Signalling Pathways in Acute Oxygen Sensing

Beschreibung

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.

Autor*in

Derek J. Chadwick

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Biowissenschaften Cell & Molecular Biology Life Sciences Molekularbiologie Zell- u. Molekularbiologie

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"This an excellent resource for those in the field of oxygen sensing." (Doody's Health Services)
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