Abstract
High density lipoproteins (HDL) not only provide a serum transport vector for paraoxonase-1 (PON1) but also contribute to enzyme activity, stability and, consequently, function. The contribution of the apolipoprotein (apo) components of HDL to overall PON1 activity and function is not clearly established. ApoAI appears of major importance in defining serum PON1 activity and stability, but in the context of an interaction with the phospholipid fraction of HDL. This may involve a role in establishing the architecture of the HDL particle that optimally integrates the PON1 peptide. As the second, major structural peptide of HDL, apoAII may accomplish a similar role. These apolipoproteins, together with others associated with HDL, may also exert a more indirect influence on PON1 function by sequestering oxidised lipids that could compromise enzyme activity. The latter has been exploited therapeutically to give rise to apolipoprotein mimetic peptides that may be useful in limiting oxidative stress within the lipoprotein system, thus permitting PON1 activity to be maximally expressed.
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References
Birjmohun RS, Dallinga-Thie GM, Kuivenhoven JA et al. (2007). Apolipoprotein A-II is inversely associated with risk of future coronary artery disease. Circulation 116:2029–2035.
Blatter M-C, James RW, Messmer S et al. (1993). Identification of a distinct human high-density lipoprotein subspecies defined by a lipoprotein-associated protein, K-45. Identity of K-45 with paraoxonase. Eur J Biochem 211:871–879.
Boucher J, Ramsamy TA, Braschi S et al. (2004). Apolipoprotein A-II regulates HDL stability and affects hepatic lipase association and activity. J Lipid Res 45:849–858.
Cabana VG, Reardon CA, Feng N et al. (2003). Serum paraoxonase: effect of the apolipoprotein composition of HDL and the acute phase response. J Lipid Res 44:780–792.
Cascorbi I, Laule M, Mrozikiewicz PM et al. (1999). Mutations in the human paraoxonase 1 gene: frequencies, allelic linkages, and association with coronary artery disease. Pharmacogenet 9:755–761.
Cheung MC, Albers JJ (1984). Characterization of lipoprotein particles isolated by immunoaffinity chromatography: particles containing A-I and A-II and particles containing A-I but no A-II. J Biol Chem 259:12201–12209.
Deakin S, Leviev I, Gomaraschi M et al. (2002). Enzymatically active paraoxonase-1 is located at the external membrane of producing cells and released by a high affinity, saturable, desorption mechanism. J Biol Chem 277:4301–4308.
Deakin S, Moren X, James RW (2005). Very low density lipoproteins provide a vector for secretion of paraoxonase-1 from cells. Atherosclerosis 179:17–25.
Forte TM, Subbanagounder G, Berliner JA et al. (2002). Altered activities of anti-atherogenic enzymes, LCAT, paraoxonase, and platelet activating factor acetylhydrolase in atherosclerosis-susceptible mice. J Lipid Res 43:477–485.
Gaidukov L, Rosenblat M, Aviram M et al. (2006). The 192R/Q polymorphs of serum paraoxonase PON1 differ in HDL binding, lipolactonase stimulation, and cholesterol efflux. J Lipid Res 47:2492–2502.
Gaidukov L, Tawfik DS (2005). High affinity, stability, and lactonase activity of serum paraoxonase PON1 anchored on HDL with ApoA-I. Biochemistry 44:11843–11854.
Gupta H, White CR, Handattu S et al. (2005). Apolipoprotein E mimetic peptide dramatically lowers plasma cholesterol and restores endothelial function in watanabe heritable hyperlipidemic rabbits. Circulation 111:3112–3118.
James RW, Blatter Garin MC, Calabresi L et al. (1998). Modulated serum activities and concentrations of paraoxonase in high density lipoprotein deficiency states. Atherosclerosis 139:77–82.
Kelso GJ, Stuart WD, Richter RJ et al. (1994). Apolipoprotein J is associated with paraoxonase in human plasma. Biochemistry 33:832–839.
La Du BN (1992). Human serum paraoxonase/arylesterase. Pharmacogenetics of drug metabolism. W. Kalow (ed.). New York: Pergamon Press 51–91.
Mackness B, Hunt R, Durrington PN et al. (1997). Increased immunolocalization of paraoxonase, clusterin, and apolipoprotein A-I in the human artery wall with the progression of atherosclerosis. Arterioscler Thromb Vasc Biol 17:1233–1238.
Moren X, Deakin S, Liu M-L et al. (2008). HDL subfraction distribution of paraoxonase-1 and its relevance to enzyme activity and resistance to oxidative stress. J Lipid Res 49:1228–1234.
Navab M, Anantharamaiah GM, Reddy ST et al. (2005a). Oral small peptides render HDL anti-inflammatory in mice and monkeys and reduce atherosclerosis in apoE null mice. Circulation Res 97:524–532.
Navab M, Anantharamaiah GM, Reddy ST et al. (2007). Peptide mimetics of apolipoproteins improve HDL function. J Clin Lipidol 1:142–147.
Navab M, Anantharamaiah GM, Reddy ST et al. (2004). Human apolipoprotein A-I and A-I mimetic peptides: potential for atherosclerosis reversal. Curr Opin Lipidol 15:645–649.
Navab M, Anantharamaiah GM, Reddy ST et al. (2005b). An oral apoJ peptide renders HDL antiinflammatory in mice and monkeys and dramatically reduces atherosclerosis in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol 25:1932–1937.
Navab M, Hama-Levy S, Van Lenten B et al. (1997). Mildly oxidised LDL induces an increased apolipoprotein J/paraoxonase ratio. J Clin Invest 99:2005–2019.
Navab M, Hama SY, Cooke CJ et al. (2000). Normal high density lipoprotein inhibits three steps in the formation of mildly oxidised low density lipoprotein: step 1. J Lipid Res 41:1481–1494.
Oda MN, Bielicki JK, Berger T et al. (2001). Cysteine substitutions in apolipoprotein A-I primary structure modulate paraoxonase activity. Biochemistry 40:1710–1718.
Ribas V, Sanchez-Quesada JL, Anton R et al. (2004). Human apolipoprotein A-II enrichment displaces paraoxonase from HDL and impairs its antioxidant properties: a new mechanism linking HDL protein composition and antiatherogenic potential. Circ Res 95:789–797.
Segrest JP, Jones MK, De Loof H et al. (1992). The amphipathic helix in the exchangeable apolipoproteins: a review of secondary structure and function. J Lipid Res. 33:141–166.
Sorenson RC, Bisgaier CL, Aviram M et al. (1999). Human serum paraoxonase/arylesterase’s retained hydrophobic N-terminal leader sequence associates with HDLs by binding phospholipids: apolipoprotein A-I stabilizes activity. Arterioscler Thromb Vasc Biol 19:2214–2225.
Tailleux A, Duriez P, Fruchart JC et al. (2002). Apolipoprotein A-II, HDL metabolism and atherosclerosis. Atherosclerosis 164:1–13.
Trougakos IP, Gonos ES (2006). Regulation of clusterin/apolipoprotein J, a functional homologue to the small heat shock proteins, by oxidative stress in ageing and age-related diseases. Free Radic Res 40:1324–1334.
Winkler K, Hoffmann MM, Seelhorst U et al. (2008). Apolipoprotein A-II is a negative risk indicator for cardiovascular and total mortality: findings from the Ludwigshafen Risk and Cardiovascular Health Study. Clin Chem 54:1405–1406.
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James, R.W., Deakin, S.P. (2010). The Contribution of High Density Lipoprotein Apolipoproteins and Derivatives to Serum Paraoxonase-1 Activity and Function. In: Reddy, S. (eds) Paraoxonases in Inflammation, Infection, and Toxicology. Advances in Experimental Medicine and Biology, vol 660. Humana Press. https://doi.org/10.1007/978-1-60761-350-3_16
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DOI: https://doi.org/10.1007/978-1-60761-350-3_16
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