title: Clusterin/apolipoprotein J binds to aggregated LDL in human plasma and plays a protective role against LDL aggregation.
abstract: Clusterin/apolipoprotein J (apoJ) is an extracellular chaperone involved in the quality control system against protein aggregation. A minor part of apoJ is transported in blood bound to LDLs, but its function is unknown. Our aim was to determine the role of apoJ bound to LDLs. Total LDL from human plasma was fractionated into native LDL [LDL(+)] and electronegative LDL [LDL(-)]. The latter was separated into nonaggregated [nagLDL(-)] and aggregated LDL(-) [agLDL(-)]. The content of apoJ was 6-fold higher in LDL(-) than in LDL(+) and 7-fold higher in agLDL(-) than in nagLDL(-). The proportion of LDL particles containing apoJ (LDL/J+) was 3-fold lower in LDL(+) than in LDL(-). LDL/J+ particles shared several characteristics with agLDL(-), including increased negative charge and aggregation. apoJ-depleted particles (LDL/J-) showed increased susceptibility to aggregation, whether spontaneous or induced by proteolysis or lipolysis, as was revealed by turbidimetric analysis, gel filtration chromatography, lipoprotein precipitation, native gradient gel electrophoresis, circular dichroism, and transmission electronic microscopy. The addition of purified apoJ to total LDL also prevented its aggregation induced by proteolysis or lipolysis. These findings point to apoJ as a key modulator of LDL aggregation and reveal a putative new therapeutic strategy against atherosclerosis.
authors.affiliation: *Cardiovascular Biochemistry Group, Research Institute of the Hospital de Sant Pau (IIB Sant Pau), Barcelona, Spain; Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain; and Protein Folding and Stability Group, Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Martínez-Bujidos
authors.affiliation: *Cardiovascular Biochemistry Group, Research Institute of the Hospital de Sant Pau (IIB Sant Pau), Barcelona, Spain; Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain; and Protein Folding and Stability Group, Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Rull
authors.affiliation: *Cardiovascular Biochemistry Group, Research Institute of the Hospital de Sant Pau (IIB Sant Pau), Barcelona, Spain; Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain; and Protein Folding and Stability Group, Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: González-Cura
authors.affiliation: *Cardiovascular Biochemistry Group, Research Institute of the Hospital de Sant Pau (IIB Sant Pau), Barcelona, Spain; Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain; and Protein Folding and Stability Group, Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Pérez-Cuéllar
authors.affiliation: *Cardiovascular Biochemistry Group, Research Institute of the Hospital de Sant Pau (IIB Sant Pau), Barcelona, Spain; Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain; and Protein Folding and Stability Group, Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain.
authors.forename: Laia
authors.initials: L
authors.lastname: Montoliu-Gaya
authors.affiliation: *Cardiovascular Biochemistry Group, Research Institute of the Hospital de Sant Pau (IIB Sant Pau), Barcelona, Spain; Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain; and Protein Folding and Stability Group, Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Villegas
authors.affiliation: *Cardiovascular Biochemistry Group, Research Institute of the Hospital de Sant Pau (IIB Sant Pau), Barcelona, Spain; Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain; and Protein Folding and Stability Group, Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Ordóñez-Llanos
authors.affiliation: *Cardiovascular Biochemistry Group, Research Institute of the Hospital de Sant Pau (IIB Sant Pau), Barcelona, Spain; Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain; and Protein Folding and Stability Group, Biochemistry and Molecular Biology Department, Universitat Autònoma de Barcelona, Cerdanyola, Spain jsanchezq@santpau.cat.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Sánchez-Quesada
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D051152:Clusterin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008066:Lipolysis; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000378:metabolism*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D010949:Plasma / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C495242:CLU protein, human; D051152:Clusterin; D008077:Lipoproteins, LDL; D034741:RNA, Small Interfering
keywords: atherosclerosis; chaperones; electronegative LDL