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Staff Members of the Institute of Biochemistry, TU - Institut für ...

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an important subfamily <strong>of</strong> <strong>the</strong> oxidized phospholipids containing long hydrocarbon chains in<br />

position sn-1 and short polar acyl residues in position sn-2 <strong>of</strong> <strong>the</strong> glycerol backbone. The<br />

respective compounds trigger an intracellular signaling network including sphingomyelinases,<br />

(MAP) kinases and transcription factors <strong>the</strong>reby inducing proliferation or apoptosis <strong>of</strong><br />

vascular cells. Both phenomena largely depend on <strong>the</strong> specific action <strong>of</strong> sphingolipid<br />

mediators that are acutely formed upon cell stimulation by <strong>the</strong> oxidized lipids. Fluorescence<br />

microscopic studies on labeled lipid analogs revealed that <strong>the</strong> short-chain<br />

phosphatidylcholines are easily transferred from <strong>the</strong> aqueous phase into <strong>the</strong> cell plasma<br />

membrane and eventually spread throughout <strong>the</strong> cells. Under <strong>the</strong>se circumstances, <strong>the</strong> biologi-<br />

cally active compounds are very likely to interfere<br />

directly with various signaling components inside<br />

<strong>the</strong> cells, which finally decide about cell growth or<br />

death. Investigations are being performed on <strong>the</strong><br />

levels <strong>of</strong> <strong>the</strong> lipidome, <strong>the</strong> apparent enzyme<br />

activities, <strong>the</strong> proteome an <strong>the</strong> transcriptome to find<br />

<strong>the</strong> primary molecular targets and <strong>the</strong>ir downstream<br />

elements that are <strong>the</strong> key compnents <strong>of</strong> lipid-induced<br />

cell death.<br />

1.2. Oxidative stress and antioxidants<br />

Antioxidants protect biomolecules against<br />

oxidative stress and thus, may prevent its<br />

pathological consequences. Specific fluorescent<br />

markers have been established for high-throughput<br />

screening <strong>of</strong> lipid and protein oxidation and its<br />

inhibition by natural and syn<strong>the</strong>tic antioxidants.<br />

These methods can also be used for <strong>the</strong><br />

determination <strong>of</strong> antioxidant capacities <strong>of</strong><br />

biological fluids (e.g. serum) and edible oils. A<br />

prominent example is pumpkin seed oil which<br />

contains a variety <strong>of</strong> antioxidants (e.g. tocopherols<br />

and phenolic substances) and o<strong>the</strong>r secondary plant<br />

components that possess useful biological<br />

properties.<br />

2. Functional proteomic analysis <strong>of</strong> lipolytic enzymes<br />

The functional properties <strong>of</strong> lipases and phospholipases are <strong>the</strong> subject <strong>of</strong> our studies in <strong>the</strong><br />

framework <strong>of</strong> two joint research programs (GOLD-Genomics <strong>of</strong> Lipid-associated Disorders at<br />

KFU Graz and <strong>the</strong> Research center Applied Biocatalysis at <strong>TU</strong> Graz). Lipolytic enzymes<br />

catalyze intra- and extracellular lipid degradation. Dysfunctions in lipid metabolism may lead<br />

to various diseases including obesity, diabetes or a<strong>the</strong>rosclerosis. In chemistry, lipases and<br />

28

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