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ANTI-POLLUTION 15


Preventing epigenetic changes fights urban pollution


n Daniel Schmid, Franziska Wandrey, Esther Belser, Fred Zülli - Mibelle Biochemistry, Switzerland


Environmental pollution is one of the major areas of concern when it comes to skin ageing. In particular, air pollution is directly in contact with our skin and it contributes to skin ageing on a daily basis. The main sources of air pollution are industrial combustion (diesel exhaust fumes and coal), traffic and construction works. Air pollution consists of gases such as ozone and very fine particles that are known as particulate matter (PM). These particles, which are between 0.1 μm – 10 μm in size, can remain in the atmosphere for weeks and contain toxic compounds such as heavy metals and allergens. Particulate matter is especially dangerous for the skin as it not only sits on the surface but can also penetrate into pores and therefore transport toxic substances into deeper skin layers. In combination with exposure to UV light, these particles cause oxidisation reactions within the skin, which lead to the formation of reactive oxygen species (ROS), inflammation and the loss of collagen. ROS can cause protein carbonylation, and these damaged proteins contribute to skin ageing. Furthermore, lipid peroxidation caused by ROS leads to skin barrier dysfunction, which creates a vicious cycle as more PM can enter the skin. The result is irritated, uneven skin that will age more rapidly.


Expression of detox and antioxidant enzymes in the skin It is obvious that our cells are in constant danger by toxic influences from the environment and thus need an efficient defence or detoxification system. Fortunately, our cells are able to produce enzymes that assist in the detoxification and removal of toxic substances. The genes encoding for detoxification and antioxidant enzymes, which are also called phase II enzymes, are activated by a specific mechanism. The transcription of these genes is regulated by a special control sequence in the promoter region of the gene. To start the expression of detoxification and antioxidant enzymes, a specific protein interacts with this control sequence. This “switch-on-protein”, which


November 2018 Abstract


Environmental pollution is one of the main contributing factors towards skin ageing and a dull complexion. For full protection, only a multi-level approach will succeed. Here an approach is described where a first line of defence is built up by a film-forming polysaccharide complex which physically prevents binding of pollutants. Activation of the cell’s own detoxification system is used as the second line of defence. And because pollution also induces epigenetic changes with long-term effects, a third line of defence was established where these epigenetic changes are prevented or reversed.


Chromosome


Histone tail with chemical tags


Histone


DNA strand


Methylation Phosphorylation Acetylation


Figure 1: Epigenetic changes on histone proteins which are responsible for the packaging and organisation of the DNA strand.


is called transcription factor Nrf2, is normally blocked by the repressor Keap1. A stimulus such as oxidative stress can disrupt the Nrf2-Keap1 complex. The released Nrf2 then binds to the control sequence and cells start to produce detoxification and antioxidant enzymes. In this way, cells can react to their environment by producing the correct response enzymes. Interestingly, a molecule found in plants of the Brassicaceae family, sulforaphane, has also been shown to disrupt the Nrf2-Keap1 complex and therefore activate the cellular detoxification system.


In this work, an extract of garden cress


sprouts (Lepidium sativum, belonging to the Brassicaceae family) was used as activator of the detoxification system in the skin. Cress sprouts have the highest concentration of sulforaphane.


Air pollution induces epigenetic changes in the skin


Epigenetics, which studies modulation of gene expression caused by mechanisms other than changes in the DNA sequence, can explain how environmental factors influence our body. Whereas oxidative stress acts at the moment, epigenetic modifications may lead to a long-term effect, even when the environmental stress is not present anymore. This is the reason why air pollution should be analysed for epigenetic effects. Epigenetics is based on chemical modification, mainly methylation or acetylation, of the nucleosome which comprises the DNA and histone proteins. The histone proteins are responsible for the packaging and organisation of the DNA (Fig 1). Modifications of histone proteins define the access of transcription factors to


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