Transcriptional regulation of human Paraoxonase 1 by nuclear receptors

A direct and an indirect relationship between paraoxonase 1 (PON1) and atherosclerosis exists. Given PON1's physical location within high‐density lipoprotein (HDL) particles and its recognized enzyme activity, it is certainly reasonable to suggest that PON1 facilitates the antiatherogenic nature of HDL particles. PON1 also plays a role in regulating reverse cholesterol transport, antioxidative, anti‐inflammatory, antiapoptotic, vasodilative, and antithrombotic activities and several endothelial cell functions. HDL dysfunctionality is a more recent issue and seems to be centered on pathological conditions affecting HDL structure and size profiles. This review is focused on the role of PON1 status in different atherosclerosis‐related diseases that we have studied over the last twenty years (coronary heart disease, acute ischemic stroke, diabetes mellitus type 2, end‐stage renal disease, chronic obstructive pulmonary disease, and sarcoidosis) with the aim to determine the true value of PON1 as a biomarker. The role of PON1 in cancer is also covered, as risk factors and mechanisms underlying both atherosclerosis and cancer share common features.

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“…PON1 showed atheroprotective effects by lowering MDA and tumor necrosis factor alpha. This was not the case for PON3 …”

Section: Pon Gene Expression In Animal Studies—role In Atherosclerosismentioning

confidence: 87%

Paraoxonase 1 and atherosclerosis‐related diseases

et al. 2019

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“…Rainwater et al [149] estimated that only 1 to 6% of PON1 activity is determined by external factors and that genotype could influence even this external effect. Recently, Ruiz et al [150] revised the role of several nuclear receptors on the modulation of PON1 expression.…”

Section: Pon1 As a Novel Target In Psychiatric Disordersmentioning

confidence: 99%

Why Should Psychiatrists and Neuroscientists Worry about Paraoxonase 1?

et al. 2019

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Background: Nitro-oxidative stress (NOS) has been implicated in the pathophysiology of psychiatric disorders. The activity of the polymorphic antioxidant enzyme paraoxonase 1 (PON1) is altered in diseases where NOS is involved. PON1 activity may be estimated using different substrates some of which are influenced by PON1 polymorphisms. Objectives: 1) to review the association between PON1 activities and psychiatric diseases using a standardized PON1 substrate terminology in order to offer a state-of-the-art review; and 2) to review the efficacy of different strategies (nutrition, drugs, lifestyle) to enhance PON1 activities. Methods: The PubMed database was searched using the terms paraoxonase 1 and psychiatric diseases. Moreover, the database was also searched for clinical trials investigating strategies to enhance PON1 activity. Results: The studies support decreased PON1 activity as determined using phenylacetate (i.e., arylesterase or AREase) as a substrate, in depression, bipolar disorder, generalized anxiety disorder (GAD) and schizophrenia, especially in antipsychotic-free patients. PON1 activity as determined with paraoxon (i.e., POase activity) yields more controversial results, which can be explained by the lack of adjustment for the Q192R polymorphism. The few clinical trials investigating the influence of nutritional, lifestyle and drugs on PON1 activities in the general population suggest that some polyphenols, oleic acid, Mediterranean diet, no smoking, being physically active and statins may be effective strategies that increase PON1 activity. Conclusion: Lowered PON1 activities appear to be a key component in the ongoing NOS processes that accompany affective disorders, GAD and schizophrenia. Treatments increasing attenuated PON1 activity could possibly be new drug targets for treating these disorders.

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“…These polymorphisms may also affect the risk for disease development and the severity of disease. 15 Studies have identified two common polymorphisms in the coding region (at positions 55 and 192) that have been reported to affect the activity and concentration of PON1. 16 The leucine/methionine polymorphism at position 55 of the amino acid sequence (L55M) has been associated with changes in PON1 serum concentrations, and an association with the occurrence of cardiovascular disease was also observed.…”

Section: Pon1 Polymorphismsmentioning

confidence: 99%

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

Shunmoogam¹,

Naidoo²,

Chilton³

2018

VHRM

121

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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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Transcriptional regulation of human Paraoxonase 1 by nuclear receptors

Cited by 29 publications

References 77 publications

Paraoxonase 1 and atherosclerosis‐related diseases

Paraoxonase 1 and atherosclerosis‐related diseases

Why Should Psychiatrists and Neuroscientists Worry about Paraoxonase 1?

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

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