Paraoxonase 1 Interactions with HDL, Antioxidants and Macrophages Regulate Atherogenesis – A Protective Role for HDL Phospholipids

Efrat, Michal; Aviram, Michael

doi:10.1007/978-1-60761-350-3_14

Cited by 56 publications

(36 citation statements)

References 66 publications

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Section: Exposure To Ufps Reduced Hdl Anti-oxidant Capacity and Pon Amentioning

confidence: 99%

“…Paraoxonase 1 (PON1) is an HDL-associated lactonase harboring anti-oxidant and anti-atherogenic properties ( 34 ). PON1 increases HDL binding to macrophages which, in turn, promotes HDLmediated cholesterol effl ux ( 34 ). The ability of HDL to inhibit LDL oxidation and lipid peroxidation is mediated, in part, through PON ( 35 ).…”

Section: Exposure To Ufps Reduced Hdl Anti-oxidant Capacity and Pon Amentioning

confidence: 99%

See 1 more Smart Citation

Ambient ultrafine particles alter lipid metabolism and HDL anti-oxidant capacity in LDLR-null mice

Navab

Pakbin

et al. 2013

Journal of Lipid Research

100

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Section: Exposure To Ufps Reduced Hdl Anti-oxidant Capacity and Pon Amentioning

confidence: 99%

Section: Exposure To Ufps Reduced Hdl Anti-oxidant Capacity and Pon Amentioning

confidence: 99%

Ambient ultrafine particles alter lipid metabolism and HDL anti-oxidant capacity in LDLR-null mice

Navab

Pakbin

et al. 2013

Journal of Lipid Research

100

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“…It has been shown that small HDL3 particles have higher PON1 antioxidant activity than large HDL2 particles 18) . This protective effect is mediated by HDL and its associated proteins as PON1 19) . However, it is also known that there is an inverse relationship between HDL-C and the risk of CAD development 20) .…”

Section: Subjectsmentioning

confidence: 99%

Effects of Anaerobic Training on Paraoxonase-1 Enzyme (PON1) Activities of High Density Lipoprotein Subgroups and Its Relationship with PON1-Q192R Phenotype

Turgay

Şişman

Aksu

2015

JAT

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Aim: Paraoxonase-1 (PON1) is an antiatherosclerotic enzyme located on high-density lipoprotein (HDL). The effects of anaerobic exercise on PON1 activity are unknown. Here we investigated the effects of anaerobic judo training on three different activities of same PON1 enzyme (TDPON1), including basal PON1, salt-stimulated PON1 (SPON1), and arylesterase (AE) activities, of serum, HDL, and HDL subgroups (HDLs; HDL and its subgroups) and its relationship with PON1-Q192R phenotype (PON1P). Methods: Our study included 18 Turkish national female judoists (mean age: 17.9 0.8 years). Before and after 5 months of anaerobic training, critical speed (CS), TDPON1 activities, cholesterol levels in the serum and supernatants of HDLs obtained by polyethylene glycol, and other major blood lipids and lipoproteins (BLLPs) including triglycerides were determined using blood samples taken after overnight fasting. PON1P groups (PGs) were categorized as QQ (QG; persons with low activity) and R carriers (QR RR) (RG; persons with high activity) according to SPON1/AE activity ratios. The results were considered statistically significant at P ≤ 0.05. Results: Anaerobic training resulted in significantly increased the cholesterol levels of HDLs (except HDL2-C) in all subjects, but not HDLs-C in PGs. Anaerobic training resulted in significant increases in most TDPON1 activities of serum and HDLs in all subjects and (except AE) in PGs, whereas SPON1 and HDL2 AE activities increased only in the RG, which was related to PON1P. However, PON1P was not related to other measured markers, including basal BLLP profiles. Conclusions: Anaerobic training improved most TDPON1 activities of serum and HDLs and HDLs -C levels (except HDL2-C) in all subjects, but not HDLs-C in PGs. The beneficial effects of anaerobic training on SPON1 and HDL2 AE activities were depend on PON1P. The lack of response of HDL2-C to anaerobic exercise will require further research. J Atheroscler Thromb, 2015; 22: 313-326.

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“…The scavenger receptor class B type 1 (SR-B1) represents an alternate pathway for HDL-mediated cholesterol efflux. While PON1 protects HDL and LDL particles against oxidation, it also enhances RCT by facilitating the binding of HDL particles to macrophages (22–24). Incubation of J774A.1 macrophages with fluorescently labeled PON1 shows that PON1 binds to low-affinity sites and is internalized (25).…”

Section: Hdl Pon1 and Reverse Cholesterol Transportmentioning

confidence: 99%

Cholesterol reduction and macrophage function: role of paraoxonases

White¹,

Anantharamaiah

2017

Current Opinion in Lipidology

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Purpose of review Unregulated uptake of oxidized LDL by macrophages to form foam cells is the hallmark for atherosclerosis. The paraoxonase (PON) family of enzymes play a critical role in attenuating atherosclerotic lesion formation by hydrolyzing lipid peroxides (LOOHs) and preventing the oxidation of LDL particles and by enhancing HDL-mediated cholesterol efflux. Findings in recent years suggest novel mechanisms by which PON isoforms interact with macrophages to regulate cholesterol metabolism and cellular function. Recent findings The association of PON with HDL particles facilitates binding of the particle to macrophages and ABCA1-dependent cholesterol efflux. The hydrolysis of membrane phospholipids by PON generates lysophosphatidylcholine which is shown to regulate expression of cholesterol transport proteins. The PON family also regulates multiple aspects of macrophage function. PON attenuates inflammation and prevents induction of apoptosis via activation of an SR-B1-dependent signaling mechanism. PON limits macrophage-dependent oxidant formation by preventing activation of the membrane-associated NADPH oxidase and by stabilizing mitochondria. PON also promotes the differentiation of macrophages to an anti-inflammatory phenotype. This function appears to be independent of PON enzymatic activity and, rather, is dependent on the ability of endogenous sulfhydryls to neutralize pro-inflammatory peroxides. Summary In recent years, the therapeutic efficacy of HDL-based therapies has been subject to dispute. Pharmacological approaches that target an increase in the expression and/or activity of PON may facilitate macrophage cholesterol metabolism and attenuate inflammatory injury.

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Paraoxonase 1 Interactions with HDL, Antioxidants and Macrophages Regulate Atherogenesis – A Protective Role for HDL Phospholipids

Cited by 56 publications

References 66 publications

Ambient ultrafine particles alter lipid metabolism and HDL anti-oxidant capacity in LDLR-null mice

Ambient ultrafine particles alter lipid metabolism and HDL anti-oxidant capacity in LDLR-null mice

Effects of Anaerobic Training on Paraoxonase-1 Enzyme (PON1) Activities of High Density Lipoprotein Subgroups and Its Relationship with PON1-Q192R Phenotype

Cholesterol reduction and macrophage function: role of paraoxonases

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