Chapters authored
Measurement of H2AX Phosphorylation as a Marker of Ionizing Radiation Induced Cell Damage
Part of the book: Current Topics in Ionizing Radiation Research
Multiple Modes of Nrf2 Regulation and Transcriptional Response
Cells have defense systems to deal with chemical insults from the environment. Some examples are chemical scavengers like glutathione and enzymes such as superoxide dismutase that inactivate radicals and other reactive chemicals in the cytoplasm. It is perhaps surprising that these protective systems are not maximally expressed in an unstressed cell. Rather, the ability to inactivate toxic chemicals is tightly regulated and only induced when needed. As a consequence, unstressed cells are usually very sensitive to radicals, but become more resistant as the cellular defense system has been appropriately upregulated after a few hours. The transcription factor Nrf2 is known to be a master regulator of many cytoprotective enzymes and proteins. Chemical inducers of Nrf2 inactivate its repressor, Keap1, when they react with critical cysteine residues in Keap1. The release of Nrf2 from Keap1 results in enhanced expression of genes involved in detoxification. This generates a feedback loop where Nrf2 induces protective enzymes capable of inactivating the chemical that reacted with Keap1. An unproven, but likely, scenario is that Nrf2 transcriptional response can vary depending on the nature of the chemical insult. The aim of this chapter is to examine the mechanisms by which the cell can sense different reactive chemicals and modulate protective responses. It is likely that this knowledge is of vital importance in the development of clinical Nrf2 activators in preventive medicine.
Part of the book: The Transcription Factor Nrf2