Vitamin A (eBook)

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2011 | 1. Auflage
432 Seiten
Elsevier Science (Verlag)
978-0-08-047516-5 (ISBN)

Infos

First published in 1943, Vitamins and Hormones is the longest-running serial published by Academic Press. In the early days of the serial, the subjects of vitamins and hormones were quite distinct. The Editorial Board now reflects expertise in the field of hormone action, vitamin action, X-ray crystal structure, physiology, and enzyme mechanisms. Under the capable and qualified editorial leadership of Dr. Gerald Litwack, Vitamins and Hormones continues to publish cutting-edge reviews of interest to endocrinologists, biochemists, nutritionists, pharmacologists, cell biologists, and molecular biologists. Others interested in the structure and function of biologically active molecules like hormones and vitamins will, as always, turn to this series for comprehensive reviews by leading contributors to this and related disciplines.

Inhalt

Vitamin A 4
Copyright Page 5
Former Editors 6
Contents 8
Contributors 16
Preface 20
Chapter 1: RXR: From Partnership to Leadership in Metabolic Regulations 22
I. Introduction 23
II. RXRs and Their Many Partners Belong to the Nuclear Receptor Superfamily 24
A. Overview of the Nuclear Receptor Superfamily 24
B. Classifying Nuclear Receptors: An Informative Mean for Positioning RXR-Related Signaling Pathways 25
III. RXR in Partnership: The Permissive Heterodimers as Metabolic Sensors 28
A. An Overview of LXR:RXR Physiological Activities 28
B. An Overview of FXR:RXR Physiological Activities 30
C. An Overview of PPAR:RXR Physiological Activities 31
IV. The Rexinoid-Signaling Pathways: From Partnership to Leadership 36
A. The Receptors 36
B. The Nature of the Endogenous Ligand(s) 37
C. The Nature of the Functional Complexes 38
D. RXR Functional Activities 39
V. Conclusions 42
Acknowledgments 42
References 43
Chapter 2: The Intersection Between the Aryl Hydrocarbon Receptor (AhR)- and Retinoic Acid-Signaling Pathways 54
I. Introduction 55
II. Retinoid Signaling 59
III. The AhR/Arnt Pathway 61
IV. AhR and RA Availability 66
A. RA Synthesis 67
B. RA Catabolism 69
C. Interconversion 70
D. Storage and Transport 71
V. Molecular Interactions Between the RA and AhR Pathways 73
References 77
Chapter 3: Role of Retinoic Acid in the Differentiation of Embryonal Carcinoma and Embryonic Stem Cells 90
I. Introduction 91
II. Molecular Mechanism of Action of RA 92
III. Model Systems to Study Differentiation 94
A. EC Cells 94
B. ES Cells 96
IV. Role of RARs 98
V. RA-Regulated Genes 99
VI. Role of Specific RA-Regulated Genes 101
VII. Conclusions 107
Acknowledgments 108
References 108
Chapter 4: Metabolism of Retinol During Mammalian Placental and Embryonic Development 118
I. General Aspects of Retinol Transport and Metabolism in Mammalian Species 119
II. Placental Transport and Metabolism of Retinol During Mammalian Development 122
III. Embryonic Metabolism of Retinol During Mammalian Development 126
Acknowledgments 130
References 130
Chapter 5: Conversion of beta-Carotene to Retinal Pigment 138
I. General Aspects of Vitamin A Metabolism 139
II. Conversion of beta-Carotene to Vitamin A 141
A. Historical BackGround 141
B. Cloning of the Enzymes from Drosophila, Chicken, Mouse, and Human 141
C. An Enzyme for Eccentric Cleavage of beta-Carotene 142
D. Cleavage Mechanisms: Eccentric Versus Central Monooxygenase Versus Dioxygenase
E. Regulatory Mechanisms 143
F. Carotenoid Cleavage Enzymes During Development and in Various Tissues of the Adult 144
III. beta-Carotene as Provitamin A in Retinal Pigment Epithelial Cells 145
IV. Alternative Routes of Vitamin A Supply 147
References 149
Chapter 6: Vitamin A-Storing Cells (Stellate Cells) 152
I. Introduction 153
II. Morphology of HSCs 154
III. Regulation of Vitamin A Homeostasis by HSCs 155
IV. HSCs in Arctic Animals 158
V. Roles of HSCs During Liver Regeneration 162
VI. Production and Degradation of ECM Components by HSCs 164
VII. Reversible Regulation of Morphology, Proliferation, and Function of the HSCs by 3D Structure of ECM 167
VIII. Stimulation of Proliferation of HSCs and Tissue Formation of the Liver by a Long-Acting Vitamin C Deriva 170
IX. Extrahepatic Stellate Cells 172
X. Conclusions 173
Acknowledgments 174
References 174
Chapter 7: Use of Model-Based Compartmental Analysis to Study Vitamin A Kinetics and Metabolism 182
I. Introduction 183
II. Highlights of Whole-Body Vitamin A Metabolism 184
III. Early Kinetic Studies of Vitamin A Metabolism 185
IV. Overview of Compartmental Analysis 187
V. Use of Model-Based Compartmental Analysis to Study Vitamin A Kinetics 190
A. Whole-Body Models 190
B. Effects of Vitamin A Status on Vitamin A Kinetics 194
C. Vitamin A Kinetics in Specific Organs 197
D. Exogenous Factors That Affect Vitamin A Metabolism 201
E. Physiological Interpretation of Three- and Four-Compartment Models 209
F. Vitamin A Kinetic Studies in Humans 210
VI. Conclusions 212
References 213
Chapter 8: Vitamin A Supplementation and Retinoic Acid Treatment in the Regulation of Antibody Responses In Vivo 218
I. Introduction 220
II. Rationale for Interest in VA Supplementation and Antibody Production 220
III. VA and the Response to Immunization in Children 223
IV. Experimental Studies of VA or RA Supplementation and Antibody Production In Vivo 225
A. Experimental Models 225
B. RA Treatment and Antibody Production in a VA-Deficient Model 226
C. RA Treatment and Antibody Production in VA-Adequate Models 228
D. RA Supplementation in a Neonatal Model 230
E. Cytokine Production and Th1:Th2 Antibody Isotype Balance 231
V. Innate Immune Cells and Factors Regulated by VA and RA That May Affect Immunization Outcome 232
VI. Discussion and Perspectives 236
Acknowledgments 239
References 239
Chapter 9: Physiological Role of Retinyl Palmitate in the Skin 244
I. Introduction 245
II. Structure and Physiological Functions of the Skin 247
III. Cutaneous Absorption and Deposition of Dietary and Topically Applied Retinol and Retinyl Esters 249
A. Absorption and Deposition of Dietary Vitamin A by the Skin 250
B. Absorption and Deposition of Topically Applied Retinol and Retinyl Palmitate 256
C. Physiological and Environmental Factors Affecting Cutaneous Levels of Retinol and Retinyl Esters 261
IV. Mobilization and Metabolism of Retinol and Retinyl Esters in the Skin 262
V. Effects on Selected Biological Responses of the Skin 264
A. Immune Response 265
B. Wound Healing 266
C. Aging 266
D. Response to UV Light 267
VI. Summary 270
References 270
Chapter 10: Retinoic Acid and the Heart 278
I. Introduction 279
II. Role of RA in Heart Development and Congenital Heart Defects 280
A. Normal Heart Development 280
B. RA Signaling 281
C. RA and Heart Development 284
III. Postnatal Development Effects of RA in the Heart 289
A. Antihypertrophic Effects of RA in Neonatal Cardiomyocytes 290
B. Effects of RA Signaling in Cardiac Remodeling 292
C. Role of RA Signaling in the Regulation of the Renin-Angiotensin System 293
IV. Conclusions 294
References 295
Chapter 11: Tocotrienols in Cardioprotection 306
I. Introduction 306
II. A Brief History of Vitamin 307
A. Vitamin E, Now and Then 308
B. Tocotrienols Versus Tocopherols 310
C. Sources of Tocotrienols 313
III. Tocotrienols and Cardioprotection 313
IV. Atherosclerosis 314
V. Tocotrienols in Free Radical Scavenging and Antioxidant Activity 315
VI. Tocotrienols in Ischemic Heart Disease 316
VII. Conclusions 317
Acknowledgments 317
References 317
Chapter 12: Cytodifferentiation by Retinoids, a Novel Therapeutic Option in Oncology: Rational Combinations with Other Therapeutic Agents 322
I. Premise and Scope: Differentiation Therapy with Retinoids Is a Significant Goal in the Management of the Neoplastic Diseases 324
II. The Classical Nuclear RAR Pathway Is Complex and Has Led to the Development of Different Types of Synthetic Retinoids 326
III. Retinoids Promote Differentiation in Numerous Types of Neoplastic Cells 328
A. Myeloid Leukemia 329
B. Neuroblastoma 330
C. Head and Neck Cancer 331
D. Breast Carcinoma 332
E. Teratocarcinoma 332
F. Melanoma 333
IV. Retinoids Exert Pleiotropic Effects Interacting with Multiple Intracellular Pathways: An Opportunity for Combination Therapy 334
A. Growth Factors and Cytokines: G-CSF, TGF-beta, and Interferons 335
B. THE cAMP Pathway 339
C. The MAP Kinase Pathway 341
D. THE PI3K/AKT Pathway 346
E. Protein Kinase C 349
F. Histone Acetylation and DNA Methylation 352
V. Retinoid-Based Differentiation Therapy, General Observations, and Conclusion 355
Acknowledgments 357
References 357
Chapter 13: Effects of Vitamins, Including Vitamin A, on HIV/AIDS Patients 376
I. Introduction 378
II. Vitamins and Immune Function 379
III. Vitamins, HIV Transmission, and Pregnancy Outcomes 381
A. Evidence from Observational Studies 382
B. Evidence from Trials 383
IV. Vitamins and HIV Disease Progression in Adults 387
A. Evidence from Observational Studies 387
B. Evidence from Trials 391
V. Vitamins, Growth, and Disease Progression in HIV-Infected Children and HIV-Negative Children Born to HIV-Infected Mothers 393
VI. Comment 395
VII. Future Research 398
Acknowledgments 398
References 398
Chapter 14: Vitamin A and Emphysema 406
I. Does Vitamin A Protect Against Pulmonary Emphysema? 407
A. Vitamin A and Its Functions 407
B. Vitamin A and The Lung 408
C. Vitamin A and the Type II Pneumocyte 408
D. Emphysema 409
E. Emphysema and Vitamin A 410
F. Cigarette Smoking, Vitamin A Deficiency, and the Development of Emphysema 410
G. Emphysema, Vitamin A, and Elastin Metabolism 414
H. Mechanisms for Protection Against Emphysema by Vitamin A 414
I. Vitamin A, Lung Inflammation, and Emphysema 415
J. Evidence for Lung Restoration by Vitamin A 418
II. Conclusions 418
References 419
Index 424

Textauszug

2

The Intersection Between the Aryl Hydrocarbon Receptor (AhR)- and Retinoic Acid-Signaling Pathways

Kyle A. Murphy*; Loredana Quadro†; Lori A. White*    * Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901
† Department of Food Science, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901

Abstract

Data from a variety of animal and cell culture model systems have demonstrated an interaction between the aryl hydrocarbon receptor (AhR)- and retinoic acid (RA)-signaling pathways. The AhR1 was originally identified as the receptor for the polycyclic aromatic hydrocarbon family of environmental contaminants; however, recent data indicate that the AhR binds to a variety of endogenous and exogenous compounds, including some synthetic retinoids. In addition, activation of the AhR pathway alters the function of nuclear hormone-signaling pathways, including the estrogen, thyroid, and RA pathways. Activation of the AhR pathway through exposure to environmental compounds results in significant changes in RA synthesis, catabolism, transport, and excretion. Some effects on retinoid homeostasis mediated by the AhR pathway may result from the interactions of these two pathways at the level of activating or repressing the expression of specific genes. This chapter will review these two pathways, the evidence demonstrating a link between them, and the data indicating the molecular basis of the interactions between these two pathways.

I Introduction

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related polycyclic and halogenated aromatic hydrocarbons (PAH/HAH) are ubiquitous environmental contaminants that are the unintentional by-products of industrial combustion (Bertazzi et al., 1989, 2001). Exposure to these compounds results in a variety of lesions in mammals, including alterations in liver function and lipid metabolism, weight loss, immune system suppression, endocrine and nervous system dysfunction, as well as severe skin lesions (Mukerjee, 1998). TCDD is of particular interest due to its persistence in biological tissues (DeVito et al., 1995; Ott and Zober, 1996). TCDD exposure occurs mainly through oral ingestion and is concentrated through the food chain. As TCDD accumulates in the adipose tissue, an individual's body burden increases with age (DeVito et al., 1995). Although the exact mechanism underlying TCDD-mediated pathologies has not been completely elucidated, it is accepted that TCDD mediates the majority of these effects through activation of the aryl hydrocarbon receptor (AhR)-signaling pathway. However some AhR-independent effects of TCDD have been reported (Ahmed et al., 2005; Kondraganti et al., 2003; Park et al., 2003, 2005a,b; Sanders et al., 2005).

Retinoic acid (RA) is a natural product (lipid soluble hormone) derived from the metabolism of vitamin A. Vitamin A is an essential nutrient obtained from food either as preformed vitamin A (retinyl ester, retinol, and small amounts of RA) from animal products (eggs, liver, and milk) or as provitamin A (carotenoids) from fruits and vegetables (Fisher and Voorhees, 1996; Sporn et al., 1994). Vitamin A and its natural and synthetic derivatives are also known as retinoids. Dietary-derived all-trans RA (atRA) is the main signaling retinoid in the body and is vital for biological functions such as embryogenesis, growth and differentiation, as well as for vision and reproduction (Dragnev et al., 2000). Levels of atRA in the tissue are tightly regulated through its biosynthesis, metabolism, and storage in the liver (Fig. 1).

Figure 1 Vitamin A is obtained from food either as preformed vitamin A (retinyl ester), retinol, and small amount of RA from animal products (eggs, liver, milk) or as provitamin A (carotenoids) from fruits and vegetables. In the small intestine, retinyl esters (REs) are hydrolyzed to retinol (ROH) by retinyl ester hydrolases (REHs) on the cell surface of the enterocyte or in the intestinal lumen. While in the enterocyte, the ROH is bound to cellular retinol-binding protein II (CRBPII) and is reesterified back to RE by lecithin:retinol acyltransferase (LRAT). The REs are incorporated along with other dietary lipids into chylomicrons and transferred into the lymphatic system. These chylomicrons are specifically internalized into the hepatocytes of the liver, where the RE is converted to ROH through the action of REHs. Within the hepatocytes and stellate cells, the ROH is bound to CRBPI which is thought to transfer the ROH to the RBP for transport out of the liver, where the RBP–ROH complex is transferred to the circulation for use in extrahepatic tissues. In situations where vitamin A is in excess, it is stored in the stellate cells as RE.

The observation that TCDD exposure results in lesions that are reminiscent of those observed in vitamin A-deficient animals of several species, including reduced growth, abnormal immune function, and developmental abnormalities, was the first suggestion that TCDD and related compounds had an impact on retinoid homeostasis and the RA-signaling pathway (Table I). In addition, the low endogenous retinoid levels in the kidney are increased by both exposure to TCDD (Hakansson and Ahlborg, 1985) and vitamin A deficiency (Morita and Nakano, 1982). These observations led to the hypothesis that TCDD and the AhR pathway were altering retinoid metabolism to mimic a vitamin A-deficient state. Indeed, a reduction in hepatic retinoid storage following exposure to TCDD was observed in a variety of species (Fletcher et al., 2001; Hakansson et al., 1991). Evidence for a link between TCDD exposure and vitamin A deficiency is further strengthened by findings demonstrating that rats pretreated with TCDD store and metabolize an oral dose of vitamin A as if they were deficient, despite considerable retinoids in storage (Hakansson and Ahlborg, 1985). Further, vitamin A-administered post-TCDD exposure accumulates to a lesser extent than in control rats, and endogenously stored retinoids are released more rapidly following TCDD treatment (Hakansson and Ahlborg, 1985; Hakansson and Hanberg, 1989; Kelley et al., 1998, 2000).

Table I

TCDD Exposure Produces Lesions That Are Similar to Vitamin A Deficiency in a Variety of Animal Model Systems

General effects

Loss of appetite

r, mu, g, h, mo

r, mu, g, h, mo

Growth inhibition

r, mu, g, h, mo

r, mu, g, h, mo

Adipose reduction

r, mu, mo

r, mu, g, h

Inactivity/listlessness

r, mu

r, mu, g

Rough coat

r, mu, g, h, mo

r, mu, g, h

Death

r, mu, g, h, mo

r, mu, g, h, mo

Hyperplasia/metaplasia

Gastrointestinal

r, g, mo

g, h, mo

Urinary tract

r, mu, g, mo

g, mo

Bile duct/gall bladder

r

r, mu, mo

Respiratory system

r, mu, g, h, mo

r

Uterus

r, g

r

Reproduction

Testes degeneration

r, mo, h

r, mu, g, mo

Spermatogenesis

mo

Abnormal estrous cycle

r, mu

r, mu, mo

Fetus resorption

r, mu

r, mu, mo

Congenital abnormalities

Cleft palate

r

mu, mo*

Abnormal kidneys

r

r*, mu, mo*

Immunosuppression

Thymic atrophy

r, mu*, g

r, mu, g, h, mo

Impaired cellular immunity

r, mu

r, mu, g

Impaired humoral immunity

r*, mu

r#, mu, g*

Eye lesions

Xerophthalmia

r, mu, g*, h, mo

Not tested

Closed eyes/exudate

r, mu

r, mo

Effects of TCDD exposure and vitamin A deficiency. This table is modified from Nilsson and Hakansson (2002). Many of the lesions observed following TCDD exposure resemble those seen in vitamin A deficiency. The animal model demonstrating the effect is indicated by r—rat, mu—mouse, g—guinea pig, h—hamster, and mo—monkey. All denote an increase in the described lesion, except when noted by an

* :reduction or a

# :moderate to small effect.

However, not all data support the conclusion that exposure to TCDD and related compounds...

Produkt-Details

• Erscheint lt. Verlag: 21.9.2011
• Mitarbeit: Chef-Herausgeber: Gerald Litwack
• Sprache: englisch
• Themenwelt: Sachbuch/Ratgeber
• Themenwelt: Medizinische Fachgebiete ► Innere Medizin ► Endokrinologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Biochemie
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Themenwelt: Naturwissenschaften ► Physik / Astronomie ► Angewandte Physik
• Themenwelt: Technik
• ISBN-10: 0-08-047516-7 / 0080475167
• ISBN-13: 978-0-08-047516-5 / 9780080475165