Thrombin (eBook, PDF)

Physiology and Disease
Redaktion: Maragoudakis, Michael E.; Tsopanoglou, Nikos E.

• Format: PDF

Produktbeschreibung

It has become increasingly evident in recent years that, apart from the key role that thrombin plays in the blood coagulation cascade, thrombin also elicits cellular actions via the activation of proteinase-activated receptors, which are present in many cell types. These effects of thrombin are seen in a variety of physiological as well as pathological phenomena, including vascular development and physiology, tumor progression and metastasis, neuronal functions, inflammation, angiogenesis. Thrombin: Physiology and Disease, edited by Michael E. Maragoudakis and Nikos E. Tsopanoglou, emphasizes the new developments in this important field of research and provides the basis for translating these findings into therapeutic targets."

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Produktdetails

• Verlag: Springer-Verlag GmbH
• Seitenzahl: 266
• Erscheinungstermin: 2. April 2010
• Englisch
• ISBN-13: 9780387096377
• Artikelnr.: 37288598

Inhaltsangabe

Table of contents 1. Thrombin: structure, functions and regulation 1.1. Introduction 1.2. Thrombin and Na+ 1.3. Thrombin structure 1.4. Kinetics of Na+ activation 1.5. Structures of E*, E and E:Na+ 1.6. Thrombin interaction with protein C 1.7. Thrombin interaction with the PARs 1.8. Dissociating procoagulant and anticoagulant activities 1.9. WE: a prototypic anticoagulant/antithrombotic thrombin 1.10. References 2. Thrombin: to PAR or not to PAR, and the regulation of inflammation 2.1. Introduction 2.2. Thrombin and the search for its receptor 2.3. Enzymes other than thrombin that are potential physiological regulators of PARs 2.3.1. Enzymes of the coagulation pathway 2.3.2. Proteinases of the gastrointestinal tract 2.3.3. PAR-regulating proteinases in the central nervous system 2.3.4. Immune cell-derived proteinases and PARs 2.3.5. Tumor-derived proteinases and a possible physiological role for kallikrein-related peptidases (KLKs) as PAR regulators 2.3.6. Pathogen-derived proteinases and PAR activation 2.4. Receptor dynamics and cell signaling: enzyme versus peptide-mediated activation 2.4.1. PAR-mediated signaling 2.4.2. PAR activation by enzyme versus peptide 2.5. PAR activation and the inflammation actions of thrombin 2.6. Non-PAR mechanisms of cell regulation mediated by thrombin and other proteinases 2.6.1. Signaling targets that are not 'classical' receptors 2.6.2. Non-catalytic mechanisms for proteinase-mediated signaling 2.6.3. Thrombin-mediated generation of agonists from fibrin and other substrates 2.7. Therapeutic implications of thrombin action via PAR and non-PAR mechanisms 2.7.1. Targeting thrombin and other serine proteinases 2.7.2. Targeting the PARs 2.8. Summary 2.9. Acknowledgements 2.10. References 3. Regulation of thrombin receptor signaling 3.1. Introduction 3.2. Cell type specific expression of thrombin receptors 3.3. Thrombin receptor activation and signaling 3.3.1. Proteolytic mechanism of thrombin receptor activation 3.3.2. Thrombin receptor signaling to heterotrimeric G-proteins 3.3.3. Cell type specific thrombin receptor signaling 3.4. Regulation of thrombin receptor signaling 3.4.1. Thrombin receptor desensitization 3.4.2. Thrombin receptor internalization 3.4.3. Thrombin receptor down-regulation 3.5. PAR activation and signaling by other proteases 3.6. Conclusions 3.7. Acknowledgements 3.8. References 4. Thrombin-activated protein C: integrated to regulate vascular physiology 4.1. The protein C pathway is localized to the endothelial cell surface and limits thrombin generation through negative feedback 4.2. APC has protective effects in systemic inflammation that are independent of its anticoagulant function 4.3. The thrombin receptor PAR1 mediates APC signaling in tissues culture 4.4. APC and thrombin can mediate opposite cellular responses in endothelial cells through PAR1 activation 4.4.1. Barrier integrity 4.4.2. Adhesion molecule expression 4.4.3. Apoptosis 4.5. Role of the sphingosine-1 phosphate pathway in mediating protective signaling by PAR1. 4.6. Protective PAR1 signaling by APC is mechanistically coupled to PC activation by thrombin 4.7. Not PAR1- or EPCR-dependent mechanisms for signaling by the PC pathway? 4.8. Thrombin-PAR1 and APC-PAR1 signaling in in vivo models of inflammation 4.9. How can activation of the thrombin receptor PAR1 by the PC pathway be of physi