Serum homocysteine levels and paraoxonase 1 activity in preschool aged children in Greece

Karikas, George A.; Kriebardis, Anastasios G.; Samara, Ioanna; Schulpis, Kleopatra H.; Papachristodoulou, Maria; Fytou-Pallikari, Athena

doi:10.1515/cclm.2006.110

Cited by 13 publications

(9 citation statements)

References 12 publications

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“…In clinical investigations, serum PON activity has been reported to be negatively associated with the serum Hcy concentration (118,163,165,182,185). One study reported that the hydrolytic activity of human PON1 toward Hcythiolactone is associated with the PON1-192-Arg/Arg and PON1-55-Leu/Leu genotypes and strongly correlated with PON1's hydrolytic activity toward organophosphate paraoxon substrates (182).…”

Section: B Pons Protect Against Hcy Toxicitymentioning

confidence: 99%

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: B Pons Protect Against Hcy Toxicitymentioning

confidence: 99%

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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“…Now an elevated plasma tHcy level is well recognized as an important vascular risk factor and atherosclerosis in the coronary, cerebrovascular and peripheral arterial circulation [6–9], even if the degree of hyperhomocysteinaemia is moderate. Among the determinants which predispose to premature thromboembolic and atherothrombotic events, serum activity of paraoxonase 1 (PON1), which is mainly synthesized in the liver [10], has been shown to be a predictor of cardiovascular disease [11,12] and to be negatively correlated with serum tHcy levels [13,14]. Moreover, PON1 is a thiolactonase, which hydrolyses homocysteine thiolactone to Hcy.…”

Section: Introductionmentioning

confidence: 99%

Homocysteine threshold value based on cystathionine beta synthase and paraoxonase 1 activities in mice

Hamelet

Aït-Yahya-Graison

et al. 2007

Eur J Clin Investigation

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“…Furthermore, preterm babies have 24% lower activities compared with term babies (Ecobichon and Stephens 1973), suggesting that PON1 levels in the fetus may be even lower. A few studies have measured PON1 activities in healthy young children at single points in time (Garces et al 2008; Karikas et al 2006; Sumegova et al 2007; Vincent-Viry et al 2003), but only one study has described the ontogenetic profile of PON1 activity in the same individuals over time. This study (Cole et al 2003) of nine children demonstrated high inter-individual variation of PON1 from birth to 2 years of age; PON1 activities increased over time and reached a plateau between 6 months and 2 years of age in most, but not all, individuals.…”

mentioning

confidence: 99%

Developmental Changes in PON1 Enzyme Activity in Young Children and Effects of PON1 Polymorphisms

Huen

Harley

Brooks

et al. 2009

Environ Health Perspect

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BackgroundParaoxonase 1 (PON1) is an enzyme that detoxifies activated organophosphorus pesticides (OPs) and is also involved in oxidative stress pathways.ObjectivesPON1 activity in newborns is lower than in adults, but the ontogeny of PON1 activity is poorly characterized in young children. We examined the effects of age and PON1 genotype on enzyme activity in a birth cohort of Mexican-American children.MethodsWe determined three substrate-specific measures of PON1 activity in 1,143 plasma samples collected longitudinally from 458 children at five time points from birth through 7 years of age, and genotyped PON1 polymorphisms at positions 192 and –108 in these children.ResultsContrary to previous reports that PON1 activities plateau by 2 years of age, we observed an age-dependent increase in all three PON1 measures from birth through 7 years of age (p < 0.0001). The PON1192 genotype significantly modified the effect of age on paraoxonase (POase) activity (p < 0.0001) such that increases in enzyme activity with age were influenced by the number of R alleles in a dose-dependent manner. Children with the PON1-108CC192RR diplotype had significantly higher mean PON1 activities and also experienced steeper increases of POase activity over time compared with children with the PON1-108TT192QQ diplotype.ConclusionsLower levels of the PON1 enzyme, which is involved in protection against OPs and oxidative stress, persist in young children past 2 years of age through at least 7 years of age. Future policies addressing pesticide exposure in children should take into account that the window of vulnerability to OPs in young children may last beyond infancy.

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Serum homocysteine levels and paraoxonase 1 activity in preschool aged children in Greece

Cited by 13 publications

References 12 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

Homocysteine threshold value based on cystathionine beta synthase and paraoxonase 1 activities in mice

Developmental Changes in PON1 Enzyme Activity in Young Children and Effects of PON1 Polymorphisms

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