Paraoxonase-1 status in patients with hereditary hemochromatosis

Martinelli, Nicola; García-Heredia, Anabel; Roca, Helena; Aranda, Núria; Arija, Victoria; Mackness, Bharti; Mackness, Michael I.; Busti, Fabiana; Aragonès, Gerard; Pedro‐Botet, Juan; Pedica, Federica; Cataldo, Ivana; Marsillach, Judit; Joven, Jorge; Girelli, Domenico; Camps, Jordi

doi:10.1194/jlr.p028977

Cited by 22 publications

(18 citation statements)

References 50 publications

(48 reference statements)

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“…Gonzalez et al (42) reported that hyperandrogenemia activated and sensitized leukocytes to glucose and increased leukocytic NADPH oxidase P47(phox) subunit gene expression and reactive oxygen species generation in normal-weight PCOS women. The increased oxidative stress was reportedly associated with insulin resistance (43), systemic inflammation, endothelial dysfunction (44,45), stimulated proliferation, testosterone production of theca cells (45,46), and increased hepatic PON1 protein expression (47,48). These findings support our results that the elevated lactonase activities and levels of PON1 might be a compensation for increased oxidative stress and inflammation in PCOS patients.…”

Section: Discussionsupporting

confidence: 81%

“…These findings support our results that the elevated lactonase activities and levels of PON1 might be a compensation for increased oxidative stress and inflammation in PCOS patients. Conversely, PON1 is sensitive to the oxidative stress status which can lead to enzyme inactivation and consumption (49), which may explain the decreased serum PON1 activity and/or levels that are associated with increased PON1 protein expression in some disease statuses (47,48). In brief, PON1 plays an important role in preventing oxidative stress and controlling inflammation, and the absolute or relative lack of PON1 lactonase activity may contribute to PCOS pathology.…”

Section: Discussionmentioning

confidence: 99%

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Lactonase activity and status of paraoxonase 1 in Chinese women with polycystic ovarian syndrome

Zhang

Liu

et al. 2015

European Journal of Endocrinology

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Objective: To study the relationship between the lactonase activities and status of paraoxonase 1 (PON1) and its association with the PON1 genetic polymorphisms in women with polycystic ovarian syndrome (PCOS). Design: A case-control study. Methods: A total of 455 PCOS patients and 441 control women were included in this study. The lactonase activities and concentrations of PON1 were assayed using 5-thiobutyl butyrolactone (TBBL) and 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase:DEPCyMCase activity. The PON1 genotypes, serum malondialdehyde (MDA) levels and total antioxidant capacity were analyzed. Results: The lactonase activities and levels of PON1 were higher in PCOS patients than in the control women. However, the NLA did not significantly differ between groups. The K108C/T variation of the PON1 gene showed decreased lactonase activities and levels of PON1 in a genotype-dependent manner (CCOCTOTT); the 192Q/R variation of the PON1 gene showed increased PON1 lactonase activities and NLA; and the 55L/M variation of the PON1 gene showed decreased lactonase activities and levels of PON1 but an increased NLA. A multivariable regression analysis showed that the K108C/T, 192Q/R, and 55L/M variations of the PON1 gene, serum apolipoprotein A1, and MDA levels were significant predictors of PON1 lactonase activity, PON1 level, and NLA. Conclusions: The serum lactonase activities and concentrations of PON1 are increased in PCOS patients. The increased oxidative stress and the K108C/T, 192Q/R, and 55L/M genetic polymorphisms of PON1 may be associated with these changes.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Lactonase activity and status of paraoxonase 1 in Chinese women with polycystic ovarian syndrome

Zhang

Liu

et al. 2015

European Journal of Endocrinology

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“…In this regard, it is worth examining Figure 8 from the publication by Besler et al [45] which shows high PON1 activity in healthy individuals, but low activity in individuals with CVD, data consistent with other studies by Camps, Joven and colleagues [46–50]. Measurement of PON1 protein levels, however show that there is apparently much higher levels of inactive or less active PON1 in the diseased individuals, suggesting that an additional measurement of PON1 protein levels (by mass spectrometry, quantitative Western blot or ELISA) will provide additional information on PON1 status and risk of disease.…”

Section: Pon1supporting

confidence: 80%

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

Furlong

Marsillach

Jarvik

et al. 2016

Chemico-Biological Interactions

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163

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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“…Serum PON1 concentrations were determined using an in-house enzyme-linked immunosorbent assay [18]. The serum concentration of C-reactive protein (CRP) was measured using a high sensitivity method (Horiba ABX, Montpellier, France).…”

Section: Biochemical Analysesmentioning

confidence: 99%

Preliminary study on serum paraoxonase-1 status and chemokine (C-C motif) ligand 2 in hospitalized elderly patients with catheter-associated asymptomatic bacteriuria

Iftimie

García-Heredia

Pujol

et al. 2016

Eur J Clin Microbiol Infect Dis

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Urinary tract infections (UTI) are common among elderly patients in residential care facilities, as well as in the hospital setting. Identifying new biochemical markers of UTI is an active line of research since UTI management is resource intensive. Paraoxonase-1 (PON1) forms part of the patient's immune system, the response-to-injury and inflammation. Our study sought to evaluate alterations in inflammation-related paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2) in patients with an indwelling catheter to assess their potential usefulness as biomarkers of infection. Patients (n = 142) who had had the urinary catheter removed and 100 healthy volunteers were recruited. In all participants we measured serum PON1 activity, PON1 concentration, CCL2, procalcitonin and C-reactive protein (CRP). Results indicated that patients had higher CCL2, CRP and procalcitonin concentrations than the control group, and lower paraoxonase activity. There were no significant differences in PON1 concentrations. When comparing the diagnostic accuracy of CRP, procalcitonin, CCL2 and the PON1-related variables in discriminating between patients with and those without UTI, we found a considerable degree of overlap between groups, i.e., a low diagnostic accuracy. However, there were significant inverse logarithmic correlations between serum paraoxonase activity and the number of days the urinary catheter had been in situ. Our results suggest that measurement of these biochemical variables may be useful in investigating complications of long-term use of these devices and help to improve the economic and clinical investment required in the management of the often-associated infection.

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Paraoxonase-1 status in patients with hereditary hemochromatosis

Cited by 22 publications

References 50 publications

Lactonase activity and status of paraoxonase 1 in Chinese women with polycystic ovarian syndrome

Lactonase activity and status of paraoxonase 1 in Chinese women with polycystic ovarian syndrome

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

Preliminary study on serum paraoxonase-1 status and chemokine (C-C motif) ligand 2 in hospitalized elderly patients with catheter-associated asymptomatic bacteriuria

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