Exploiting Thiol Modifications

1714 As the premier biological electron acceptor, molecular oxygen (O2) serves a vital role in fundamental cellular functions, including the process of aerobic respiration. Nevertheless, with the benefi cial properties of O2 comes the inadvertent formation of reactive oxygen species, including superoxide (O2 −), hydrogen peroxide (H2O2), and hydroxyl radical (•OH); these differ from O2 in having one, two, and three additional electrons, respectively (Figure 1). Cells also encounter elevated levels of these reactive oxygen species when they are released by animals, plants, and insects as a defense against detrimental organisms such as microbial pathogens. Reactive oxygen species can damage cells in many ways: by inactivating proteins, damaging nucleic acids, and altering the fatty acids of lipids, which leads in turn to perturbations in membrane structure and function. The accumulation of this oxidative damage underlies the formation of many disease states in humans. It is postulated that tissue injury by these reactive oxygen species accumulates over a long period of time and plays roles in the aging process and the development of heart disease, diabetes, chronic infl ammatory diseases, cancer, and several neurodegenerative diseases (Halliwell 1999). Many organisms have evolved strategies to remove reactive oxygen species and repair damage, which have enabled them to prosper from the tremendous oxidizing potential of O2 without succumbing to oxidative damage. Bacteria, yeast, and mammalian cells all induce the synthesis of global regulatory responses to survive oxidative insults. The consequences of oxidative stress and the corresponding defense responses have been extensively studied in Escherichia coli. For ease of study in the laboratory, the stress responses are often provoked by the external addition of chemical oxidants that specifi cally elevate the levels of reactive oxygen species within cells, or by the use of mutant strains that disrupt the normal “homeostatic mechanisms” for removing reactive oxygen species or the damage they do. While this primer focuses on a particular set of protective and regulatory protein modifi cations induced by oxidative stress in E. coli, it should be noted that many of the same mechanisms are present in other organisms; some specifi c examples from other species will also be described. The major target of O2 − damage identifi ed in bacteria is a class of Primer