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Wirkmechanismen der Resveratrol-Behandlung in Fibroblasten

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Wowro,  Sylvia
Nutrigenomics and Gene Regulation (Sascha Sauer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Masterarbeit_Sylvia Wowro.pdf
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Citation

Wowro, S. (submitted). Wirkmechanismen der Resveratrol-Behandlung in Fibroblasten.


Cite as: https://hdl.handle.net/11858/00-001M-0000-000E-F85E-0
Abstract
Resveratrol, a well-known phytoalxin, is present in numerous plants, and produced as protection against environmental risks. In mammals Resveratrol exhibits diverse effects, including anti-inflammatory and anti-oxidative properties as well as a broad range of health benefits by activating mitochondrial biogenesis. Most studies have shown the impact in cardiovascular diseases, cancer and metabolic dysfunctions, but little is known about the influence on the skin. Many skin diseases are associated with oxidative stress and inflammation. Daily, human skin is exposed to environmental oxidants including UV radiation, which leads to formation of reactive oxygen species (ROS) and thereby causing inflammation. An accumulation of oxidative damage and decrease of mitochondrial function are resulting in enhanced skin aging processes. This study shows the anti-inflammatory and anti-oxidative effects of resveratrol in human dermal fibroblasts, accompanied by the induction of mitochondrial biogenesis. Cells were treated for 16 hours with 100 μM resveratrol. This results in activation of metabolic sensors such as AMPK and Sirt1, while NAD+/NAD ratio is increased and ATP/ATP remained unchanged. Moreover, activity of PGC1α, CREB and transcription factor FOXO3, PPARα, and PPARγ was increased. As a result, significant increase in SOD2, CAT, GSR, PTGS2, UCP and PDK4 gene expression was detected, whereas MMP3 was significantly down regulated. Taken together, these results confirm known mechanisms observed in several cell models. Additionally, there was no evidence of resveratrol causing generation of hydrogen peroxide only. Formation of several ROS and thereby inducing oxidative stress seems more likely. In summary: resveratrol was shown to exhibit cellular stress and thereby activating anti-oxidative and anti-inflammatory mechanisms in human dermal fibroblast. This hormesis effect of resveratrol might protect cells against accumulation of oxidative damage and support cell survival. Furthermore, skin aging might be postponed by reduction of oxidative stress and thus reduced ROS formation. In addition reduction of proteases helps to maintain skin's connective tissue and might delay skin photoaging.