The effect of HDL-bound and free PON1 on copper-induced LDL oxidation

Bayrak, Ahmet; Bayrak, Tülin; Bodur, Ebru; Kılınç, Kamer; Demirpençe, Ediz

doi:10.1016/j.cbi.2016.08.007

Cited by 14 publications

(11 citation statements)

References 65 publications

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“…RR homozygotes show a greater efficacy detoxifying substrates including paraoxon, 4-(chloromethyl)phenylacetate (CMPA) and 5-thiobutil butyrolactone (Richter et al, 2008;Marsillach et al, 2009;Bayrak et al, 2016). Importantly, Kenned et al (2013) reported that PON activity may be lowered in CKD patients.…”

Section: Introductionmentioning

confidence: 99%

Tratment With Folic Acid Increases Paraoxonase 1 Activity Thereby Improving Chronic Kidney Disease

Matsumoto¹,

Maes²,

Michelin³

et al. 2020

Preprint

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Introduction: Increased oxidative stress, including elevated homocysteine (Hcy) plasma levels, and lowered levels of antioxidants participate in the pathophysiology and progression of chronic kidney disease (CKD). Paraoxonase (PON)1 activity and folic acid are antioxidants which play a role in Hcy metabolism. However, there are no data whether, in CKD, treatment with folic acid improves glomerular filtration rate (GFR) through effects on PON1 activity and Hcy concentrations. Methods: In the current study, we determined PON1 genotypes and activity, Hcy and estimated GFR (eGFR) both before and after treatment with folic acid (5 mg/d) versus no treatment during three consecutive months in 113 outpatients with CKD classified into stages 4, 3b and 3a. Results: PON1 CMPAase and AREase activities were significantly lower in patients allocated to CKD stage 4 as compared with stages 3b and 3a. Treatment with folic acid significantly improved eGFR and increased levels of CMPAase and AREase in patients allocated to classes 4 and 3b, but not 3a. The improvement of eGFR was associated with increased CMPAase and AREase activities, while the latter were associated with increased levels of folic acid. Treatment with folic acid significantly reduced plasma Hcy levels and the Hcy/PON1 activity ratio. The effects of folic acid increasing PON1 activities were not mediated by changes in Hcy. Discussion: Treatment of CKD patients in early/intermediate stages of CKD patients improves oxidative stress by rebalancing the prooxidant (Hcy) / antioxidant (PON1 activities) ratio. Treatment with folic acid significantly improves eGFR and these effects are mediated via increased PON1 activities. Treatment with folic acid in phase G3b and G4 may reduce renal disease progression by enhancing antioxidant defenses.

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Section: Introductionmentioning

confidence: 99%

Tratment With Folic Acid Increases Paraoxonase 1 Activity Thereby Improving Chronic Kidney Disease

Matsumoto¹,

Maes²,

Michelin³

et al. 2020

Preprint

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“…Genetic and epigenetic factors may cause significant differences among individuals in terms of PON1 levels and enzymatic activity. The most studied PON1 polymorphism is Q192R, which influences the catalytic activity of PON1 thereby modulating PON1 antioxidant properties including lipid oxidation (Bayrak et al, 2016;Atagün et al, 2017). The R allozyme is more efficient to detoxify substrates such as paraoxon, 4-(chloromethyl)phenyl acetate (CMPA) and 5-thiobutil butyrolactone (Richter et al, 2008;Marsillach et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…The R allozyme is more efficient to detoxify substrates such as paraoxon, 4-(chloromethyl)phenyl acetate (CMPA) and 5-thiobutil butyrolactone (Richter et al, 2008;Marsillach et al, 2009). R allozyme homozygotes (RR carriers) metabolize lipids more efficiently than QQ carriers and additionally have a stronger defense against lipid peroxidation (Bayrak et al, 2016;Atagün et al, 2017). Moreover, PON1 hydrolyzes N-(3-oxo-dodecanoyl)-homoserine lactone, a quorum-sensing molecule, which regulates virulence and biofilm formation in many bacteria, indicating that PON1 activities have antimicrobial properties (Bar-Rogovsky et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

In Schizophrenia, PON1 Q192R Genotypes and/or Lowered Paraoxonase 1 (PON1) Enzymatic Activity are Significantly Associated with the Deficit Syndrome, Negative Symptoms, Formal Thought Disorders, Psychomotor Retardation, Excitation and Increased IgA Levels to Gram-Negative Microbiota

Matsumoto¹,

Maes²,

Maes³

et al. 2019

Preprint

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Background: Primary deficit schizophrenia (DS) is characterized by enduring negative symptoms and represents a qualitatively different disease entity with respect to non-deficit schizophrenia (NDS). No studies investigated the association between the enzyme paraoxonase 1 (PON1) and DS and its phenomenology. Methods: In this case-control study, Thai women and men, aged 18-65 years, were divided in DS (n=40) and NDS (n=40) and were compared to controls (n=40). PON1 activities against 4-(chloromethyl)phenyl acetate (CMPA) and phenylacetate were determined. Moreover, subjects were genotyped for their PON1 Q192R polymorphism and IgA levels responses directed to Gram-negative bacteria were measured. Results: DS is significantly associated with the QQ genotype and the Q allele as compared with NDS and controls. PON1 activities are significantly and inversely associated with negative symptoms, formal thought disorders, psychomotor retardation, excitation and DS. The presence of the Q allele is associated with increased IgA responses to Pseudomonas aeruginosa, Morganella morganii, and Pseudomonas putida as compared with RR carriers. Conclusions: The PON1 Q allele and lower PON1 activities especially against CMPA are associated with DS, indicating lowered quorum quenching abilities as well as lowered defenses against lipoperoxidation and immune activation. It is suggested that lowered PON1 activity in DS constitutes an impairment in the innate immune system which together with lowered natural IgM may cause lower immune regulation thereby predisposing towards greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.

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“…6 Copperinduced oxidation of isolated LDL is frequently used as an in vitro model for the resistance of LDL lipids to oxidation. 7,8 The lengthy procedure involved in LDL fractionation and the possible modification of the lipids during isolation of LDL, limit the clinical usefulness of kinetic data on LDL 'oxidizability' and justify further efforts aimed at the evaluation of the susceptibility of lipids to oxidation in no fractionated plasma or serum. 9 Several studies have used plasma or serum as a biological model in this context.…”

Section: Introductionmentioning

confidence: 99%

Association Between Plasma Lipids Profile and Lipids Oxidizability in Healthy Men

Jafari

Khan-Abadi

Nejadi

et al. 2019

J Apple Biotechnol Rep

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The aim of the present study was to determine the susceptibility of lipids to Cu-induced peroxidation in diluted plasma and its relation with plasma lipids and lipoproteins in a group of healthy men. Materials and Methods: In 100 healthy men volunteers (age range 20-55 years with a mean of 36.8±10.3 years), fasting plasma levels of lipoprotein (a) [Lp (a)], total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TG) were assayed. The Cu2+-induced lipid peroxidation was evaluated. Lipid oxidation was estimated by monitoring the change of conjugated dienes in the diluted plasma following the addition of Cu 2+. The kinetic curves of the accumulation of lipid peroxide products were prepared, and a number of quantitative parameters including lag time, time of maximal oxidation rate (T-max), and maximal accumulation of absorbing products (OD-max) were evaluated. Results: The TG concentrations were positively correlated with lag time and T-max (r=0.33, P < 0.01 and r=0.24, P < 0.05) respectively. Also, TC and LDL-C were positively correlated with OD-max (r=0.28, P < 0.01 and r=0.26, P < 0.05 respectively), and HDL-C was negatively correlated (r=-0.23, P < 0.05) with T-max. No significant correlation was observed between other variables and lipid oxidizability parameters. Conclusions: Results of this research indicate that TG increased the resistance of LDL and VLDL against initiation of lipid oxidation. In addition, HDL-C induced the susceptibility of lipid oxidizability.

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The effect of HDL-bound and free PON1 on copper-induced LDL oxidation

Cited by 14 publications

References 65 publications

Tratment With Folic Acid Increases Paraoxonase 1 Activity Thereby Improving Chronic Kidney Disease

Tratment With Folic Acid Increases Paraoxonase 1 Activity Thereby Improving Chronic Kidney Disease

In Schizophrenia, PON1 Q192R Genotypes and/or Lowered Paraoxonase 1 (PON1) Enzymatic Activity are Significantly Associated with the Deficit Syndrome, Negative Symptoms, Formal Thought Disorders, Psychomotor Retardation, Excitation and Increased IgA Levels to Gram-Negative Microbiota

Association Between Plasma Lipids Profile and Lipids Oxidizability in Healthy Men

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