ABSTRACT
Eukaryotic cells continuously produce reactive oxygen species (ROS) as side products of electron transfer reactions, and above-normal lev els of ROS are referred to as oxidative stress (1-7). This condition oc curs frequently in cells exposed to UV light, gamma rays, or low con centrations of H20 2, but also upon stimulation of cells with cytokines in inflammatory tissues (1-7). The intracellular concentrations of ROS, or cellular redox state, seem to be finely tuned to preserve cellular homeostasis through the expression and regulation of many enzymes (1-7). Currently, the cellular redox state is considered to regulate gene expression via both direct and indirect pathways (1-7). Hypoxic and hyperoxic stresses can activate or repress the transcription of certain genes by pathways that probably involve protein kinases (8). On the other hand, the response to severe oxidative stress may involve an ad ditional effect in which redox-sensitive factors can be directly activated
or inactivated through the oxidation of sulfhydryl residues. Already, the DNA binding activity of a number of transcription factors-e.g., AP-1, Spi, Egr-1, NF-kB, c-Myb, E2, IRE-BP, p53, NFI, TTF-I, arylhydrocarbon receptor, and USF-are shown to be reduced or lost when critical cysteine residues are oxidized (9-31). The cellular buff ering system against oxidative stress, therefore, is extremely important for maintenance of homeostatic control of expression of certain genes.
