Klotho

 
 
Academic Press
  • 1. Auflage
  • |
  • erschienen am 25. April 2016
  • |
  • 352 Seiten
 
E-Book | ePUB mit Adobe DRM | Systemvoraussetzungen
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978-0-12-805235-8 (ISBN)
 

Klotho is the latest edition of a series first published in 1943 on Vitamins and Hormones and the longest-running serial published by Academic Press. It provides up-to-date information on vitamin and hormone research spanning data from molecular biology to the clinic, with volumes focusing on a single molecule or on a disease that is related to vitamins or hormones that are interpreted broadly so that related substances, such as transmitters, cytokines, growth factors, and others can be reviewed.


  • Contains contributions from experts in the field of vitamins and hormones
  • Covers a vast array of subjects
  • In-depth, current information at the molecular to clinical levels
0083-6729
  • Englisch
  • San Diego
  • |
  • USA
Elsevier Science
  • 14,26 MB
978-0-12-805235-8 (9780128052358)
012805235X (012805235X)
weitere Ausgaben werden ermittelt
  • Front Cover
  • Klotho
  • Copyright
  • Former Editors
  • Contents
  • Contributors
  • Preface
  • Chapter One: Klotho-Related Protein KLrP: Structure and Functions
  • 1. Introduction
  • 2. The Functions and Crystal Structure of KLrP
  • 2.1. Metabolic Pathway for GSLs Involving acid GCase GBA1
  • 2.2. Identification of KLrP as a Novel Cytosolic Neutral GCase
  • 2.3. KLrP Crystal Structure
  • 2.4. Mammalian GCases Other than GBA1 and KLrP (GBA3)
  • 3. KLrP and GD
  • 4. Conclusions and Perspectives
  • Acknowledgments
  • References
  • Chapter Two: The FGF21 Receptor Signaling Complex: Klothoß, FGFR1c, and Other Regulatory Interactions
  • 1. Introduction
  • 2. The Components of the Signaling Complex
  • 2.1. Klotho-Beta
  • 2.1.1. The Klotho Family of Receptors
  • 2.1.2. KLB Structure
  • 2.1.3. KLB Tissue Expression
  • 2.2. Fibroblast Growth Factor Receptors
  • 2.2.1. The Fibroblast Growth Factor Receptor Family
  • 2.2.2. Fibroblast Growth Factor Receptor Structure
  • 2.2.3. FGFR1c Tissue Expression
  • 2.3. Endocrine FGF21
  • 2.3.1. The Fibroblast Growth Factor Family
  • 2.3.2. FGF Structure
  • 2.3.3. Endocrine FGF21 Structure
  • 2.3.4. Endocrine FGF21 Tissue Expression
  • 3. Specific Interactions Driving Complex Formation
  • 3.1. Interaction of FGF21 and KLB
  • 3.2. Interaction of FGF21 and FGFR1
  • 3.3. Interaction of KLB and FGFR1
  • 3.4. KLB Domains Relevant for Binding
  • 4. Stoichiometry of the Signaling Complex
  • 4.1. Preformed KLB Heterodimers with FGFR1c/4
  • 5. Other Regulators of the Signaling Complex Formation
  • 5.1. KLB Inactivation by the Galectin Lattice
  • 5.2. ECM Regulation of FGFRs
  • 5.3. Fibroblast Growth Factor Receptor 5
  • 6. Summary
  • References
  • Chapter Three: Klotho-Dependent Cellular Transport Regulation
  • 1. Introduction
  • 1.1. Gene Structure and Klotho Protein Types
  • 1.2. Ectodomain Shedding and Some Functions Mediated by Klotho
  • 1.3. Transport Proteins in the Different Types of Plasma Membrane Transport Systems
  • 2. Klotho in the Regulation of Cellular Transport
  • 2.1. Klotho in the Regulation of Ion Channels
  • 2.2. Klotho in the Regulation of Carriers
  • 2.3. Klotho in the Regulation of Na+/K+-ATPase
  • 3. Conclusion and Future Directions
  • Acknowledgment
  • References
  • Chapter Four: Klotho and the Growth Hormone/Insulin-Like Growth Factor 1 Axis: Novel Insights into Complex Interactions
  • 1. The Pituitary Gland and the GH/IGF-1 Axis
  • 1.1. Regulation of GH Transcription and Secretion
  • 1.1.1. Hypothalamic Regulation of GH Secretion
  • 1.1.2. Peripheral Regulation of GH Secretion
  • 1.1.3. Autocrine and Paracrine Regulation of GH Secretion
  • 1.2. The Activities of GH and IGF-1
  • 2. Klotho: History, Structure, Functions
  • 3. Klotho as a Circulating Hormone
  • 3.1. Available Tests
  • 3.2. Factor Affecting Circulating Klotho Levels
  • 3.3. Regulation of Klotho Shedding
  • 4. Klotho and the Pituitary: Lessons from Mice and Humans
  • 5. Klotho Regulates GH Secretion
  • 5.1. Mechanisms of Klotho Activity on GH Secretion
  • 6. Klotho and the GH/IGF-1 Axis in Humans: Health and Disease States
  • 6.1. Healthy Subjects
  • 6.2. GH/IGF-1 Deficiency
  • 6.2.1. GH Deficiency
  • 6.2.2. Klotho in Anorexia Nervosa
  • 6.2.3. Klotho in Obesity
  • 6.2.4. Klotho and Aging
  • 6.3. Klotho and GH/IGF-1 Excess: Acromegaly
  • 7. Concluding Remarks
  • References
  • Chapter Five: Klotho Prevents Translocation of NF?B
  • 1. Introduction
  • 2. Klotho Structure
  • 3. The Functions of Klotho
  • 3.1. Klotho Is a Specific Coreceptor for FGF-23
  • 3.2. Klotho Mediates Ion Exchange Processes
  • 3.3. Klotho Functions as a Hormone That Regulates Insulin
  • 3.4. Klotho Regulates Intracellular Signaling
  • 4. Mechanisms of Klotho
  • 4.1. Klotho-FGF-23 Axis
  • 4.2. Klotho Activates FoxO Transcription Factors
  • 4.3. Klotho and Nitric Oxide Production
  • 4.4. Klotho in the Wnt Signaling Pathway
  • 4.5. Klotho and TWEAK
  • 4.6. Klotho and NF?B
  • 5. Pathophysiological Implications of Klotho/NF?B
  • 5.1. Klotho in Inflammation
  • 5.2. Klotho in Cellular Senescence
  • 6. Klotho and Pathologies
  • 6.1. Cardiovascular Disease
  • 6.2. CKD and Klotho
  • 6.2.1. Klotho and Cardiovascular Disease in CKD
  • 6.2.2. Vascular Calcification
  • 6.3. Klotho and Chronic Obstructive Pulmonary Disease
  • 6.4. Klotho and Diabetes
  • 7. Conclusions and Perspectives
  • Acknowledgments
  • References
  • Chapter Six: The FGF23/KLOTHO Regulatory Network and Its Roles in Human Disorders
  • 1. Introduction
  • 2. Klotho
  • 2.1. Structure of KL
  • 2.2. Expression Profile and Function of KL
  • 3. KL as a Coreceptor for the FGF23/FGFR Pathway
  • 3.1. Structure of FGF23
  • 3.2. Regulation of FGF23 Expression
  • 3.3. FGF23 Signaling Pathway
  • 3.3.1. KL-Dependent Pathway
  • 3.3.2. KL-Independent Pathway
  • 3.4. Functions of the FGF23/KL Axis
  • 3.4.1. Regulation of Pi Metabolism
  • 3.4.2. Regulation of Vitamin D Metabolism
  • 3.4.3. Regulation of PTH Synthesis and Secretion
  • 4. Human Diseases Related to a Dysregulated FGF23/KL Axis
  • 4.1. Mutations in the FGF23 Gene
  • 4.2. Mutations that Elevate FGF23 Concentrations and/or Bioactivity
  • 4.3. Mutations Reducing GF23 Concentrations and/or Bioactivity
  • 4.4. CKD and FGF23
  • 5. Conclusions and Future Directions
  • Acknowledgment
  • References
  • Chapter Seven: MicroRNA-34a and Impaired FGF19/21 Signaling in Obesity
  • 1. Introduction
  • 2. MicroRNAs as Powerful Regulators of Lipid and Glucose Metabolism
  • 3. Metabolic Hormones FGF19/FGF21 and Their Obligate Coreceptor ßKL
  • 3.1. Atypical FGFs, FGF19, FGF21, and FGF23
  • 3.2. ßKL, the Obligate Coreceptor for FGF19 and FGF21
  • 4. MiR-34a and Impaired Hepatic FGF19 Signaling in Obesity
  • 4.1. Role of the miR-34a/ßKL/FGF19 Axis in Liver
  • 4.2. Regulation of Hepatic miR-34a Expression in Physiology and Obesity
  • 5. MiR-34a and Impaired FGF21 Signaling in Obesity
  • 5.1. Role of miR-34a in the ßKL/FGF21 Axis in Liver
  • 5.2. Role of miR-34a in ßKL/FGF21 Signaling in Adipose Tissue
  • 5.3. Role of miR-34a in the ßKL/FGF21 Axis in Other Tissues
  • 6. Therapeutic and Diagnostic Potential of miRs
  • 6.1. Therapeutic Potential of miRs
  • 6.2. Diagnostic Potential of miRs
  • 7. Conclusion
  • Acknowledgments
  • References
  • Chapter Eight: The Role of Alpha-Klotho as a Universal Tumor Suppressor
  • 1. Klotho Structure, Functions, and Activities
  • 2. Klotho and Cancer
  • 2.1. Expression of Klotho in Malignant Tissue Compared to Normal Tissue
  • 2.2. Correlation Between Tumor Aggressiveness and Klotho Expression
  • 2.3. Means of Silencing
  • 2.4. Klotho Single-Nucleotide Polymorphisms
  • 3. Therapeutic Effect of Klotho on Cancer Development and Progression
  • 3.1. Effects of Klotho on Tumor Cells In Vitro
  • 3.2. Klotho Anticancer Activity In Vivo
  • 4. Klotho and Chemotherapies
  • 4.1. Cisplatin
  • 4.2. 5FU and Gemcitabine
  • 5. Circulating Klotho in Cancer
  • 6. Cellular Targets of Klotho in Cancer Cells
  • 6.1. IGF-1/PI3K/AKT
  • 6.2. Wnt/ß-Catenin
  • 6.3. TGF-ß1
  • 7. Klotho Active Fragment
  • References
  • Chapter Nine: Klotho Is a Neuroprotective and Cognition-Enhancing Protein
  • 1. Introduction
  • 2. The Expression and Localization of Klotho in the Brain
  • 3. Klotho and Cognition
  • 3.1. Antioxidant and Neuroprotective Role of Klotho in the Hippocampus
  • 3.2. Klotho and LTP
  • 3.3. Klotho and the Neuroendocrine System
  • 3.4. The Klotho-VS Polymorphism and Human Cognition
  • 3.5. The White Matter, Aging, and Cognition
  • 3.6. Klotho, Aging, and Neuroinflammation
  • 4. Klotho, Oligodendrocyte Biology, and Myelination
  • 5. Klotho, Oxidative Stress, and Neurodegeneration
  • 6. Klotho Enhancers as a Potential Treatment for Neurodegeneration
  • References
  • Chapter Ten: Function and Change with Aging of a-Klotho in the Kidney
  • 1. Introduction
  • 2. a-Klotho Expression in the Kidney
  • 3. a-Klotho, Phosphate, and Vitamin D
  • 3.1. a-Klotho and FGF23
  • 3.2. a-Klotho and Na+,K+-ATPase
  • 4. a-Klotho and Calpain
  • 4.1. Calpain Overactivation in the Kidney
  • 4.2. Calpain as a Therapeutic Target for Aging-Related Disorders
  • 4.3. Calpain Overactivation via Aberrant Calcium Transport
  • 5. a-Klotho and Nonsulfated HNK-1 Glycan in the Aging Kidney
  • 6. Conclusion
  • References
  • Chapter Eleven: aKlotho and Chronic Kidney Disease
  • 1. Introduction
  • 2. CKD Is a State of Klotho Deficiency
  • 2.1. The Kidney Is the Main Origin for Systemic aKlotho
  • 2.2. Renal aKlotho Deficiency in CKD
  • 2.3. Circulating aKlotho Deficiency in CKD
  • 3. aKlotho Deficiency Contributes to CKD Development and Progression
  • 3.1. Increased Cell Senescence and Reduced Ability of Regeneration
  • 3.2. Defective Endothelial Function and Impaired Vasculogenesis
  • 3.3. Promotion of Renal Fibrosis
  • 4. aKlotho Deficiency Exacerbates Disorders of Mineral Metabolism in CKD
  • 4.1. Hyperphosphatemia
  • 4.2. Increased FGF23 Levels
  • 4.3. Hypovitaminosis D
  • 4.4. Secondary Hyperparathyroidism
  • 5. aKlotho Deficiency in CV Disease in CKD
  • 5.1. Pathological Uremic Cardiomyopathy
  • 5.1.1. aKlotho as a Modulator of Pathological Cardiac Remodeling
  • 5.1.2. aKlotho Protection Against Stress-Induced Cardiac Hypertrophy
  • 5.1.3. aKlotho Protection Against Indoxyl Sulfate-Induced Myocardial Hypertrophy
  • 5.2. Vascular Medial Calcification
  • 5.2.1. aKlotho and Endothelium
  • 5.2.2. aKlotho and Vascular Smooth Muscle
  • 6. aKlotho Deficiency as a Biomarker of CKD
  • 6.1. Functional Biomarkers in Human CKD
  • 6.2. Injury Biomarkers in Human CKD
  • 6.3. FGF23 in Human CKD
  • 6.4. The Role of aKlotho as a Marker of Adverse Outcomes in Human CKD
  • 6.4.1. alotho and CV Disease in CKD
  • 6.4.2. aKlotho and Progressive CKD
  • 7. aKlotho as a Promising Treatment Strategy for CKD
  • 7.1. Epigenetic regulation of aKlotho Expression
  • 7.2. Reactivation of Endogenous aKlotho Expression Independently of Epigenetics
  • 7.3. Administration of Soluble aKlotho Protein
  • 8. Conclusion and Future Directions
  • Acknowledgments
  • References
  • Chapter Twelve: Deficiency of Soluble a-Klotho as an Independent Cause of Uremic Cardiomyopathy
  • 1. Introduction
  • 2. Clinical Manifestations of Uremic Cardiomyopathy
  • 2.1. Definition of Uremic Cardiomyopathy
  • 2.2. Epidemiology of Uremic Cardiomyopathy
  • 2.3. Mechanism of Cardiac Hypertrophy in CKD Patients
  • 2.3.1. New CKD-Specific Risk for Cardiac Hypertrophy Should Be Proposed
  • 2.3.2. Secondary Hyperparathyroidism and Uremic Cardiomyopathy
  • 2.3.3. Vitamin D Deficiency and Uremic Cardiomyopathy
  • 2.3.4. Indoxyl Sulfate/p-Cresyl Sulfate and Uremic Cardiomyopathy
  • 2.3.5. Phosphate Retention and Uremic Cardiomyopathy
  • 3. Mineral Metabolism Disorder of CKD
  • 3.1. Klotho and Its Role in Phosphate Metabolism
  • 3.2. Role of FGF23 and Klotho in CKD-MBD
  • 4. Decrease in Circulating Soluble Klotho Contributes to Uremic Cardiomyopathy: Evidence and Mechanism
  • 4.1. Klotho-Deficiency Aggravates Stress-Induced and Uremic Cardiomyopathy, Independently of Hypertension, Hyperphosphate...
  • 4.2. Transgenic klotho-Expression Attenuates Stress-Induced and Uremic Cardiomyopathy
  • 4.3. Klotho Protects the Heart by Downregulation of TRPC6
  • 4.3.1. TPRC6 Channel and Cardiomyopathy
  • 4.3.2. Klotho Downregulates TRPC6 in Heart: Genetics Evidence
  • 4.3.3. Soluble Klotho Inhibits TRPC6 Activity by Downregulating Its Exocytosis
  • 5. Conclusion
  • References
  • Index
  • Color Plate
  • Back Cover

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