Pharmacological Interactions of Paraoxonase 1 (PON1): A HDL-Bound Antiatherogenic Enzyme

Mahrooz, Abdolkarim

doi:10.2174/1574884711666160915153433

Cited by 25 publications

(19 citation statements)

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“…A detailed review of the relationship between PON1 and pharmacological agents is beyond the scope of this review. A comprehensive review by Mahrooz 48 describes the interactions of PON1 with cardiovascular drugs, antidiabetic drugs, antibiotics, anticancer drugs, antidepressants and contraceptives. There remains a large amount of incongruences in the study findings, and the clinical relevance of PON1 remains to be further investigated.…”

Section: Pharmacological Interactions Of Pon1mentioning

confidence: 99%

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Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance

Shunmoogam¹,

Naidoo²,

Chilton³

2018

VHRM

122

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Paraoxonase-1 (PON1) is a high-density lipoprotein-associated esterase and is speculated to play a role in several human diseases including diabetes mellitus and atherosclerosis. Low PON1 activity has been associated with increased risk of major cardiovascular events, therefore a variety of studies have been conducted to establish the cardioprotective properties and clinical relevance of PON1. The major aim of this review was to highlight the important studies and to subsequently assess if PON1 has clinical relevance. A review of the literature showed that there is currently insufficient data to suggest that PON1 has clinical relevance. It is our opinion that robust studies are required to clarify the clinical relevance of PON1.

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Section: Pharmacological Interactions Of Pon1mentioning

confidence: 99%

“…Mahrooz attributes “dosage and type of drug, length of treatment, genetic variations, particularly loss-of-function polymorphisms, and the model used (cultured cells, animal studies, or human studies)” for the variability of study results. 48 …”

Section: Pharmacological Interactions Of Pon1mentioning

confidence: 99%

Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance

Shunmoogam¹,

Naidoo²,

Chilton³

2018

VHRM

122

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“…PON is an antioxidant enzyme with cardioprotective activities such as lipids detoxification and removing oxidized lipid from lipoproteins [11,12]. Regarding the increased ROS production and increased oxidative stress in OSA patients, PON activity is expected to increase in these patients to reduce the damages in this condition.…”

Section: Discussionmentioning

confidence: 99%

“…Lactonase activity is the primary activity of PON. Furthermore, PON degrades lipid peroxides in lipoproteins; it also protects lipoproteins from oxidation [12]. In addition, it has esterase activity degrading the nerve agents and organophosphates [12].…”

Section: Introductionmentioning

confidence: 99%

Paraoxonase Activity in Patients with Obstructive Sleep Apnea: a Systematic Review and Meta-analysis

Fadaei

Safari‐Faramani

Rezaei

et al. 2019

SN Compr. Clin. Med.

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Obstructive sleep apnea (OSA) is a common sleep disorder affecting high proportion of the population. This disorder is associated with an increase in the oxidative stress and cardiovascular disease. Paraoxonase (PON) is a lipolactonase enzyme removing toxic lipids and decreasing lipoprotein oxidation. The present study was conducted to reassess possible alternation of PON activities in OSA patients. Studies measured PON activities in OSA were searched in PubMed, Scopus, EMBASE, Web of Science databases, and Cochrane Library from January 1990 to February 2019. Screening of the studies was performed by two authors independently according to title, abstract, and full text. Quality of studies was assessed by Newcastle-Ottawa Quality Assessment Scale, and random-effect model was used for evaluating the effect of OSA on PON activities. A total of 97 records were found in searching, 39 duplicated records were removed, and 5 studies for PON activity and 2 studies for aryl-esterase (ARE) activity were included in the meta-analysis. Pooled analysis showed no significant difference in terms of PON activity between OSA and control groups (p = 0.434). Similarly, ARE demonstrated no significant difference between OSA and control groups (p = 0.515). Subgroup meta-analysis according to age, BMI, AHI, and diagnosis criteria demonstrated no significant difference between two groups. The results of this study indicated no association between OSA and PON activities as an antioxidant enzyme. However, a relatively low number of studies limited us to conclude a definite conclusion; therefore, more studies are needed in this regard.

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“…both paraoxonase and arylesterase activities for hydrolyzing and detoxifying toxic organophosphorus compounds, interaction with various drugs, and antioxidant activity by hydrolyzing oxidized phospholipids in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) (2)(3)(4)(5)(6). PON1 expression can be modulated by diet, life-style and pharmaceuticals (7), but also by genetic polymorphisms in the promoter and coding regions (8)(9)(10).…”

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confidence: 99%

PON1 deficiency promotes TREM2 pathway-mediated microglial phagocytosis and inhibits LPS-induced pro-inflammatory cytokines release

Zhang

Dong

et al. 2020

Preprint

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Background Paraoxonase 1 (PON1), an HDL-associated enzyme, plays an anti-inflammatory role in the cardiovascular system. Levels of serum PON1 and polymorphisms in this gene were linked to Alzheimer disease (AD) and Parkinson disease (PD), but its function in the neuroimmune system and AD are not clear. Methods PON1 knockout rats previously generated by our lab were used to investigate the role of PON1 in microglia. Wild type (WT) rats and PON1 knockout (KO) rats were injected with lipopolysaccharide (LPS, 5 or 20 mg/kg) and the survival rates were compared. Microglia on the sections of rat brain tissues were immunostained with anti-Iba1 antibody and the microglia morphology was compared. The phagocytosis, cytokines release and transcriptome of primary microglia cells treated with or without LPS were analyzed. The interactions between PON1 and TREM2 were detected by co-immunoprecipitation (co-IP) using rat brain tissues or over-expressed BV2 cell lysates. Results The expression of PON1 was detected in human and rat brain tissues and rat primary microglia. Knockout of PON1 in rat brain tissues protected against LPS-induced lethality by decreasing TNF-α expression. PON1 knockout in microglia increased TREM2 (triggering receptor expressed in myeloid cells 2) expressing and phagocytosis, but decreased production of pro-inflammatory cytokines such as IL-1β, IL-6, IL-12, IL-18 especially TNF-α (M1-phenotype markers) and increased IL-10 (M2-phenotype marker) release induced by LPS. PON1 knockout activated TREM2 pathway but decreased LPS-induced ERK activation. The phagocytosis promoting effect was reversed by administration of recombinant PON1 protein. The interaction between PON1 and TREM2 was verified and was associated with the localization of TREM2 in lysosomes. Conclusions These results suggest an inhibitory role of PON1 in microglial phagocytosis dependent on its interaction with TREM2. These findings provide novel insights into the role of PON1 in neuroinflammation and highlight TREM2 as a potential target for Alzheimer’s disease therapy.

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Pharmacological Interactions of Paraoxonase 1 (PON1): A HDL-Bound Antiatherogenic Enzyme

Cited by 25 publications

References 0 publications

Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance

Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance

Paraoxonase Activity in Patients with Obstructive Sleep Apnea: a Systematic Review and Meta-analysis

PON1 deficiency promotes TREM2 pathway-mediated microglial phagocytosis and inhibits LPS-induced pro-inflammatory cytokines release

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