Retinoids: The Biochemical and Molecular Basis of Vitamin A and Retinoid Action

ISBN-13: 9783540658924 / Angielski / Twarda / 1999 / 619 str.

Heinz Nau; William S. Blaner; H. Nau

Opis

In the future' the decade of the 1990s will likely be viewed as a Golden Age for retinoid research. There have been unprecedented research gains in the understanding of retinoid actions and physiology; since the retinoid nuclear receptors were first identified and the importance of retinoic acid in develop- mental processes was first broadly recognized in the late 1980s. Between then and now, our knowledge of retinoid action has evolved from one of a near complete lack of understanding of how retinoids act within cells to one of sophisticated understanding of the molecular processes through which retinoids modulate transcription. In this volume, we have tried to provide a comprehensive update of the present understanding of retinoid actions, with an emphasis on re- cent advances. The initial chapters of the volume, or Section A, focus on the physicochemical properties and metabolism of naturally occurring retinoids: - N OY provides an uncommonly encountered view of retinoid effects from the perspective of the physiochemical properties of retinoids. - V AKIANI and BUCK lend a perspective on the biological occurrence and actions of retro- and anhydro-retinoids. Section B considers both the retinoid nuclear receptors and their mechanisms of action as well as synthetic retinoids that have been used exper- imentally to provide mechanistic insights into receptor actions and have potential therapeutic use for treating disease: - PIEDRAFITA and PFAHL provide a comprehensive review of retinoid nuclear receptor biochemistry and molecular biology.

Spis treści

Section A: Metabolism, Pharmocokinetics and Action of Retinoids.- 1 Physical-Chemical Properties and Action of Retinoids.- A. Introduction.- B. Behavior of Retinoids in an Aqueous Environment.- I. Aqueous Solubility.- II. Self-Association of Retinoids in Water.- III. Lability of Retinoids in Water.- C. Interactions of Retinoids with Membranes.- I. Effects of Membrane Lipid Composition on Membrane- Retinoid Interactions.- II. Effects of the Radius of Curvature of Membranes on Membrane-Retinoid Interactions.- III. Ionization Behavior of Retinoic Acid in Membranes.- D. Interactions of Retinoids with Proteins.- I. Binding Affinities.- 1. Ligand Binding Affinities of Retinoid-Binding Proteins.- 2. Ligand Binding Affinities of Retinoid Nuclear Receptors.- II. Kinetics of the Interactions of Retinoids with Proteins.- 1. Rates of Dissociation of Retinoids from Retinoid- Binding Proteins.- E. Some Implications for Retinoid Transport Processes.- I. Uptake of Retinol by Target Cells.- II. Targeting of Retinoids by IRBP.- F. Concluding Remarks.- References.- 2 Biosynthesis, Absorption, Metabolism and Transport of Retinoids.- A. Introduction.- B. Intestinal Absorption of Retinol and Biosynthesis of Retinol from Carotenoids.- I. Uptake and Luminal Metabolism of Dietary Preformed Vitamin A (Retinyl Esters, Retinol, and Retinoic Acid).- II. Uptake and Metabolism of Dietary Provitamin A Carotenoids.- III. Intramucosal Metabolism.- 1. Retinoic Acid Formation from Retinal Derived from Carotenoids.- 2. Role of Cellular-Retinol Binding Protein, Type II.- 3. Retinol Esterification and the Packaging of Dietary Retinoid into Chylomicrons.- C. Circulating Chylomicrons and Chylomicron Remnant Formation.- I. Hepatic Clearance of Chylomicron Remnants.- II. Extrahepatic Tissues and Chylomicron Remnant Retinoid.- D. Retinoid Processing and Metabolism within the Liver.- I. Uptake and Processing of the Chylomicron Remnant Retinyl Ester by Hepatocytes.- II. Retinoid Metabolism and Storage in the Hepatocyte.- 1. Cellular Retinol-Binding Protein, Type I.- 2. Hepatic LRAT Activity.- III. Retinoid Transfer Between Hepatocytes and Stellate Cells.- IV. Retinoid Metabolism and Storage in Hepatic Stellate Cells.- E. Extrahepatic Processing and Metabolism of Retinol and Retinyl Ester.- F. Retinoid Delivery to Target Tissues.- I. Retinol Bound to RBP.- 1. Cellular Synthesis and Secretion of Retinol-RBP and Its Regulation.- 2. The RBP Gene and Its Regulation.- 3. Structural and Physiochemical Properties of RBP, TTR, and the RBP-TTR Complex.- 4. Retinol-RBP Turnover from the Circulation.- 5. RBP Receptor.- II. Plasma all-trans-Retinoic Acid.- III. Plasma 13-cis-Retinoic Acid.- IV. Lipoprotein Bound Retinyl Ester.- V. Glucuronides of Retinol and Retinoic Acid.- VI. Retro-Metabolites of Retinol.- G. Summary.- References.- 3 Retro-Retinoids: Metabolism and Action.- A. Introduction.- B. Vitamin A and the Immune System.- C. General Properties of Retro-Retinoids.- D. Cellular Effects of Retro-Retinoids.- I. Growth of B Lymphocytes.- II. Activation of T Lymphocytes.- III Activation of Fibroblasts.- IV. Cell Growth vs. Cell Differentiation: Retinol Metabolism in HL-60 Cells.- V. Intracellular Signaling.- 1. Anhydroretinol-Induced Cell Death.- 2. Evidence for a Transmembrane or Cytoplasmic Receptor.- E. Retro-Retinoid Metabolism.- I. 14-Hydroxy-Retro-Retinol.- II. 13,14-Dihydroxy-Retinol.- III. Biosynthesis of Anhydroretinol.- F. Conclusion.- References.- 4 Retinoic Acid Synthesis and Metabolism.- A. Introduction.- B. Cellular and Extracellular Retinoid Binding Proteins.- I. Cellular Retinol Binding Proteins.- II. Cellular Retinoic Acid Binding Proteins.- III. Other Retinoic Acid Binding Proteins.- C. Retinoic Acid Synthesis.- I. Oxidation of Retinol.- 1. Role of Cytosolic Dehydrogenases.- 2. Role of Microsomal Dehydrogenases.- II. Oxidation of Retinal.- III. Formation of 9-cis-Retinoic Acid.- IV. Direct Synthesis of Retinoic Acid from Carotenoids.- D. Oxidative Metabolism of Retinoic Acid.- I. Role of the Cytochrome P450 System in Retinoic Acid Oxidation.- II. Other Metabolism of Retinoic Acid.- E. Summary and Future Needs.- References.- Section B: Binding Proteins and Nuclear Receptors.- 5 Nuclear Retinoid Receptors and Mechanisms of Action.- A. Introduction.- B. The Nuclear Retinoid Receptors and Their Cousins.- C. The RAREs: Further Specification of the Ligand Response.- D. Interaction of Retinoid Receptors with Coactivators, Corepressors, and Basal Transcription Factors.- E. Differentiation-Proliferation Switches: Interaction with Other Signal Transducers.- F. CBP/p300, a Cointegrator of Multiple Signaling Pathways.- G. A Role for Histone Acetylation in Receptor-Mediated Transactivation?.- H. Apoptosis Induction by Special Retinoids: A Novel Pathway?.- I. Future Prospects.- References.- 6 RAR-Selective Ligands: Receptor Subtype and Function Selectivity.- A. Introduction.- B. Structural Differences Between RAR-Selective and RXR-Selective Ligands.- I. The Effect of Bridging Groups on Conformationally Restricted Retinoids.- II. The ?-Methyl Effect.- III. 9-Cis-Locked vs 9-Trans-Locked Retinoids.- C. RAR Subtype Selective Agonists.- I. RAR? Selective Agonists.- II. RAR? Selective Agonists.- III. RAR?Selective Agonists.- D. RAR Antagonists, Neutral Antagonists, and Inverse Agonists.- I. RAR Antagonists.- II. RAR Inverse Agonists and Neutral Antagonists.- E. Pharmacology of RAR Selective Agonists and Antagonists.- I. RAR? Selective Agonists.- II. RAR? Selective Agonists.- III. RAR?Selective Agonists.- IV. RAR Antagonists and Inverse Agonists.- References.- 7 RXR-Speeific Agonists and Modulators: A New Retinoid Pharmacology.- A. Introduction.- B. Ligand-Dependent Activation of Transcription By RXR.- I. Activation of Permissive Heterodimers.- II. RXR Agonists Activate RXR-RAR Heterodimers When The RAR Binding Pocket Is Occupied.- III. The Phantom Ligand Effect.- C. RXR Pharmacology.- I. Sensitization of Diabetic Mice to Insulin by RXR Agonists.- II. Chemoprevention/Chemotherapy of Carcinogen-Induced Breast Cancer.- D. Conclusions and Future Directions.- References.- Section C: Differentiation, Proliferation, and Cancer.- 8 Growth Control by Retinoids: Regulation of Cell Cycle Progression and Apoptosis.- A. Introduction.- B. Mechanisms of Retinoid Action.- I. Retinoid Receptor-Dependent Mechanisms.- II. Retinoid Receptor-Mediated Control of Cell Proliferation.- III. Receptor-Independent Regulation of Cell Proliferation.- C. Control of Cell Cycle Progression by Retinoids.- I. Overview of Cell Cycle Regulation.- II. Cell Cycle Regulatory Targets of Retinoid Action.- 1. Retinoids Can Affect the Rb Pathway at Several Levels.- 2. Regulation of c-myc Expression.- 3. Modulation of AP-1-Mediated Growth Signals.- 4. Effects on Miscellaneous Cell Cycle Proteins.- D. Regulation of Apoptosis.- I. Apoptotic Mechanisms.- II. Regulation of Apoptosis by Retinoids.- 1. Receptor-Mediated Induction of Apoptosis.- 2. Receptor-Mediated Inhibition of Apoptosis.- 3. Retinoid Receptor Independent Mechanisms.- a) Mechanisms of 4-HPR Action in Apoptosis.- b) Mechanisms of AHPN Action.- E. Summary.- References.- 9 Retinoids and Differentiation of Normal and Malignant Hematopoietic Cells.- A. Introduction.- B. Retinoids and Hematopoiesis.- I. Effect of Retinoic Acid on Cellular Proliferation, Differentiation, and Apoptosis of Hematopoietic Leukemic Cells.- 1. Effect on Myeloid Leukemic Cell Differentiation.- 2. Effect on Acute Promyelocytic Leukemic Cells.- 3. Effect on Induced Myeloid Leukemic Cell Apoptosis.- II. Retinoic Acid as a Novel Myeloid Differentiation Factor.- III. Retinoic Acid Control of Myeloproliferative Growth.- C. Retinoic Acid Signaling Pathways in Hematopoietic Cells.- I. Differential Expression of Nuclear Retinoic Acid Receptors and Retinoid-Binding Proteins.- II. Alteration of RARa in Hematopoietic Malignancies.- 1. Molecular Characteristics of APL.- 2. Alterations of RARa in Other Malignancies.- D. Retinoic Acid as a Therapeutic Agent in Hematopoietic Malignancies.- I. Acute Promyelocytic Leukemia.- 1. Retinoid Resistance in APL.- 2. Retinoic Acid Syndrome and Other Side Effects of RA Therapy.- 3. Mechanisms of retinoic acid induced differentiation in APL patients.- II. Retinoids as Therapeutic Alternative to Myeloproliferative Disorders.- E. Summary and Perspectives.- References.- 10 The Retinoids: Cancer Therapy and Prevention Mechanisms.- I. Summary.- II. Mechanisms of Retinoid Action.- IV. Retinoids and Cancer Chemoprevention.- V. In Vitro Models for Retinoid Activity in Cancer Therapy and Prevention.- A. The Multipotent NT2/D1 Human Embryonal Carcinoma Line.- B. Acute Promyelocytic Leukemia In Vitro Models.- C. An In Vitro Lung Cancer Prevention Model.- VI. Summary and Future Directions.- References.- 11 Aberrant Expression and Function of Retinoid Receptors in Cancer.- A. Introduction.- B. Aberrant nuclear retinoid receptor expression and function in cultured cancer cell lines.- I. Expression of Nuclear Retinoid Receptors in Lung Cancer Cell Lines.- II. Expression of Nuclear Retinoid Receptors in Head and Neck Squamous Cell Carcinoma Cell Lines.- III. Expression of Nuclear Retinoid Receptors in Esophageal Cancer Cell Lines.- IV. Expression of Nuclear Retinoid Receptors in Breast Cancer Cell Lines.- V. Expression of Nuclear Retinoid Receptors in Normal Skin and Skin Cancer Cell Lines.- VI. Expression of Nuclear Retinoid Receptors in Cervical Cancer Cell Lines.- VII. Expression of Nuclear Retinoic Acid Receptors in Embryonal Carcinoma Cell Lines.- VIII. Expression of Nuclear Retinoid Receptors in Myeloid Leukemia.- C. Aberrant Nuclear Retinoid Receptor Expression in Specimens from Normal, Premalignant, and Malignant Tissues.- I. Expression of Aberrant RAR? in Acute Promyelocytic Leukemia.- II. Expression of Nuclear Retinoid Receptors in Adjacent Tissues and Head and Neck Squamous Cell Carcinoma.- III. Expression of Nuclear Retinoic Acid Receptors in Hamster Cheek-Pouch Mucosa During 7,12-Dimethylbenz[a]anthracene-Induced Carcinogenesis.- IV. Expression of Nuclear Retinoid Receptors in Adjacent Bronchial Epithelium and Non-small Cell Lung Cancer.- V. Expression of Nuclear Retinoid Receptors in Adjacent Normal, Premalignant, and Malignant Breast Tissues.- VI. Expression of Nuclear Retinoid Receptors in Normal Skin and Skin Cancers.- VII. Expression of the Nuclear Retinoid Receptors in Normal Uterine Cervix and Cervical Cancer.- D. Mechanisms of Altered Receptor Expression and Function In Vitro and In Vivo.- References.- Section D: Development and Teratogenesis.- 12 Genetic and Molecular Approaches to Understanding the Role of Retinoids in Mammalian Spermatogenesis.- A. Introduction.- I. Historical Perspective of the Role of Vitamin A in Spermatogenesis.- II. Focus of This Review.- B. Serum and Cellular Retinoid Binding Proteins.- I. Sites of Synthesis and Action.- 1. Retinol Binding Protein and Transthyretin.- 2. Cellular Retinol and Retinoic Acid Binding Proteins.- II. Potential Functions During Spermatogenesis.- C. Receptors.- I. Retinoic Acid and Retinoid X Receptors and Their Ligands.- II. Regulation of Transcription by Ligand-Activated Retinoid Receptors.- III. RAR and RXR Expression in the Testis.- D. The Vitamin A Deficient Testis.- E. Genetic Analysis of Retinoid Function.- I. Overview of Mouse Mutants.- II. Mutations in Retinoid Receptors and Binding Proteins with no Testicular Phenotype.- III. Mutations in Retinoid Receptors that Result in Male Sterility.- 1. RARs.- 2. RXRs.- F. Where Do We Go From Here?.- I. Assessment of Lineage Specificity of Receptor Function in the Testis.- II. Identification of In Vivo Cofactors.- III. Potential Targets of Retinoid Action During Spermatogenesis.- 1. Mutations Affecting Spermatogenesis.- 2. Genes Whose Testicular Expression Is Affected by Retinoids.- 3. Other Retinoid-Responsive Genes.- References.- 13 The Role of Retinoids in Vertebrate Limb Morphogenesis: Integration of Retinoid- and Cytokine-Mediated Signal Transduction.- A. Introduction.- B. An Overview of Retinoid Signal Transduction in the Vertebrate Embryo.- I. Retinoid Requirement in Development.- II. Retinoic Acid Synthesizing Enzymes and Degrading Enzymes in Embryos.- III. RARs and RXRs Mediate Retinoic Acid Signal Transduction In Vivo and Are Required for Development.- IV. Retinoid Target Genes.- C. Retinoids in Vertebrate Limb Development.- I. Embryology of the Vertebrate Limb.- II. The Zone of Polarizing Activity.- III. Retinoids and the Generation of the ZPA.- IV. Retinoids in Limb Differentiation.- D. Retinoids in Limb Regeneration.- References.- 14 Retinoids in Neural Development.- A. The Induction of Neuronal Differentiation in Culture.- I. Embryonal Carcinoma Cells and Neuroblastoma Cells.- II. Dissociated or Explanted Neuronal Cells.- III. Neural Crest Cells.- B. The Effects of Excess Retinoids on the CNS.- I. Effect 1: Posteriorisation.- II. Effect 2: Loss of Anterior Hindbrain.- III. Effect 3: Transformation of Anterior Hindbrain.- C. The Effects of RA on Associated CNS Structures.- D. The Effects of a Deficiency of Retinoids on the CNS.- I. Deprivation of Retinoids.- II. Inhibition of RA Synthesis.- E. Endogenous RA in the CNS.- I. HPLC Data.- II. Transgenic Embryos.- III. Reporter Cells.- IV. RA Synthesising Enzymes.- V. Which Cells in the Nervous System Synthesise RA?.- E Binding Proteins and Receptors in the Developing CNS.- I. CRBP I.- II. CRABPI.- III. CRABP II.- IV. RARs and RXRs.- V. Knockouts of Binding Proteins and Receptors.- VI. Disruption of Function.- VII. Receptor Selective Agonists.- G. Conclusions.- References.- 15 Avian Embryo as Model for Retinoid Function in Early Development.- A. Introduction.- B. Teratogenic Effects of Vitamin A Deficiency and Excess.- C. Mammalian Models.- D. Avian Embryo “Retinoid Ligand Knockout ” Model.- E. Cardiogenesis.- F. Left-Right Asymmetry.- G. Vasculogenesis.- H. Central Nervous System.- I. Ethanol-Induced Retinoid Depletion.- J. Retinoid Metabolism.- K. Future Directions.- References.- 16 Retinoid Receptors, Their Ligands, and Teratogenesis: Synergy and Specificity of Effects.- A. Introduction.- B. Ligands of the Retinoid Receptors.- I. Endogenous Ligands of the Retinoid Receptors.- II. Retinoid Receptor Ligands in the Embryo.- C. Retinoid Receptors and Binding Proteins in the Embryo.- I. Retinoid Binding Proteins in the Embryo.- II. Retinoid Receptors in the Embryo.- D. Experimental Models for the Study of the Significance of Retinoid Receptors in Teratogenesis.- I. “Loss of Function ” Approach: Studies with Null Mutant Mice.- II. “Gain of Function ” Approach: Administration of Selective Retinoid Receptor Ligands.- E. Synergistic Teratogenic Action Following Combined Administration of RAR and RXR Ligands.- F. Molecular Pathways of Vitamin A and Retinoid Teratogenesis.- G. Conclusions.- References.- Section E: Skin.- 17 Vitamin A Homeostasis in Human Epidermis: Native Retinoid Composition and Metabolism.- A. Introduction.- B. Total Vitamin A Content of the Epidermis.- C. Vitamin A Metabolites in the Epidermis.- D. Retinoid Composition of Epidermal Compartments.- E. Retinoid Composition of Cultured Human Keratinocytes.- F. Extracellular Retinoid Transport.- I. Retinol.- II. Retinoic Acid.- G. Retinoid Metabolism in Epidermis.- I. Retinoid-Binding Proteins.- 1. Cellular Retinol-Binding Protein.- 2. Cellular Retinoic Acid Binding Proteins.- II. Vitamin A Storage, Retinyl Ester Synthesis and Hydrolysis.- III. Retinoic Acid Synthesis.- IV. Retinoic Acid Metabolism.- V. 3,4-Didehydroretinol Synthesis and Metabolism.- H. Summary and Working Model for Retinoid Metabolism in Epidermis.- I. Future Prospects.- References.- 18 New Concepts for Delivery of Topical Retinoid Activity to Human Skin.- A. Introduction.- B. The “Proligand-Nonligand ” Concept.- C. All-trans-Retinol.- D. All-trans-Retinyl Esters.- E. All-trans-Retinal.- F. All-trans-Retinoyl-?-Glucuronide.- G. Conclusions and Perspectives.- References.- 19 Retinoid Receptor-Selective Agonists and Their Action in Skin.- A. The Molecular Aspects of Retinoid Signaling.- I. The Role of Retinoid Receptors.- II. RAR Receptor-Selective Retinoids.- III. RXR Receptor Selective Retinoids.- B. Vitamin A and the Skin.- I. Proliferation and Differentiation Within the Epidermis.- II. Vitamin A and the Skin: The Historical Aspects.- III. RARs and RXRs and the Development of the Skin.- IV. Retinoid Effects upon Keratinocyte Proliferation and Differentiation.- V. Modulation of Inflammation and the Immune Response in Skin by RA.- VI. Retinoid Receptors and Skin Function.- VII. The Development of Synthetic Retinoids and Their Action in Skin.- 1. Adapalene (CD271).- 2. Tazarotene (AGN 190168).- C. Apoptosis: An Emerging Role for Retinoids.- D. Future Prospects.- References.- Section F: Special Effects.- 20 Retinoids in Mammalian Vision.- A. Introduction.- I. Overview of the Visual Process.- II. Anatomy.- III. Nourishment of the Outer Retina.- IV. Overview of the Visual Cycle.- B. Structure and Function of Visual Pigments.- I. Interaction of 11-cis-Retinal and Opsin.- II. Cone Visual Pigments.- III. Identification of the Activated Photoproducts.- C. Visual Pigment Regeneration.- I. All-trans-Retinol Dehydrogenase.- II. Movement of Retinoids Between RPE and Photoreceptors.- III. Regeneration in Rods Compared to Cones.- IV Müller Cells.- V. Control of the Visual Cycle.- VI. Communication Between Neural Retina and RPE.- D. Cellular and Extracellular Retinoid-Binding Proteins.- I. Cellular Retinal-Binding Protein.- II. Interphotoreceptor Retinoid-Binding Protein.- III. Cellular Retinol-Binding Protein.- IV. Retinol-Binding Protein.- E. Diseases Associated with Retinoid Metabolism or Function in the Retina.- I. Congenital Stationary Night Blindness.- II. Autosomal Recessive Retinitis Pigmentosa.- III. Retinoids and Lipofuscin.- F. Summary.- References.- 21 Retinoids and Immunity.- A. Introduction.- B. Innate Immunity.- I. Natural Killer Cells.- II. Phagocytic Cells.- C. Adaptive Immunity.- I. Antibody-Mediated Immunity.- II. Cell-Mediated Immunity.- D. Immunity to Infections.- I. Measles Infection.- II. Human Immunodeficiency Virus Type 1 Infection.- III. Parasitic Infections.- E. Autoimmunity.- I. Rheumatoid Arthritis.- II. Multiple Sclerosis.- F. Lymphocyte Turnover.- G. Vitamin A Metabolism.- I. Active Metabolites for Immune Function.- II. Metabolism During Infection or Inflammation.- H. Mechanisms of Vitamin A Action in the Immune System.- I. Summary and Future Research Directions.- References.