Signalling Pathways in Acute Oxygen Sensing: Novartis Foundation Symposium 272

Copyright © Novartis Foundation 2006

Signalling Pathways in Acute Oxygen Sensing: Novartis Foundation Symposium 272

Editor(s): Derek J. Chadwick, Jamie Goode

Published Online: 7 OCT 2008

Print ISBN: 9780470014578

Online ISBN: 9780470035009

DOI: 10.1002/9780470035009

Series Editor(s): Novartis Foundation

About this Book

Product Information

About The Product

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.

Table of contents

    1. You have free access to this content
      Front Matter (pages i–xi)

    2. Chair's Introduction (page 1)

      Michael Duchen

    3. Regulation of Gene Expression by HIF-1 (pages 2–14)

      Gregg L. Semenza, Larissa A. Shimoda and Nanduri R. Prabhakar

    4. Regulation of HIF: Prolyl Hydroxylases (pages 15–32)

      Ineke P. Stolze, David R. Mole and Peter J. Ratcliffe

    5. General Discussion I (pages 33–36)

    6. Regulation of HIF: Asparaginyl Hydroxylation (pages 37–53)

      Daniel Peet and Sarah Linke

    7. Oxygen-Sensing by Ion Channels and Mitochondrial Function in Carotid Body Glomus Cells (pages 54–72)

      José López-Barneo, Patricia Ortega-Sáenz, José I. Piruat and María García-Fernández

    8. The Role of TASK-Like K+ Channels in Oxygen Sensing in the Carotid Body (pages 73–94)

      Keith J. Buckler, Beatrice A. Williams, Rodrigo Varas Orozco and Christopher N. Wyatt

    9. Reactive Oxygen Species Facilitate Oxygen Sensing (pages 95–105)

      Nanduri R. Prabhakar, Ying-Jie Peng, Guoxiang Yuan and Ganesh K. Kumar

    10. Oxygen Sensing in Neuroepithelial and Adrenal Chromaffin Cells (pages 106–118)

      C. A. Nurse, J. Buttigieg, R. Thompson, M. Zhang and E. Cutz

    11. Hypoxic Regulation of Ca2+ Signalling in Astrocytes and Endothelial Cells (pages 119–130)

      C. Peers, P. Kang, J. P. Boyle, K. E. Porter, H. A. Pearson, I. F. Smith and P. J. Kemp

    12. General Discussion II (pages 131–140)

    13. Functional Proteomics of BK Potassium Channels: Defining the Acute Oxygen Sensor (pages 141–156)

      Paul J. Kemp, Sandile E. J. Williams, Helen S. Mason, Phillippa Wootton, David E. Iles, Daniela Riccardi and Chris Peers

    14. A Central Role for Oxygen-Sensitive K+ Channels and Mitochondria in the Specialized Oxygen-Sensing System (pages 157–175)

      Stephen L. Archer, Evangelos D. Michelakis, Bernard Thébaud, Sebastien Bonnet, Rohit Moudgil, Xi-Chen Wu and E. Kenneth Weir

    15. Role for Mitochondrial Reactive Oxygen Species in Hypoxic Pulmonary Vasoconstriction (pages 176–195)

      Gregory B. Waypa and Paul T. Schumacker

    16. Hypoxic Pulmonary Vasoconstriction—Triggered by an Increase in Reactive Oxygen Species? (pages 196–213)

      Norbert Weissmann, Ralph T. Schermuly, Hossein A. Ghofrani, Jörg Hänze, Parag Goyal, Friedrich Grimminger and Werner Seeger

    17. General Discussion III (pages 214–217)

    18. The Role of Twin Pore Domain and Other K+ Channels in Hypoxic Pulmonary Vasoconstriction (pages 218–233)

      Alison M. Gurney and Shreena Joshi

    19. AMP-Activated Protein Kinase Couples Mitochondrial Inhibition by Hypoxia to Cell-Specific Ca2+ Signalling Mechanisms in Oxygensensing Cells (pages 234–258)

      A. Mark Evans, D. Grahame Hardie, Antony Galione, Chris Peers, Prem Kumar and Christopher N. Wyatt

    20. Role of Capacitative Ca2+ Entry But Not Na+/Ca2+ Exchange in Hypoxic Pulmonary Vasoconstriction in Rat Intrapulmonary Arteries (pages 259–273)

      Silke Becker, Gregory A. Knock, Vladimir Snetkov, Jeremy P. T. Ward and Philip I. Aaronson

    21. Final General Discussion (pages 274–279)

    22. You have free access to this content
      Index of Contributors (pages 280–281)

    23. You have free access to this content
      Subject Index (pages 282–288)

SEARCH