Molecular basis of heme oxygenase-1 induction: implications for chemoprevention and chemoprotection

Heme oxygenase (HO)-1, involved in the heme degradation process, is an important antioxidant enzyme. The induction of HO-1 gene expression, in response to diverse oxidative stimuli, represents a critical event in adaptive cellular response. Experimental models of various diseases, including acute inflammation, atherosclerosis, degenerative diseases, and carcinogenesis, have demonstrated that the induction of HO-1 can prevent or mitigate the symptoms associated with these ailments. Recent progress in our understanding of cellular signaling networks as critical modulators of gene transcription sheds light on the molecular basis of HO-1 gene expression. A panel of redox-sensitive transcription factors such as activator protein-1, nuclear factor- kappaB, and nuclear factor E2-related factor-2, and some of the upstream kinases have been identified as regulators of HO-1 gene induction. The scope of this review is limited to focus on molecular mechanisms underlying HO-1 expression and the significance of targeted induction of HO-1 as a strategy to achieve chemoprevention and chemoprotection.