Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Gauster, M.
The role of Endothelial Lipase (EL) in High Density Lipoprotein (HDL) metabolism
[ Dissertation ] Medical University of Graz; 2005. pp.
- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Frank Sasa
- Kostner Gerhard
- Altmetrics:
- Abstract:
- Endothelial Lipase (EL), a member of the triglyceride lipase gene family, has high homology to Lipoprotein Lipase (LPL) and Hepatic Lipase (HL). EL exhibits substantial phospholipase activity and has low triglyceride lipase activity. Expression in endothelial cells i9s a unique feature of this lipase within the triglyceride lipase family and was therefore referred to as Endothelial Lipase. It was shown to be expressed in various tissues like liver, lung thyroid, placenta, testis and ovaries. The studies performed in the course of this thesis have demonstrated that EL is cleaved after secretion form cell. This cleavage was found to be a consequence of the action of pro-protein convertases on EL. The pro-protein recognize a specific consensus sequence within the EL, resulting in a cleavage and inactivation of EL. The EL cleavage was attenuated by specific inhibitors of the pro-protein convertases and completely abolished by amino acid substitution in the consensus sequence. Studies addressing the enzymatic activity of EL showed that EL hydrolyse saturated and unsaturated fatty acids form HDL phosphatidylcholine in an sequential manner. First, the sn-1 fatty acid is released by the phospholipase activity of EL, followed by the release of the sn-2 fatty acid from the lysophosphatidylcholine intermediate by the lysophospholipase activity of EL. Furthermore, the impact of EL on biochemical and physical properties of HDL was studied. In vitro incubation of human HDL with EL conditioned cell culture medium resulted in an abundant release of fatty acids and lysophosphatidylcholine, which partially remained in HDL: The resulting HSL particles, enriched in free fatty acids and lysophosphatidylcholine, were more negatively charged but unaltered in size compared with untreated HDL. EL treated HDL exhibited a diminished binding to the HDL receptor and a decreased ability to mediate cholesterol efflux from cells.