ABSTRACT

This chapter demonstrates that induction of multiple antioxidant-regulated genes may also provide a way to increase an antioxidative potential and protect cells from apoptosis. Identification of the antioxidant-responsive element (ARE) was an initial step leading to elucidation of the molecular mechanism for antioxidant response. One of the major clusters of transcriptionally activated genes in IMR-32 cells was the phase II detoxification enzymes. Within this category of genes were early-response genes and late-response genes. Interestingly, unlike other phase II detoxification enzymes, heme oxygenase-1 was transiently upregulated at 8 hr of treatment and not changed at 24 or 48 hr. The apoptotic process and development of cell injury in H2O2-treated IMR-32 cells was prevented and/or delayed by strengthening the antioxidant capacity of these cells through the transcriptional activation of ARE-driven genes in response to treatment with tert-butylhydroquinone.