Vitamin D Vitamin D Oxidative Stress, Immunity, and Aging 1 Oxidative Stress in Cancer, AIDS, and Neurodegenerative Diseases, edited by Luc Montagnier, René Olivier, and Catherine Pasquier 2 Understan.
Vitamin D Oxidative Stress, Immunity, and Aging OXIDATIVE STRESS AND DISEASE Series Editors Lester Packer, PhD Enrique Cadenas, MD, PhD University of Southern California School of Pharmacy Los Angeles, California Oxidative Stress in Cancer, AIDS, and Neurodegenerative Diseases, edited by Luc Montagnier, René Olivier, and Catherine Pasquier Understanding the Process of Aging: The Roles of Mitochondria, Free Radicals, and Antioxidants, edited by Enrique Cadenas and Lester Packer Redox Regulation of Cell Signaling and Its Clinical Application, edited by Lester Packer and Junji Yodoi Antioxidants in Diabetes Management, edited by Lester Packer, Peter Rösen, Hans J Tritschler, George L King, and Angelo Azzi Free Radicals in Brain Pathophysiology, edited by Giuseppe Poli, Enrique Cadenas, and Lester Packer Nutraceuticals in Health and Disease Prevention, edited by Klaus Krämer, Peter-Paul Hoppe, and Lester Packer Environmental Stressors in Health and Disease, edited by Jürgen Fuchs and Lester Packer Handbook of Antioxidants: Second Edition, Revised and Expanded, edited by Enrique Cadenas and Lester Packer Flavonoids in Health and Disease: Second Edition, Revised and Expanded, edited by Catherine A Rice-Evans and Lester Packer 10 Redox–Genome Interactions in Health and Disease, edited by Jürgen Fuchs, Maurizio Podda, and Lester Packer 11 Thiamine: Catalytic Mechanisms in Normal and Disease States, edited by Frank Jordan and Mulchand S Patel 12 Phytochemicals in Health and Disease, edited by Yongping Bao and Roger Fenwick 13 Carotenoids in Health and Disease, edited by Norman I Krinsky, Susan T Mayne, and Helmut Sies 14 Herbal and Traditional Medicine: Molecular Aspects of Health, edited by Lester Packer, Choon Nam Ong, and Barry Halliwell 15 Nutrients and Cell Signaling, edited by Janos Zempleni and Krishnamurti Dakshinamurti 16 Mitochondria in Health and Disease, edited by Carolyn D Berdanier 17 Nutrigenomics, edited by Gerald Rimbach, Jürgen Fuchs, and Lester Packer 18 Oxidative Stress, Inflammation, and Health, edited by Young-Joon Surh and Lester Packer 19 Nitric Oxide, Cell Signaling, and Gene Expression, edited by Santiago Lamas and Enrique Cadenas 20 Resveratrol in Health and Disease, edited by Bharat B Aggarwal and Shishir Shishodia 21 Oxidative Stress and Age-Related Neurodegeneration, edited by Yuan Luo and Lester Packer 22 Molecular Interventions in Lifestyle-Related Diseases, edited by Midori Hiramatsu, Toshikazu Yoshikawa, and Lester Packer 23 Oxidative Stress and Inflammatory Mechanisms in Obesity, Diabetes, and the Metabolic Syndrome, edited by Lester Packer and Helmut Sies 24 Lipoic Acid: Energy Production, Antioxidant Activity and Health Effects, edited by Mulchand S Patel and Lester Packer 25 Dietary Modulation of Cell Signaling Pathways, edited by Young-Joon Surh, Zigang Dong, Enrique Cadenas, and Lester Packer 26 Micronutrients and Brain Health, edited by Lester Packer, Helmut Sies, Manfred Eggersdorfer, and Enrique Cadenas 27 Adipose Tissue and Inflammation, edited by Atif B Awad and Peter G Bradford 28 Herbal Medicine: Biomolecular and Clinical Aspects, Second Edition, edited by Iris F F Benzie and Sissi Wachtel-Galor 29 Flavonoids and Related Compounds: Bioavailability and Function, edited by Jeremy P E Spencer and Alan Crozier 30 Mitochondrial Signaling in Health and Disease, edited by Sten Orrenius, Lester Packer, and Enrique Cadenas 31 Vitamin D: Oxidative Stress, Immunity, and Aging, edited by Adrian F Gombart Vitamin D Oxidative Stress, Immunity, and Aging Edited by Adrian F Gombart Boca Raton London New York CRC Press is an imprint of the Taylor & Francis Group, an informa business CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2013 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S Government works Version Date: 20120627 International Standard Book Number-13: 978-1-4398-5021-3 (eBook - PDF) This book contains information obtained from authentic and highly regarded sources Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint Except as permitted under U.S Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers For permission to photocopy or use material electronically from this work, please access www.copyright.com (http:// www.copyright.com/) or contact the Copyright Clearance Center, Inc (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400 CCC is a not-for-profit organization that provides licenses and registration for a variety of users For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com Contents Series Preface ix Preface .xi Editor xiii Contributors xv SECTION I Vitamin D: An Overview Chapter Vitamin D: A Fountain of Youth in Gene Regulation Peter W Jurutka, G Kerr Whitfield, Ryan Forster, Shane Batie, Jamie Lee, and Mark R Haussler Chapter Vitamin D Receptor: Genomic and Epigenomic Effects 37 Prashant K Singh and Moray J Campbell Chapter Vitamin D Analogs and Their Clinical Uses 65 Glenville Jones Chapter Extrarenal CYP27B1 and Vitamin D Physiology .99 Martin Hewison SECTION II Oxidative Stress Chapter Vitamin D and Oxidative Stress 131 Huei-Ju Ting and Yi-Fen Lee Chapter Vitamin D3 Upregulated Protein (VDUP1): Roles in Redox Signaling and Stress-Mediated Diseases 151 Dong Oh Kim, Hyun-Woo Suh, Haiyoung Jung, Young Jun Park, and Inpyo Choi Chapter Vitamin D and Its Role in Photoprotection of the Skin 165 Clare Gordon-Thomson, Wannit Tongkao-on, and Rebecca S Mason Chapter Vitamin D and Adipose Tissue: 1α, 25-Dihydroxyvitamin D3 (Calcitriol) Modulation of Energy Metabolism, Reactive Oxygen Species, and Inflammatory Stress 185 Antje Bruckbauer and Michael B Zemel vii viii Contents Chapter Membrane Receptors for Vitamin D Metabolites and the Role of Reactive Oxygen Species 201 Ramesh C Khanal and Ilka Nemere SECTION III Immunity and Disease Chapter 10 Vitamin D and Human Innate Immunity 223 Eun-Kyeong Jo, Dong-Min Shin, and Robert L Modlin Chapter 11 Vitamin D and Autoimmune Disease 239 Colleen E Hayes, Corwin D Nelson, and Justin A Spanier Chapter 12 Vitamin D: Anti-Inflammatory Actions to Prevent and Treat Diseases 307 Jun Sun Chapter 13 Vitamin D and Infection 323 Jim Bartley and Carlos A Camargo, Jr SECTION IV Aging Chapter 14 Potential Role of Vitamin D and Fibroblast Growth Factor 23–Klotho System in Aging 351 Nasimul Ahsan, Syed K Rafi, Beate Lanske, and Mohammed S Razzaque Chapter 15 Vitamin D and Cardiovascular Disease 363 Jared P Reis and Pamela L Lutsey Chapter 16 Vitamin D, Aging, and Chronic Diseases 385 Pentti Tuohimaa Chapter 17 Vitamin D: Defending the Aging Nervous System 407 Cédric Annweiler Series Preface Through evolution, oxygen—itself a free radical—was chosen as the terminal electron acceptor for respiration; hence, the formation of oxygen-derived free radicals is a consequence of aerobic metabolism These oxygen-derived radicals are involved in oxidative damage to cell components inherent in several pathophysiological situations Conversely, cells convene antioxidant mechanisms to counteract the effects of oxidants by either a highly specific manner (e.g., superoxide dismutases) or in a less specific manner (e.g., through small molecules such as glutathione, vitamin E, vitamin C, etc.) Oxidative stress—as classically defined—entails an imbalance between oxidants and antioxidants However, the same free radicals that are generated during oxidative stress are produced during normal metabolism and, as a corollary, are involved in both human health and disease by virtue of their involvement in the regulation of signal transduction and gene expression, activation of receptors and nuclear transcription factors, antimicrobial and cytotoxic actions of immune system cells, as well as aging and age-related degenerative diseases In recent years, the research disciplines interested in oxidative stress have increased our knowledge of the importance of the cell redox status and the recognition of oxidative stress as a process with implications for many pathophysiological states From this multidisciplinary and interdisciplinary interest in oxidative stress emerges a concept that attests to the vast consequences of the complex and dynamic interplay of oxidants and antioxidants in cellular and tissue settings Consequently, our view of oxidative stress is growing in scope and new future directions Likewise, the term reactive oxygen species, adopted at some stage in order to highlight nonradical/radical oxidants, now fails to reflect the rich variety of other species in free radical biology and medicine, encompassing nitrogen-, sulfur-, oxygen-, and carbon-centered radicals These reactive species are involved in the redox regulation of cell functions, and, as a corollary, oxidative stress is increasingly viewed as a major upstream component in cell signaling cascades involved in inflammatory responses, stimulation of cell adhesion molecules, and chemoattractant production and as an early component in agerelated neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases and amyotrophic lateral sclerosis Hydrogen peroxide is probably the most important redox signaling molecule that, among others, can activate NFκB, Nrf2, and other universal transcription factors and is involved in the redox regulation of insulin and MAPK signaling These pleiotropic effects of hydrogen peroxide are largely accounted for by changes in the thiol/disulfide status of the cell, an important determinant of the cell’s redox status with clear involvement in adaptation, proliferation, differentiation, apoptosis, and necrosis The identification of oxidants in regulation of redox cell signaling and gene expression was a significant breakthrough in the field of oxidative stress: the classical definition of oxidative stress as an imbalance between the production of oxidants and the occurrence of antioxidant defenses now seems to provide a limited depiction of oxidative stress, but it emphasizes the significance of cell redox status Because individual signaling and control events occur through discrete redox pathways rather than through global balances, a new definition of oxidative stress was advanced by Dean P Jones as a disruption of redox signaling and control that recognizes the occurrence of compartmentalized cellular redox circuits These concepts are anticipated to serve as platforms for the development of tissue-specific therapeutics tailored to discrete, compartmentalized redox circuits This, in essence, dictates principles of drug development-guided knowledge of mechanisms of oxidative stress Hence, successful interventions will take advantage of new knowledge of compartmentalized redox control and free radical scavenging Virtually all diseases thus far examined involve free radicals In most cases, free radicals are secondary to the disease process, but in some instances, causality is established by free radicals ix x Series Preface Thus, there is a delicate balance between oxidant and antioxidants in health and diseases Their proper balance is essential for ensuring healthy aging Compelling support for the involvement of free radicals in disease development originates from epidemiological studies showing that enhanced antioxidant status is associated with reduced risk of several diseases Of great significance is the role that micronutrients play in modulation of cell signaling: this establishes a strong linking of diet and health and disease centered on the abilities of micronutrients to regulate redox cell signaling and modify gene expression Oxidative stress is an underlying factor in health and disease In this series of books, the importance of oxidative stress and diseases associated with organ systems is highlighted by exploring the scientific evidence and clinical applications of this knowledge The series is intended for researchers in the basic biomedical sciences and clinicians The potential of such knowledge for healthy aging and disease prevention warrants further knowledge about how oxidants and antioxidants modulate cell and tissue function This series volume provides an update on the essential role of vitamin D in optimal human nutritional requirements and in health and disease Further insights are provided into the protective role of vitamin D in autoimmune, infectious, and inflammatory diseases, oxygen metabolism, and healthy aging In recent years, many new tissue-specific actions of vitamin D have been recognized This area of research is rapidly expanding We congratulate Adrian Gombart, the editor-inchief, for providing this valuable addition to the science of vitamin D Enrique Cadenas Lester Packer Dehouck, F Rigault, P Brachet, A Girault, G Torpier, and F Darcy 1996 1,25-Dihydroxyvitamin D3 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The British Journal of Nutrition 89 (5):552–572 Zou, J., A Minasyan, T Keisala, Y Zhang, J H Wang, Y R Lou, A Kalueff, I Pyykko, and P Tuohimaa 2008 Progressive hearing loss in mice with a mutated vitamin D receptor gene Audiology & NeuroOtology 13 (4):219–230 1,25D RXR-VDR 1,25D RXR-VDR Small intestine Absorption Resorption Net result = High PO 3– PO 3– sensor postulated in blood Ectopic calcification Osteoclast RANKL Bone Osteoblast Osteocyte FGF23 Degraded FGF23 FGF23 gene Intermediary transfactors Reabsorption FGFR CYP27B1 25OHD I n t r a c r i n e c o n v e r s i o n Kidney Klotho 1,25D DMP-1 PHEX HTTs Cell surface generated signals DMP-1 gene PHEX gene 1,25D Immune modulation T-cells B-cells Macrophages Immune cells Catabolism to Vasculature Cardiovascular influences Anticancer/detox effects Parathyriod gland Epithelial cells Breast Prostate Skin Colon FGF23 PTH Secreted klotho F G F , D 1,24,25D, etc Mineralization Blood Low Ca 2+ Ca 2+ receptor (sensor) in blood Net result = Osteopenia Ca-PO 1,25D RXR-VDR TRPV6 Npt2b Ca 2+ PO 3– PO 3– PO 3– Ca 2+ 1,25D RXR-VDR Npt2c PTH gene Npt2a Ca 2+ 1,25D RXR-VDR C Y P A FIGURE 1.2 (a) DBD CTE Ligand binding/heterodimerization Transactivation H1 H2 H7 H8H3 β s t r a n d s 165 ∆ 215 Proposed strand region deleted from hVDR ∆ 165–215 1,25(OH) D H9 H10 L o o p H5 hVDR R X R hPXR/SXR 177–198 (unstructured) SR12813 H12 (AF2) Heterodimerization (b) (c) Loop Helix C o a c t i v a t o r Helix H e l i x H e l i x H e l i x H e l i x 274 420 391 FIGURE 1.3 Resveratrol 2000 1000 cpm bound Log of competitor dose in M Vasculature Anti-aging “activity” Other target tissue sKlotho sKlotho ADAM10 SIRT1 mKlotho Resveratrol Proteolytic cleavage (or RNA splicing) Curcumin VDR RXR VDR RXR VDR RXR VDR RXR 1,25D 1,25D Kidney No competitor –8 –7 –6 –5 –4 –3 –2 –1 DHA Dex 1,25D No VDR (DHA) (b) (c ) (a) Human kidney (HEK-293) Human kidney (HEK-293) Human colon (HCT-116) Human colon (HCT-116) 1,500 40,000 8,000 6,000 4,000 2,000 30,000 20,000 10,000 80 60 40 20 V D R E m e d i a t e d a c t i v i t y fi r e fl y / r e n i l l a V D R E m e d i a t e d a c t i v i t y fi r e fl y / r e n i l l a V D R E m e d i a t e d a c t i v i t y fi r e fl y / r e n i l l a V D R E m e d i a t e d a c t i v i t y fi r e fl y / r e n i l l a 1,000 500 EtOH EtOH 1,25D RES+1,25D EtOH 1,25D RES+1,25DEtOH RES RES FIGURE 1.8 S100A8/9 1,25(OH) D -VDR Resveratrol PTH/PTHrP SOSTDC1 OPG NF ĸB IL-2/17 COX-2 PHEX FOXO1 p21 CaSR Npt2b/c FOXO3 Cathelicidin CYP24A1 CYP3A4 FGF23/Klotho BGP TRPV6/5 LRP5 RANKL SPP1 Cystathionine β-synthase SULT2 p53 FIGURE 1.10 Vitamin D CYP27B1 Parathyroids regulation Bone OB/OC function CYP27B1 Parathyroids regulation PTH CYP27B1 bone OB/OC function CYP27B1 small intestine Ca/PO uptake immunity Small intestine regulation Ca/PO uptake PTH CYP24A1 1,25(OH) D 1,25(OH) D FGF23 25OHD PTH FIGURE 4.1 Microbiota IEC CPY27B1 Injury Infection 1,25(OH) D TLR TGFβ1 25OHD Vitamin D 25OHD DCs CYP27B1 Catabolism IFNγ IL-15 IL-4 CYP24A1 M O 25OHD 25OHD Colon Monocyte/macrophage Skin Infection TLR TLR 25OHD Decidua Trophoblast Placenta CPY27B1 CPY27B1 1,25(OH) D CPY27B1 CPY27B1 1,25(OH) D 25OHD 1,25(OH) D FIGURE 4.2 505 aa 505 aa FIGURE 9.3 D e n d r i t i c c e l l s M o n o c y t e s / m a c r o p h a g e s D i ff e r e n t i a t i o n i n t o m a c r o p h a g e s C D , C D U V B D P r o V i t D T L R s M H C I I , C D T o l e r o g e n i c D C D C m a t u r a t i o n A n t i g e n p r e s e n t a t i o n B a c t e r i a k i l l i n g P r o l i f e r a t i o n , D D M C P , M I P α , I L C a t h e l i c i d i n , D E F B T L R , N O D N O s y n t h e s i s , D E p i t h e l i u m / K e r a t i n o c y t e s M a s t c e l l s C a t h e l i c i d i n D E F B I L I L , I L I L , I L I L , I L D N A r e p a i r D i ff e r e n t i a t i o n P r o l i f e r a t i o n U V B i n d u c e d s k i n p a t h o l o g y L e u k o c y t e a c c u m u l a t i o n � r e s p o n s e I n f e c t i o n T L R s I n j u r y F I G U R E ... 50kb Mouse klotho gene chr 12 CYP24A1 100 10 200X Fold change in mRNA level (log scale) 100 CYP24A1 Fold change in mRNA level (log scale) (c) (b) 1400X 567 910 Human klotho gene chr 13 11 12 13... al 2 010) using lysates from COS-7 cells transfected with expression plasmids for both human VDR and human RXRα Five μL of lysate were X combined with μL of [3H]1,25D (approximately × 10 ? ?10 M)... (Baur 2 010) SIRT1 catalyzes deacetylation of VDR, RXR, or comodulators to increase the capacity of 1,25D binding to VDR SIRT1 activation also leads to ADAM10 stimulation (Donmez et al 2 010) to