Staff Members of the Institute of Biochemistry, TU Graz http://www ...

Biophysical chemistry group
Group leader: Albin Hermetter
Post-docs: Heidrun Susani-Etzerodt, Jo-Anne Rasmussen
Graduate students: Maria Morak, Jessica Schatte, Maximilian Schicher, Ute Stemmer
Undergraduate students: Peter Krempl, Andreas Gasser, Martina Geier
Technicians: Elfriede Zenzmaier
General description
Our research deals with the role of glycero(phospho)lipids and lipid modifying enzymes
as components of membranes and lipoproteins, as mediators in cellular
(patho)biochemistry, and their application as analytical tools in enzyme technology.
Fluorescence spectroscopy is used as a main technique to investigate the behaviour of
these biomolecules in the respective supramolecular systems.
Section 1 of the following report summarizes our studies on lipid oxidation, the effects
of oxidized lipids on intracellular signalling, and the inhibition of these processes by
synthetic and natural antioxidants.
Section 2 describes the development of fluorescence and chip technology for functional
proteomic analysis of lipolytic enzymes in microbial, animal and human cells.
1. Lipid oxidation and atherosclerosis – Lipotoxicity
1.1. Interaction of oxidized phospholipids with vascular cells
Sphingomyelin
acid
Sphingomyelinase
Oxidized -
Phospholipids
O
H
O
O
O
O
O
O
O
O
O
O P O
OH
O
O
O
O P O
OH
+
N
N +
Ceramide
JNK
p38 MAPK
Caspase 3
ERK
AKT/PKB
NFkB
PROLIFERATION
SURVIVAL
Interactions of oxidized lipoproteins with
the cells of the arterial wall induce and
influence the progress of atherosclerosis.
Accumulation of foam cells originating
from macrophages and excessive intimal
growth of vascular smooth muscle cells
(SMC) alternating with focal massive cell
death are characteristics typical of the atherosclerotic lesion. These phenomena are
largely mediated by the oxidized phospholipid components of the modified particles that
are generated under the conditions of oxidative stress. In the framework of the research
consortium LIPOTOX, we investigate the “Toxicity of oxidized phospholipids in
macrophages”. This study aims at identifying the molecular and cellular effects of an
important subfamily of the oxidized phospholipids containing long hydrocarbon chains
in position sn-1 and short polar acyl residues in position sn-2 of the glycerol backbone.
The respective compounds trigger an intracellular signaling network including
sphingomyelinases, (MAP) kinases and transcription factors thereby inducing
proliferation or apoptosis of vascular cells. Both phenomena largely depend on the
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