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Graz University of Technology Austria Institute of Biochemistry ...

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Biophysical chemistry group<br />

Group leader: Albin Hermetter<br />

Postdoctoral Fellow: Heidemarie Ehammer<br />

PhD students: Ute Stemmer, Daniel Koller, Claudia Ramprecht, Lingaraju Marlingapla<br />

Halasiddappa, Bojana Stojcic<br />

Master students: Andreas Gasser, Gabriel Pürstinger, Hannah Jaritz<br />

Technicians: Elfriede Zenzmaier<br />

General description<br />

Our research deals with the role <strong>of</strong> glycero(phospho)lipids and lipid modifying enzymes as<br />

components <strong>of</strong> membranes and lipoproteins, their function as mediators in cellular<br />

(patho)biochemistry, and their application as analytical tools in enzyme technology.<br />

Fluorescence spectroscopy is used as a main technique to investigate the behaviour <strong>of</strong> these<br />

biomolecules in the respective supramolecular systems.<br />

Section 1 <strong>of</strong> the following report summarizes our studies on lipid oxidation, the effects <strong>of</strong><br />

oxidized lipids on intracellular signalling, and the inhibition <strong>of</strong> these processes by synthetic<br />

and natural antioxidants.<br />

Section 2 describes the development <strong>of</strong> fluorescence for functional proteomic analysis <strong>of</strong><br />

lipolytic enzymes in microbial, animal and human cells.<br />

1. Lipid oxidation and atherosclerosis – Lipotoxicity<br />

1.1. Interaction <strong>of</strong> oxidized phospholipids with vascular cells<br />

Sphingomyelin<br />

acid<br />

Sphingomyelinase<br />

Oxidized -<br />

Phospholipids<br />

O<br />

H<br />

O<br />

O<br />

O<br />

O<br />

O<br />

O<br />

O<br />

O<br />

O<br />

O P O<br />

OH<br />

O<br />

O<br />

O<br />

O P O<br />

OH<br />

+<br />

N<br />

N +<br />

Ceramide<br />

OXPHOS-EuroMEMBRANE<br />

JNK<br />

p38 MAPK<br />

Caspase 3<br />

ERK<br />

AKT/PKB<br />

NFkB<br />

PROLIFERATION<br />

SURVIVAL<br />

Interactions <strong>of</strong> oxidized lipoproteins with<br />

the cells <strong>of</strong> the arterial wall induce and<br />

influence the progress <strong>of</strong> atherosclerosis.<br />

Accumulation <strong>of</strong> foam cells originating<br />

from macrophages and excessive intimal<br />

growth <strong>of</strong> vascular smooth muscle cells<br />

(SMC) alternating with focal massive cell<br />

death are characteristics typical <strong>of</strong> the atherosclerotic lesion. These phenomena are largely<br />

mediated by the oxidized phospholipid components <strong>of</strong> the modified particles that are<br />

generated under the conditions <strong>of</strong> oxidative stress. In the framework <strong>of</strong> the research consortia<br />

LIPOTOX (SFB) and OXPHOS (EuroMEMBRANE), we investigate the “Toxicity <strong>of</strong><br />

oxidized phospholipids in macrophages” and “The protein targets and apoptotic signaling <strong>of</strong><br />

oxidized phospholipids”. These studies aim at identifying the molecular and cellular effects <strong>of</strong><br />

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

27

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