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Role of lipoprotein lipase for plasma lipid transport

Research project An enzyme located at the walls of blood vessels determines how fast and where in the body blood lipids are unloaded.

Lipids are transported in blood in small,spherical fat droplets covered by a surface layer of specialized proteins.

Head of project

Project overview

Project period:

2007-02-28 2009-12-31

Funding

Finansår , 2003, 2004, 2005, 2006, 2007, 2008, 2009

huvudman: G. Olivecrona, finansiar: VR-M, y2003: 400, y2004: 700, y2005: 700, y2006: 700, y2007: 600, y2008: 600, y2009: 600,

huvudman: G. Olicecrona, finansiar: Druvan AB, y2003: 300, y2004: , y2005: , y2006: , y2007: , y2008: , y2009: ,

huvudman: T. Olivecrona, finansiar: VR-M, y2003: 300, y2004: 325, y2005: 325, y2006: 275, y2007: 275, y2008: , y2009: ,

huvudman: G. Olivecrona, finansiar: Gustaf V:s jub.f., y2003: , y2004: 200, y2005: 200, y2006: 200, y2007: 200, y2008: , y2009: ,

huvudman: G. Olivecrona, finansiar: Sv. diabetesförbundet, y2003: , y2004: , y2005: , y2006: , y2007: 130, y2008: , y2009: ,

Participating departments and units at Umeå University

Department of Medical Biosciences

Research area

Clinical medicine, Molecular medicine

Project description

Lipoprotein lipase (LPL) is the main enzyme responsible for clearance of lipids from blood. Our project involves detailed molecular studies of LPL and its activator protein apolipoprotein CII (apoCII), as well as of an inhibitor for LPL action (apoCIII). A main focus is to study how the active form of LPL (a non-covalent dimer) is formed, under which conditions it dissociates to inactive monomers and the potential possibilities to reverse the inactivation. The monomer-dimer conversion is important since it is involved in the physiological, post-translational regulation of LPL.



Another focus is to understand, in molecular detail, the mechanism for activation of LPL by apoCII. This work will involve site-directed mutagenesis of both LPL and apoCII, studies of enzyme kinetics and protein conformation (spectroscopy and NMR).



A third part involves investigation of the (non-catalytic) role of LPL for uptake of cholesterol-rich lipoproteins (LDL) in monocyte-derived macrophages and the potential importance of LPL for development of atherosclerosis. This will be investigated mostly in cell culture experiments, where the focus will be on the detailed mechanisms for the LPL-mediated uptake.



A fourth part involves studies of LPL in human tissues (biopsies from skeletal muscle, adipose tissue and artery wall), by measurements of LPL activity, mass, mRNA and localization by immunocytochemistry.