title: Paradoxical effects of SAA on lipoprotein oxidation suggest a new antioxidant function for SAA.
abstract: Oxidative stress and inflammation, which involve a dramatic increase in serum amyloid A (SAA) levels, are critical in the development of atherosclerosis. Most SAA circulates on plasma HDL particles, altering their cardioprotective properties. SAA-enriched HDL has diminished anti-oxidant effects on LDL, which may contribute to atherogenesis. We determined combined effects of SAA enrichment and oxidation on biochemical changes in HDL. Normal human HDLs were incubated with SAA, oxidized by various factors (Cu2+, myeloperoxidase, H2O2, OCl-), and analyzed for lipid and protein modifications and biophysical remodeling. Three novel findings are reported: addition of SAA reduces oxidation of HDL and LDL lipids; oxidation of SAA-containing HDL in the presence of OCl-generates a covalent heterodimer of SAA and apoA-I that resists the release from HDL; and mild oxidation promotes spontaneous release of proteins (SAA and apoA-I) from SAA-enriched HDL. We show that the anti-oxidant effects of SAA extend to various oxidants and are mediated mainly by the unbound protein. We propose that free SAA sequesters lipid hydroperoxides and delays lipoprotein oxidation, though much less efficiently than other anti-oxidant proteins, such as apoA-I, that SAA displaces from HDL. These findings prompt us to reconsider the role of SAA in lipid oxidation in vivo.
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118. Electronic address: Shobini@bu.edu.
authors.forename: Shobini
authors.initials: S
authors.lastname: Jayaraman
authors.affiliation: Institute of Protein Biochemistry, University of Ulm, 89081 Ulm, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Haupt
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118. Electronic address: Gursky@bu.edu.
authors.forename: Olga
authors.initials: O
authors.lastname: Gursky
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000502:physiology; D016632:Apolipoprotein A-I / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D006801:Humans; D015227:Lipid Peroxidation; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000737:chemistry*; D051379:Mice; D009195:Peroxidase / Q000737:chemistry; D000685:Serum Amyloid A Protein / Q000737:chemistry* / Q000502:physiology
chemical_list: D000975:Antioxidants; D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D000685:Serum Amyloid A Protein; D003300:Copper; D009195:Peroxidase
keywords: amyloid A and apolipoprotein A-I amyloidosis; apolipoprotein release; high density lipoprotein; inflammation and atherosclerosis; lipoprotein peroxidation kinetics; low density lipoprotein; serum amyloid A