A homogeneous cell-based assay for measurement of endogenous paraoxonase 1 activity

Ahmad, Syed Sayeed; Carter, Jade J.; Scott, J. E.

doi:10.1016/j.ab.2010.01.023

Cited by 14 publications

(17 citation statements)

References 35 publications

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“…Traditionally used as a platelet aggregation inhibitor, low-dose aspirin (acetylsalicylic acid) was reported to increase serum PON1 activity (by *13%) in coronary patients (44), although administration of aspirin did not alter the serum PON1 activity of healthy volunteers (180). Aspirin was also found to increase PON1 activity in HuH7 cells (6). Some derivatives of aspirin, such as nitro-aspirin and the aspirin metabolite salicylic acid, were also able to increase PON1 expression and activity (292).…”

Section: Pharmacological Modulators Of Ponsmentioning

confidence: 96%

The Human Paraoxonase Gene Cluster As a Target in the Treatment of Atherosclerosis

She

Chen

Yan

et al. 2012

Antioxidants & Redox Signaling

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The paraoxonase (PON) gene cluster contains three adjacent gene members, PON1, PON2, and PON3. Originating from the same fungus lactonase precursor, all of the three PON genes share high sequence identity and a similar b propeller protein structure. PON1 and PON3 are primarily expressed in the liver and secreted into the serum upon expression, whereas PON2 is ubiquitously expressed and remains inside the cell. Each PON member has high catalytic activity toward corresponding artificial organophosphate, and all exhibit activities to lactones. Therefore, all three members of the family are regarded as lactonases. Under physiological conditions, they act to degrade metabolites of polyunsaturated fatty acids and homocysteine (Hcy) thiolactone, among other compounds. By detoxifying both oxidized low-density lipoprotein and Hcy thiolactone, PONs protect against atherosclerosis and coronary artery diseases, as has been illustrated by many types of in vitro and in vivo experimental evidence. Clinical observations focusing on gene polymorphisms also indicate that PON1, PON2, and PON3 are protective against coronary artery disease. Many other conditions, such as diabetes, metabolic syndrome, and aging, have been shown to relate to PONs. The abundance and/or activity of PONs can be regulated by lipoproteins and their metabolites, biological macromolecules, pharmacological treatments, dietary factors, and lifestyle. In conclusion, both previous results and ongoing studies provide evidence, making the PON cluster a prospective target for the treatment of atherosclerosis. Antioxid. Redox Signal. 16, 597-632.

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Section: Pharmacological Modulators Of Ponsmentioning

confidence: 96%

The Human Paraoxonase Gene Cluster As a Target in the Treatment of Atherosclerosis

She

Chen

Yan

et al. 2012

Antioxidants & Redox Signaling

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“…Activation of the transcription factors was in turn mediated by activation by pivastatin of mitogen activated protein kinases p44/42, raising the possibility that other factors acting through this pathway may affect PON1 expression. Still, in HuH7 cells, simvastatin was recently shown to increase PON1 activity by two-fold with an EC50 of 6.8 uM [28]. …”

Section: Factors That May Increase Pon1 Activity or Expressionmentioning

confidence: 99%

“…It should also be noted that PON1 had been reported to hydrolyze aspirin and nitro-aspirin [35]. Aspirin also increased PON1 activity (by 2-fold) in HuH7 cells with an EC50 of 19 uM [28]. The cholesterol lowering drug probucol (500 mg/kg/day for 14 weeks) was found to up-regulate serum paraoxonase activity and PON1 expression in hepatocytes of hypercholesterolemic rabbits [36].…”

Section: Factors That May Increase Pon1 Activity or Expressionmentioning

confidence: 99%

Pharmacological and dietary modulators of paraoxonase 1 (PON1) activity and expression: The hunt goes on

Costa

Giordano

Furlong

2011

Biochemical Pharmacology

170

115

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Paraoxonase 1 (PON1) is a high density lipoprotein (HDL)-associated enzyme displaying esterase and lactonase activity. PON1 hydrolyzes several organophosphorus (OP) insecticides and nerve agents, a number of exogenous and endogenous lactones, and metabolizes toxic oxidized lipids of low density lipoproteins (LDL) and HDL. As such, PON1 plays a relevant role in determining susceptibility to OP toxicity, cardiovascular diseases and several other diseases. Serum PON1 activity in a given population can vary by at least 40-fold. Most of this variation can be accounted for by genetic polymorphisms in the coding region (Q192R, L55M) and in the promoter region (T-108C). However, exogenous factors may also modulate PON1 activity and/or level of expression. This paper examines various factors that have been found to positively modulate PON1. Certain drugs (e.g. hypolipemic and anti-diabetic compounds), dietary factors (antioxidants, polyphenols), and life-style factors (moderate alcohol consumption) appear to increase PON1 activity. Given the relevance of PON1 in protecting from certain environmental exposure and from cardiovascular and other diseases, there is a need for further mechanistic, animal, and clinical research in this area, and for consideration of possible alternative strategies for increasing the levels and activity of PON1.

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“…However, administration of aspirin to healthy volunteers did not alter serum PON1 activity in another study. Aspirin also increased PON1 activity in HuH7 cells 36 . Various other pharmaceutical drugs have been investigated in different experimental protocols for their effects on PON1 activityand/or expression.…”

Section: Discussionmentioning

confidence: 99%

Antidepressant and antipsychotic drugs differentially affect PON1 enzyme activity

Avcıkurt

Sinan

Köçkar

2014

Journal of Enzyme Inhibition and Medicinal Chemistry

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Human serum paraoxonase (PON1, EC 3.1.8.1.) is a high-density lipid (HDL)-associated, calciumdependent enzyme. In this study, the effects of Haloperidol, Fluoxetine hydrochloride, Diazepam and Acepromazine drugs used for the therapy of antidepressant and antipsychotic diseases, on paraoxonase enzyme activity was studied in in vitro inhibition studies on purified human serum PON1. PON1 enzyme was purified from human blood using two-step procedures, namely, ammonium sulfate precipitation and sepharose-4B-l-tyrosine-1-napthylamine hydrophobic interaction chromatography. The overall purification of human serum PON1 was obtained in a activity of 109.29 U/mL and this enzyme was purified 125-fold. The SDSpolyacrylamide gel electrophoresis of the enzyme indicates a single band with an apparent MW of 43 kDa. Inhibition studies indicated that haloperidol and fluoxetine hydrocloride were effective inhibitors on purified human serum PON1 activity with IC 50 of 0.187 and 3.08 mM values, respectively. The kinetics of interaction of haloperidol and fluoxetine hydrocloride with the purified human serum PON1 indicated uncompetitive inhibiton pattern with K i of 4.15 and 0.007 mM, respectively.

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A homogeneous cell-based assay for measurement of endogenous paraoxonase 1 activity

Cited by 14 publications

References 35 publications

The Human Paraoxonase Gene Cluster As a Target in the Treatment of Atherosclerosis

The Human Paraoxonase Gene Cluster As a Target in the Treatment of Atherosclerosis

Pharmacological and dietary modulators of paraoxonase 1 (PON1) activity and expression: The hunt goes on

Antidepressant and antipsychotic drugs differentially affect PON1 enzyme activity

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