UV radiation of the skin

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UV radiation of the skin

UV radiation causes encompassing effects in the skin on processes like tanning, modulation of the immune system and the synthesis of active vitamin D (Cholecalciferol).
UV radiation can lead to carcinogenesis. This is mediated by the incorporation of DNA damages and activation of inflammatory and immunosuppressive metabolic pathways. Corresponding to its wavelength, UV radiation is divided into three regions: UVA (400–320 nm), UVB (320–290 nm) and UVC (290–200 nm). 95 % of UVA from the sunlight are reaching the earth and only 1 –  19 % of the UVB radiation. The remaining radiation and the complete UVC radiation are  absorbed by the ozone layer of the atmosphere. UV radiation directly targets macromolecules in the skin like proteins, lipids and nucleic acids. If nucleic acids from genes acting in processes like apoptosis, cell cycle or DNA repair mechanisms are affected, cellular transformation followed by tumor genesis might be the consequence [1].
Mutations also can be provoked by reactive oxygen species (ROS). Singlet oxygen can be generated in a type 1 photo sensitization reaction, triggering the oxidative damage in nucleic acids. The main target of these oxidative reactions are guanine bases leading to the generation of 8-Hydroxyguanin. which disables the homologous paring with adenosine. As a consequence a G>C substitution, followed in later stages of DNA synthesis by a transition [1]. In figure 1 resulting base pairings are shown.

oxoGuaninenglFigure 1: The generation of oxoguanine by reaction of guanine with singlet oxygen leads to a G-T transversion and in consequence a substitution of guanine by cytosine (graphic source Source: WIKIPEDIA( 2014).

The introduction of 7,8-dihydro-8-oxoguanine in the DNA sequence is causing specific mutations, if the transversion is not repaired. UVA radiation is mainly causing G-T transversions and G-A- transitions. UVA can cause  cyclobutane-pyrimidine-dimers (CPDs by similar mechanisms as UVB,).UVB causes photochemical reactions between neighbored pyrimidine nucleotides, leading to photoproducts like CPDs and pyrimidine dimers [1].

 

UV-signalling in skin pigmentation   

UV radiation caused DNA damages activate the p53 tumor suppressor gen. P53 drives the transcriptional activation of proopiomelanocortin. This is cleaved to produce α-melanocyte stimulating hormone (α-MSH). α-MSH is released by keratinocytes. Binding to the melatonin 1 receptor (MC1R) on melanocytes a cascade of reactions is started in the melanocytes. The activation of melanocytes leads to an increase of cAMP, which in turn leads to the induction of the microphtalmia associated factor (MITF) [2-5]. As a consequence, the synthesis of melanin is induced. The melanin is packaged concentrated in melanosomes and transported to keratinocytes. The melanosomes are deposited around the nuclei as a protection for the DNA [1].

Literature
1.    Chen, H., Q.Y. Weng, and D.E. Fisher, UV Signaling Pathways within the Skin. J Invest Dermatol, 2014. 134(8): p. 2080-5.
2.    Hearing, V.J., Determination of melanin synthetic pathways. J Invest Dermatol, 2011. 131(E1): p. E8-E11.
3.    Hearing, V.J., Milestones in melanocytes/melanogenesis. J Invest Dermatol, 2011. 131(E1): p. E1.
4.    Khaled, M., C. Levy, and D.E. Fisher, Control of melanocyte differentiation by a MITF-PDE4D3 homeostatic circuit. Genes Dev, 2010. 24(20): p. 2276-81.
5.    Tran, T.T., J. Schulman, and D.E. Fisher, UV and pigmentation: molecular mechanisms and social controversies. Pigment Cell Melanoma Res, 2008. 21(5): p. 509-16.