Abstract
The transcriptional activation of the phase II detoxification enzymes and/or antioxidant genes by redox-cycling chemicals has been traced to a cis-acting element called the antioxidant responsive element (ARE) or the electrophile response element (EpRE) that regulates either or both constitutive and inducible gene expression. ARE sequences are detected in the promoter region of genes, including rat and mouse glutathione S-transferases (GSTs)-Ya, rat GST-P, rat and human NQO1, murine heme oxygenase-1 (HO1), murine ferritin heavy chain, as well as the α-glutamylcysteine ligase catalytic (GCLC) and regulatory (GCLR) subunits. Antioxidant responsive element activation elicits a potential chemoprotective response, and the identification of the ARE-targeting genes is an initial step in the explanation of the molecular mechanism of this chemoprotective response. Microarray analysis reveals a cluster of phase 2 detoxification enzymes and some antioxidant genes that are coordinately upregulated through Nrf2-dependent ARE activation and are responsible for tert-butylhydroquinone (tBHQ) protective effect against oxidative damage in the multiple culture systems. Detailed information is expected in the future to explain how quinone compounds like tBHQ encourage Nrf2 nuclear translocation and subsequent ARE activation through a PI3-kinase pathway.
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