Principle investigators: Heike Kahlert and Michael Lalk
Co-supervisor: U. Lendeckel

Natural compounds (e.g. plant extracts) and synthetic drugs will be investigated with several methods to evaluate the radical scavenger activity of these materials. In vitro assays of radical scavengers are routinely performed with rather stable radicals [1,2]. Recently, a novel strategy has been developed to identify scavengers for the highly reactive and toxic hydroxyl radicals based on electrochemical measurements (destructive interactions of radicals with electrode surfaces) [3]. Differences in the results obtained with established methods and our novel electrochemical approach, and reasons for these differences will be investigated and clearly defined. The electrochemical assay has been further developed allowing direct measurements in cell cultures.
The investigation of the metabolic adaptation of organisms to the environment and their response to stress conditions is a challenging task. Only by a comprehensive characterization of the physiology of the cell in the environment and its metabolism a holistic overview of the processes involved in stress adaption is possible. The investigation of the metabolome is here of utmost importance. In this context, modern NMR spectroscopic methods, HPLC-MS methodology and selected GC-MS approaches will be used [4,5]. The metabolome data obtained in this project will help to obtain a comprehensive overview on the adaptation of the cell culture towards different stress factors (like reactive oxygen and nitrogen species; ROS and RNS) on a cellular level. We will investigate the exometabolome and the intracellular metabolome of cells and use these model cell lines in collaborative studies with respect to the impact of antioxidative compounds. The planned studies will reveal how radical scavengers can be assayed yielding biologically relevant results that will allow to understand, how radical scavengers act in living cells (with respect to chemical target molecules and subcellular organelles). For membrane protection it is important to know, which components of plant extracts contain maximal radical scavenging activity, and under which conditions (pH, temperature, location, etc.) they act as radical scavengers. Both approaches will provide a complete picture of the influence of radical scavengers on living cells. Intensive cooperations are envisaged with A2 (Bornscheuer), A3 (Mayerle), A4 (Lenzen/Elsner), C1 (Antelmann) and C3 (Stöhr).

Literature

1 Lopez Alarcon, C., Lissi, E.: Free Radical Res. (2006) 40, 979.

2 Alarcon, E., Campos, A.M., Edwards, A M., Lissi, E., Lopez Alarcon, C.: Food Chem. (2008) 107, 1114.

3 Hilgemann, M., Scholz, F., Kahlert, H., Machado de Carvalho, L., Barcellos da Rosa, M., Lindequist, U., Wurster, M., do Nascimento, P.C., Bohrer, D.: Electroanalysis (2010) 22, 406.

4 Liebeke, M., Dörries, K., Zühlke, D., Bernhardt, J., Fuchs, S., Pane-Farre, J., Engelmann, S., Völker, U., Bode, R., Dandekar, T., Lindequist, U., Hecker, M., Lalk, M.: Mol. BioSyst. (2011) 7, 1241.

5 Liebeke, M., Meyer, H., Donat, S., Ohlsen, K., Lalk, M.: Chem. Biol. (2010) 17, 820.