The role of paraoxonase 1 in regulating high-density lipoprotein functionality during aging

Khalil, Abdelouahed; Simo, Olivier Kamtchueng; Ikhlef, Souade; Berrougui, Hicham

doi:10.1139/cjpp-2017-0117

Cited by 8 publications

(6 citation statements)

References 125 publications

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“…In the multivariate analyses, age and BMI are predictors of circulating PON lactonase activity in CKD subjects. This finding is corroborated by previous studies showing that decrease in PON activity is associated with decrease in age [61,62,63,64] and an increase in BMI [65,66,67,68]. Notably, hemodialysis patients show a significant correlation between PON-1 activity and BMI, where obese patients had significantly lower PON-1 paraoxonase activity compared to controls [69].…”

Section: Discussionsupporting

confidence: 86%

Circulating Lactonase Activity but Not Protein Level of PON-1 Predicts Adverse Outcomes in Subjects with Chronic Kidney Disease

Mohammed

Xie

Brewster

et al. 2019

JCM

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The burden of cardiovascular disease and death in chronic kidney disease (CKD) outpaces that of the other diseases and is not adequately described by traditional risk factors alone. Diminished activity of paraoxonase (PON)-1 is associated with increased oxidant stress, a common feature underlying the pathogenesis of CKD. We aimed to assess the prognostic value of circulating PON-1 protein and PON lactonase activity on adverse clinical outcomes across various stages and etiologies of CKD. Circulating PON-1 protein levels and PON lactonase activity were measured simultaneously in patients with CKD as well as a cohort of apparently healthy non-CKD subjects. Both circulating PON-1 protein levels and PON lactonase activity were significantly lower in CKD patients compared to the non-CKD subjects. Similarly, across all stages of CKD, circulating PON-1 protein and PON lactonase activity were significantly lower in patients with CKD compared to the non-CKD controls. Circulating PON lactonase activity, but not protein levels, predicted future adverse clinical outcomes, even after adjustment for traditional risk factors. The combination of lower circulating protein levels and higher activity within the CKD subjects were associated with the best survival outcomes. These findings demonstrate that diminished circulating PON lactonase activity, but not protein levels, predicts higher risk of future adverse clinical outcomes in patients with CKD.

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Section: Discussionsupporting

confidence: 86%

Circulating Lactonase Activity but Not Protein Level of PON-1 Predicts Adverse Outcomes in Subjects with Chronic Kidney Disease

Mohammed

Xie

Brewster

et al. 2019

JCM

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“…Paraoxonase 1 (PON1) is carried on HDL and it is a multifunctional enzyme with paraoxonase (POXase: hydrolysis of paraoxon), arylesterase (AREase: hydrolysis of aromatic esters), lactonase and diazoxonase activities 11) . The anti-atherosclerotic effects of HDL, particularly its antioxidant, antiinflammatory, and CEC activities, are largely attributable to PON1 12) . A close relationship between PON1 gene deficiency and an accelerated progression of arteriosclerosis has been found in animal models 13,14) , and a meta-analysis based on 43 clinical studies showed that decreased POXase and AREase activities are associated with an increased susceptibility to coronary heart disease 15) .…”

Section: Measurements Of Cecmentioning

confidence: 99%

The Association of the Cholesterol Efflux Capacity with the <i>Paraoxonase 1</i> Q192R Genotype and the Paraoxonase Activity

Oniki,

Ohura,

Endo

et al. 2024

JAT

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Aims: Paraoxonase 1 (PON1) binds to high-density lipoprotein (HDL) and protects against atherosclerosis. However, the relationship between functional PON1 Q192R polymorphism, which is associated with the hydrolysis of paraoxon (POXase activity) and atherosclerotic cardiovascular disease (ASCVD), remains controversial. As the effect of PON1 Q192R polymorphism on the HDL function is unclear, we investigated the relationship between this polymorphism and the cholesterol efflux capacity (CEC), one of the biological functions of HDL, in association with the PON1 activity. Methods:The relationship between PON1 Q192R polymorphisms and CEC was investigated retrospectively in 150 subjects without ASCVD (50 with the PON1 Q/Q genotype, 50 with the Q/R genotype, and 50 with the R/ R genotype) who participated in a health screening program. The POXase and arylesterase (AREase: hydrolysis of aromatic esters) activities were used as measures of the PON1 activity. Results:The AREase activity was positively correlated with CEC independent of the HDL cholesterol levels. When stratified by the PON1 Q192R genotype, the POXase activity was also positively correlated with CEC independent of HDL cholesterol. PON1 Q192R R/R genotype carriers had a lower CEC than Q/Q or Q/R genotype carriers, despite having a higher POXase activity. Moreover, in a multiple regression analysis, the PON1 Q192R genotype was associated with the degree of CEC, independent of the HDL cholesterol and POXase activity. Conclusions:The PON1 Q192R R allele is associated with reduced CEC in Japanese people without ASCVD. Further studies on the impact of this association on the severity of atherosclerosis and ASCVD development are thus called for.

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“…Therefore, the dropping in ARE activity in β-thalassemia may reflect the disturbance in serum and blood cells oxidant/antioxidant balance that leads to OS. It has been reported that ARE-PON1is involved in the antioxidant system through preventing LDL oxidation [23] . Hence, it can be hypothesized that the variation in ARE-PON1 level is associated with diseases in which OS is a major part in their pathogenesis such as breast cancer [24] and brain cancer [25] .…”

Section: Table (1) Are-pon1 Activity Tp Concentration and Lipid Profile Levels In Patients With β-Thalassemia Minor Compared To Healthy Imentioning

confidence: 99%

Arlyesterase activity of Paraoxonase-1 enzyme in Iraqi patients with β-thalassemia minor

Al-Ani¹,

Fadel²

2019

ATMPH

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Background: Arylesterase activity of Paraoxonase-1 (ARE-PON-1) exhibits an antioxidant role which protects lipoprotein from oxidation. It is known that ARE-PON-1 antioxidant activity associated with high density lipoprotein cholesterol (HDL-C) reduces the oxidative damage mediated by low density lipoprotein cholesterol (LDL-C). The present study was aimed to examine the level of serum ARE-PON1 in Iraqi patients with β-thalassemia minor and its relationship with lipid profile (total cholesterol (TC), HDL-C, very low density lipoprotein (VLDL-C), and LDL-C) and hematologic changes as a part of antioxidant system action. Methods: In the present study, the ARE-PON-1 activity was investigated in serum of patients with β-thalassemia minor. Results: It has been revealed that the ARE-PON-1 activity was significantly decreased (P>0.0001) in patients group compared to healthy group. This was associated with slight decrease in the lipid profile of patient group (HDL, LDL-C, very low density lipoprotein cholesterol (VLDL-C), and total cholesterol (TC), except of triglyceride (TG) which showed a significant decrease (P>0.0001) compared to healthy group). Also, hematologic changes were investigated and showed depleting in most of white blood cell (WBC) and red blood cell (RBC) components. Conclusion: Patients with β-thalassemia minor are suffering from weakness in the antioxidant defence system expressed by dropping in the ARE-PON1 level and lipid profile that stimulate oxidation of many cell particles such as HGB, promote EOS apoptosis and rise of CD risk development.

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The role of paraoxonase 1 in regulating high-density lipoprotein functionality during aging

Cited by 8 publications

References 125 publications

Circulating Lactonase Activity but Not Protein Level of PON-1 Predicts Adverse Outcomes in Subjects with Chronic Kidney Disease

Circulating Lactonase Activity but Not Protein Level of PON-1 Predicts Adverse Outcomes in Subjects with Chronic Kidney Disease

The Association of the Cholesterol Efflux Capacity with the <i>Paraoxonase 1</i> Q192R Genotype and the Paraoxonase Activity

Arlyesterase activity of Paraoxonase-1 enzyme in Iraqi patients with β-thalassemia minor

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