Reactive oxygen species: the unavoidable environmental insult?

Reactive oxygen species (ROS) are generated by a variety of sources from th e environment (e.g., photo-oxidations and emissions) and normal cellular fu nctions (e.g., mitochondrial metabolism and neutrophil activation). ROS inc lude free radicals (e.g., superoxide and hydroxyl radicals), nonradical oxy gen species (e.g., hydrogen peroxide and peroxynitrite) and reactive lipids and carbohydrates (e.g., ketoaldehydes, hydroxynonenal). Oxidative damage to DNA can occur by many routes including the oxidative modification of the nucleotide bases, sugars, or by forming crosslinks. Such modifications can lead to mutations, pathologies, cellular aging and death. Oxidation of pro teins appears to play a causative role in many chronic diseases of aging in cluding cataractogenesis, rheumatoid arthritis, and various neurodegenerati ve diseases including Alzheimer's Disease (AD). Our goal is to elucidate th e mechanism(s) by which oxidative modification results in the disease. Thes e studies have shown that (a) cells from old individuals are more susceptib le to oxidative damage than cells from young donors; (b) oxidative protein modification is not random; (c) some of the damage can be prevented by anti oxidants, but there is an age-dependent difference; and (d) an age-related impairment of recognition and destruction of modified proteins exists. It i s believed that mechanistic insight into oxidative damage will allow preven tion or intervention such that these insults are not inevitable. Our studie s are also designed to identify the proteins which are most susceptible to ROS damage and to use these as potential biomarkers for the early diagnosis of diseases such as AD. For example, separation of proteins from cells or tissues on one- and two-dimensional gels followed by staining for both tota l protein and specifically oxidized residues (e.g., nitrotyrosine) may allo w identification of biomarkers for AD. (C) 1999 Elsevier Science B.V. All r ights reserved.