title: Novel phospholipolytic activities associated with electronegative low-density lipoprotein are involved in increased self-aggregation.
abstract: Electronegative low-density lipoprotein (LDL(-)) is a minor LDL subfraction present in plasma with increased platelet-activating factor acetylhydrolase (PAF-AH) activity. This activity could be involved in the proinflammatory effects of LDL(-). Our aim was to study the presence of additional phospholipolytic activities in LDL(-). Total LDL was fractionated into electropositive (LDL(+)) and LDL(-) by anion-exchange chromatography, and phospholipolytic activities were measured by fluorometric methods. Phospholipolytic activity was absent in LDL(+) whereas LDL(-) presented activity against lysophosphatidylcholine (LPC, 82.4 +/- 34.9 milliunits/mg of apoB), sphingomyelin (SM, 53.3 +/- 22.5 milliunits/mg of apoB), and phosphatidylcholine (PC, 25.7 +/- 4.3 milliunits/mg of apoB). LDL(-), but not LDL(+), presented spontaneous self-aggregation at 37 degrees C in parallel to phospholipid degradation. This was observed in the absence of lipid peroxidation and suggests the involvement of phospholipolytic activity in self-aggregation of LDL(-). Phospholipolytic activity was not due to PAF-AH, apoE, or apoC-III and was not increased in LDL(+) modified by Cu (2+) oxidation, acetylation, or secretory phospholipase A 2 (PLA 2). However, LDL(-) efficiently degraded phospholipids of lipoproteins enriched in LPC, such as oxidized LDL or PLA 2-LDL, but not native or acetylated LDL. This finding supports that LPC is the best substrate for LDL(-)-associated phospholipolytic activity. These results reveal novel properties of LDL(-) that could play a significant role in its atherogenic properties.
authors.affiliation: Servei de Bioquímica, Institut de Recerca, Hospital de la Santa Creu i Sant Pau.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bancells
authors.forename: Sònia
authors.initials: S
authors.lastname: Benítez
authors.forename: Sandra
authors.initials: S
authors.lastname: Villegas
authors.forename: Oscar
authors.initials: O
authors.lastname: Jorba
authors.forename: Jordi
authors.initials: J
authors.lastname: Ordóñez-Llanos
authors.forename: José Luis
authors.initials: JL
authors.lastname: Sánchez-Quesada
mesh_terms: D000837:Anion Exchange Resins / Q000737:chemistry; D053305:Apolipoprotein C-III / Q000494:pharmacology; D001057:Apolipoproteins E / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002852:Chromatography, Ion Exchange; D004789:Enzyme Activation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D009636:Norbornanes; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D013109:Sphingomyelins / Q000737:chemistry / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000837:Anion Exchange Resins; D053305:Apolipoprotein C-III; D001057:Apolipoproteins E; D001952:Bridged-Ring Compounds; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D009636:Norbornanes; D010713:Phosphatidylcholines; D010726:Phosphodiesterase Inhibitors; D010743:Phospholipids; D013109:Sphingomyelins; D013450:Sulfones; D013859:Thiocarbamates; D013871:Thiones; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; C046498:tricyclodecane-9-yl-xanthogenate; D008274:Magnesium