Skin stress response pathways

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Georg T. Wondrak Editor Skin Stress Response Pathways Environmental Factors and Molecular Opportunities Skin Stress Response Pathways Georg T Wondrak Editor Skin Stress Response Pathways Environmental Factors and Molecular Opportunities 123 Editor Georg T Wondrak Department of Pharmacology and Toxicology College of Pharmacy & The University of Arizona Cancer Center University of Arizona Tucson, AZ USA ISBN 978-3-319-43155-0 DOI 10.1007/978-3-319-43157-4 ISBN 978-3-319-43157-4 (eBook) Library of Congress Control Number: 2016946320 © Springer International Publishing Switzerland 2016 This work is subject to copyright All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed The use of general descriptive names, registered names, trademarks, service marks, etc in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG Switzerland Preface If the skin were parchment and the blows you gave were ink, Your own handwriting would tell you what I think (William Shakespeare, The Comedy of Errors) It is now understood that the interplay between environmental exposure and cellular stress response pathways plays a critical role in skin structure and function, and a refined mechanistic understanding of this phenomenon at the molecular level promises to open novel avenues for targeted therapeutic strategies that may benefit skin health of patients in the near future The comprehensive coverage of cutaneous cell stress response pathways as presented for the first time in this book is intended to provide a state-of-the-art perspective that is of interest to both basic researchers focusing on fundamental skin biology in the context of environmental exposure as well as translational biomedical health care professionals With the completion of this project, I would like to express my gratitude to those who were instrumental in its creation First and foremost, I would like to thank my co-authors from four continents who have graciously contributed their talent and time to assemble this first in a kind perspective on skin stress response pathways Second, I am indebted to my department head Walt Klimecki for allowing me to pursue this project Moreover, I am grateful for this outstanding opportunity and the expert support provided by Melania Ruiz and Ilse Hensen-Kooijman at Springer Science+Business Media B.V Finally, I would like to thank my family, Claudia, Gil, Philip, and Annie, for letting me divert precious time and energy from them in pursuit of this book project Tucson June 2016 Georg T Wondrak v Contents The Skin Lipidome Under Environmental Stress—Technological Platforms, Molecular Pathways and Translational Opportunities Florian Gruber Squalene and Skin Barrier Function: From Molecular Target to Biomarker of Environmental Exposure Boudiaf Boussouira and Dang Man Pham 29 Sunlight-Induced DNA Damage: Molecular Mechanisms and Photoprotection Strategies Thierry Douki 49 Urocanic Acid and Skin Photodamage: New Light on an Old Chromophore Leopold Eckhart 79 The Skin Extracellular Matrix as a Target of Environmental Exposure: Molecular Mechanisms, Prevention and Repair 101 Kieran T Mellody, Mike Bell and Michael J Sherratt Nitric Oxide Derivatives and Skin Environmental Exposure to Light: From Molecular Pathways to Therapeutic Opportunities Christoph V Suschek 127 Melanocortin Receptor (MC1R) as a Global Regulator of Cutaneous UV Responses: Molecular Interactions and Opportunities for Melanoma Prevention 155 Erin M Wolf Horrell and John A D’Orazio The Cutaneous Melanocyte as a Target of Environmental Stressors: Molecular Mechanisms and Opportunities 175 Laurent Marrot vii viii Contents The Role of Epidermal p38 Signaling in Solar UV Radiation-Induced Inflammation: Molecular Pathways and Preventive Opportunities 197 Jin Mo Park and Yasuyo Sano 10 UV-Induced Chemokines as Emerging Targets for Skin Cancer Photochemoprevention 211 Scott N Byrne and Gary M Halliday 11 TLR3 and Inflammatory Skin Diseases: From Environmental Factors to Molecular Opportunities 235 Risa Tamagawa-Mineoka, Mayumi Ueta and Norito Katoh 12 Sirtuins and Stress Response in Skin Cancer, Aging, and Barrier Function 251 Yu-Ying He 13 Cutaneous Opioid Receptors and Stress Responses: Molecular Interactions and Opportunities for Therapeutic Intervention 265 Hanane Chajra 14 Regulation of Cutaneous Stress Response Pathways by the Circadian Clock: From Molecular Pathways to Therapeutic Opportunities 281 Elyse van Spyk, Milton Greenberg, Faraj Mourad and Bogi Andersen 15 Endocannabinoids and Skin Barrier Function: Molecular Pathways and Therapeutic Opportunities 301 Sergio Oddi and Mauro Maccarrone 16 The Aryl Hydrocarbon Receptor (AhR) as an Environmental Stress Sensor and Regulator of Skin Barrier Function: Molecular Mechanisms and Therapeutic Opportunities 325 Rebecca Justiniano and Georg T Wondrak 17 Biological Cell Protection by Natural Compounds, a Second Line of Defense Against Solar Radiation 361 Ludger Kolbe 18 The Cutaneous Microbiota as a Determinant of Skin Barrier Function: Molecular Interactions and Therapeutic Opportunities Julia J van Rensburg, Lana Dbeibo and Stanley M Spinola 379 19 Sensing Environmental Factors: The Emerging Role of Receptors in Epidermal Homeostasis and Whole-Body Health Mitsuhiro Denda 403 Contents ix 20 The Cutaneous Circadian Clock as a Determinant of Environmental Vulnerability: Molecular Pathways and Chrono-pharmacological Opportunities 415 Kyongshin Cho, Rajendra P Gajula, Kenneth I Porter and Shobhan Gaddameedhi 21 Psychological Stress as a Determinant of Skin Barrier Function: Immunological Pathways and Therapeutic Opportunities 433 Mark E Mummert Index 449 Chapter The Skin Lipidome Under Environmental Stress—Technological Platforms, Molecular Pathways and Translational Opportunities Florian Gruber Abstract The skin is an organ with a high level of lipid metabolism and is divided into regions with very differing lipid composition Skin lipids determine the barrier function of the skin but are also important signaling mediators Environmental stressors can modify lipid composition, reactivity and distribution and thereby influence skin biology In the last decade the technology to investigate the lipids made explosive progress, allowing now for in-depth investigation of the role of lipids in skin biology In this chapter the current developments in lipidomic analysis of environmental skin stress and the translational opportunities of this technology are discussed Á Á Á Á Á Keywords Oxidized lipids Lipidomic Mass spectrometry Redox Stress Eicosanoids Reactive oxygen species Ultraviolet Skin Keratinocyte Fibroblast Phospholipids Á 1.1 Á Á Á Á Á Introduction Redox biologists, (bio-) chemists, skin researchers, physicians—we are all usually not trained to deal with the big data from the inflationary—omics approaches that pour in over us As soon as we have accepted that such projects are interdisciplinary, require adequate statistics, that they often are exploratory and hypothesis generating—then the benefits of such approaches become accessible We learn to use the huge potential of lipidomic/metabolomic—postgenomic—data formats that F Gruber (&) Department of Dermatology, Division for Biology and Pathobiology of the Skin and Christian Doppler Laboratory for the Biotechnology of Skin Aging, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria e-mail: florian.gruber@meduniwien.ac.at © Springer International Publishing Switzerland 2016 G.T Wondrak (ed.), Skin Stress Response Pathways, DOI 10.1007/978-3-319-43157-4_1 F Gruber not adhere to the familiar linear information format provided under the central dogma of molecular biology (DNA-RNAs-protein) The ultimate aim of lipidomic analyses of the skin, its cells or the subcellular structures like membrane subdomains is to identify those compounds, networks, pathways, physical forces, and interactions that keep the skin functioning in a hostile, changing milieu In this chapter I will review, from the viewpoint of a molecular biologist of the skin, what has been learned by lipidomic approaches about how environmental stress affect the skin’s lipids in their function as signaling mediators or structural molecules, and what translational potential such technology may yield 1.1.1 Lipids of the Skin—Distribution of Stress Accessible Lipid Classes The skin displays an active and diverse lipid metabolism, and lipids are essential for the barrier—and signaling functions of this organ (Feingold and Elias 2014; van Smeden et al 2014b; Kendall et al 2015) Any disturbance of lipid homeostasis by environmental stressors thus may result in impairment of these functions, and may cause disease or accelerated aging The most common stressor the skin is exposed to and affects the lipids is sunlight, with very distinct effects on skin biology that are governed by wavelength and penetration depth But also physical, chemical or biological stress can affect the cutaneous biology by changing lipid composition or structure (Fig 1.1) Fig 1.1 Lipids of the skin 442 M.E Mummert using search terms related to hypnosis and skin disease (Shenefelt 2011) Results from MEDLINE showed that a wide range of dermatological disorders could be improved using hypnosis as an alternative or complementary therapy for skin disease treatment, including (1) atopic dermatitis, (2) psoriasis, (3) alopecia areata, (4) rosacea, (5) vitiligo, (6) hyperhidrosis, and (7) ichthyosis vulgaris (Shenefelt 2000) The apparent psychophysiologic responses of many dermatoses suggests that treatment programs structured at the dermatology/psychiatry interface may be useful for patient treatment, including programs that incorporate (1) psychotherapy, (2) biofeedback, (3) hypnosis, and (4) cognitive behavioral methods (Heller et al 2011; Shenefelt 2000, 2003) Other psychological methods have also been found to lead to resolution of skin disease For example, Fortune et al has reported that patients that chose to participate in a cognitive behavioral therapy program reported less frequencies and numbers of psoriasis symptoms up to months after the program ended (Fortune et al 2004) 21.8 Conclusions Skin is a highly innervated organ that arises from an ectodermal origin in common with the nervous system Both the innate and adaptive immune responses of the skin respond to psychological stimuli In fact, many skin diseases have been shown to precede or to be exacerbated by psychological stress Perhaps the most studied human skin disease to date is atopic dermatitis, which is a TH2 disease with TH1 chronification Psychological stress impedes TH1 activity via the suppressed HPA axis skewing the TH1/TH2 balance to TH2 and thus, acute disease symptoms In addition to disease, psychotropic medications can affect skin, mostly by inducing exanthematous eruptions Conversely, drugs used to treat skin diseases can also induce psychiatric comorbidity The ability to manipulate reactions in the skin by psychological means may be one way to alleviate skin disease The apparent psychophysiologic responses of many dermatoses suggests that treatment programs structured at the dermatology/psychiatry interface may be useful for patient treatment, including programs that incorporate (1) psychotherapy, (2) biofeedback, (3) hypnosis, and (4) cognitive behavioral methods References Aberg KM, Radek KA, Choi EH, Kim DK, Demerjian M, Hupe M, Kerbleski J, Gallo RL, Ganz T, Mauro T, Feingold KR, Elias PM (2007) Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice J Clin Invest 117:3339–3349 21 Psychological Stress and Skin Barrier Function 443 Arndt KA, Jick H (1976) Rates of cutaneous reactions to drugs a report from the Boston Collaborative Drug Surveillance Program JAMA 235:918–923 Asadi S, Alysandratos KD, Angelidou A, Miniati A, Sismanopoulos N, Vasiadi M, Zhang B, Kalogeromitros D, Theoharides TC (2012) Substance P 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Transmitter release in skin and muscle blood vessels during sympathetic stimulation Am J Physiol 212:1043–1054 Index 0-9 12-LOX, 10 15-LOX, 10 2-(1′H-indole-3′-carbonyl)thiazole-4-carboxylic acid methyl ester (ITE), 330, 343, 345 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), 328, 329, 331, 341, 342, 344, 347 TCDD-Induced Chloracne, 336 2,4-Dinitrofluorobenzene (DNFB), 314, 438 2-Arachidonoylglycerol (2-AG), 303 3’,5’-cyclic adenosine monophosphate (cAMP), 309 3-Hydroxyanthranilic acid (HA), 330 5-Flourouracil (5-FU), 426 5-methoxy-psoralen (5-MOP), 187 6-Formylindolo[3,2-b]Carbazole (FICZ), 328, 331–333 as a nanomolar endogenous UVA-photosensitizer, 334 as endogenous activator of LINE-1, 335 functions independent of AhR ligand activity, 333 8-methoxy-psoralen (8-MOP), 187 8-oxo-7,8-dihydro-2′-deoxyguanosine (8oxoG), 222 8-oxoGua, 64 8-Oxo-guanine glycosylase (OGG1), 422 A Acne vulgaris, 393 Adaptive immune response to stress, 438 Adrenocorticotropic hormone (ACTH), 435 Age-Related Changes, 30 Aging, 287 See also Skin aging Airway/skin irritants, 18 Allergic contact dermatitis (ACD), 238, 313 Alopecia, 17 Alzheimer’s disease, 19 Anandamide, 14, 303 Anti-ageing treatments, 115, 117 Anti-genotoxic protection, 188 Anti-inflammatory activity botanicals with, 224 Anti-inflammatory drugs, 363, 365, 367–369 Antioxidant responsive element (ARE), 340 Antioxidants, 37, 68, 287, 290, 291, 362, 364–366, 373 Aryl hydrocarbon receptor (AhR), 184, 190, 325 as an environmental stress sensor, 326 barrier function maintenance, 339 human skin, 338 ozone, 338 cancer and, 347 cutaneous AhR, 342 cutaneous functions, 336 endogenous, 328 epidermal barrier function and, 336 exogenous, 328 harnessing AhR-Nrf2 crosstalk, 339 in malignant melanomagenesis, 346 in melanogenesis, 346 in vitiligo, 346 target genes, 328 therapeutic opportunities, 336 Ataxia and rad3-related (ATR) protein, 168 Atmospheric pressure chemical ionization (APCI), 35 Atopic dermatitis (AD), 18, 86, 93, 258, 312, 343, 391 Atopic eczema, 312 ATP binding casette transporters, 11 Autoimmune disease, 293 B Bacterial community, 388 Barrier function, 32 © Springer International Publishing Switzerland 2016 G.T Wondrak (ed.), Skin Stress Response Pathways, DOI 10.1007/978-3-319-43157-4 449 450 Barrier repair, 235 See also Skin barrier repair Base excision repair (BER), 61, 422 Biological cell protection, 361 See also Photoprotection C Caffeine, 364 Calcitonin gene-related peptide (CGRP), 436 cAMP signaling, 159, 168–170 Cancer AhR and, 347 Candidate receptors, 404 Cannabinoid receptors, 305 Carbamazepine, 441 Carbonylic malondialdehyde, 16 Carcinogenesis AhR in, 342 Cardiolipin, Carotenoids, 365 C-C motif chemokine family members, 217 Cell cycle, 286, 289 Ceramidase, 11 Ceramides (Cer), 6, 16 Chemokines, 212 Chlorinated fatty acids, Chlorinated phospholipids, Cholesterol esters (CE), Cholesterol hydroperoxides, Cholesterol in human skin, 16 Cholesterol sulphate, 16 Chronotherapy circadian clock and, 425 Cinnabarinic acid, 330 Circadian clock, 416 See also Cutaneous circadian clock at an organismal level, 283 body-autonomous, 282 chronotherapy and, 425 epigenetics and, 427 in cellular metabolism regulation, 286 in skin, 285 in skin adaptive immunity, 293 in skin Immunity regulation, 292 in skin response in cell cycle regulation, 286 in skin innate immunity, 292 in unfolded protein response control, 287 to endogenous stressors, 286 to external stressors, 286 molecular mechanism of, 284 response to wounding, 288 Index skin cancer and, 422 skin stress response and, 282 stress response pathway regulation by, 281 Circadian disruption, 416, 424, 425 Circadian immune regulation, 426 Circadian melatonin regulation, 423 Circadian molecular pathways, 417 Circadian physiological effects, 419 Circadian rhythm sleep disorder (CRSD), 419 cis-UCA, 92 Clock genes, 417–420, 425, 427 Collagens, 102 Compound-skin interactions, 19 Cone opsins, 408 Contact dermatitis, 238, 242 Contact hypersensitivity (CHS) reactions, 438 Corneocytes, 403 Cornified protecting barrier, 32 Corticotropin-releasing hormone (CRH), 435 Cutaneous AhR agonists skin microbiome as a source of, 332 Cutaneous circadian clock environmental vulnerability as determinant of, 415 mammalian circadian system, 416 skin, 420 tissue-specific expression patterns of circadian genes, 418 Cutaneous Cytokines/Chemokines, 213 Cutaneous endocannabinoid system, 307 Cutaneous microbiota acne vulgaris, 393 as skin barrier function determinant of, 379 atopic dermatitis (AD), 391 characterization, 384 composition, factors influencing, 387 identifying methods, 382 immune system and, 389 in infectious disease, 394 in skin diseases prevention, 396 in skin pathologies, 391 psoriasis, 393 rosacea, 392 Cutaneous side effects to psychtropic medications, 441 Cutaneous T cell-Attracting ChemoKine (CTACK), 217 C-X-C motif chemokine ligand 12 (CXCL12), 218 Cyclobutane pyrimidine dimers (CPDs), 51, 222, 420 Cyclo-oxygenase-2 (COX-2), 10, 220, 304 Index Cytochrome oxidases, 11 Cytochrome P450 monooxygenases (CYP1A1), 328, 329, 331, 332, 337, 341–343, 345, 348 Cytokines, 212 See also UV-induced cytokines D Dead keratinocytes, 403 Delta opioid receptor (DOR), 265, 267, 269, 270, 273–276 Dendritic epidermal T-cells (DETC), 343 Dermatological diseases psychological methods for, 441 Dewar valence isomers, 54, 55 Diabetes, 18 Diacylglycerol lipase (DAGL), 307 Diacylglycerols (DAGs), 303 Dihydroxy-indole (5,6-DHI), 180 Direct UV-Induced DNA oxidation, 58 Disease specific metabolites, 19 DNA damage, sunlight-induced, 49, 54, 55 damage formation, 50 from damage to mutation, 60 in vitro, 62 in vivo, 65 oxidative damage, 55 prevention, 66 prevention, natural products and extracts, 68 prevention, sunscreens, 66 prevention, systemic photoprotection, 67 secondary oxidative damage, 57 DNA damage, 282, 283 c irradiation induced, 289 UVB-Induced, 289 DNA damage repair and skin circadian control, 420 DNA photodamage, 176, 177, 179, 181–183, 188 DNA repair, 60, 68, 163, 168, 169 sirtuins in, 252, 253, 255 Double strand breaks (DSBs), 57 Drug-induced hyperpigmentation, 187 E Eicosanoids, 5, 11, 13, 18 Eicosapentaenoic acid (EPA), 5, 14, 221 Endocannabinoid (eCB) cutaneous, 307 cutaneous, expression, 307 description, 303 in epidermal barrier formation, 309 metabolism, 303 molecular targets, 304 451 molecular targets, cannabinoid receptors, 305 molecular targets, PPARs, 307 molecular targets, TRPV1 channel, 306 skin barrier functions and, 301, 309 therapeutic opportunities, 312 therapeutic opportunities, allergic contact dermatitis, 313 therapeutic opportunities, atopic dermatitis, 312 therapeutic opportunities, localized scleroderma, 315 therapeutic opportunities, psoriasis, 316 Endocannabinoid system, 301, 303 Endogenous AhR ligands, 329 Endogenous Antioxidants, 188 Endogenous TLR3 Ligands, 240 Endogenous UVA-photosensitizer, 334 Endothelin-1 (EDN1), 178 Environmental factors upon squalene oxidization, 43 Environmental pollution, 19 Environment exposure changes, 31 Epidermal barrier and defects, 18 Epidermal barrier formation, 309 Epidermal barrier function AhR and, 336 Epidermal homeostasis information processing in, 409 receptors role in, 403 responses to humidity changes, 407 signals from keratinocytes to whole body and brain, 410 sound response to, 409 visible radiation response to, 408 Epidermal keratinocytes environmental factors effects on, 404 Epidermal melanocytes, 176 Epidermis, 80, 86, 87, 198, 201, 202 UCA formation in, 82 UVB radiation absorption by, 87 vitamin D in, 89 Epigenetics circadian clock and, 427 Exogenous AhR ligands, 329 Experimental autoimmune encephalomyelitis (EAE), 343 Extracellular matrix (ECM), 102 ageing and, 114 architecture, 102 collagens, 102 composition, 102 elastic fibres, 104 IR and tobacco smoke, 113 452 Extracellular matrix (ECM) (cont.) minor Components of, 105 non-dermal ECM, 107 preventing environmental damage, 114 skin photo-damage and, 110 skin remodelling and, 110 topical Agents, 115 UV exposure and, 110, 112 F Fatty acid amide hydrolase (FAAH), 304 Fatty acids, Fibroblast, 3, 7, 10, 12, 14, 15 Filaggrin, 82, 87, 88 Fluorescein isothiocyanate (FITC), 312 Forensics, 19 G Galactosyl ceramides, 16 Gangliosides, Glutathione peroxidases (GPx), 11 Glycated PLs, Glycosaminoglycan (GAG), 103 Glycosphingolipids, 16 Glycoxidized PLs, Green tea Catechins, 364 H Herpes simplex virus (HSV)-1, 238 Herpes virus infection, 238 Histidase, 82, 84, 85, 93 Histidinemia, 85, 88 Homeostasis, 301–303, 306, 307, 309, 310, 316 HPLC-mass spectrometry, 59 Human papilloma virus, 238 Human sebum, 33 qualitative aspects, 33 quantitative aspects, 33 Human skin, 30, 380 Human skin diseases linked to psychological stress, 440 Human skin physiology no In, 128 Hydrogen peroxide, 12 Hydroperoxyoctadecadienoic acids (HODEs), 13 Hydroxyeicosatetraeonic acids (HETEs), 13 Hydroxyl radical, 12 Hyperpigmentation, 186 Hypochlorous acid, 12 Hypothalamic-pituitary-adrenal (HPA) axis, 435 Index I Immune function AhR in, 342 Immune responses, 435 psychological stress impact on adaptive immune responses, 438 innate immune responses, 436 Immunity adaptive immunity, 293 crcadian regulation of, 292 innate immunity, 292 Immunomodulation, 311, 312 Immunosuppression, 87, 92, 93 Indoleamine-pyrrole 2,3-dioxygenase (IDO), 347 Inflammation AhR in, 342 Inflammatory Stress, 186 Influenza, 18 Information processing in epidermis, 409 Innate Immune Responses to Stress, 437 Interleukin (IL)-1, 214 Interleukin (IL)-33, 215 Interleukin (IL)-6, 216 Intrinsic Pro-oxidant Potential of Melanin, 180 In vitro efficacy of Licochalcone A, 367 in vivo efficacy of Licochalcone A, 370 In vivo studies, 40 Irritant contact dermatitis, 238 Itching, 242, 265, 267, 268 K Kappa opioid receptor (KOR), 265, 266, 269, 273, 274, 276 Keratinocyte differentiation SIRT3 in, 258 sirtuins in, 258 Keratinocytes, 3, 9–11, 13, 15, 19, 81–84, 86, 91, 92, 197, 198, 201–206, 403 as sensory system responsive to mechanical stimuli, 406 dead, 403 photodamage in, 177 Ketoconazole (KCZ), 329, 341 Kynurenines, 330 L Lactosyl ceramides, 16 Langerhans cells (LC), 213 Leprosy, 19 Leukotriene A4 hydrolase, 11 Licochalcone A, 366 anti-inflammatory pathways modulation by, 369 Index anti-oxidative pathways modulation by, 369 in vitro efficacy of, 367 in vivo efficacy of, 370 Licorice, 366, 368 Limit Of Detection (LOD), 35 Limit Of Quantification (LOQ), 35 Lipid mediators, 219 Lipidomic analyses, 1, 2, 4–6, 10, 12, 13, 18 Lipid peroxidation, 12 Lipoxygenases 12 (12-LOX), 304 Localized scleroderma, 315 Long interspersed nucleotide element-1 (LINE-1), 335 M Malassezin, 332, 347 Malignant Melanomagenesis AhR in, 346 Mammalian circadian system, 416 Mass spectrometry (MS), 4–8, 19 Matrikines, 116 MC1R See Melanocortin receptor (MC1R) Melanin, 176, 177, 422 for Melanocytes, 180 Intrinsic Pro-oxidant Potential Os, 180 precursors, 183 Melanin Photoreactivity, 182 in vitro data, 182 in vivo data, 182 Melanocortin receptor (MC1R), 155, 168, 169 antagonists, 165 bD3 role at, 166 in melanoma Prevention, 169 melanocytes in, 169 signaling activity of, 159 signaling axis, melanocortin, 164 Melanocyte, 156–158 cutaneous, 158 in MC1R-defective individuals, 169 keratinocytes and, 158 Melanocytes, 31 as targets of (bio) chemical toxicity, 184 sunlight and, 177 Melanocyte-specific cytotoxicity, 186 Melanocyte-specific defensive capabilities, 188 Melanocyte stimulating hormone (a-MSH), 155, 164 Melanogenesis, 177, 180 AhR in, 346 Melanoma, 17, 155, 156, 254 incidence, 156 in skin, 156 prevention strategy, 169 453 risk factor for, 162 UV causing, 156 Melatonin (5-methoxy-N-acetyltryptamine), 423 Microbiome, 382, 388, 396 Microbiota, 382 See also Cutaneous microbiota Microphthalmia-associated transcription factor (MITF), 177 Minimal erythemal dose (MED), 222 Molluscum contagiosum virus, 238 Monoacylglycerol lipase (MAGL), 304 Mu opioid receptor (MOR), 266–270, 274–276 Mutations, 65, 156 DNA damage to, 60 in key melanocyte survival, 160 in MC1R, 165 UV-induced, 169 N N-acylethanolamines (NAE), 14 N-acyl-phosphatidyl-ethanolamine (NArPE), 14, 303 N-arachidonoylethanolamine (AEA), 303 Nei-like DNA glycosylase (NEIL1), 61 Neuroendocrine System Skin and, 435 NF(B activation), 369, 370 Nicotinamide (NAM), 222 Nicotinamide adenine dinucleotide (NAD), 222 Nitrated fatty acids, Nitrated PL, Nitric Oxide (NO) against UV-induced injuries, 136 antimicrobial effects of, 129 antiviral effects of, 129 generation in human skin, 138 in cutaneous blood flow, 131 in cutaneous wound healing, 130 in human skin physiology, 128 in UV-exposed skin, 134 on UV-induced cutaneous inflammation, 135 on UV-modulated cutaneous immune response, 135 UVA enhancing, 143 Nitric Oxide (NO) derivatives skin environmental exposure to light, 127 Nitro-oxidized fatty acids, Non-dermal Extracellular Matrix Proteins, 107 Non-enzymatically generated lipid mediators, 13 Non-hydroxyacyl epidermal ceramides, Non-keratinocyte skin cells, 310 Nonmelanoma Skin Photocarcinogenesis, 347 454 Nonsteroidal Anti-inflammatory Drugs (NSAIDS), 363 NO radical, 12 Norepinehrine, 435 Normal human epidermal keratinocytes (NHEKs), 339 Nrf2 transcription factor, 188–190 Nth-like DNA glycosylase (NTHL1), 61 Nuclear export signal (NES), 326 Nuclear factor-E2-related factor (Nrf2), 339–342, 369, 370 Nuclear localization signal (NLS), 326 Nucleotide excision repair (NER), 61, 166, 422 O Opioid receptors cutaneous tissue wound healing and, 270 skin ageing and, 276 skin homeostasis and, 274 skin sensations and, 267 stress responses and, 265 Over the counter (OTC) formulations, 115 Oxidation of sebum lipids, 19 Oxidative environment, 29, 31 SQ as bio-marker of, 40 Oxidative skin microflora, 35 Oxidative stress, 57–59, 62, 67 Oxidized lipids, 15 Ozone, 338 P P38( protein kinase), 197, 200 P38 Signaling by UV Radiation, 199 in natural compounds Inhibiting, 204 in skin epithelium, 202 in solar UV radiation-induced inflammation, 197 loss of, effect on skin inflammation, 201 synthetic compounds inhibiting, 204 P53 protein, 177, 178, 179, 187, 188, 191 PAF acetylhydrolase, 11 PAF acetyltransferase, 11 PAF-like lipids, 15 Peptides, 116 Peroxinitrous acid, 12 Peroxiredoxins (PRDX1), 11 Peroxisome proliferator-activated receptors (PPARs), 307 Peroxynitrite, 12 Phenol compounds, 186 Phosphatidic acid (PA), Phosphatidylcholines, 14 Phosphatidylethanolamines, 14 Index Phosphatidylglycerol (PG), Phospholipase A2 (PLA2), Phospholipids (PL), 3, 6, 9, 10 Phosphorylated ceramides, Photoaging, 89 Photocarcinogenesis, 67, 340, 345, 347, 348 Photochemopreventative agents, 221 Photoimmunosuppression AhR in, 342 Photoisomerization into Dewar valence isomers, 55 Photoprotection, 66–68, 362 by nonsteroidal anti-inflammatory drugs, 363 by Retinoids, 363 systemic, 67 with natural compounds, 364 systemic versus topical application, 372 Photosensitized formation, 56 Picolinic acid, 330 Platelet activating factor (PAF), 219 Polluted aerial environment, 42 Polychlorinated biphenyls (PCBs), 346 Polychlorinated di-benzofurans (PCDFs), 346 Polychlorinated dibenzo-p-dioxin (PCDDs), 346 Polyinosinic, polycytidylic acid, 237 Polyketides, Polyphenols, 364, 365, 373 Polypodium Leucotomos Extract, 365 Polyunsaturated fatty acids (PUFA), 221 Porphyrins, 35, 36 Post-inflammatory hyperpigmentation (PIH), 186 Post-traumatic stress disorder (PTSD), 410 Proopiomelanocortin protein (POMC), 436 Prostaglandin, 13 Prostaglandin (PG)-E2, 219 Prostanoid lipid species, 13 Protein kinase A (PKA), 162, 164, 168, 177 Proteoglycans, 103 Psoriasis, 18, 316, 344, 393 Psychological methods to reduce dermatological diseases, 441 Psychological stress adaptive immune responses to, 438 human skin diseases linked to, 440 Impact on skin immune responses, 436 skin barrier function as determinant of, 433 types of, 434 Psychtropic medications cutaneous side effects to, 441 Pyrimidine (6-4) photoproducts, 54 Pyrimidine (6-4) pyrimidone photoproducts Index formation of, 54 Pyrimidine dimers, 51, 58, 60–63, 65–68 Q Quinolinic acid, 330 R Radiation therapy, 425 Reactive oxygen species (ROS), 9, 12, 282, 286, 287, 290, 291, 294 Receptor activator of NF-(B ligand (RANKL), 213 Redox state, Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES), 217, 239 Resolvins, Retinoids, 363 Rhodopsin, 408 Rosacea, 392 S Saccharolipids, Scleroderma, 345 Seborrheic dermatitis, 332, 333, 345 Secondary oxidative DNA damage, 57 Severe ocular complications (SOC), 244 Simulated sunlight (SSL), 59 Singlet oxygen, 12 SIRT1 See Sirtuins 1-7 SIRT2 See Sirtuins 1-7 SIRT3 See Sirtuins 1-7 SIRT6 See Sirtuins 1-7 Sirtuins (SIRT1-7) description, 251 in keratinocyte differentiation, 258 in skin cancer, 252 SIRT1 in skin cancer, 253 SIRT6 on skin, 255 skin aging and, 256 skin aging and, SIRT1 in, 256 skin aging and, SIRT6 in, 256 skin barrier function and, 258 skin barrier function and, SIRT1 in, 258 stress response and, 251, 258 Skin adaptive immunity, circadian rhythm in, 293 antioxidant mechanisms in, 290 circadian clock and, 285, 286 immunity, circadian regulation of, 292 innate immunity, circadian rhythm in, 292 neuroendocrine system and, 435 response to external stressors, 281 455 structure of, 283 Skin ageing, 197, 198, 265, 269, 270 opioid receptors and, 276 sirtuins in, 256 Skin barrier function endocannabinoids and, 301, 309 SIRT1 disrupting, 258 sirtuins in, 258 Skin barrier repair, 242 Skin biology, 301 Skin cancer, 49, 67, 68, 155, 156, 164, 197, 199 circadian clock and, 422 SIRT1 Role in, 253 Skin Complexion and, 160 UV radiation and, 157, 159, 161 Skin circadian clock, 420 Skin circadian control DNA damage repair and, 420 Skin diseases, 238 TLR3 and, 235 See also Toll-like receptors (TLRs) Skin habitat, 380 Skin homeostasis, 266, 267, 274 Skin immunity, 310 Skin Inflammation, 197, 199 P38 signaling loss effect in, 201 UVB-induced, 202, 204 UVR-induced, 198, 201, 205 Skin lipidome under environmental stress, bioactive prenol lipids, 16 bioactive sterol lipids, 16 biomarker discovery, 19 cosmetic applications, 18 cyclooxygenases, 10 drug development opportunities, 17 endocannabinoids, 14 extracellular stress, fatty acyls, fatty acyls derived bioactive lipids, 13 glycerolipids, 6, 14 glycerophospholipids, 6, 14 lipid classes, lipid imaging, lipid organization, lipoxygenases, 10 non-enzymatic pathways, 11 PAF Acetyltransferase and Hydrolase, 11 peroxiredoxins, 11 PLA2, prenol lipids, sphingolipid changes, 16 sphingolipids, sterol lipids, 456 Skin lipids, 44 Skin microbiome as a source of AhR agonists, 332 Skin microbiota, 384 See also Cutaneous microbiota Skin moisturization, 19 Skin sensations opioid receptors and, 267 Skin sensitization, 19 Skin, soriatic, 274 Skin stress response circadian clock and, 282 Skin stress response pathways environmental factors and, 102, 415 molecular opportunities and, 190 Skin ulcers, 19 Solar lentigo (SL), 186 Sphingomyelin (SM), Sphingosine phosphate (S1P), 219 Squalene (SQ), 7, 16, 29 as bio-marker of oxidative environment, 40 as oxygen forms acceptor, 35 biological consequences of, 44 biological human curiosity, 34 facing singlet oxygen released by porphyrins, 36 importance, 34 properties, 34 resident oxidative skin microflora and, 35 skin barrier function and, 29 SQOOH properties, 38 structure, 34 Stem Cell Factor (SCF), 217 Stem cells, 281, 283, 286, 291 Stevens-Johnson Syndrome (SJS), 244 Stratum Corneum (SC), 32, 82, 85–89, 91 specificities of, 31 Stress, 2, distribution, enzymatic pathways induced by, lipid metabolizing enzymes regulated by, 11 lipid modifications generated by, 13 lipitome and, Stress induced oxidative damage, 18 Stress response circadian clock regulating, 281 sirtuins in, 258 Stromal cell derived factor (SDF), 212 Stromal derived factor (SDF)-1a, 218 Sunscreens, 66, 67, 115 Superoxide anion, 11 Suprachiasmatic nuclei (SCN), 282, 416 Index Surfactant alkyl chain length, 19 Synergistic effects, 117 T Tetrahydrocannabinol (THC), 303 Thymic stromal lymphopoietin- (TSLP-), 311 Tissue-specific expression patterns of circadian genes, 418 TNF-related apoptosis-inducing ligand (TRAIL) expression, 370 Toll-like receptors (TLR3), 235 endogenous TLR3 ligands, 240 inflammatory skin diseases and, 235 Itching and, 242 skin barrier repair, 242 Stevens–Johnson syndrome (SJS), 244 toxic epidermal necrolysis (TEN), 244 Toxic Epidermal Necrolysis (TEN), 244 Trans Epidermal Water Loss (TEWL), 32 Transient Receptor Potential (TRP) Receptor Family, 404 Transient Receptor Potential Vanilloid Type-1 (TRPV1) Channel, 306 Translesion synthesis (TLS) polymerases, 64 Trier Social Stress Test (TSST), 440 Triplet-triplet energy transfer (TTET), 53 Tryptophan, 330, 333, 334, 345, 348 to FICZ, 332 Tryptophan 2,3-dioxygenase (TDO), 330, 347 Tumor suppressor in skin, SIRT2 as, 255 Tumour necrosis factor-((TNF), 213 U Ultra-performance liquid chromatography (UPLC), 35 Ultraviolet A radiation (UVA), 198 Ultraviolet B radiation (UVB), 198 Ultraviolet light, Ultraviolet (UV) radiation, 79, 82, 155, 161, 420, 422, 423 absorption by UCA, 81 as carcinogen, 161 by UCA, 87 cancer risk and, 160 cutaneous responses to, 163 in skin cancer, 253 melanoma and, 156 P38 signaling activation by, 199 photolesions, 163 skin cancer and, 157 skin interaction and, 131 tanning and, 164 UCA Absorption by, 87 Index Ultraweak photon emission (UPE), 370 Un-oxidized linoleic acids, 13 Un-oxidized palmitic acid, 13 Urocanic Acid (UCA) chemical properties of, 80 cis-UCA, 92 direct effects of, 90 effects on skin cells, 90 effects via receptors, 91 enzymatic formation of, 82 histidine as precursor of, 82 histidine to, 84 Indirect effects of, 90 in epidermis, formation, 82 physical properties of, 80 radicals interaction with, 89 removal of, 86 skin photodamage and, 79 use of, 93 UV absorption and, 81 UV radiation absorption by, 87 UVA-induced CPDs, 52 UVA-induced oxidative stress on DNA repair, 62 UVA-induced photolysis of nitrite in vivo, 141 UVA-irradiated melanocytes, 53 UVA penetration into human skin, 131 UVA-photolysis of nitrite in vitro, 140 UVA-photosensitizer, 334, 339, 340, 342, 346, 348, 349 UVB absorption, 51 UVB-induced DNA damage, 254, 255 UVB-induced p53-mediated apoptosis, 254 UV exposure, 287 UV-induced cytokines, 212 UV-induced photoproducts in cells and skin, 58 UV-Induced pigmentation, 182, 183, 188 as stress response, 177 melanogenesis and, 179 457 omnipresence of P53, 177 photodamage in keratonocytes, 177 UV irradiation physiological effects of, 132 UV radiation-induced inflammation, 205 chronicity of, 198 p38 signaling in, 197, 198 UVR-induced dermal remodelling, 110 V Viruses, 237 herpes virus infection, 238 human papilloma virus, 238 molluscum contagiosum virus, 238 Vitamin C, 366 Vitamin D, 223 Vitamin E, 366 Vitiligo AhR in, 346 Volatile organic compounds on lipid assembly, 19 W Whole-body health receptors role in, 403 Wound healing, 265, 269, 270, 273, 274, 276 opioid receptors and, 270 X Xeroderma pigmentosum Xeroderma pigmentosum Xeroderma pigmentosum Xeroderma pigmentosum 253 A (XPA), 18 A (XPA) gene, 422 C (XPC), 253 protein A (XPA), Z Zeta opioid receptor, 266, 270, 273, 274, 276 Zinc pyrithione (ZnPT), 185 .. .Skin Stress Response Pathways Georg T Wondrak Editor Skin Stress Response Pathways Environmental Factors and Molecular Opportunities... Katoh 12 Sirtuins and Stress Response in Skin Cancer, Aging, and Barrier Function 251 Yu-Ying He 13 Cutaneous Opioid Receptors and Stress Responses: Molecular Interactions... composition or structure (Fig 1.1) Fig 1.1 Lipids of the skin The Skin Lipidome Under Environmental Stress Environmental stressors affect lipids of the skin from its surface down to the dermis, which
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Xem thêm: Skin stress response pathways , Skin stress response pathways , 1 Introduction: The Human Skin, a Constantly Adaptive Organ, 3 Squalene (SQ), a Key Element, 5 Biological Consequences of Squalene (Per)oxides on the Skin, 2 The Extracellular Matrix: Composition and Architecture in Young, Healthy Skin, 13 Future Directions: The Melanocortin-MC1R Axis as an Exploitable Melanoma Prevention Strategy, 2 The Melanocyte and Sunlight: A Cooperative but High-Risk Relationship, 2 Cutaneous Cytokines/Chemokines Affected by UV Exposure, 7 Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), 4 Sirtuins in Keratinocyte Differentiation, Stress Response, and Skin Barrier Function, 4 Role of the Circadian Clock in the Skin’s Response to Endogenous and External Stressors, 1 The Aryl Hydrocarbon Receptor: An Environmental Stress Sensor in Skin, 6 AhR: Cutaneous Functions and Therapeutic Opportunities, 4 Photoprotection with Natural Compounds—Systemic Versus Topical Application

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