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Graz University of Technology Austria Institute of Biochemistry ...

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

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

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

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

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

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

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

membrane and eventually spread throughout the cells. Under these circumstances, the biologically<br />

active compounds are very likely to interfere<br />

directly with various signaling components inside<br />

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

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

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

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

the primary molecular targets and their downstream<br />

elements that are the 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 synthetic antioxidants.<br />

These methods can also be used for the<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 other 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 the subject <strong>of</strong> our studies in the<br />

framework <strong>of</strong> the joint research program GOLD-Genomics <strong>of</strong> Lipid-associated Disorders at<br />

KFU <strong>Graz</strong>. Lipolytic enzymes catalyze intra- and extracellular lipid degradation.<br />

Dysfunctions in lipid metabolism may lead to various diseases including obesity, diabetes or<br />

atherosclerosis. In chemistry, lipases and esterases are important biocatalysts for<br />

(stereo)selective reactions on synthetic and natural substrates leading to defined products for<br />

pharmaceutical or agrochemical use.<br />

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