Design And Application Of A Genetically Encoded Probe For Peroxiredoxin 2 Oxidation In Human Cells
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| Author | : Troy Frederick Langford |
| Publisher | : |
| Total Pages | : 153 |
| Release | : 2018 |
| Genre | : |
| ISBN | : |
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.
| Author | : Margreet C M Vissers |
| Publisher | : CRC Press |
| Total Pages | : 456 |
| Release | : 2017-10-19 |
| Genre | : Medical |
| ISBN | : 1498776167 |
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.
| Author | : Isabella Dalle-Donne |
| Publisher | : John Wiley & Sons |
| Total Pages | : 978 |
| Release | : 2006-08-11 |
| Genre | : Science |
| ISBN | : 0471973114 |
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.
| Author | : Leopold Flohé |
| Publisher | : Springer |
| Total Pages | : 0 |
| Release | : 2010-11-11 |
| Genre | : Medical |
| ISBN | : 9789048175178 |
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.
| Author | : Christophe Furger |
| Publisher | : John Wiley & Sons |
| Total Pages | : 280 |
| Release | : 2016-07-25 |
| Genre | : Science |
| ISBN | : 1848218583 |
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.
| Author | : Jose Antonio Morales-Gonzalez |
| Publisher | : BoD – Books on Demand |
| Total Pages | : 516 |
| Release | : 2013-05-22 |
| Genre | : Science |
| ISBN | : 953511123X |
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.
| Author | : Paul T. Sharpe |
| Publisher | : Springer Science & Business Media |
| Total Pages | : 752 |
| Release | : 2008-02-02 |
| Genre | : Science |
| ISBN | : 1592592708 |
Most people have some interest in embryos; this probably results, in part, from their interest in understanding the biological origins of themselves and their offspring and, increasingly, concerns about how environmental change such as pollution might affect human development. Obviously, et- cal considerations preclude experimental studies of human embryos and, c- sequently, the developmental biologist has turned to other species to examine this process. Fortunately, the most significant conclusion to be drawn from the experimental embryology of the last two decades is the manner in which orthologous or closely related molecules are deployed to mediate similar - velopmental processes in both vertebrates and invertebrates. The molecular mechanisms regulating processes fundamental to most animals, such as axial patterning or axon guidance, are frequently conserved during evolution. (It is now widely believed that the differences between phyla and classes are the result of new genes, arising mostly by duplication and divergence of extant sequences, regulating the appearance of derived characters. ) Other vertebrates are obviously most likely to use the same devel- mental mechanisms as humans and, within the vertebrate subphylum, the - parent degree of conservation of developmental mechanism is considerable. It has long been recognized that particular vertebrate species offer either d- tinct advantages in investigating particular stages of development or are - pecially amenable to particular manipulations. No single animal can provide all the answers because not all types of experiments can be carried out on a single species.
| Author | : Keshav Singh |
| Publisher | : Springer Science & Business Media |
| Total Pages | : 294 |
| Release | : 2009-04-05 |
| Genre | : Medical |
| ISBN | : 0387848355 |
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.
| Author | : Trygve O. Tollefsbol |
| Publisher | : Springer Science & Business Media |
| Total Pages | : 844 |
| Release | : 2008-02-03 |
| Genre | : Science |
| ISBN | : 1597453617 |
This book investigates the various processes that are affected by the age of an organism. Several new tools for the analysis of biological aging have been introduced recently, and this volume provides methods and protocols for these new techniques in addition to its coverage of established procedures. Researchers seeking new technology and techniques will find this volume of tremendous benefit as they move towards new directions.
| Author | : Dong-Hee Lee |
| Publisher | : Springer |
| Total Pages | : 1181 |
| Release | : 2017-08-28 |
| Genre | : Science |
| ISBN | : 9402410791 |
Taurine 10 contains original articles and critical reviews based on the oral and poster presentations of XX International Taurine Meeting held in Seoul, Korea in May 2016. The purpose of the book is to present current ideas, new avenues and research regarding biological functions and clinical applications of taurine and taurine derivatives. It focuses on all aspects of taurine research including the cardiovascular system, the immune system, diabetes, the central nervous system, endocrine system and the role of taurine supplements in nutrition. It also includes presentations of novel animal experimental models using Cdo1 and CSAD knock-out mice.
