Download Free Design And Application Of A Genetically Encoded Probe For Peroxiredoxin 2 Oxidation In Human Cells Book in PDF and EPUB Free Download. You can read online Design And Application Of A Genetically Encoded Probe For Peroxiredoxin 2 Oxidation In Human Cells and write the review.

Hydrogen peroxide (H2O2) is a well-known oxidant species commonly produced in eukaryotic organisms as a result of cellular metabolism that plays a central role in numerous processes in cells, and dysregulation of this species can result in a number of different disease states in human cells. In the case of cancer, elevated metabolism is believed to result in higher rates of H2O2 production in these cells, as well as more susceptibility to H2O2-induced apoptosis than normal cells. To this end, researchers have identified several therapeutic compounds that are believed to kill cancer cells via the intracellular elevation of one or more oxidants. However, due to the limitations of current tools for detection of these species, little is known about which therapeutic compounds induce toxicity via elevation of specific oxidants, which would aid in the identification of susceptible tumors to these treatments. Currently, the main limitation of genetically-encoded tools for detection of H2O2 in these applications is the low sensitivity to H2O2 . Most genetically-encoded probes for this species used in human cells utilize H2O2-responsive domains with reaction rate coefficients nearly two orders of magnitude lower than other, more reactive peroxidases in the cell, such as peroxiredoxins (Prxs). In this regard, several studies have demonstrated that Prxs should react with the majority of intracellular H2O2 on the basis of a high reaction rate coefficient with H2O2 and intracellular abundance. In light of these studies, research in the field of redox biology has shifted to focus more on Prxs' role as natural sensors of H2O2 fluctuations in human cells. To this end, the first part of my thesis project focuses on the development of a genetically-encoded probe for H2O2-mediated human Prx2 oxidation in human cells. The second part of my thesis focuses on the application of this probe in a high-throughput screen to identify small-molecule cancer therapeutics that act through H2O2-mediated mechanisms. Together, this thesis lays the foundation for a new class of genetically-encoded sensors that enable specific, sensitive measurement of H2O2 perturbations in human cells in response to redox-based therapeutics, which will facilitate the advancement of these therapeutic compounds in the future.
Much of the biology of oxidative stress and oxidative signalling centres on the generation and handling of hydrogen peroxide. The overall aim for this book would be to provide an insightful and useful forum to assist with the understanding of the relevance of hydrogen peroxide generation and how this is managed in human biology. The target audience would be those who currently have an interest in the generation of ROS, but who do not have expertise in chemistry, as well as those experts in the chemistry of oxidative stress, but without detailed understanding of the biologically relevant setting. We would aim to bridge the gap in understanding between chemistry and biology.
This book contains a broad survey on the peroxiredoxins. It involves almost all groups that contributed significant insights into the emerging field. Coverage discusses the diverse biological roles of the new protein family in the context of other antioxidant systems like those based on heme or selenium catalysis. In addition, the book highlights related future perspectives.
Methodology and applications of redox proteomics The relatively new and rapidly changing field of redox proteomics has the potential to revolutionize how we diagnose disease, assess risks, determine prognoses, and target therapeutic strategies for people with inflammatory and aging-associated diseases. This collection brings together, in one comprehensive volume, a broad array of information and insights into normal and altered physiology, molecular mechanisms of disease states, and new applications of the rapidly evolving techniques of proteomics. Written by some of the finest investigators in this area, Redox Proteomics: From Protein Modifications to Cellular Dysfunction and Diseases examines the key topics of redox proteomics and redox control of cellular function, including: * The role of oxidized proteins in various disorders * Pioneering studies on the development of redox proteomics * Analytical methodologies for identification and structural characterization of proteins affected by oxidative/nitrosative modifications * The response and regulation of protein oxidation in different cell types * The pathological implications of protein oxidation for conditions, including asthma, cardiovascular disease, diabetes, preeclampsia, and Alzheimer's disease Distinguished by its in-depth discussions, balanced methodological approach, and emphasis on medical applications and diagnosis development, Redox Proteomics is a rich resource for all professionals with an interest in proteomics, cellular physiology and its alterations in disease states, and related fields.
This detailed volume explores the NADPH oxidase family of enzymes in human physiology and genetic disease, in which early discoveries represent prime examples of the finest translational “from bed to bench and back” studies. Methods are included for testing assembly and function of multicomponent oxidase complexes and for analyzing reactive oxygen species (ROS) generation in different systems by various means, while addressing pitfalls of ROS probes currently being used, as well as protocols on NADPH oxidase regulation and their function in cells. Written in the highly successful Methods in Molecular Biology series format, chapters include introduction to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, NADPH Oxidases: Methods and Protocols will aid researchers working with the NOX/DUOX family in continuing and expanding upon their vital research.
Cell assays include all methods of measurements on living cells. Confined for a long time to research laboratories, these emerging methods have, in recent years, found industrial applications that are increasingly varied and, from now on, regulatory. Based on the recent explosion of knowledge in cell biology, the measurement of living cells represents a new class of industry-oriented research tests, the applications of which continue to multiply (pharmaceuticals, cosmetics, environment, etc.). Cellular tests are now being positioned as new tools at the interface between chemical methods, which are often obsolete and not very informative, and methods using animal models, which are expensive, do not fit with human data and are widely discussed from an ethical perspective. Finally, the development of cell assays is currently being strengthened by their being put into regulatory application, particularly in Europe through the REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals) and cosmetic directives.
This work responds to the need to find, in a sole document, the affect of oxidative stress at different levels, as well as treatment with antioxidants to revert and diminish the damage. Oxidative Stress and Chronic Degenerative Diseases - a Role for Antioxidants is written for health professionals by researchers at diverse educative institutions (Mexico, Brazil, USA, Spain, Australia, and Slovenia). I would like to underscore that of the 19 chapters, 14 are by Mexican researchers, which demonstrates the commitment of Mexican institutions to academic life and to the prevention and treatment of chronic degenerative diseases.
This detailed book provides an overview of various classes of computational techniques, including machine learning techniques, commonly used for evaluating kinetic parameters of biological systems. Focusing on three distinct situations, the volume covers the prediction of the kinetics of enzymatic reactions, the prediction of the kinetics of protein-protein or protein-ligand interactions (binding rates, dissociation rates, binding affinities), and the prediction of relatively large set of kinetic rates of reactions usually found in quantitative models of large biological networks. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of expert implementation advice that leads to successful results. Authoritative and practical, Computational Methods for Estimating the Kinetic Parameters of Biological Systems will be of great interest for researchers working through the challenge of identifying the best type of algorithm and who would like to use or develop a computational method for the estimation of kinetic parameters.
Nearly a century of scientific research has revealed that mitochondrial dysfunction is one of the most common and consistent phenotypes of cancer cells. A number of notable differences in the mitochondria of normal and cancer cells have been described. These include differences in mitochondrial metabolic activity, molecular composition of mitochondria and mtDNA sequence, as well as in alteration of nuclear genes encoding mitochondrial proteins. This book, Mitochondria and Cancer, edited by Keshav K. Singh and Leslie C. Costello, presents thorough analyses of mitochondrial dysfunction as one of the hallmarks of cancer, discusses the clinical implications of mitochondrial defects in cancer, and as unique cellular targets for novel and selective anti-cancer therapy.
This volume provides a collection of contemporary perspectives on using activity-based protein profiling (ABPP) for biological discoveries in protein science, microbiology, and immunology. A common theme throughout is the special utility of ABPP to interrogate protein function and small-molecule interactions on a global scale in native biological systems. Each chapter showcases distinct advantages of ABPP applied to diverse protein classes and biological systems. As such, the book offers readers valuable insights into the basic principles of ABPP technology and how to apply this approach to biological questions ranging from the study of post-translational modifications to targeting bacterial effectors in host-pathogen interactions.