Transcriptional Regulators of Oxidative Stress Responses

Abstract

Many organisms have adaptive responses to oxidative stress, and the levels of several antioxidant defense enzymes have been shown to be induced by changes in the levels of hydrogen peroxide or superoxide. Reactive oxygen species have also been proposed to be second messengers and to signal cellular fates such as proliferation and apoptosis. These observations suggest that cells have mechanisms to sense reactive oxygen species and induce specific responses. The mechanisms by which hydrogen peroxide and superoxide are sensed are not well understood, but a number of transcription factors that regulate the expression of antioxidant genes and/or whose activities are modulated by oxidation and reduction are known. In this chapter, we provide an overview of these transcriptional regulators in bacteria, yeast, and mammalian cells. REGULATORS IN PROKARYOTES As for many genetic responses, the regulators of oxidative stress responses have been best characterized in Escherichia coli. Wild-type cells show distinct adaptive responses to hydrogen peroxide and superoxide anion, and the key regulators of these two responses are OxyR and SoxR together with SoxS (see Table 1). In addition to these transcription factors, several SoxS homologs and the rpoS -encoded σ s subunit of RNA polymerase have also recently been shown to regulate the expression of antioxidant defense genes. OxyR The expression of at least nine of the hydrogen-peroxide-inducible proteins is controlled by OxyR in E. coli and Salmonella typhimurium (Christman et al. 1985). Several of the genes whose expression is activated by OxyR have been identified and include katG (hydroperoxidase I), ahpCF (an...