Download Free A Master Regulator Of Oxidative Stressthe Transcription Factor Nrf2 Book in PDF and EPUB Free Download. You can read online A Master Regulator Of Oxidative Stressthe Transcription Factor Nrf2 and write the review.

Due to that at present, the majority of diseases are associated with alterations in oxidative stress and inflammatory processes, and in that Nrf-2 is a modulator of these processes; knowing how this transcriptional factor functions and is regulated opens a therapeutic window to diverse diseases. Therefore, the efforts of various investigation groups are centered on finding activators and/or inhibitors of Nrf-2 to prevent or control diverse diseases, for example, cancer, where it would be important to regulate Nrf-2 in order for it to activate apoptosis pathways in cancerogenous cells, or in neurodegenerative diseases where cell death is predominant, it would be important for Nrf-2 to activate antiapoptotic pathways.
Nuclear factor E2-related factor 2 (Nrf2) is a key regulator of ARE-mediated gene expression of Phase II detoxifying enzymes and antioxidant enzymes. In the proposed study, we tested whether nuclear receptor-associated coactivator-3 (RAC3) could participate in the stimulation of transactivation activity of Gal4-Nrf 2 (1-370) with other coactivators. We showed for the first time that the p160 coactivator RAC3 could stimulate the transactivation activity of Gal4-Nrf 2 (1-370) and this could be further enhanced by the coregulators CBP, p/CAF, CARM-1, and PRMT1. Besides, we found that regulation of Nrf2-dependent ARE-driven gene expression by small Mafs protein is dependent on dosage and the ratio of Maf to Nrf2. On the other hand, ERK2 significantly enhanced the expression of ARE-driven luciferase. ERK2 and MafG synergistically upregulated the Nrf2-activated ARE-driven luciferase expression. Nrf2 was identified as a direct substrate of ERK2 both in vivo as well as in vitro for the first time. The phosphorylation of Nrf2 by ERK2 increased its heterodimerization with small Maf proteins. To extrapolate the implication of Nrf2 in inflammation, we compared the anti-inflammatory effect of sulforaphane on LPS-stimulated inflammation in primary peritoneal macrophages derived from Nrf2 (+/+) and Nrf2 mice. The anti-inflammatory effect was attenuated in Nrf2 ( -/- ) primary peritoneal macrophages. We concluded that sulforaphane exerts its anti-inflammatory activity mainly via activation of Nrf2 in mouse peritoneal macrophages. To better facilitate application of sulforaphane in therapeutics, the pharmacokinetics characterization was investigated in rats. Toxicogenomics study of peroxisome proliferator-activated receptor [gamma] agonist (PPAR[gamma]) troglitazone (TGZ) in mouse liver as well as to identify TGZ modulated Nuclear Factor-E2-related factor 2 (Nrf2)--dependent genes was performed. Utilization of animal model of cellular defense deficiency identified Nrf2-dependent genes in response to TGZ and reveals the role of Nrf2 molecule in toxicity caused by TGZ.
Regulation of cellular redox homeostasis determines the fate of the cell. Perturbation in redox status is known to elicit multiple cellular pathways. Role of oxidative stress modulation in channelizing the cell towards apoptosis or rescuing the cell by activating pro-survival pathways, depends on the levels of generated oxidative stress. High levels of generated oxidative stress induce cell death pathways whereas mild and low levels are known to elicit the cell survival pathways. Generation of ROS for a short duration of time inducing Redox ticking also triggers the pro-survival pathways inside the cell. Nrf2 is the redox sensitive prosurvival transcription factor which acts as master regulator of redox equilibrium. Nrf2 and its dependent genes including HO-1, GCLC, NQO1 etc. are involved in maintaining the cellular redox homeostasis. Role of Nrf2 as dual edges sword has been highlighted in past decade. The cross talk between the Nrf2 and NF-κB is at the focal point of building the redox response network. The present chapter is aimed at providing the insight on the role of Nrf2 and NF-κB as redox sensitive transcription factors in regulating cellular redox status. Further, the chapter brings in light the therapeutic potential of targeting Nrf2 under multiple clinical settings.
The nuclear factor erythroid 2-related factor 2 (Nrf2) was described as a master regulator of the cellular antioxidant response. Moreover, many critical biological functions linked to cell viability, metabolism, autophagy, inflammation, immunity, and differentiation have been attributed to Nrf2, which regulates over 600 genes. It is well known that oxidative stress, which Nrf2 can ameliorate, plays a key role in many pathologic processes such as aging, obesity, diabetes, cancer, and neurodegenerative diseases. Flavonoids, on the other hand, through their ability to activate and upregulate Nrf2, can have anti-oxidative, anti-inflammatory, anti-mutagenic, and anti-carcinogenic properties. Flavonoids are an essential ingredient in nutraceuticals, functional foods, and pharmaceuticals. The present book Flavonoids and Anti-Aging: The Role of Transcription Factor Nuclear Erythroid 2-Related Factor2 focuses on the interaction between Nrf2 and flavonoids and their applications in various conditions such as aging, osteoporosis, cardiovascular diseases, and neurodegenerative disease and many other areas. Key Features: Focuses on the mechanisms and use of flavonoids in activating Nrf2 as an anti-aging and "WELLNESS" molecule Provides a specific approach to flavonoid activation of Nrf2 and its implications in aging and various disease conditions and its applications as nutraceuticals Presents flavonoid-based functional foods Discusses the flavonoid nutraceuticals market and future trends Written by experts in the field, this book provides a unique approach to understanding the flavonoid activation of the transcription factor Nrf2, which is responsible for many different disease conditions due to increased reactive oxidative species in the body caused by some physiological triggers.
The transcription factor (nuclear factor-erythroid 2 p45-related factor 2, NRF2) is a master regulator of the cellular response to oxidative insults. While antioxidant response enzymes are well-characterized transcriptional targets of NRF2, it is recently becoming clear that NRF2 also supports cellular detoxification through metabolic rewiring to support the antioxidant systems. In this chapter, we discuss the regulation of NRF2 and how NRF2 activation promotes the antioxidant defense of cells. Furthermore, we discuss how reactive oxygen species influence cellular metabolism and how this affects antioxidant function. We also discuss how NRF2 reprograms cellular metabolism to support the antioxidant response and how this functions to funnel metabolic intermediates into antioxidant pathways. This chapter concludes by exploring how these factors may contribute to both normal physiology and disease.
"This report provides estimates of dietary supplement use for specific population groups over time. In addition to overall use of dietary supplements, this report focuses on estimates for specific nutrients consumed through dietary supplement use."--Cover.
Ineffective cellular stress responses contribute to the development of multiple diseases. A family of the highly conserved transcription factors represented by Cnc proteins in Drosophila and Nrf proteins in mammals includes important mediators of such stress responses. One such protein, mammalian, Nrf2, is a master regulator of oxidative stress defense genes. The related Nrf1 protein, in contrast plays an important role in preventing or ameliorating unfolded protein stress and maintaining effective proteasomal protein degradation. The cap’n’collar (cnc) gene encodes the sole member of this family in Drosophila. Work by the Bohmann lab has previously shown the Cnc C-splice form, CncC, to be a functional homolog of Nrf2 and to regulate the expression of many antioxidant genes in response to oxidative stress. No other cnc family gene is present in the Drosophila genome and whether a fly homolog of Nrf1 exists had remained unclear. I and others, however, noticed, sequence similarities between CncC and Nrf1, raising the possibility that the Drosophila cnc locus encodes one or several proteins that combine the functions of Nrf1 and Nrf2. Here, I provide evidence in support of this hypothesis. I show that CncC mediates the transcriptional response to oxidative stress and proteasome dysfunction by two distinct mechanisms. I show that the activation of CncC in response to impaired proteasome function requires the aspartic protease Rings Lost (Rngo) and Nglycanase 1 (Ngly1). Intriguingly, since a recessive mutation of the human ngly1 gene is the cause of a rare neurological syndrome (N-glycanase deficiency), loss of Nrf1 function may contribute to the pathology of this disease. My work establishes Drosophila CncC as an interesting model to study the interplay and coordination of the cellular responses to proteotoxic and oxidative stresses. Taking advantage of the Drosophila system to investigate the biology of the Nrf protein family may thus contribute to the understanding of human diseases that are associated with cellular stress, possibly including N-glycanase deficiency. The second chapter of my thesis focuses on the relationship between high sugar diet, obesity and oxidative stress. It has been shown that obesity is associated with increased oxidative stress in multiple tissues. This increased oxidative stress can be caused by either increased ROS production or decreased antioxidant mechanisms. While it has been shown that overnutrition increases ROS production in mitochondria, how nutrition surplus affects antioxidant defense pathways is less well understood. I hypothesized that nutrition surplus compromises the oxidative stress defense. To explore this idea, I established an obesity model in which Drosophila is exposed to a high-sucrose diet. Consistent with the starting hypothesis, I found that high-sucrose food suppresses the fly’s oxidative stress defense. Further experiments are needed to understand the molecular mechanism by which high-sucrose diet reduces antioxidant responses. My experiments establish a connection between high-sucrose diet and oxidative stress defense and demonstrate the advantage of using the fruit fly as an animal model to study the health effects of obesity and related metabolic diseases.