American Society for Photobiology

ASP Conference 2016: 21-26 May 2016
Tampa Marriott Waterside Hotel & Marina

Single Session

[Schedule Grid]

13 - Frontiers in Skin Photodamage and Sun Protection

Florida 2   14:00 - 17:00

Chair(s): Georg Wondrak, Ludger Kolbe
13-1   14:00  UVA and oxidative stress: Will antioxidants enhance endogenous protection? RM Tyrrell*, University of Bath

Abstract: UVA radiation leads to a sustained and diffusible oxidative stress in skin .This has led to a belief that the damage caused may be prevented by exogenous antioxidants. Among the reactive oxygen species generated by UVA radiation are singlet oxygen and hydrogen peroxide and various radical species including superoxide which probably results from tissue specific UVA activation of NADPH oxidases,including 1 and 4.UVA radiation also directly leads to a rapid increase in the labile iron pool as a result of ferritin degradation and cyclooxygenase-dependent release of free heme and activation of quite distinct and cell-type dependent stress pathways including heme oxygenase 1 and metalloproteinases. UVA-mediated oxidative stress and disruption of heme and iron homeostasis is modulated by the activities of constitutive endogenous antioxidants, as well as constitutive and inducible antioxidant enzymes. These factors contribute to the restoration of cellular homeostasis following an oxidant stress and must be understood when considering the potential of supplemented topical and systemic antioxidants to enhance protection.

13-2   14:30  Phospholipid oxidation in UV stress and cellular senescence in the skin. MS Narzt, Medical University of Vienna, CDL Skin AUT ; IM Nagelreiter, Medical University of Vienna, AUT; VN Bochkov, University of Graz, AUT; J Latreille, Chanel PB, Pantin, FRA; J Grillari, VBIT-BOKU, CDL Skin, Vienna, AUT; E Tschachler, Medical University of Vienna, AUT; F Gruber*, Medical University of Vienna, CDL Skin, Vienna, AUT

Abstract: Oxidation of lipids and proteins is a hallmark of photodamagend and aged skin, and also potentially causative for age-related aesthetic decline and pathologic damage. To study which oxidation products are generated by long wavelength UV light, by age promoting stressors and in cellular senescence of various skin cell types, we developed and applied lipidomic analysis of oxidized and non-oxidized phospholipids (PL) using a HPLC-MS/MS method. With that approach we could quantify >400 oxidized lipid species in keratinocytes and fibroblasts and could determine UV fluence dependent changes. In parallel, we also performed analysis of global mRNA expression and of selected cyto/chemokines and stress response enzymes on protein level. We will present an overview of lipid species regulation patterns in UV stress and in recovery in kerationcytes and fibroblasts, and how UV-generated oxidized lipids can act as bioactive mediators in cellular stress and senescence.

13-3   15:00  Deleterious synergy between pollution and sunlight: pollutants from particulate matter aggravate oxidative impact of UVA1 in skin models. L MARROT*

Abstract: Atmospheric pollution is becoming a serious health concern in industrial countries and particulate matter (PM) from combustion is considered as particularly deleterious. In fact, ultrafine particles carry toxic compounds such as poly aromatic hydrocarbons (PAH). Moreover, they can translocate from lung capillaries to blood circulation and be distributed in the whole body. Up to now, no precise estimation of pollutants concentration in living skin is available. However, pollutants might reach dermis and epidermis either by penetration from skin surface or by systemic exposure. Some PAH are photo-reactive and phototoxic: sunlight and pollution might thus synergistically compromise skin health. After summing up current knowledge about dermatological damage induced by pollution, experimental data obtained in vitro using normal human keratinocytes or reconstructed epidermis will be presented. At very low concentrations (in the nanomolar range), some PAH such as benzopyrene or indenopyrene displayed a strong phototoxicity under UVA1 irradiation (340-400 nm). Even when cytotoxicity was low, PAH-induced photo-oxidative stress could impair mitochondrial function (membrane polarization and ATP production) and impact endogenous glutathione (GSH) homeostasis. Interestingly, among genes controlling GSH metabolism, SLC7A11 was particularly overexpressed (at gene and protein levels). This protein is an antiporter in charge of cystine supply. SLC7A11 upregulation suggests that regeneration of GSH might be of huge importance to ensure protection against "photo-pollution" stress. As proof, pretreatment of cells by buthionine sulfoximine BSO, an inhibitor of GSH biosynthesis, significantly increased PAH-induced phototoxicity. Our results highlight that pollutants could aggravate skin photodamage: specific photoprotection strategies for skin care in polluted area will be discussed.

13-4   15:30  Hormonal regulation of the repair of UV photodamage in melanocytes by the MSH-MC1R signaling axis SG Jarrett, Univ. KY ; EM Wolf Horrell, Univ. KY; JA D'Orazio*, Univ. KY

Abstract: UV radiation represents a major causative risk factor for melanoma by promoting the formation of UV signature mutations. Nucleotide excision repair (NER), the genomic maintenance pathway responsible for clearing UV photodamage to prevent mutagenesis and malignant degeneration, is regulated hormonally by melanocyte stimulating hormone (MSH) and the melanocortin 1 receptor (MC1R). Loss-of-signaling MC1R polymorphisms that lead to defective cAMP second messenger generation are major inherited risk factors for melanoma development in part because of suboptimal NER and higher rates of UV mutagenesis. We have determined that the MC1R-cAMP signaling axis enhances NER through activation of cAMP-dependent protein kinase (PKA) and phosphorylation of ataxia telangiectasia and Rad3-related protein (ATR) on the S435 residue. This post-translational event recruits the key NER factor XPA to ATR and together, XPA and p-S435 ATR efficiently localize to sites of UV photodamage in chromatin to facilitate NER. The MC1R agonists melanocyte stimulating hormone (MSH) or adrenocorticotropic hormone (ACTH) efficiently promote generation of p-S435 ATR, accelerate repair of UV photoproducts and reduce UV mutagenesis. In contrast, MC1R antagonists agouti signaling protein (ASIP) or beta-defensin 3 (BD3) inhibit PKA-mediated ATR phosphorylation, impair NER and increase UV mutagenesis. Our data suggest that melanocytic NER is directly influenced by MC1R signaling ability znc and the presence of MC1R agonists and antagonists in the melanocytic milieu.

13-6   16:00  Redox-directed Interventions Targeting Skin Photodamage: An 'Inside-Out' Approach Harnessing NRF2 GT Wondrak*, UA Cancer Center and College of Pharmacy, University of Arizona

Abstract: Exposure to solar ultraviolet (UV) radiation is a causative factor in skin photodamage and carcinogenesis. Recent studies suggest that pharmacological modulation of cellular stress response pathways may protect skin against environmental insult. The protective role of cutaneous gene expression orchestrated by the transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) in solar photoprotection, wound healing, and antioxidant defense against environmental carcinogenic insult has now been substantiated. We have explored the molecular mechanism underlying skin photoprotection by natural product-based NRF2-inducers (including tanshinone I and dihydrotanshinone) that protect human skin cells and reconstructed skin against solar UV. In addition, in an attempt to test feasibility of NRF2-dependent systemic photoprotection by dietary constituents, we focused our photoprotection studies on the apocarotenoid bixin, an FDA-approved food colorant from the seeds of the achiote tree (Bixa orellana) native to tropical America. Consumed by humans since pre-Columbian times, this apocarotenoid is now used worldwide as a dietary additive and cosmetic ingredient (referred to as 'annato'; E160b) with established safety record and systemic bioavailability/pharmacokinetic profile upon oral administration. Our research indicates that bixin activates NRF2 through the critical Cys-151 sensor residue in KEAP1, orchestrating a broad cytoprotective response in cultured human keratinocytes as revealed by antioxidant gene expression array analysis (AKR1C2, GCLC, NQO1, SLC7A11, FTH1, TXNRD1, NCF2, SRXN). Systemic administration of bixin suppressed acute skin photodamage, attenuating epidermal oxidative DNA damage and inflammatory responses in Nrf2+/+ (but not in Nrf2-/-) SKH-1 mice, confirming the NRF2-dependence of bixin-based systemic photoprotection. Taken together, these data demonstrate feasibility of achieving NRF2-dependent 'Inside-Out' skin photoprotection by systemic administration of a natural food additive consumed worldwide.

13-5   16:30  Photoprotective Properties Of Licochalcone A From Glycyrrhiza Inflata On Human Skin In Vitro And In Vivo L Kolbe*, Beiersdorf AG

Abstract: Licorice extract is frequently used in the western world as for candies and as a sweetener in the food and tobacco industry. In the Far East, however, licorice is well known as a basic compound for several traditional medicines for a broad range of diseases. Pharmacological activities have been attributed to several phenolic ingredients and terpene saponins found in different Glycyrrhiza species. Licochalcone A from Glycyrrhiza inflata has previously been shown to possess anti-bacterial and anti-parasitic anti-inflammatory activity. We focused on the anti-oxidative and anti-inflammatory properties of licochalcone A. The production of reactive oxygen species (ROS), induced by UV irradiation and environmental stress leads to oxidative tissue damage and is one of the major causes of premature skin aging. We examined the in vitro inhibitory effects of licochalcone A on various pro-oxidative/ pro-inflammatory reaction cascades including: fMLP and zymosan induced oxidative burst of neutrophils, UV-induced lipid peroxidation and interference with signal transduction cascade in fibroblasts and keratinocytes. Licochalcone A inhibits the activation of NFB after UV-irradiation and activates protective Nrf2 pathways. In vivo, licochalcone A reduces skin redness after irradiation of human skin with solar simulated radiation. A study with a licochalcone-containing formulation confirmed the anti-oxidative efficacy on UVA-induced ultra weak photon emission. Taken together these data demonstrate the potent inhibitory capability of topically applied licochalcone A against oxidative skin damage caused by ROS. The anti-oxidative activity of Licochalcone A at submicromolar concentrations and the broad action profile makes it a promising candidate for dermatological and cosmetic topical products in photoprotection.

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