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• W2051238291 abstract "High-density lipoproteins (HDLs) prevent atherosclerosis by removing cholesterol from macrophages and by providing antioxidants for low-density lipoproteins. Oxidation of HDLs affects their functions via the complex mechanisms that involve multiple protein and lipid modifications. To differentiate between the roles of oxidative modifications in HDL proteins and lipids, we analyzed the effects of selective protein oxidation by hypochlorite (HOCl) on the structure, stability, and remodeling of discoidal HDLs reconstituted from human apolipoproteins (A-I, A-II, or C-I) and phosphatidylcholines. Gel electrophoresis and electron microscopy revealed that, at ambient temperatures, protein oxidation in discoidal complexes promotes their remodeling into larger and smaller particles. Thermal denaturation monitored by far-UV circular dichroism and light scattering in melting and kinetic experiments shows that protein oxidation destabilizes discoidal lipoproteins and accelerates protein unfolding, dissociation, and lipoprotein fusion. This is likely due to the reduced affinity of the protein for lipid resulting from oxidation of Met and aromatic residues in the lipid-binding faces of amphipathic α-helices and to apolipoprotein cross-linking into dimers and trimers on the particle surface. We conclude that protein oxidation destabilizes HDL disk assembly and accelerates its remodeling and fusion. This result, which is not limited to model discoidal but also extends to plasma spherical HDL, helps explain the complex effects of oxidation on plasma lipoproteins." @default.
• W2051238291 created "2016-06-24" @default.
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• W2051238291 date "2008-02-27" @default.
• W2051238291 modified "2023-10-15" @default.
• W2051238291 title "Effects of Protein Oxidation on the Structure and Stability of Model Discoidal High-Density Lipoproteins" @default.
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• W2051238291 doi "https://doi.org/10.1021/bi7023783" @default.
• W2051238291 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2823073" @default.
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• W2051238291 hasPublicationYear "2008" @default.
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