The importance of high-density lipoproteins for paraoxonase-1 secretion, stability, and activity

James, Richard; Deakin, Sara

doi:10.1016/j.freeradbiomed.2004.08.012

Cited by 187 publications

(135 citation statements)

References 56 publications

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“…In the current study, serum paraoxonase, arylesterse, and DEPCyMCase activities were signifi cantly decreased in HH patients. Changes in HDL structure and composition are known to infl uence PON1 activity because this enzyme is profoundly dependent on the lipid and protein compositional environment of the HDL particles for its activity ( 32 ). Since our HH patients had a reduced HDL-cholesterol concentration but normal apolipoprotein A-I levels, such a compositional change could explain our fi ndings.…”

Section: Pon1 Genotypingmentioning

confidence: 79%

Paraoxonase-1 status in patients with hereditary hemochromatosis

Martinelli

García-Heredia

Roca

et al. 2013

Journal of Lipid Research

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Section: Pon1 Genotypingmentioning

confidence: 79%

Paraoxonase-1 status in patients with hereditary hemochromatosis

Martinelli

García-Heredia

Roca

et al. 2013

Journal of Lipid Research

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“…The weaker positive association between paraoxonase activity and the atherogenic lipid fraction, LDL cholesterol (difference of 12 nmol/mL/min between highest and lowest LDL cholesterol quartiles) probably reflects association of paraoxonase with other factors such as SREBP-2, a cholesterol transcription factor, which regulates PON1 expression (31)(32)(33). The positive association between paraoxonase activity and triglycerides (difference of 8 nmol/mL/min between highest and lowest triglyceride quartiles) reflects the small fraction of paraoxonase enzyme that is carried on the triglyceride fraction (Ͻ5%) (34 ).…”

Section: Discussionmentioning

confidence: 99%

Factors Associated with Paraoxonase Genotypes and Activity in a Diverse, Young, Healthy Population: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

et al. 2008

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Background: Paraoxonase may mitigate oxidative damage and thus lower risk of macrovascular disease. Methods: DNA samples from 2252 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study were genotyped for the L55M and Q192R polymorphisms of the PON1 (paraoxonase 1) gene, and paraoxonase activity was measured in serum. Results: The 192R (67.4% vs 29.7%) and 55L (80.0% vs 63.8%) alleles were more common in blacks vs whites. The Q192R locus was the strongest correlate of paraoxonase activity (100.4 nmol/mL/min greater in the 192RR than the 192QQ genotype). After adjustment for the Q192R locus, the L55M locus (12.7 nmol/mL/min difference between 55LL and 55MM) and race (6.6 nmol/mL/min difference between blacks and whites) were correlated with paraoxonase activity (P ≤0.0001), as were concentrations of HDL cholesterol (23.9 nmol/mL/min difference between highest and lowest quintiles), triglycerides (12.6 nmol/mL/min difference between highest and lowest quintiles), LDL cholesterol (8.2 nmol/mL/min difference between highest and lowest quintiles), smoking status (6.3 nmol/mL/min difference between current smokers of ≥15 cigarettes/day and never smokers), and glucose concentrations at the highest quintile (6.5 nmol/mL/min difference between highest and lowest quintiles in nondiabetic participants). There was no cross-sectional or longitudinal association between paraoxonase enzyme activity and coronary artery calcification (CAC), an early marker of cardiovascular disease, or its progression over 5 years. Conclusions: Paraoxonase may not play an important role during the early pathogenesis of cardiovascular disease. However, associations with lipids and glucose suggest that paraoxonase may modify or react to macrovascular disease pathogenesis.

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“…HDL provides a vector that facilitates the secretion of the enzyme by liver (1), essentially by offering a hydrophobic harbor for the retained signal peptide of PON1 and coincidentally stabilizing the enzyme. The lipoprotein also furnishes a hydrophobic environment that could be important for PON1 function (2). In return, the enzyme prevents or limits the oxidation of HDL (3), although the extent to which this provides physiological benefit to HDL in vivo is less well established.…”

mentioning

confidence: 99%

Paraoxonase-1 and serum concentrations of HDL-cholesterol and apoA-I

Garin¹,

Moren

James

2006

Journal of Lipid Research

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Paraoxonase-1 (PON1) and HDL are tightly associated in plasma, and this is generally assumed to reflect the need for the enzyme to associate with a hydrophobic complex. The association has been examined in coronary cases and agematched controls. Highly significant (P , 0.0001), positive associations were observed between PON1 activities and concentrations and HDL-cholesterol and apolipoprotein A-I (apoA-I) concentrations in cases and controls. Corrected slopes were significantly different in cases (cases vs. controls: arylesterase, r 5 0.19 vs. 0.38, P , 0.02 for apoA-I and r 5 0.15 vs. 0.34, P , 0.02 for HDL-cholesterol) such that if PON1 should influence serum HDL, it would be less effective in coronary cases. When examined as a function of the PON1 gene promoter polymorphism CÀ107T, highly significant differences (P , 0.001) in HDL-cholesterol and apoA-I were observed between genotypes for controls, with high expresser alleles having the highest HDL concentrations. This relationship was lost in cases with coronary disease. The coding region polymorphisms Q192R and L55M of the PON1 gene showed no association with HDL. The promoter polymorphism was an independent determinant of HDL concentrations in multivariate analyses. These data are consistent with an impact of PON1 on plasma concentrations of HDL, with detrimental modifications to the relationship in coronary cases.-Blatter Garin, M-C., X. Moren, and R. W. James. Paraoxonase-1 and serum concentrations of HDL-cholesterol and apoA-I. J. Lipid Res. 2006. 47: 515-520. Supplementary key words atherosclerosis . oxidative stress . low density lipoprotein . high density lipoprotein . apolipoprotein A-I

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The importance of high-density lipoproteins for paraoxonase-1 secretion, stability, and activity

Cited by 187 publications

References 56 publications

Paraoxonase-1 status in patients with hereditary hemochromatosis

Paraoxonase-1 status in patients with hereditary hemochromatosis

Factors Associated with Paraoxonase Genotypes and Activity in a Diverse, Young, Healthy Population: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Paraoxonase-1 and serum concentrations of HDL-cholesterol and apoA-I

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