Transcriptional activation of an anti-oxidant mouse Pon2 gene by dexamethasone

Lim, Ji Ae; Kim, Sang Hoon

doi:10.5483/bmbrep.2009.42.7.421

Cited by 17 publications

(11 citation statements)

References 29 publications

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“…Arachidonic acid [116], unesterified cholesterol [117], the licorice phytoestrogen glabidrin [118], and the hypocholesterolemic drug atorvastatin [119] also upregulate PON2 expression in various cell types. Urokinase plasminogen activator upregulates PON2 in macrophages via NADPH oxidase and the transcription factor SREBP-2 [120, 121], while in mouse fibroblasts dexamethasone increases PON2 mRNA levels [122]. In one study, pomegranate juice was found to increase PON2 in macrophages [123], while quercetin was reported to increase PON2 mRNA and protein in macrophages in vitro [124].…”

Section: Pon2mentioning

confidence: 99%

Paraoxonases-1, -2 and -3: What are their functions?

Furlong

Marsillach

Jarvik

et al. 2016

Chemico-Biological Interactions

161

122

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Paraoxonase-1 (PON1), an esterase/lactonase primarily associated with plasma high-density lipoprotein (HDL), was the first member of this family of enzymes to be characterized. Its name was derived from its ability to hydrolyze paraoxon, the toxic metabolite of the insecticide parathion. Related enzymes PON2 and PON3 were named from their evolutionary relationship with PON1. Mice with each PON gene knocked out were generated at UCLA and have been key for elucidating their roles in organophosphorus (OP) metabolism, cardiovascular disease, innate immunity, obesity, and cancer. PON1 status, determined with two-substrate analyses, reveals an individual’s functional Q192R genotype and activity levels. The three-dimensional structure for a chimeric PON1 has been useful for understanding the structural properties of PON1 and for engineering PON1 as a catalytic scavenger of OP compounds. All three PONs hydrolyze microbial N-acyl homoserine lactone quorum sensing factors, quenching Pseudomonas aeruginosa’s pathogenesis. All three PONs modulate oxidative stress and inflammation. PON2 is localized in the mitochondria and endoplasmic reticulum. PON2 has potent antioxidant properties and is found at 3- to 4-fold higher levels in females than males, providing increased protection against oxidative stress, as observed in primary cultures of neurons and astrocytes from female mice compared with male mice. The higher levels of PON2 in females may explain the lower frequency of neurological and cardiovascular diseases in females and the ability to identify males but not females with Parkinson’s disease using a special PON1 status assay. Less is known about PON3; however, recent experiments with PON3 knockout mice show them to be susceptible to obesity, gallstone formation and atherosclerosis. Like PONs 1 and 2, PON3 also appears to modulate oxidative stress. It is localized in the endoplasmic reticulum, mitochondria and on HDL. Both PON2 and PON3 are upregulated in cancer, favoring tumor progression through mitochondrial protection against oxidative stress and apoptosis.

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Section: Pon2mentioning

confidence: 99%

Paraoxonases-1, -2 and -3: What are their functions?

Furlong

Marsillach

Jarvik

et al. 2016

Chemico-Biological Interactions

161

122

View full text Add to dashboard Cite

show abstract

“…Arachidonic acid (Rosenblat et al 2010), unesterified cholesterol (Shiner et al 2007a), the licorice phytoestrogen glabidrin (Yehuda et al 2011), and the hypocholesterolemic drug atorvastatin (Rosenblat et al 2004) also upregulate PON2 expression in various cell types. Urokinase plasminogen activator upregulates PON2 in macrophages via NADPH oxidase and the transcription factor SREBP-2 (Fuhrman et al 2008; 2009), while in mouse fibroblasts dexamethasone increases PON2 mRNA levels (Lim and Kim, 2009). …”

Section: Modulation Of Pon2mentioning

confidence: 99%

Paraoxonase-2 (PON2) in brain and its potential role in neuroprotection

Costa¹,

Laat²,

Dao³

et al. 2014

NeuroToxicology

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Paraoxonase 2 (PON2) is a member of a gene family which also includes the more studied PON1, as well as PON3. PON2 is unique among the three PONs, as it is expressed in brain tissue. PON2 is a lactonase and displays anti-oxidant and anti-inflammatory properties. PON2 levels are highest in dopaminergic regions (e.g. striatum), are higher in astrocytes than in neurons, and are higher in brain and peripheral tissues of female mice than male mice. At the sub-cellular level, PON2 localizes primarily in mitochondria, where it scavenges superoxides. Lack of PON2 (as in PON2−/− mice), or lower levels of PON2 (as in male mice compared to females) increases susceptibility to oxidative stress-induced toxicity. Estradiol increases PON2 expression in vitro and in vivo, and provides neuroprotection against oxidative stress. Such neuroprotection is not present in CNS cells from PON2−/− mice. Similar results are also found with the polyphenol quercetin. PON2, given its cellular localization and antioxidant and anti-inflammatory actions, may represent a relevant enzyme involved in neuroprotection, and may represent a novel target for neuroprotective strategies. Its differential expression in males and females may explain gender differences in the incidence of various diseases, including neurodevelopmental, neurological, and neurodegenerative diseases.

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“…NADPH oxidase, which produces superoxide anion free radicals, has been previously shown to be a molecular target of quercetin [15]. Furthermore, it has been recently demonstrated that the transcriptional activation of the PON2 gene is directly regulated by glucocorticoid-glucocorticoid receptor complexes, which in turn may affect the transactivation of AP-1 [16]. …”

Section: Resultsmentioning

confidence: 99%

Effect of Quercetin on Paraoxonase 2 Levels in RAW264.7 Macrophages and in Human Monocytes—Role of Quercetin Metabolism

Boesch-Saadatmandi

Pospissil

Graeser

et al. 2009

IJMS

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There is increasing evidence that the intracellular antioxidant enzyme paraoxonase 2 (PON2) may have a protective function in the prevention of atherogenesis. An enhancement of PON2 activity by dietary factors including flavonoids is therefore of interest. In the present study we determined the effect of quercetin on paraoxonase 2 levels in cultured murine macrophages in vitro and in overweight subjects with a high cardiovascular risk phenotype supplemented with 150 mg quercetin/day for 42 days in vivo. Supplementation of murine RAW264.7 macrophages in culture with increasing concentrations of quercetin (1, 10, 20 μmol/L) resulted in a significant increase in PON2 mRNA and protein levels, as compared to untreated controls. Unlike quercetin, its glucuronidated metabolite quercetin-3-glucuronide did not affect PON2 gene expression in cultured macrophages. However the methylated quercetin derivative isorhamnetin enhanced PON2 gene expression in RAW264.7 cells to similar extent like quercetin. Although supplementing human volunteers with quercetin was accompanied by a significant increase in plasma quercetin concentration, dietary quercetin supplementation did not change PON2 mRNA levels in human monocytes in vivo. Current data indicate that quercetin supplementation increases PON2 levels in cultured monocytes in vitro but not in human volunteers in vivo.

show abstract

Transcriptional activation of an anti-oxidant mouse Pon2 gene by dexamethasone

Cited by 17 publications

References 29 publications

Paraoxonases-1, -2 and -3: What are their functions?

Paraoxonases-1, -2 and -3: What are their functions?

Paraoxonase-2 (PON2) in brain and its potential role in neuroprotection

Effect of Quercetin on Paraoxonase 2 Levels in RAW264.7 Macrophages and in Human Monocytes—Role of Quercetin Metabolism

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