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The influence of light on the skin barrier
Department of Dermatology, Medical University of Warsaw, Warszawa, Poland
The outermost layer of the skin, the stratum corneum, primarily mediates permeability barrier function. The formation of corneocytes is considered to be result of finely regulated differentiation process. During terminal differentiation process structural change of the keratinocyte is associated with the sequential formation of differentiation marker protein: keratin 5 and 14 present in stratum basale, keratin 1 and 10 in the stratum spinosum and late differentiation marker proteins: filaggrin, loricrin and involucrin in the granular layer. Granular layer is composed of secretory cells producing polar lipids and lipid converting enzymes. Polar lipids are packed into lamellar bodies and secreted into the intercellular space to be converted by enzymes to form non polar lipid structures. The stratum corneum lipid matrix constitutes of ceramides, fatty acids and cholesterol. Small amount of cholesterol esters and cholesterol sulfates are also present in the stratum corneum and both play a critical role in proper structural organization of the lipids, low pH, lipids crystallization, desquamation process and therefore, in normal barrier function .
Solar ultraviolet radiation (UV) is a major environmental factor that dramatically alters the homeostasis of the skin by affecting the survival, proliferation and differentiation of various cutaneous cell types. The horny layer of the epidermis reflecting and/or absorbing about 90% of UVB and 50% of UVA radiation. However, the rest of UV radiation can penetrate into the deeper layers of the epidermis induces DNA damage and apoptosis in epidermal cells, including those in the germinative basal layer. The epidermis contains several major solar UV radiation absorbing endogenous chromophores including DNA, urocanic acid, lipids, melanins and their precursors and metabolites. Melanin plays an important role in protecting the skin against UV radiation and levels of melanin correlate inversely with amounts of DNA damage induced by UV radiation. Epidermal melanocytes synthesize two main types of melanin: eumelanin and pheomelanin. Melanin, particularly eumelanin, represents the major photoprotective mechanism in the skin. Melanin limits the extent of UV penetration through the epidermal layers, and scavenges reactive oxygen radicals that may lead to oxidative DNA damage . Skin pigmentation is accomplished by production of melanin in specialized membrane-bound organelles termed melanosomes and by transfer of these organelles from melanocytes to surrounding keratinocytes.
Urocanic acid (UCA), present in the upper layer of epidermis, is a metabolite of filaggrin. UCA is a major UV-absorbing chromophore in the upper epidermis and has been suggested to act as one of the initiators of UV-induced immunosuppression. Especially, cis-UCA, the isomer from UCA that is formed upon UV exposure, has been shown to impair some cellular immune responses . UV radiation induces pyrimidine dimers in DNA, which are recognized and repaired by a number of unique cellular surveillance systems. The most direct biochemical mechanism responding to this kind of genotoxicity involves direct photoreversal by the enzyme endonuclease. UV-light induces DNA damage in human epidermal keratinocyte triggering p53 activation, and subsequent apoptosis involving distinct cell layers which reduced the carcinogenic effects of sunlight .
© Cezary Kowalewski (text) and Radoslaw Spiewak (source code).
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Document created: 31 August 2009, last updated: 8 September 2009.