Paraoxonase (PON1) deficiency is associated with increased macrophage oxidative stress: studies in PON1-knockout mice

Rozenberg, Orit

doi:10.1016/s0891-5849(02)01429-6

Cited by 257 publications

(169 citation statements)

References 44 publications

Supporting

Mentioning

154

Contrasting

Unclassified

Order By: Relevance

“…Together, these events decreased the OSI after three months of atorvastatin administration. The mechanism involved in this phenomenon may be the ability of atorvastatin to reduce the production of reactive oxygen species [34,39,40,45]. On the other hand, atorvastatin may play a role in protecting LDL, and HDL from oxidation by increasing antioxidant activity of the HDL-associated enzyme, PON1 [16,20,31,36,41].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, PON1 protects LDL particles against copper-induced lipid oxidation in vitro [3,28,29] and transgenic mice overexpressing the human PON1 gene have reduced atherosclerotic lesions [48]. Moreover, PON1 knockout mice display accelerated atherosclerosis progression and increased lipid oxidation [40,42,43]. Epidemiological studies indicate that high PON1 activity is inversely associated with the progression of atherosclerosis and reduction in the incidence of coronary artery disease [2,4,25,26,30,33].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of atorvastatin on paraoxonase1 (PON1) and oxidative status

Nagila

Permpongpaiboon

Tantrarongroj

et al. 2009

Pharmacological Reports

View full text Add to dashboard Cite

Abstract:It has been proposed that paraoxonase1 (PON1), a high density lipoprotein (HDL)-associated esterase/lactonase, has antiatherosclerotic properties. The activity of PON1 is influenced by PON1 polymorphisms. However, the influence of PON1 polymorphisms on PON1 activity and oxidative stress in response to lipid-lowering drugs remains poorly understood. The objective of the present study was to investigate the effects of atorvastatin on PON1 activity and oxidative status. The influence of PON1 polymorphisms on PON1 activity and oxidative status in response to atorvastatin treatment was also evaluated. In total, 22 hypercholesterolemic patients were treated with atorvastatin at a dose of 10 mg/day for 3 months. Lipid profile, lipid oxidation markers (malondialdehyde (MDA), conjugated diene (CD), total peroxides (TP)), total antioxidant substance (TAS), oxidative stress index (OSI), and paraoxonase1 activity were determined before and after treatment. L55M, Q192R, and T(-107)C PON1 polymorphisms were also determined. Atorvastatin treatment significantly reduced the levels of total cholesterol (24.5%), low density lipoprotein (LDL) cholesterol (25.4%), triglycerides (24.4%), CD (4.4%), MDA (15.2%), TP (13.0%) and OSI (24.0%), and significantly increased the levels of TAS (27.3%), and PON1 activity (14.0%). Interestingly, the increase in PON1 activity and the reduction in oxidative stress in response to atorvastatin were influenced only by the PON1 T-107C polymorphism. Atorvastatin treatment improved the lipid profile, lipid oxidation, and oxidative/antioxidative status markers including the activity of PON1 towards paraoxon. These beneficial effects may be attributed to the antioxidant properties of statins and the increase in PON1 activity. The increase in PON1 activity was enhanced by the PON1 T-107C polymorphism.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of atorvastatin on paraoxonase1 (PON1) and oxidative status

Nagila

Permpongpaiboon

Tantrarongroj

et al. 2009

Pharmacological Reports

View full text Add to dashboard Cite

show abstract

“…In vitro uptake of unchanged LDL particles by those cells is very slow. In mice with PON1 knockout, macrophages have shown increased oxidative stress and reduction of cellular glutathione concentrations (an antioxidant) (Rozenberg et al 2003), thus leading to LDL oxidation and resulting in macrophage foam cell formation (Aviram and Rosenblat 2004). In addition, mice lacking PON1/apo E proteins exhibited more severe atheroslerotic changes as their LDL particles were more sensitive to oxidation .…”

Section: Pon1 Changes In Different Diseasesmentioning

confidence: 99%

A review of paraoxonase 1 properties and diagnostic applications

Kulka¹

2016

Polish Journal of Veterinary Sciences

View full text Add to dashboard Cite

Paraoxonase 1 (PON1) is an arylesterase associated with serum high density lipoprotein particles. Its name is derived from hydrolyzing one of several organophosphate compounds, namely paraoxon. Recent studies have shown that PON1 plays a protective role in diseases associated with oxidative stress such as atherosclerosis and diabetes mellitus. Studies have demonstrated reduction-oxidative state changes involving PON1 in humans and laboratory animal models. Although there is less information about the role of this enzyme in veterinary medicine, new data suggest that PON1 might be a new oxidative stress marker in animal patients, similarly to humans.

show abstract

“…A third relevant enzyme is the PON protein product of the paraoxonase PON1 gene, which destroys environmental toxins that target AChE (12). PON also possesses peroxidase-like activity (13), and can directly reduce oxidative stress in macrophages and in serum (14). Polymorphisms in the ACHE, BCHE, and PON1 genes could therefore affect both the environmental and the experience-related elements of anxiety.…”

mentioning

confidence: 99%

Acetylcholinesterase/paraoxonase genotype and expression predict anxiety scores in Health, Risk Factors, Exercise Training, and Genetics study

Sklan

Lowenthal

Korner

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

125

View full text Add to dashboard Cite

Anxiety involves complex, incompletely understood interactions of genomic, environmental, and experience-derived factors, and is currently being measured by psychological criteria. Here, we report previously nonperceived interrelationships between expression variations and nucleotide polymorphisms of the chromosome 7q21-22 acetylcholinesterase-paraoxonase 1 (ACHE-PON1) locus with the trait-and state-anxiety measures of 461 healthy subjects from the Health, Risk Factors, Exercise Training, and Genetics Family Study. The AChE protein controls the termination of the stress-enhanced acetylcholine signaling, whereas the PON protein displays peroxidase-like activity, thus protecting blood proteins from oxidative stress damages. Serum AChE and PON enzyme activities were both found to be affected by demographic parameters, and showed inverse, reciprocal associations with anxiety measures. Moreover, the transient scores of state anxiety and the susceptibility score of trait anxiety both appeared to be linked to enzyme activities. This finding supported the notion of corresponding gene expression relationships. Parallel polymorphisms in the ACHE and PON1 genes displayed apparent associations with both trait-and state-anxiety scores. Our findings indicate that a significant source of anxiety feelings involves inherited and acquired parameters of acetylcholine regulation that can be readily quantified, which can help explaining part of the human variance for state and trait anxiety.

show abstract

Paraoxonase (PON1) deficiency is associated with increased macrophage oxidative stress: studies in PON1-knockout mice

Cited by 257 publications

References 44 publications

Effect of atorvastatin on paraoxonase1 (PON1) and oxidative status

Effect of atorvastatin on paraoxonase1 (PON1) and oxidative status

A review of paraoxonase 1 properties and diagnostic applications

Acetylcholinesterase/paraoxonase genotype and expression predict anxiety scores in Health, Risk Factors, Exercise Training, and Genetics study

Contact Info

Product

Resources

About