Signalling Pathways In Acute Oxygen Sensing

Oxygen sensing is a key physiological function of many tissues, but the identity of the sensor, the signalling pathways linking the sensor to the effector, and the endpoint effector mechanisms are all subjects of controversy. This book evaluates the various mediators that have been proposed, including the mitochondria, NAD(P)H oxidases, cytochrome p450 enzymes, and direct effects on enzymes and ion channels. There has been a resurgence of interest in the role of mitochondria, based partly on the ability of mitochondrial inhibitors to mimic hypoxia, but there is little consensus concerning mechanisms. Some favour the view that the primary signalling event is a reduction in cell redox state and reactive oxygen species (ROS) due to general inhibition of the electron transport chain (ETC); others support a key role for complex III of the ETC and an increase in ROS generation, while others doubt either of these components is the key intermediary. All these hypotheses are discussed in the book, together with conceptual problems concerning the ability of mitochondria to respond to physiological hypoxia. The other area of controversy covered in the book is the identity of the endpoint effector(s). Some authors favour K+ channel inhibition, followed by depolarization and Ca2+ entry via L-type channels, while others propose that release of Ca2+ from intracellular stores, or capacitative Ca2+ entry and other voltage-independent pathways may be more important. The book also describes evidence for an endothelium-dependent Ca2+-sensitizing pathway involving Rho and possibly other kinases. While some of these differences can be attributed to variation between tissues, many must be related to differences in interpretation or methodology. In this book, experts in the field of acute oxygen sensing working in different tissues address these controversies and their possible origins, and discuss possible approaches whereby these controversies might be resolved. The book will be of great interest to all those working in fields where oxygen sensing is important, particularly cancer and wound healing, as well as researchers in drug discovery and biotechnology.

This book represents an updated review of the physiology of the carotid body chemoreceptors. It contains results in the topics at the frontiers of future developments in O2-sensing in chemoreceptor cells. Additionally, this volume provides data from studies carried out in other O2-sensing tissues including pulmonary vasculature and erythropoietin producing cells. It is a prime source of information and a guideline for arterial chemoreception researchers.

The ability of cells to sense and respond to changes in oxygenation underlies a multitude of developmental, physiological, and pathological processes. This volume provides a comprehensive compendium of experimental approaches to the study of oxygen sensing in 48 chapters that are written by leaders in their fields.

This book describes the methods of analysis and determination of oxidants and oxidative stress in biological systems. Reviews and protocols on select methods of analysis of ROS, RNS, oxygen, redox status, and oxidative stress in biological systems are described in detail. It is an essential resource for both novices and experts in the field of oxidant and oxidative stress biology.

This book represents an updated review of the physiology of the carotid body chemoreceptors. It contains results in the topics at the frontiers of future developments in O2-sensing in chemoreceptor cells. Additionally, this volume provides data from studies carried out in other O2-sensing tissues including pulmonary vasculature and erythropoietin producing cells. It is a prime source of information and a guideline for arterial chemoreception researchers.

Gas molecules such as O2, NO, CO and ethylene are present in the environment and are endogenously (enzymatically) produced to act as signalling molecules in biological systems, including the regulation of metabolic networks, chemotaxis, circadian rhythms, mammalian hypoxia responses, and plant ethylene responses by transcriptional, translational, or post translational control. Sensing these gas molecules is the first step in their acting as signalling molecules. When a sensor domain/protein senses an external signal, intra- and inter-molecular signal transductions take place to regulate the biological function of a regulatory domain/protein such as DNA-binding, enzymatic activity, or protein–protein interaction. Interaction between gas molecules and sensor proteins is essential for recognition of gas molecules. Metal-containing prosthetic groups such as haem, iron–sulfur clusters, and non-haem iron centres are widely used. As these metal-containing centres are good spectroscopic probes, detail characterizations have utilized spectroscopic techniques along with X-ray crystallography. Covering both the signalling and sensing of gaseous molecules, this book provides the first comprehensive overview of gas sensor proteins in both prokaryotic and eukaryotic cells. This book will be particularly interesting to postgraduates and researchers in biochemistry, molecular biology and metallobiology.

The formation of blood vessels is an essential aspect of embryogenesis in vertebrates. It is a central feature of numerous post-embryonic processes, including tissue and organ growth and regeneration. It is also part of the pathology of tumour formation and certain inflammatory conditions. In recent years, comprehension of the molecular genetics of blood vessel formation has progressed enormously and studies in vertebrate model systems, especially the mouse and the zebrafish, have identified a common set of molecules and processes that are conserved throughout vertebrate embryogenesis while, in addition, highlighting aspects that may differ between different animal groups. The discovery in the past decade of the crucial role of new blood vessel formation for the development of cancers has generated great interest in angiogenesis (the formation of new blood vessels from pre-existing ones), with its major implications for potential cancer-control strategies. In addition, there are numerous situations where therapeutic treatments either require or would be assisted by vasculogenesis (the de novo formation of blood vessels). In particular, post-stroke therapies could include treatments that stimulate neovascularization of the affected tissues. The development of such treatments, however, requires thoroughly understanding the developmental properties of endothelial cells and the basic biology of blood vessel formation. While there are many books on angiogenesis, this unique book focuses on exactly this basic biology and explores blood vessel formation in connection with tissue development in a range of animal models. It includes detailed discussions of relevant cell biology, genetics and embryogenesis of blood vessel formation and presents insights into the cross-talk between developing blood vessels and other tissues. With contributions from vascular biologists, cell biologists and developmental biologists, a comprehensive and highly interdisciplinary volume is the outcome.

This new volume of the book series Advances in Anatomy, Embryology and Cell Biology provides a complete and exhaustive overview of the morphofunctional organization of the mammalian carotid body, a polymodal chemosensory organ responsible for the maintenance of blood gas homeostasis. The authors review the state of the art of the neurochemical anatomy of carotid body ́s cell populations with a special reference to their structural and neurochemical plasticity. The essential role of this organ in the generation, progression and maintenance of cardiorespiratory and metabolic diseases in humans and other mammals is presented. Finally, the book summarizes current knowledge on the stem cell niche in the mammalian carotid body and discusses its contribution to replacement cell therapy and other potential applications in translational research. This book represents an essential reading for physiologists, anatomists, cell, and developmental biologists, as well as physicians, veterinarians, and biomedical researchers.