Molecular Imaging Approaches To Understanding The Roles Of Copper In Biology
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Molecular Imaging Approaches To Understanding The Roles Of Copper In Biology
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Author : Dylan Domaille
language : en
Publisher:
Release Date : 2011
Molecular Imaging Approaches To Understanding The Roles Of Copper In Biology written by Dylan Domaille and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with categories.
Cells exert precise control over their cellular copper pools through a sophisticated array of uptake, trafficking, and storage mechanisms that effectively maintain a low concentration of thermodynamically free copper ions while maintaining excellent kinetic lability of cellular copper stores. In higher eukaryotes and humans, and particularly in specialized cell types associated with brain, heart, intestine, and liver tissue, the molecular specifics of how kinetically labile copper pools are regulated at the subcellular level and the consequences of copper misregulation in aging and disease remain insufficiently understood. Biochemical and genetic studies have established a broad understanding of how cells acquire, maintain, redirect and release copper ions, while also identifying key proteins involved in these activities. The precise role of the copper ion, however, is more difficult to determine, owing mainly to a dearth of methods for directly following the fate of cellular copper stores. This dissertation describes the design, synthesis, and characterization a several new Cu(I)-responsive fluorophores. Through a targeted synthetic survey and comprehensive electrochemical study, the properties of our previously reported fluorophore, Coppersensor-1, were improved to yield a compound (Coppernsensor-3) that exhibits the largest fluorescent response to Cu(I) to date. Along with X-ray fluorescence microscopy, CS3 was used to investigate disruptions in copper homeostasis in a cell model for Menkes disease. The following report describes the synthesis, characterization and applications of Ratio-Coppersensor-1 (RCS1), the first ratiometric fluorophore for live-cell imaging. This compound was used to investigate the effect of ascorbate on rat brain and human kidney cells, and proved able to be able to detect increases in endogenous labile Cu(I) that occurs upon ascorbate treatment. A slight alteration to the ligand of RCS1 gave RCS2, which has similar spectroscopic properties to RCS1. Single-molecule X-ray crystallography and VT-NMR studies provide molecular dynamic details of RCS2 coordination to Cu(I).
Development Of New Imaging Agents For The Study Of Cellular Copper Dynamics
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Author : Karla Michelle Ramos Torres
language : en
Publisher:
Release Date : 2016
Development Of New Imaging Agents For The Study Of Cellular Copper Dynamics written by Karla Michelle Ramos Torres and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with categories.
Copper is an essential element in biological systems. Its participation as a catalytic and structural cofactor in enzymes that function in biological processes such as energy generation, oxygen transport, cellular metabolism and signal transduction renders it vital for the life of eukaryotic organisms. However, if misregulated, it can cause cellular oxidative damage through the production of highly reactive oxygen species. Consequently, it is not surprising that organisms have developed intricate cellular machineries to tightly regulate the trafficking of copper. The fascinating balance between the functional and pathological roles of copper has significantly motivated the study of the processes involved in the proper management of this metal in the cell by inspection of the total metal content in biological samples and its distribution into static and labile cellular pools. Traditional bulk techniques, in combination with biochemical and genetic methods, have been used probe the static copper pool and provide a general understanding of how cells handle copper ions, allowing for the identification of major proteins and ligands involved in copper homeostasis. Alternatively, molecular imaging provides a complementary, versatile approach that can be used to monitor dynamic fluxes of the labile copper pools in real time with spatial and temporal resolution. This dissertation describes the design, synthesis and characterization of new copper-responsive fluorescent sensors in order to expand the available toolbox for molecular imaging of copper dynamics. Application of a novel carbo-rhodol scaffold allowed for the development of the Copper CarboRhodol (CCR) and Copper CarboFluor (CCF) probes, that in combination with additional rhodol platforms extended the available color palette of copper-selective probes. Additionally, the design of unique metal binding motifs with altered ligand architectures, binding geometries and coordination units resulted in the synthesis of new copper-responsive fluorophores. Alteration of the coordination unit and inclusion of a tripodal ligand topology afforded a family of xanthene-based sensors with an assortment of fluorescent responses to copper and ability to sense fluctuations in endogenous, labile copper pools. Finally, development of a modified donor set that increases the number of available donors in the ligand framework was investigated as an alternative strategy to modulate the binding properties of the resulting copper sensors.
Development Of Molecular Imaging Tools For Investigating Copper And Oxidation Biology
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Author : Catherine Danielle Antonuk
language : en
Publisher:
Release Date : 2010
Development Of Molecular Imaging Tools For Investigating Copper And Oxidation Biology written by Catherine Danielle Antonuk and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.
Development And Applications Of New Chemical Tools For Studying The Cell Biology Of Metals
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Author : Sheel Dodani
language : en
Publisher:
Release Date : 2013
Development And Applications Of New Chemical Tools For Studying The Cell Biology Of Metals written by Sheel Dodani and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013 with categories.
Cells have evolved intricate mechanisms that coordinate the activity of transporters, chaperones, and small-molecule ligands to control the spatial and temporal positioning of metal ions. Alkali and alkaline earth metal ions are known to play essential roles in cellular signaling and charge balance whereas transition metals are typically found in the active sites of enzymes to carry out organic transformations. In order to carry out these functions the cell maintains static and labile metal ion pools. These pools can be characterized by bulk molecular biology and bioinorganic techniques on fixed samples in combination with fluorescent indicators that afford the ability to track metal ions in real-time through molecular imaging. In this regard, cellular calcium has been well characterized in variety of biological contexts, but methods to monitor biologically relevant transition metal ions in real-time have not been well established. This dissertation describes the synthesis, characterization, and applications of new fluorescent sensors for Ni(II) and Cu(I), as well as approaches to discover new roles of biological copper in cell signaling. Nickelsensor-1 is a new water-soluble, turn-on fluorescent sensor that is capable of selectively responding to Ni(II) in aqueous solution and in living cells. Coppersensor-3 and X-ray fluorescence microscopy reveal that neuronal cells mobilize significant pools of copper from their cell bodies to peripheral processes in a calcium dependent fashion upon depolarization with KCl. Mitochondrial Coppersensor-1 (Mito-CS1) is a bifunctional reporter that combines a Cu(I)-responsive fluorescent platform with a mitochondrial-targeting triphenylphosphonium moiety for the reversible detection of endogenous, exchangeable mitochondrial Cu(I) pools. Mito-CS1 in conjunction with ICP metal analyses, show that both the exchangeable Cu(I) and total mitochondrial copper pools are only mildly perturbed in fibroblasts with mutant SCO1 and SCO2 mitochondrial copper chaperones. Molecular imaging of neural calcium transients reveals that that endogenous copper is used to tune inhibitory and excitatory inputs during neural circuit development through the dynamic functions of CTR1. Finally, methods for high-throughput RNAi screening and immunofluorescence have been optimized to understand how the kinome regulates the copper mediated mobilization of ATP7A in mammalian cells.
Metals In Cells
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Author : Valeria Culotta
language : en
Publisher: John Wiley & Sons
Release Date : 2016-03-16
Metals In Cells written by Valeria Culotta and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-03-16 with Science categories.
Over the last three decades a lot of research on the role of metals in biochemistry and medicine has been done. As a result many structures of biomolecules with metals have been characterized and medicinal chemistry studied the effects of metal containing drugs. This new book (from the EIBC Book Series) covers recent advances made by top researchers in the field of metals in cells [the “metallome”] and include: regulated metal ion uptake and trafficking, sensing of metals within cells and across tissues, and identification of the vast cellular factors designed to orchestrate assembly of metal cofactor sites while minimizing toxic side reactions of metals. In addition, it features aspects of metals in disease, including the role of metals in neuro-degeneration, liver disease, and inflammation, as a way to highlight the detrimental effects of mishandling of metal trafficking and response to "foreign" metals. With the breadth of our recently acquired understanding of metals in cells, a book that features key aspects of cellular handling of inorganic elements is both timely and important. At this point in our understanding, it is worthwhile to step back and take an expansive view of how far our understanding has come, while also highlighting how much we still do not know. The content from this book will publish online, as part of EIBC in December 2013, find out more about the Encyclopedia of Inorganic and Bioinorganic Chemistry, the essential online resource for researchers and students working in all areas of inorganic and bioinorganic chemistry.
Biochemistry Of Copper
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Author : Maria C. Linder
language : en
Publisher: Springer Science & Business Media
Release Date : 2013-11-21
Biochemistry Of Copper written by Maria C. Linder and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-11-21 with Science categories.
Copper has long been known as essential to living systems, in part through its fundamental role in electron transport and respiration. Over the years into the present, its involvement in an ever increasing number of processes in all kinds of organisms has become apparent, and new and exciting vistas of its roles in such areas as the central nervous system, and in humoral functions, are appearing on the horizon. Although the biochemistry of this element has not been studied nearly as much as that of many others, a for midable amount of work has been carried out. It has thus been a challenge to produce a summary of what has been found that provides both breadth and depth. My goal has been to try to be as comprehensive as possible, within some limitations. I have tried to provide basic information and basic data that should continue to be useful for a long time. The goal has also been to interpret where we currently stand in our knowledge of the structure, function, regulation, and metabolism of Cu-dependent processes and sub stances, especially proteins. Thus, I have tried to make this a source book for historic as well as current information on all aspects of copper bio chemistry, and a summary of our current knowledge of copper-dependent proteins and processes. Most of the research on copper has been carried out on vertebrates, especially mammals. This has played a role in the organization of the book.
Manganese In Health And Disease
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Author : Lucio G Costa
language : en
Publisher: Royal Society of Chemistry
Release Date : 2014-11-27
Manganese In Health And Disease written by Lucio G Costa and has been published by Royal Society of Chemistry this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-11-27 with Medical categories.
Manganese in the diet is nutritionally essential for normal physiologic functioning. However, excessive exposure to manganese has been associated with developmental, neurodegenerative and other disorders. The book comprehensively covers the toxicology of manganese. Leading investigators provide perspectives from toxicology, neuroscience, nutrition, molecular biology and risk assessment disciplines and chapters cover the toxicokinetics, toxicodynamic interactions and health effects of manganese, as well as its potential role in neurodegenerative diseases. A large section devoted to health effects presents the latest research that associates manganese exposure to potential human diseases. Any scientists, health professional or regulator involved with metal exposure and toxicology should find this volume essential reading. Students and researchers in neurotoxicology will also find this book a useful reference.
Trace Metals And Infectious Diseases
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Author : Jerome O. Nriagu
language : en
Publisher: MIT Press
Release Date : 2024-06-11
Trace Metals And Infectious Diseases written by Jerome O. Nriagu and has been published by MIT Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2024-06-11 with Medical categories.
Experts explore the influence of trace metals on the pathogenesis of infectious diseases. Many parts of the world in which common infectious diseases are endemic also have the highest prevalence of trace metal deficiencies or rising rates of trace metal pollution. Infectious diseases can increase human susceptibility to adverse effects of metal exposure (at suboptimal or toxic levels), and metal excess or deficiency can increase the incidence or severity of infectious diseases. The co-clustering of major infectious diseases with trace metal deficiency or toxicity has created a complex web of interactions with serious but poorly understood health repercussions, yet has been largely overlooked in animal and human studies. This book focuses on the distribution, trafficking, fate, and effects of trace metals in biological systems. Its goal is to enhance our understanding of the relationships between homeostatic mechanisms of trace metals and the pathogenesis of infectious diseases. Drawing on expertise from a range of fields, the book offers a comprehensive review of current knowledge on vertebrate metal-withholding mechanisms and the strategies employed by different microbes to avoid starvation (or poisoning). Chapters summarize current, state-of-the-art techniques for investigating pathogen-metal interactions and highlight open question to guide future research. The book makes clear that improving knowledge in this area will be instrumental to the development of novel therapeutic measures against infectious diseases. Contributors M. Leigh Ackland, Vahid Fa Andisi, Angele L. Arrieta, Michael A. Bachman, J. Sabine Becker, Robert E. Black, Julia Bornhorst, Sascha Brunke, Joseph A. Caruso, Jennifer S. Cavet, Anson C. K. Chan, Christopher H. Contag, Heran Darwin, George V. Dedoussis, Rodney R. Dietert, Victor J. DiRita, Carol A. Fierke, Tamara Garcia-Barrera, David P. Giedroc, Peter-Leon Hagedoorn, James A. Imlay, Marek J. Kobylarz, Joseph Lemire, Wenwen Liu, Slade A. Loutet, Wolfgang Maret, Andreas Matusch, Trevor F. Moraes, Michael E. P. Murphy, Maribel Navarro, Jerome O. Nriagu, Ana-Maria Oros-Peusquens, Elisabeth G. Pacyna, Jozef M. Pacyna, Robert D. Perry, John M. Pettifor, Stephanie Pfaffen, Dieter Rehder, Lothar Rink, Anthony B. Schryvers, Ellen K. Silbergeld, Eric P. Skaar, Miguel C. P. Soares, Kyrre Sundseth, Dennis J. Thiele, Richard B. Thompson, Meghan M. Verstraete, Gonzalo Visbal, Fudi Wang, Mian Wang, Thomas J. Webster, Jeffrey N. Weiser, Günter Weiss, Inga Wessels, Bin Ye, Judith T. Zelikoff, Lihong Zhang
Molecular Bio Sensors And The Role Of Metal Ions
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Author : Thomas J. Meade
language : en
Publisher: CRC Press
Release Date : 2022-09-27
Molecular Bio Sensors And The Role Of Metal Ions written by Thomas J. Meade and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-09-27 with Science categories.
Volume 23, entitled Molecular Bio-Sensors and the Role of Metal Ions, of the series Metal Ions in Life Sciences (MILS) represents a milestone of contemporary progress and understanding of molecular bio-sensors for metal ions. It is bringing together the latest research in academia and industry, and it also emphasizes the spectrum of evolving regulations from regulatory bodies. This vibrant research area is covered by 31 internationally recognized experts. The impact of MILS-23 is manifested by more than 1300 references and close to 200 figures, more than 100 of them in color; further information is summarized in several tables. In conclusion, Volume 23 significantly advances our understanding of Molecular Bio-Sensors, it is therefore an essential resource for scientists working in the wide range from earth sciences, material sciences, physics, pharmacology, enzymology, analytical, organic, and inorganic biochemistry all the way through to medicine including the clinic. • It provides an understanding of the roles that metals play in living systems. • It offers an insight for the demands needed in the clinic. • It reveals the interplay between bio-sensors and therapies. The Series METAL IONS IN LIFE SCIENCES increases our understanding of the relationship between the chemistry of metals and life processes. The volumes reflect the interdisciplinary nature of Biological Inorganic Chemistry and coordinate the efforts of researchers in fields like biochemistry, inorganic chemistry, coordination chemistry, molecular and structural biology, enzymology, toxicology, environmental chemistry, biophysics, pharmacy, and medicine. The volumes deal with the formation, stability, structure, and reactivity of metal-containing biological compounds of low and high molecular weight. The metabolism and transport of metal ions and their complexes as well as new models of complicated natural structures and processes are in the focus. Consequently, the volumes are an essential source for researchers in the mentioned fields as well as for teachers preparing courses, e.g., in Bioinorganic Chemistry.
Environmental Pollution Of The Pearl River Estuary China
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Author : Wen-Xiong Wang
language : en
Publisher: Springer Nature
Release Date : 2020-07-19
Environmental Pollution Of The Pearl River Estuary China written by Wen-Xiong Wang and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-07-19 with Science categories.
The Pearl River Estuary (PRE) is the Western name for a very large estuary in southern China that is currently home to an industrial metropolis of staggering size, and one that is rapidly evolving. The Chinese name for the Pearl River is Zhujiang. Guangzhou lies at the head of the estuary, and Macau and Hong Kong are on the western and eastern sides, respectively, of the wide opening of the estuary to the South China Sea. The new cities of Zhuhai and Shenzhen lie immediately north of Macau and Hong Kong, respectively. The recent establishment of the Greater Bay Area (GBA), which covers the majority of the Pearl River Delta area, with a total population of over 70 million, will certainly put the PRE under strict environmental scrutiny. The PRE system itself will provide a model system for environmental scientists owing to its major anthropogenic perturbation and influences, as well as the highly dynamic nature of the estuary. This book addresses the major environmental concerns regarding this estuary, contaminants and other pollutants, e.g. toxic metals, organic contaminants and emerging compounds. Questions addressed here include: What are the sources of the contaminants? What have the environmental consequences of these contaminants been for the estuary? What will the future bring? The research presented here on the Pearl River Estuary offers a wealth of insights for other major contaminated estuaries around the world.