Signalling Pathways in Acute Oxygen Sensing
Published on 30. March 2006
300 pages
978-0-470-03499-6 (ISBN)
Description
Oxygen sensing is a key physiological function of many tissues, butthe identity of the sensor, the signalling pathways linking thesensor to the effector, and the endpoint effector mechanisms areall subjects of controversy. This book evaluates the variousmediators that have been proposed, including the mitochondria,NAD(P)H oxidases, cytochrome p450 enzymes, and direct effects onenzymes and ion channels. There has been a resurgence of interestin the role of mitochondria, based partly on the ability ofmitochondrial inhibitors to mimic hypoxia, but there is littleconsensus concerning mechanisms. Some favour the view that theprimary signalling event is a reduction in cell redox state andreactive oxygen species (ROS) due to general inhibition of theelectron transport chain (ETC); others support a key role forcomplex III of the ETC and an increase in ROS generation, whileothers doubt either of these components is the key intermediary.All these hypotheses are discussed in the book, together withconceptual problems concerning the ability of mitochondria torespond to physiological hypoxia.
The other area of controversy covered in the book is the identityof the endpoint effector(s). Some authors favour K+ channelinhibition, followed by depolarization and Ca2+ entry via L-typechannels, while others propose that release of Ca2+ fromintracellular stores, or capacitative Ca2+ entry and othervoltage-independent pathways may be more important. The book alsodescribes evidence for an endothelium-dependent Ca2+-sensitizingpathway involving Rho and possibly other kinases.
While some of these differences can be attributed to variationbetween tissues, many must be related to differences ininterpretation or methodology. In this book, experts in the fieldof acute oxygen sensing working in different tissues address thesecontroversies and their possible origins, and discuss possibleapproaches whereby these controversies might be resolved.
The book will be of great interest to all those working in fieldswhere oxygen sensing is important, particularly cancer and woundhealing, as well as researchers in drug discovery andbiotechnology.
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"This an excellent resource for those in the field of oxygen sensing." (Doody's Health Services)More details
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The Novartis Foundation is an international scientific and educational charity which promotes the study and general knowledge of science and in particular encourages international co-operation in scientific research.
Content
Symposium on Signalling pathways in acute oxygen sensing, heldat the Novartis Foundation, London, 25-27 January2005.
Editors: Derek J. Chadwick (Organizer) and JamieGoode.
This symposium is based on a proposal made by JeremyWard.
Michael Duchen Chair's introduction.
Gregg L. Semenza, Larissa A. Shimoda and Nanduri R.Prabhakar Regulation of gene expression by Hypoxia-InducibleFactor.
Discussion.
Ineke P. Stolze, David R. Mole and Peter J.Ratcliffe Regulation of HIF: prolyl hydroxylases.
Discussion.
General discussion I.
Daniel Peet and Sarah Linke Regulation of HIF:asparaginyl hydroxylation.
Discussion.
José López-Barneo, Patricia Ortega-Sáenz,José I. Piruat and MaríaGarcía-Fernández Oxygen-sensing by ion channels andmitochondrial function in carotid body glomus cells.
Discussion.
Keith J. Buckler, Beatrice A. Williams, Rodrigo VarasOrozco and Christopher N. Wyatt The role of TASK-likepotassium channels in oxygen sensing in the carotid body.
Discussion.
Nanduri R. Prabhakar, Ying-Jie Peng, Guoxiang Yuan andGanesh K. Kumar Reactive oxygen species facilitate oxygensensing.
Discussion.
C. A. Nurse, J. Buttigieg, R. Thompson, M. Zhang andE. Cutz Oxygen sensing in neuroepithelial and adrenalchromaffin cells.
Discussion.
C. Peers, P. Kang, J. P. Boyle, K. E. Porter, H. A. Pearson,I. F. Smith and P. J. Kemp Hypoxic regulation of Ca2+signalling in astrocytes and endothelial cells.
Discussion.
General discussion II.
Paul J. Kemp, Sandile E. J. Williams, Helen S. Mason,Phillippa Wootton, David E. Iles, Daniela Riccardi andChris Peers Functional proteomics of BK potassium channels:defining the acute oxygen sensor.
Discussion.
Stephen L. Archer, Evangelos D. Michelakis, BernardThébaud, Sebastien Bonnet, Rohit Moudgil, Xi-ChenWu and E. Kenneth Weir A central role for O2-sensitiveK+ channels and mitochondria in the specialized O2-sensingsystem.
Discussion.
Gregory B. Waypa and Paul T. Schumacker Role formitochondrial reactive oxygen species in hypoxic pulmonaryvasoconstriction.
Discussion.
Norbert Weissmann, Ralph T. Schermuly, Hossein A.Ghofrani, Jörg Hänze, Parag Goyal, FriedrichGrimminger and Werner Seeger Hypoxic pulmonaryvasoconstriction--triggered by an increase in reactive oxygenspecies?.
Discussion.
General discussion III.
Alison M. Gurney and Shreena Joshi The role oftwin pore domain and other K+ channels in hypoxic pulmonaryvasoconstriction.
Discussion.
A. Mark Evans, D. Grahame Hardie, Antony Galione, ChrisPeers, Prem Kumar and Christopher N. WyattAMP-activated protein kinase couples mitochondrial inhibition byhypoxia to cell-specific calcium signalling mechanisms inoxygen-sensing cells.
Discussion.
Silke Becker, Gregory A. Knock, Vladimir Snetkov, Jeremy P.T. Ward and Philip I. Aaronson Role of capacitative Ca2+entry but not Na+/Ca2+ exchange in hypoxic pulmonaryvasoconstriction in rat intrapulmonary arteries.
Discussion.
Final general discussion.
Index of contributors.
Subject index.
