**6.1 Antioxidant Response Element (ARE)**

The antioxidant response element is a *cis*-acting enhancer sequence that mediates transcriptional activation of genes in cells exposed to oxidative stress. It was initially identified in the promoters of the cell detoxification enzymes, GSTA2 (glutathione Stransferase A2) and NQO1 (NADPH: quinone oxidoreductase 1) (Friling et al., 1990; Li and Jaiswal, 1992; Rushmore and Pickett, 1990). The ARE possesses structural and biological features that characterize its unique responsiveness to oxidative stress, and its consensus sequence was identified to be 5'-TGACnnnGC-3' (Rushmore et al., 1991). In addition to being involved in inducible gene expression, the antioxidant response element is also responsible for the low-level basal expression of several genes, and is therefore crucial for maintaining cellular redox homeostasis under a variety of cell conditions. Proteins that are encoded by the ARE include enzymes associated with glutathione biosynthesis (Moinova and Mulcahy, 1998; Wild et al., 1998), redox proteins with active sulfhydryl moieties (Ishii et al., 2000; Kim et al., 2001), and drug-metabolizing enzymes (Favreau and Pickett, 1991; Rushmore and Pickett, 1990). Several of these proteins have an endogenous role in protecting the cells from oxidative damage, for example, enzymes such as GST, NQO1, and HO-1 (heme oxygenase-1) function to detoxify harmful by-products of oxidative stress. Other phase II enzymes induced by ARE activation include aldehyde dehydrogenase, glutathione peroxidase, glutathione transferases, superoxide dismutase, quinone reductase, epoxide hydrolase, UDP-glucuronosyl transferases, and gamma-glutamylcysteine synthetase, etc. The human 8-oxoguanine DNA glycosylase (OGG1) enzyme has also been shown to contain the binding sites for transcription factor Nrf2 in its promoter region (Dhenaut et al., 2000). Human OGG1 functions to remove 8-oxoG, a mutagenic base byproduct which occurs as a result of exposure to reactive oxygen, from damaged DNA and initiates base excision DNA repair.
