and maintenance of defences against their damaging effects. However, these antioxidant systems are not always able to cope, resulting in the condition of oxidative stress, which is believed to be the cause of many diseases and debilitating conditions in humans. Damage initiated in all biological systems by the reactive oxygen intermediates proceeds in a sequence of distinct steps, which correspond to the physical, chemical, biochemical, biological and medical stages. There are obvious advantages in interrupting this chain of damage as early as possible, so that none of the subsequent steps can develop. The first stage susceptible to such interruption is the biochemical, in which an initial target molecule damaged by the reactive intermediate propagates the damage by reacting with other molecular components of the organism. For effective inhibition of the assumed that this is either DNA or lipid-rich membranes, but the results have not supported these assumptions. In the last 8 years we have studied the propositions that the initial target molecules are proteins. One class of major products of the interaction between proteins and biologically relevant reactive oxygen species are protein-bound hydroperoxide groups, which we have shown to have the potential to damage other biomolecules. In our most recent work we have studied the formation of protein hydroperoxides in biological systems. In human blood serum exposed to radiation-generated by hydroxyl radicals, protein hydroperoxides were generated in high yields and, unlike lipid peroxides, without a lag period. We made similar observations with 2 lines of cultured cells, where again protein and measurable lipid oxidation were found. These findings suggest that proteins may well be the initial target for free radicals and similar species acting on living organisms and that attempts to inhibit or reverse biological damage should concentrate on these molecules