NFR2 plays a key role in maintaining homeostasis during oxidative stress and exposure to carcinogens by coordinately regulating the expression of antioxidants and detoxification enzymes [ 17] that boost protection against cancer [ 18].
Nrf2 induces the gene expression of antioxidant and detoxification enzymes and has been reported to exert anti-inflammatory effect by regulating several pro-inflammatory genes, including TNF- α, IL-1 β and IL-6 in inflammatory cells.
In vitro and in vivo, the expression of antioxidant and detoxification enzymes regulated by Nrf2 has been shown to be induced by a variety of chemical agents which act as electrophiles, including diphenols, quinones, isothiocyanates, arsenicals, and heavy metals [58].
Physiological response to environmental insult from tobacco and alcohol is particularly important in HNSCC (Johnson, 2001) and the differential expression of xenobiotic and detoxification enzymes has been reported in other transcriptome level studies (Alevizos et al, 2001).
These results indicate that P. salmonis senses iron fluctuations in the environment and adaptively responds to both iron deficiency or excess, and since both conditions are deleterious for the bacteria, expression of acquisition and detoxification systems are finely regulated [ 63, 64].
In addition, while some chemicals become active carcinogens after biotransformation by certain phase I enzymes such as the CYP family [ 17], isothiocyanates have been found to increase the expression of antioxidant and detoxification proteins such as glutathione S-transferase without increasing aryl hydrocarbon hydroxylase activity [ 18].
Moreover, level of protein carbonylation and expression of detoxification enzymes catalase (Cat) and superoxide dismutase 2 (Sodid did not differ between tumors from different dietary groups, indicating a similar level of reactive oxygen species.
The yeast oscillator regulates the expression of both metabolism and detoxification (Phase I/II response-like) genes, and creates a metabolic cycle consisting of distinct oxidative and reductive periods.
These results extend to metazoans, where the central pacemaker and tissue pacemakers control circadian expression of similar metabolism and detoxification gene sets, as well as additional genes such as those of the innate immune response [11], [12].
Nrf2 controls the coordinated expression of important antioxidant and detoxification genes (Phase II genes) through a promotor sequence termed the antioxidant response element (ARE).
