title: Altered phospholipid-apoB-100 interactions and generation of extra membrane material in proteolysis-induced fusion of LDL particles.
abstract: Lipid droplets and membrane material are produced in the extracellular matrix of the arterial intima during atherogenesis. Both in vitro and in vivo experimentation suggests that fusion of modified LDL particles leads to formation of such lipid droplets. Here we applied proton NMR spectroscopy to probe surface phospholipids phosphatidylcholine (PC) and sphingomyelin (SM) of LDL particles during proteolytic degradation of apolipoprotein B-100 (apoB-100). Initiation of apoB-100 degradation was accompanied by the abruptly increased intensity of the choline -N(CH(3))(3) resonance of PC molecules, indicating disruption of their interactions with apoB-100. However, subsequent particle fusion was accompanied by a steady decrease in the intensity of the choline resonances of both PC and SM. Electron microscopy of the proteolyzed LDL revealed irregularly shaped multilamellar membranes attached to aggregates of fused particles. This suggests formation of membrane material with low hydration, in which some of the atomic motions are hindered. Characterization of the behavior of the surface lipids of LDL particles during apoB-100 degradation and other types of LDL modification will aid in understanding molecular mechanisms leading to fusion and generation of multilamellar membrane material in the arterial intima during atherogenesis.
authors.affiliation: Wihuri Research Institute, FIN-00140 Helsinki, Finland.
authors.forename: M O
authors.initials: MO
authors.lastname: Pentikäinen
authors.forename: M T
authors.initials: MT
authors.lastname: Hyvönen
authors.forename: K
authors.initials: K
authors.lastname: Oörni
authors.forename: T
authors.initials: T
authors.lastname: Hevonoja
authors.forename: A
authors.initials: A
authors.lastname: Korhonen
authors.forename: E M
authors.initials: EM
authors.lastname: Lehtonen-Smeds
authors.forename: M
authors.initials: M
authors.lastname: Ala-Korpela
authors.forename: P T
authors.initials: PT
authors.lastname: Kovanen
mesh_terms: D001055:Apolipoproteins B / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008854:Microscopy, Electron; D008954:Models, Biological; D008958:Models, Molecular; D015233:Models, Statistical; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D013997:Time Factors
chemical_list: D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D010743:Phospholipids; D011993:Recombinant Fusion Proteins; D013109:Sphingomyelins