| Contributors |
| Preface |
| Volumes in Series |
| Hypoxia-Inducible Factor / Section I： |
| Hypoxia-Inducible Factors P[superscript ER]/ARNT/S[superscript IM] Domains: Structure and Function / Thomas H. Scheuermann ; Jinsong Yang ; Lei Zhang ; Kevin H. Gardner ; Richard K. Bruick1： |
| Introduction |
| Delineation of the HIF PAS Domains / 2： |
| Expression and Characterization of HIF PAS Domains / 3： |
| Assessing PAS Domain Protein-Protein Interactions / 4： |
| Discussion / 5： |
| Acknowledgments |
| References |
| Hypoxia-Inducible Factor Prolyl-Hydroxylase: Purification and Assays of PHD2 / Kirsty S. Hewitson ; Christopher J. Schofield ; Peter J. Ratcliffe |
| of Purified PHD2 from a Bacterial Source |
| Assaying of PHD2 Activity |
| Indirect Measurements of PHD2 Activity |
| Direct Measurements of PHD2 Hydroxylation Activity |
| Binding Assays / 6： |
| Comparison of Assay Formats / 7： |
| Determination and Modulation of Prolyl-4-Hydroxylase Domain Oxygen Sensor Activity / Renato Wirthner ; Kuppusamy Balamurugan ; Daniel P. Stiehl ; Sandra Barth ; Patrick Spielmann ; Felix Oehme ; Ingo Flamme ; Dorthe M. Katschinski ; Roland H. Wenger ; Gieri Camenisch |
| Production of Functionally Active PHDs |
| Determination of PHD by VHL Binding to Peptides Derived from the HIF-1[alpha] ODD Domain |
| Determination of Prolyl-4-Hydroxylation by Oxidative Decarboxylation of 2-Oxoglutarate |
| Crude Tissue Extracts are not a Suitable Source of PHD Activity for the 2-Oxoglutarate Conversion Assay |
| Thin Layer Chromatography to Assess the Purity of [5-[superscript 14] C]2-Oxoglutarate |
| Application of the 2-Oxoglutarate Conversion Assay to Protein Targets |
| Conclusions / 8： |
| Characterization of Ankyrin Repeat-Containing Proteins as Substrates of the Asparaginyl Hydroxylase Factor Inhibiting Hypoxia-Inducible Transcription Factor / Sarah Linke ; Rachel J. Hampton-Smith ; Daniel J. Peet |
| Experimental Techniques |
| Discussion/Conclusion |
| Transgenic Models to Understand Hypoxia-Inducible Factor Function / Andrew Doedens ; Randall S. Johnson |
| Hypoxia Response Pathway Genes and Development |
| HIF in Physiology |
| HIF Function in Tumor Biology |
| Summary |
| The Silencing Approach of the Hypoxia-Signaling Pathway / Edurne Berra ; Jacques Pouyssegur |
| A Brief History of RNAi |
| The Hypoxia-Signaling Pathway |
| HIF-[alpha] Stability |
| HIF Activity |
| HIF-1/HIF-2 Target Gene Specificity |
| RNAi as a New Potential Therapeutic Strategy |
| Cellular and Developmental Adaptations to Hypoxia: A Drosophila Perspective / Nuria Magdalena Romero ; Andres Dekanty ; Pablo Wappner |
| Drosophila melanogaster as a Model System to Study Physiological Responses to Hypoxia |
| Experimental Advantages of the Model System |
| The Drosophila Respiratory System |
| Occurrence of a Drosophila System Homologous to Mammalian HIF |
| Regulation of Sima by Oxygen Levels |
| Role of Sima and Fatiga in Drosophila Development |
| Hypoxia-Inducible Genes and the Adaptation of Drosophila to Oxygen Starvation |
| Regulation of Sima by the PI3K and TOR Pathways / 9： |
| Role of the HIF System in Growth Control and Cell Size Determination / 10： |
| Concluding Remarks / 11： |
| Erythropoietin / Section II： |
| Constitutively Overexpressed Erythropoietin Reduces Infarct Size in a Mouse Model of Permanent Coronary Artery Ligation / Giovanni G. Camici ; Thomas Stallmach ; Matthias Hermann ; Rutger Hassink ; Peter Doevendans ; Beat Grenacher ; Alain Hirschy ; Johannes Vogel ; Thomas F. Luscher ; Frank Ruschitzka ; Max Gassmann |
| Material and Methods |
| Results |
| Use of Gene-Manipulated Mice in the Study of Erythropoietin Gene Expression / Norio Suzuki ; Naoshi Obara ; Masayuki Yamamoto |
| Materials |
| Methods and Results |
| Conclusion |
| Control of Erythropoietin Gene Expression and its Use in Medicine / Wolfgang Jelkmann |
| Native EPO Gene Expression and its Pharmacologic Stimulation |
| EPO Gene Transfer |
| Recombinant EPOS |
| Role of Hypoxia-Inducible Factor-2[alpha] in Endothelial Development and Hematopoiesis / Osamu Ohneda ; Masumi Nagano ; Yoshiaki Fujii-Kuriyama |
| Vasculogenesis/Angiogenesis and HIFs |
| HIF-1[beta]/ARNT Null Mice |
| Neovascularization and HIFs |
| Hematopoiesis and HIFs |
| Hypoxia and Adaptation / Section III： |
| Organ Protection by Hypoxia and Hypoxia-Inducible Factors / Wanja M. Bernhardt ; Christina Warnecke ; Carsten Willam ; Tetsuhiro Tanaka ; Michael S. Wiesener ; Kai-Uwe Eckardt12： |
| From Ischemic to Hypoxic Preconditioning |
| Hypoxia-Inducible Transcription Factors |
| Strategies to Activate HIF and HIF Target Genes |
| Hypoxic Preconditioning and HIF |
| HIF in Chronic Hypoxic/Ischemic Diseases |
| Conclusions and Perspectives |
| Hypoxia and Regulation of Messenger RNA Translation / Marianne Koritzinsky ; Bradly G. Wouters13： |
| Changes in Global mRNA Translation During Hypoxia |
| Molecular Mechanisms that Regulate mRNA Translation During Hypoxia |
| Methods Employed to Study mRNA Translation During Hypoxia |
| Protocols |
| Hypoxia and the Unfolded Protein Response / Constantinos Koumenis ; Meixia Bi ; Jiangbin Ye ; Douglas Feldman ; Albert C. Koong14： |
| Methods Employed in Detecting Hypoxic Induction of ER Stress |
| Hypoxia and Tumor Biology / Section IV： |
| Tumor Hypoxia in Cancer Therapy / J. Martin Brown15： |
| Hypoxia in Human Tumors |
| The Dynamic Nature of Hypoxia in Tumors |
| Consequences of Tumor Hypoxia for Cancer Treatment |
| Size of the Oxygen Effect with Radiation |
| The Influence of Tumor Hypoxia on Cancer Treatment by Radiotherapy |
| Influence of Tumor Hypoxia on Response to Chemotherapy |
| Exploiting Hypoxia in Cancer Treatment |
| HIF Gene Expression in Cancer Therapy / Denise A. Chan ; Adam J. Krieg ; Sandra Turcotte ; Amato J. Giaccia16： |
| Experimental Procedures |
| Analysis of Hypoxia-Inducible Factor-1[alpha] Expression and its Effects on Invasion and Metastasis / Balaji Krishnamachary ; Gregg L. Semenza17： |
| Protocol 1: HIF-1[alpha] Immunohistochemistry |
| Protocol 2: Invasion Assay |
| Protocol 3: Transepithelial Resistance Measurement of Cell-Cell Adhesion |
| Protocol 4: Analysis of MRNA Expression by QRT-PCR |
| Macrophage Migration Inhibitory Factor Manipulation and Evaluation in Tumoral Hypoxic Adaptation / Millicent Winner ; Lin Leng ; Wayne Zundel ; Robert A. Mitchell18： |
| Modulation of MIF Levels by Targeted shRNAs and Assessment of Knockdown Efficiency |
| Analysis of MIF-Dependent CSN5 and COP9 Signalosome Function |
| Determination of Tumor-Associated MIF Expression and MIF Polymorphic Disparity |
| The Von Hippel-Lindau Tumor Suppressor Protein: An Update / William G. Kaelin, Jr.19： |
| Regulation of Epithelial Differentiation by pVHL |
| Crosstalk Between c-Met and VHL |
| Regulation of Neuronal Apoptosis by pVHL |
| Possible Links Between p53 and pVHL |
| Regulation of pVHL by Phosphorylation |
| Polyubiquitylation of pVHL |
| Mouse Models for Studying pVHL Function |
| Hypoxia-Inducible Factor 1 Inhibitors / Giovanni Melillo20： |
| Cell-Based High Throughput Screens |
| Cell-Free Assays |
| Bioassay-Directed Isolation of Natural Product HIF-1 Inhibitors |
| Hypoxia and Inflammatory Mediators / Section V： |
| Regulation of Hypoxia-Inducible Factors During Inflammation / Stilla Frede ; Utta Berchner-Pfannschmidt ; Joachim Fandrey21： |
| Regulation of HIF at the Transcriptional Level |
| Regulation of HIF at the Translational Level |
| Regulation of HIF-1[alpha] at the Posttranslational Level |
| Regulation of HIF-1 Activity |
| Perspectives |
| Superoxide and Derived Reactive Oxygen Species in the Regulation of Hypoxia-Inducible Factors / Agnes Gorlach ; Thomas Kietzmann22： |
| Reactive Oxygen Species Act as Signaling Molecules |
| HIFs are Sensitive to Oxygen |
| Reactive Oxygen Species Modulate HIF |
| How are HIFs Regulated by Reactive Oxygen Species? |
| Methods |
| The Cytochrome C Reduction Assay for Detection of Extracellular Reactive Oxygen Species |
| Chemiluminescence Assay for Detection of Extracellular Reactive Oxygen Species |
| Measuring Intracellular Production of Reactive Oxygen Species using Fluorescent Dyes |
| Detection of Reactive Oxygen Species by Electron Paramagnetic Resonance |
| Genetics of Mitochondrial Electron Transport Chain in Regulating Oxygen Sensing / Eric L. Bell ; Navdeep S. Chandel23： |
| Detecting HIF-1[alpha] Protein Levels |
| Detecting Intracellular ROS Levels |
| Method 1: Examining Hypoxic Stabilization of HIF-1[alpha] Protein in Cells Containing RNAI against the Rieske Fe-S Protein |
| Method 2: Examining the Role of ROS Generated from Mitochondrial Electron Transport in Hypoxic Stabilization of HIF-1[alpha] Protein |
| Hypoxia-Inducible Factor-1[alpha] Under the Control of Nitric Oxide / Bernhard Brune ; Jie Zhou24： |
| HIF-1 and Oxygen Sensing |
| Nitric Oxide: A Multifunctional Messenger |
| Accumulation of HIF-1[alpha] and Activation of HIF-1 by NO |
| Superoxide Stabilizes HIF-1[alpha] but Antagonizes NO Actions |
| Hypoxic Signal Transmission is Antagonized by NO |
| Summary and Conclusions |
| Hypoxic Regulation of NF-[kappa]B Signaling / Eoin P. Cummins ; Katrina M. Comerford ; Carsten Scholz ; Ulrike Bruning ; Cormac T. Taylor25： |
| Background |
| Treatment Protocols for Cellular Hypoxia Studies |
| Measurement of NF-[kappa]B Activity in Cultured Cells |
| Summary/Conclusions |
| Author Index |
| Subject Index |
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