The Retinoids E-Book

Pascal Dollé

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 1309

Veröffentlichungsjahr: 2015

Beschreibung

The Retinoids: Biology, Biochemistry, and Disease provides an overview and synthesis of the retinoid molecules, from basic biology to mechanisms of diseases and therapy. Divided into five sections, the book covers retinoic acid signaling from biochemical, genetic, developmental, and clinical perspectives. 

The text is divided into five sections, the first of which examines vitamin A metabolic and enzymatic pathways. Focus then shifts to the role of retinoic acid signaling in development, and then to retinoids and physiological function. The book concludes with chapters on retinoids, disease and therapy.

Comprehensive in scope and written by leading researchers in the field, The Retinoids: Biology, Biochemistry, and Disease will be an essential reference for biologists, biochemists, geneticists and developmental biologists, as well as for clinicians and pharmacists engaged in clinical research involving retinoids.

Leseprobe

CONTENTS

COVER

TITLE PAGE

CONTRIBUTORS

PREFACE

PART I: VITAMIN A METABOLIC AND ENZYMATIC PATHWAYS

1 VITAMIN A METABOLISM, STORAGE AND TISSUE DELIVERY MECHANISMS

I. INTRODUCTION

II. VITAMIN A METABOLISM RELEVANT TO ITS STORAGE

III. VITAMIN A STORAGE

IV. VITAMIN A TRANSPORT IN THE CIRCULATION

V. INTEGRATION WITHIN THE INTACT ORGANISM OF VITAMIN A METABOLISM, STORAGE AND TRANSPORT

ACKNOWLEDGMENTS

REFERENCES

2 ASSIMILATION AND CONVERSION OF DIETARY VITAMIN A INTO BIOACTIVE RETINOIDS

I. INTRODUCTION

II. DIETARY SOURCES OF VITAMIN A AND PROVITAMIN A CAROTENOIDS

III. INTESTINAL ABSORPTION AND METABOLISM OF DIETARY VITAMIN A AND PROVITAMIN A CAROTENOIDS

IV. FORMATION OF β-APOCAROTENOIDS

V. POSSIBLE BIOLOGICAL FUNCTIONS OF APOCAROTENOIDS

VI. CONCLUSIONS AND PERSPECTIVES

ACKNOWLEDGMENTS

REFERENCES

3 INTRACELLULAR STORAGE AND METABOLIC ACTIVATION OF RETINOIDS: LIPID DROPLETS

I. INTRODUCTION

II. MULTILOCULAR LIPID DROPLETS

III. THE MITOCHONDRIAL-ASSOCIATED MEMBRANE

IV. BIRTH OF LIPID DROPLETS

V. LIPID DROPLETS AND RETINOID HOMEOSTASIS

VI. IN THE ABSENCE OF LIPID DROPLETS, LRAT AND RDH1 LOCALIZE WITH THE ER, WHEREAS CRBP1 AND RDH10 LOCALIZE WITH MITOTRACKER

VII. DURING ACYL ESTER BIOSYNTHESIS LRAT, CRBP1 AND RDH10 ASSOCIATE WITH LIPID DROPLETS

VIII. LIPID DROPLET ASSOCIATION ACTIVATES RDH10

IX. LIPID DROPLET ASSOCIATION REQUIRES THE N-TERMINI OF LRAT AND RDH10

X. SUMMARY

XI. CONCLUSIONS AND FUTURE DIRECTIONS

REFERENCES

4 EVOLUTION OF THE RETINOIC ACID SIGNALING PATHWAY

I. INTRODUCTION

II. AN OVERVIEW OF CHORDATE RETINOID METABOLISM

III. RETINOIC ACID SIGNALING IN CHORDATES

IV. EVOLUTION OF RETINOIC ACID SIGNALING

V. CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

PART II: BIOCHEMISTRY AND CELLULAR BIOLOGY OF RETINOIC ACID SIGNALING

5 CONTROL OF GENE EXPRESSION BY NUCLEAR RETINOIC ACID RECEPTORS: POST-TRANSLATIONAL AND EPIGENETIC REGULATORY MECHANISMS

I. INTRODUCTION

II. THE BASICS OF RAR STRUCTURE

III. REPRESSIVE EPIGENETIC LANDSCAPE OF RAR TARGET GENES IN THE ABSENCE OF RETINOIC ACID

IV. REORGANIZATION OF THE EPIGENETIC LANDSCAPE AFTER RETINOIC ACID ADDITION

V. NONCODING RNAS IN THE REGULATION OF THE EPIGENETIC LANDSCAPE

VI. BACK TO A REPRESSIVE EPIGENETIC LANDSCAPE WHEN TRANSCRIPTION TURNS “OFF”

VII. PHOSPHORYLATION: ANOTHER POST-TRANSLATIONAL MODIFICATION CODE INDUCED BY RETINOIC ACID

VIII. TWO MODELS FOR THE ACTIVATION OF RAR TARGET GENES VIA A SEA OF POST-TRANSLATIONAL MODIFICATIONS AND EPIGENETIC CHANGES

IX. ABERRANT EPIGENICS IN CANCER: CONSEQUENCES ON THE RETINOIC ACID RESPONSE

X. CONCLUSION AND FUTURE PROSPECTS

REFERENCES

6 RETINOIC ACID RECEPTOR COREGULATORS IN EPIGENETIC REGULATION OF TARGET GENES

I. INTRODUCTION

II. COREGULATORS OF RARS AND RXRS

III. COREGULATORS IN EPIGENETIC REGULATION

IV. THE FUTURE

ACKNOWLEDGMENTS

REFERENCES

7 RETINOID RECEPTORS: PROTEIN STRUCTURE, DNA RECOGNITION AND STRUCTURE–FUNCTION RELATIONSHIPS

I. INTRODUCTION

II. GENERAL ORGANIZATION OF RETINOID RECEPTORS

III. STRUCTURE OF FULL-LENGTH RAR–RXR–DNA COMPLEXES

IV. COREGULATOR BINDING

V. STRUCTURAL BASIS FOR ALLOSTERIC CONTROL MECHANISMS OF COFACTOR BINDING

VI. CONCLUSIONS

REFERENCES

8 HOW THE RAR–RXR HETERODIMER RECOGNIZES THE GENOME

I. INTRODUCTION

II. HORMONE RESPONSE ELEMENTS

III. VDR AND TR OCCUPY DR3 AND DR4 ELEMENTS IN CULTURED CELLS

IV. PPAR AND LXR PREFER NONCONSENSUS ELEMENTS

V. GENOMIC BINDING OF THE RAR–RXR HETERODIMER

VI. SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

9 RETINOID RECEPTOR-SELECTIVE MODULATORS

I. INTRODUCTION

II. RXR

VERSUS

RAR SELECTIVITY AS A FUNCTION OF THE LIGAND-BINDING POCKET ARCHITECTURES

III. SYSTEMS BIOLOGY OF RETINOID ACTION

IV. CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

10 USE OF RETINOID RECEPTOR LIGANDS TO IDENTIFY OTHER NUCLEAR RECEPTOR LIGANDS

I. INTRODUCTION

II. NUCLEAR RECEPTOR AND LIGAND SIMILARITIES

III. APOPTOSIS INDUCTION BY AHPN

IV. STRUCTURE–ACTIVITY RELATIONSHIP STUDIES LEADING TO A PRECLINICAL CANDIDATE

V. IDENTIFICATION OF SMALL HETERODIMER PARTNER (SHP) AS A RETINOID-RELATED MOLECULE (RRM) TARGET

VI. SMALL HETERODIMER PARTNER STRUCTURE AND FUNCTION

VII. CONSTRUCTION OF A SMALL HETERODIMER PARTNER MODEL TO FACILITATE LIGAND DESIGN

VIII. RETINOID-RELATED MOLECULE MECHANISM OF ACTION STUDIES

IX. ADDITIONAL TARGETS OF RETINOID-RELATED MOLECULES

X. RETINOID-RELATED MOLECULE MECHANISM OF ACTION STUDIES BY OTHER GROUPS

XI. INVESTIGATIONS ON THE MECHANISM OF ACTION OF SMALL HETERODIMER PARTNER IN THE ABSENCE OF AN ADDED RETINOID-RELATED MOLECULE

REFERENCES

11 THE DUAL TRANSCRIPTIONAL ACTIVITY OF RETINOIC ACID

I. RETINOIC ACID RECEPTORS: PPARβ/δ JOINS RARS

II. RETINOIC ACID-BINDING PROTEINS: CRABP2 AND FABP5 COOPERATE WITH RAR AND PPARβ/δ

III. BIOLOGICAL ACTIVITIES OF RETINOIC ACID CRITICALLY RELY ON PRECISE BALANCE BETWEEN ITS DUAL TRANSCRIPTIONAL PATHWAYS

IV. CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

12 RETINOIDS, EPIGENETIC CHANGES DURING STEM CELL DIFFERENTIATION, AND CELL LINEAGE CHOICE

I. INTRODUCTION

II. RETINOIC ACID SIGNALING IS ASSOCIATED WITH TRANSCRIPTIONAL ACTIVATION AND EPIGENETIC CHANGES IN STEM CELLS

III. RETINOIDS AND EPIGENETIC MODIFICATIONS

IV. RETINOIC ACID AND THE DIFFERENTIATION OF EMBRYONIC STEM CELLS ALONG VARIOUS LINEAGES: SIX EXAMPLES

V. DETERMINANTS OF THE STABILITY OF THE DIFFERENTIATED PHENOTYPE

VI. SUMMARY AND FUTURE DIRECTIONS

ACKNOWLEDGMENTS

REFERENCES

PART III: RETINOIC ACID SIGNALING IN DEVELOPMENT

13 RETINOIC ACID SIGNALING AND CENTRAL NERVOUS SYSTEM DEVELOPMENT

I. INTRODUCTION

II. THE BEGINNING OF RETINOIC ACID SIGNALING AT EARLY NODE STAGES (FIGURE 13.1A, hn)

III. RETINOIC ACID SIGNALING AS THE NEURAL PLATE FORMS AND UNDERGOES ANTEROPOSTERIOR PATTERNING (FIGURE 13.1B, np)

IV. HINDBRAIN SPECIFICATION (FIGURE 13.1C, hb)

V. THE HINDBRAIN GRADIENT OF RETINOIC ACID (FIGURE 13.1C, hb)

VI. SPINAL CORD FORMATION AND PATTERNING AT THE POSTERIOR END OF THE EMBRYO (FIGURE 13.1C, 13.1D, cs)

VII. DORSOVENTRAL PATTERNING IN THE SPINAL CORD AND MOTOR NEURON SPECIFICATION (FIGURE 13.1D, sc)

VIII. RETURN TO THE FRONT OF THE EMBRYO: OUTGROWTH OF THE TELENCEPHALON (FIGURE 13.1E, fn)

IX. OLFACTORY DEVELOPMENT (FIGURE 13.1E, olf)

X. THE EYE (FIGURE 13.1E, F)

XI. PATTERNING WITHIN THE TELENCEPHALON: THE LATERAL GANGLIONIC EMINENCE (FIGURE 13.1F, lge)

XII. THE LATER HINDBRAIN AND CORTEX (FIGURE 13.1F)

XIII. CONCLUSION

REFERENCES

NOTE

14 THE ROLE OF RETINOIC ACIDIN LIMB DEVELOPMENT

I. INTRODUCTION

II. ENZYMES AND RECEPTORS FOR RETINOIC ACID SYNTHESIS AND SIGNALING

III. GENETIC MODELS FOR INVESTIGATION OF RETINOIC ACID FUNCTION DURING LIMB DEVELOPMENT

IV. RETINOIC ACID IS NOT REQUIRED FOR LIMB AXIAL PATTERNING

V. FORELIMB INDUCTION REQUIRES RETINOIC ACID SIGNALING

VI. RETINOIC ACID IS REQUIRED FOR INTERDIGITAL DEVELOPMENT

VII. CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

15 RETINOIC ACID SIGNALING AND HEART DEVELOPMENT

I. INTRODUCTION

II. EARLY FUNCTIONS IN FORMATION AND PATTERNING OF THE SECOND HEART FIELD

III. THE EPICARDIUM: A SOURCE OF RA-REGULATED SIGNALS CONTROLLING MYOCARDIAL CELL PROLIFERATION AND DIFFERENTIATION

IV. ACTIONS ON PROGENITOR CELL POPULATIONS

V. INTERACTIONS WITH OTHER SIGNALING PATHWAYS: CLUES TO CONGENITAL MALFORMATIONS

VI. CONCLUSIONS AND PERSPECTIVES

ACKNOWLEDGMENTS

REFERENCES

16 RETINOIC ACID IN THE DEVELOPING LUNG AND OTHER FOREGUT DERIVATIVES

I. INTRODUCTION

II. FROM PATTERNING OF THE FOREGUT TO LUNG DEVELOPMENT

III. RETINOIC ACID SIGNALING CONTROLS A GENE NETWORK CRUCIAL FOR EARLY LUNG DEVELOPMENT

IV. INVOLVEMENT OF RETINOIC ACID IN BRANCHING MORPHOGENESIS AND LUNG EPITHELIAL DIFFERENTIATION

V. OTHER FUNCTIONS OF RETINOIC ACID IN LUNG DEVELOPMENT

VI. RETINOIC ACID IN POSTNATAL LUNG DEVELOPMENT AND LUNG REPAIR

VII. DISTINCT ROLES FOR RETINOIC ACID IN ORGANOGENESIS OF OTHER FOREGUT DERIVATIVES

VIII. CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

17 RETINOIC ACID AND THE CONTROL OF MEIOTIC INITIATION

I. INTRODUCTION

II. GERM CELLS AND MEIOSIS

III. A ROLE FOR RETINOIC ACID IN INITIATING MEIOSIS IN THE FETAL OVARY

IV. WHAT IS THE SOURCE OF RETINOIC ACID IN THE OVARY?

V. WHAT ABOUT MEIOSIS IN THE TESTIS?

VI. RETINOIC ACID TRIGGERS MEIOSIS IN A RANGE OF VERTEBRATES

VII. WHY DO ONLY GERM CELLS RESPOND TO RETINOIC ACID BY UPREGULATING

Stra8

?

VIII. IS THERE SUFFICIENT RETINOIC ACID IN THE MOUSE FETAL OVARY TO TRIGGER EXPRESSION?