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Prof. Dr. Regina Brigelius-Flohé

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Printversion of: http://www.www.dife.de/forschung/abteilungen/kurzprofil.php?abt=BIM
Status: 13.11.2019 21:32:39

Image Biochemistry of Micronutrients

Department of Biochemistry of Micronutrients (BIM)

Due to the retirement of Prof. Dr. Regina Brigelius-Flohé the department has been closed on 30 September 2013.

The department focused on:

Profile

Field of research

The department ‘Biochemistry of Micronutrients’ investigates the biochemical and molecular mechanisms underlying the function of micronutrients in physiological and pathophysiological processes. The essential trace element selenium, vitamin E and other redox active dietary compounds are in the focus of respective research.

Background

Anti-carcinogenic effects of selenium have been demonstrated in large clinical trials. It is, however, not clear whether these properties are exerted by the different forms of selenium used for application themselves or by selenium as integral part of selenoproteins. Functions of many selenoproteins were not known for long time and are going to be understood in very recent years.
In contrast to selenium, large clinical trials did not reveal a preventive function against the development of cancer, cardiovascular or neurodegenerative diseases for vitamin E. Such a function has been expected since the diseases have been associated with oxidative stress. Certainly, the physiological functions of vitamin E are not solely based on its antioxidant properties.
In recent years certain vegetables containing glucosinolates were shown to have anticarcinogenic effects, too. The individual compounds and the impact of the pattern of dietary glucosinolates, however, remain to be characterized.

Objective

Glutathione peroxidase-2 (GPx2) which is preferentially expressed in the gastrointestinal system is the major target of the investigation of the role of selenoproteins in carcinogenesis. GPx2 is upregulated in cancer cells of epithelial origin. It is induced by Nrf2 activators such as sulforaphane, pointing to a protective role. On the other hand, it is also regulated via the Wnt pathway. This pathway is activated during carcinogenesis and supports cancer cell growth. The aim is to find out whether the upregulation of GPx2 is beneficial and, if so, how it can be achieved by selenium compounds from the diet or other dietary factors, e.g., glucosinolates able to induce GPx2 via Nrf2. At time this is studied in the mouse model of inflammation-associated colon carcinogenesis in which cancer is triggered by the combined treatment with azoxymethane (AOM) and dextran sodium sulfate (DSS).

After our seminal work on the metabolism of vitamin E, during which the degradation of vitamin E via a pathway also used for the elimination of xenobiotics was detected, the focus now is to find out what makes vitamin E essential. As lipid soluble vitamin, vitamin E is mainly found in membranes. Therefore, the investigation of membrane processes such as transport and recruitment of proteins to signal complexes in membranes appears logical.

Glucosinolates and hydrolysis products derived there from induce phase I and phase II enzymes, which are responsible for the elimination of xenobiotics. Phase I enzymes are able to convert pro-carcinogens into carcinogens, whereas phase II enzymes are involved in their excretion. Effects of the feeding of glucosinolates on the expression of GPx2, inflammation and tumor development are, therefore, investigated in the AOM/DSS cancer model also used in the selenium project.

The role of glutathione peroxidases in inflammatory processes is investigated in the model of interleukin-1 signaling to find out whether the modulation of their activity and/or expression by selenium compounds or other micronutrients can influence inflammation and finally cancer.

Investigation of novel functions of vitamin E to find out what makes vitamin E essential, how it can exert anticancerogenic effects and to understand the function of the metabolism of vitamin E.

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