Publications in Scientific Journals:

M. Brameshuber, E. Sevcsik, B. Rossboth, C. Manner, H. Deigner, B. Peksel, M. Péter, Z. Török, A. Hermetter, G. Schütz:
"Oxidized Phospholipids Inhibit the Formation of Cholesterol-Dependent Plasma Membrane Nanoplatforms";
Biophysical Journal, 110 (2016), 205 - 213.

English abstract:
We previously developed a single-molecule microscopy method termed TOCCSL (thinning out clusters while
conserving stoichiometry of labeling), which allows for direct imaging of stable nanoscopic platforms with raft-like properties
diffusing in the plasma membrane. As a consensus raft marker, we chose monomeric GFP linked via a glycosylphosphatidylinositol
(GPI) anchor to the cell membrane (mGFP-GPI). With this probe, we previously observed cholesterol-dependent
homo-association to nanoplatforms diffusing in the plasma membrane of live CHO cells. Here, we report the release of this
homo-association upon addition of 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC) or 1-palmitoyl-2-glutaroyl-
sn-glycero-3-phosphocholine, two oxidized phospholipids (oxPLs) that are typically present in oxidatively modified low-density
lipoprotein. We found a dose-response relationship for mGFP-GPI nanoplatform disintegration upon addition of POVPC, correlating
with the signal of the apoptosis marker Annexin V-Cy3. Similar concentrations of lysolipid showed no effect, indicating
that the observed phenomena were not linked to properties of the lipid bilayer itself. Inhibition of acid sphingomyelinase by NB-
19 before addition of POVPC completely abolished nanoplatform disintegration by oxPLs. In conclusion, we were able to determine
how oxidized lipid species disrupt mGFP-GPI nanoplatforms in the plasma membrane. Our results favor an indirect mechanism
involving acid sphingomyelinase activity rather than a direct interaction of oxPLs with nanoplatform constituents.

Created from the Publication Database of the Vienna University of Technology.