Author : Javier Egea
Publisher : Frontiers Media SA
Page : 257 pages
File Size : 41,16 MB
Release : 2020-01-02
Category :
ISBN : 2889633160
Author : Nirmalya Chatterjee
Publisher :
Page : 124 pages
File Size : 15,84 MB
Release : 2015
Category :
ISBN :
"Oxidative stress causes widespread damage to biomolecules, leads to different pathological conditions and contributes to aging. The Nrf2 transcription factor, a major mediator of oxidative stress responses, controls gene expression programs that protect multiple organs from oxidative damage, delay the onset of some age-associated diseases and promote longevity at least in some organisms. In an unstressed condition, Nrf2 interacts with its cytoplasmic inhibitor Keap1, which targets it for proteasomal degradation. Oxidative stress prevents Keap1-mediated degradation of Nrf2, resulting in its accumulation and nuclear translocation. In the nucleus, Nrf2 dimerizes with a small Maf protein, binds to ?Antioxidant Response Elements' and induces multiple antioxidant and detoxification genes. Complete understanding of the molecular mechanisms of Nrf2 regulation is important to assess its role in normal physiology and disease. The key components of Nrf2 signaling are conserved in Drosophila where CncC is the homolog of mammalian Nrf2. In order to study mechanisms of Nrf2 function in Drosophila, cell-based and in vivo transcriptional reporters for Nrf2 were developed. A cell-based dsRNA library screen was carried out to find novel regulators of Nrf2 signaling. Among others we identified Cdk12 and Fs(1)h. Cdk12, a RNA PolII-CTD kinase, was found to be required for CncC target gene expression in a cell-autonomous manner and to be important for oxidative stress resistance. In contrast, Fs(1)h, the sole member of the BET protein family in Drosophila, was identified as an inhibitor of CncC. Bromodomain-containing BET proteins have complex functions in chromosome organization and the control of gene expression. Fs(1)h was found to physically interact with CncC in a manner that requires the function of its bromodomains and the acetylation of CncC. Treatment of cultured Drosophila cells or adult flies with the BET protein inhibitor JQ1 de-represses CncC transcriptional activity and induces protective gene expression programs. The mechanism by which Fs(1)h inhibits CncC function is distinct from that of Keap1. Consistent with this, combinations of drugs that can specifically target Keap1 and Fs(1)h cause a synergistic and specific activation of CncC dependent gene expression. This synergism might be exploitable for the design of combinatorial therapeutic approaches, targeting Nrf2 in various diseases."--Pages vi-vii.
Author : Huai Deng
Publisher : Springer Nature
Page : 211 pages
File Size : 49,1 MB
Release : 2020-05-21
Category : Medical
ISBN : 3030445992
Nrf2, a transcription factor that mediates transcriptional responses to oxidative and xenobiotic stresses, plays a central role in cellular protection against internal or external toxins. Defects in Nrf2 and the relevant regulatory pathways are associated with a number of pathologies including inflammation, respiratory diseases, cardiovascular dysfunctions, metabolic syndrome and diabetes, neurodegeneration, and cancer. This book comprehensively reviews the up-to-date discoveries for the roles of Nrf2 in several human diseases in the context of inflammation. In particular, the molecular mechanisms that mediate the functions of Nrf2 and its interacting network in inflammation and pathogenesis are explicated. In addition, the research and therapeutic applications of Nrf2-targeting compounds in different diseases were summarized. This book is expected to be a valuable reference for worldwide researchers conducting both mechanistic and therapeutic studies of Nrf2 and relevant factors.
Author : Tongde Wu
Publisher :
Page : 492 pages
File Size : 35,53 MB
Release : 2013
Category :
ISBN :
Nrf2 (NF-E2-related factor 2) is a transcription factor that regulates a battery of downstream genes that contain the antioxidant response element (ARE) in their promoter regions, including intracellular redox-balancing proteins, phase II detoxifying enzymes, and transporters. These Nrf2-dependent proteins work in collaboration to protect against many diseases where oxidative stress plays an essential role in disease onset and progression. Consequently, it is imperative to understand the basic molecular mechanisms of how Nrf2 is regulated so that this pathway can be targeted for disease prevention and treatment. Nrf2 is mainly regulated at the protein level by the ubiquitin proteasome system. Under basal conditions Nrf2 is constantly ubiquitinated by the Keap1-Cul3-E3 ubiquitin ligase complex and subsequently degraded by the 26S proteasome. Currently, regulation of the Nrf2-Keap1 pathway by ubiquitination is largely understood. However, other mechanism responsible for modulating Nrf2-ARE signal remains to be explored. This dissertation identifies three molecular mechanisms that are important in understanding how the Nrf2-Keap1 pathway is regulated: (i) In Chapter 2, KPNA6 was identified and characterized as a negative regulatory mechanism of the Nrf2 pathway, which mediates Keap1 nuclear import and represses the Nrf2-dependent antioxidant response at post-induction phase. (ii) In Chapter 3, I identified PARP-1 as a new transcription co-activator of Nrf2, which augments ARE-specific DNA binding of Nrf2 and enhances the transcription of Nrf2 target genes. This indicates a novel function of PARP-1 and reveals another layer of regulation of Nrf2. (iii) In Chapter 4, I demonstrated that XBP1 and SYVN1 are involved in regulating the Nrf2 pathway in a Keap1-independent mechanism. During ER stress, XBP1s upregulates transcription of SYVN1, which is an ubiquitin E3 ligase. SYVN1 accelerates the clearance of Nrf2 protein through promoting ubiquitination of Nrf2, and subsequent proteasomal degradation. Moreover, we observed an inverse correlation between XBP1s/SYVN1 and Nrf2 expression in the end stage alcoholic cirrhosis liver samples, implying a pathological role of ER stress-oxidative stress crosstalk. Taken together, these findings further our understanding of how the Nrf2-Keap1 pathway is regulated, providing novel targets of chemoprevention or chemotherapy.
Author : Rajeshwar P. Sinha
Publisher : Academic Press
Page : 504 pages
File Size : 45,74 MB
Release : 2020-10-06
Category : Science
ISBN : 0128206594
Natural Bioactive Compounds: Technological Advancements deals with the latest breakthroughs in the field of screening, characterization and novel applications of natural bioactive compounds from diverse group of organisms ranging from bacteria, viruses, cyanobacteria, algae, fungi, bryophytes, higher plants, sponges, corals and fishes. Written by some of the most reputed scientists in the field, this book introduces the reader to strategies and methods in the search for bioactive natural products. It is an essential read for researchers and students interested in bioactive natural products, their biological and pharmacological properties, their possible use as chemopreventive or chemotherapeutic agents, and other future potential applications. - Explores natural sources of bioactive compounds, including cyanobacteria, bacteria, viruses, fungi and higher plants - Discusses the potential applications of biological products, such as their use in medicine (antibiotics, cancer research, immunology), as food additives, supplements and technological substances - Analyzes the contributions of emerging or developing technologies for the study of bioactive natural compounds (characterization and purification)
Author : Jose Antonio Morales-Gonzalez
Publisher : BoD – Books on Demand
Page : 212 pages
File Size : 40,87 MB
Release : 2016-12-21
Category : Science
ISBN : 953512837X
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.
Author :
Publisher :
Page : 0 pages
File Size : 18,21 MB
Release : 2018
Category :
ISBN :
Kidney disease is a complex health problem, often coinciding with cardiovascular pathology (e.g. hypertension) and metabolic disturbances (e.g. obesity and diabetes). It is also a disturbingly fast growing global public health problem, e.g. chronic kidney disease affects an estimated ~9-16% of the population. Besides the public health issues this results in a large economic burden as kidney diseases contributes disproportionally to about a quarter of total health care costs. Experimental and clinical data solidly support the view that kidney tissue hypoxia plays a critical and intricate role during the genesis and progression of both chronic and acute kidney diseases. This research field is currently at the very beginning of integrating pre-clinical with clinical research in which hypoxia related mechanism are quantified by non-invasive imaging. In combination with the fact that some key questions remain unanswered, this offers exciting new research perspectives that are waiting to be explored. With this Research Topic we aim to discuss and find answers to the following research question: 1) What are the temporal relationships between hypoxia and kidney disease? 2) Can we demonstration causation between hypoxia and kidney disease? 3) Can renal hypoxia be considered as a treatment target in kidney disease? 4) Can hypoxia (e.g. in the urine) be considered a biomarker of kidney disease? 5) Does hypoxia ramp-up sympathetic activity? 6) Does hypoxia trigger inflammation? 7) Is hypoxia caused by changes in sodium reabsorption and/or mitochondrial function? 8) Which molecular mechanisms are involved in hypoxia in kidney disease? 9) Which gene expressions change due to hypoxia in kidney disease? 10) Can we generate new and translational insights using non-invasive imaging technologies? Our overall aim is identify the mediators/controllers of hypoxia in kidney disease. If we understand more about the sequence of events leading to hypoxia, its regulation and consequences in renal disease, we might be able to have a major impact in clinical practice. I.e. more accurate and earlier diagnosis, novel treatment targets, and novel therapies.
Author : Rosalyn D. Blumenthal
Publisher : Humana Press
Page : 442 pages
File Size : 13,3 MB
Release : 2005-02-14
Category : Medical
ISBN : 9781588295866
A state-of-the art collection of readily reproducible laboratory methods for assessing chemosensitivity in vitro and in vivo, and for assessing the parameters that modulate chemosensitivity in individual tumors. Chemosensitivity,Volume 2: In Vivo Models, Imaging, and Molecular Regulators contains cutting-edge protocols for classifying tumors into response categories and for customizing therapy to individuals. These readily reproducible techniques allow measurements of DNA damage, apoptotic cell death, and the molecular and cellular regulators of cytotoxicity, as well as in vivo animal modeling of chemosensitivity. A companion volume, Volume 1: In Vitro Assays contains in vitro and in vivo techniques to identify which new agents or combination of agents are effective for each type of tumor.
Author : Pawan Kumar Maurya
Publisher : Academic Press
Page : 294 pages
File Size : 30,93 MB
Release : 2022-02-18
Category : Science
ISBN : 032390906X
Novel Therapeutic Approaches Targeting Oxidative Stress investigates the role of oxidative stress in disease and explores the latest methods and approaches to targeting oxidative stress for treatment and diagnosis. The book begins with an introduction to oxidative stress and its significance. Subsequent sections cover biochemical methods for detecting free radicals and novel therapeutic approaches for targeting oxidative stress in a number of different diseases. This includes age-related illnesses, neuropsychiatric disorders such as schizophrenia and bipolar disorder, and neurodegenerative diseases like Alzheimer's and Parkinson's disease. Novel approaches for targeting oxidative stress in cancer and cardiovascular diseases are also explored. The book then moves on to discuss advances in drug delivery systems and detecting oxidative stress biomarkers using biosensors. It concludes with case studies that illustrate the targeting of oxidative stress and future perspectives. - Explores oxidative stress in a variety of diseases, including neurological disorders, cardiovascular diseases, age-related diseases, and cancer - Covers a range of therapeutic approaches to target oxidative stress - Includes chapters on the application of novel drug delivery systems and diagnostic biosensors to oxidative stress - Features case studies illustrating the targeting of oxidative stress
Author : Bernd Nilius
Publisher : Springer Science & Business Media
Page : 126 pages
File Size : 32,46 MB
Release : 2012-05-30
Category : Medical
ISBN : 3642292569
Cardiac ion channels and mechanisms for protection against atrial fibrillation. Intrinsically photosensitive retinal ganglion cells. Quantifying and modeling the temperature-dependent gating of TRP channels.
