Cellular defence against endogenous and xenobiotic toxicants and other noxious stimuli: Role of redox-sensitive transcription factors and their regulators

抄録

In an almost every moment, living organisms are subjected to diverse types of stress both external and internal sources. While excessive stress leads to necrotic or apoptotic death, moderate amounts of noxious stimuli may render the cells adaptive to subsequent stress. Such adaptive response to stress normally accompanies de novo synthesis of proteins via activation of distinct stress-responsive signaling. One of the key signaling molecules involved in cellular adaptation or tolerance to a wide array of stressful conditions is NF-κB. Nrf2 is another important redox-sensitive transcription factor that is involved induction of phase-2 detoxifying or antioxidant genes in response to oxidative and electrophilic insults. Many dietary phytonutrients can induce ARE-driven antioxidant/phase-2 detoxifying gene expression, thereby fortifying cellular defence against oxidative insult. Cysteine thiols present in various transcription factors and their regulators function as redox sensors in fine-tuning of transcriptional regulation of many genes essential for maintaining cellular homeostasis. Thus, oxidation or covalent modification of thiol groups present in the above redox-sensitive transcription factors and their regulating molecules can provide a unique strategy for molecular target-based chemoprevention and cytoprotection.