Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The serum enzyme paraoxonase (PON) protects LDLs from oxidative stress. We recently identified promoter polymorphisms of the PON gene that strongly affect gene expression and serum levels of the enzyme. The present study tested the hypothesis that promoter polymorphism T(-107)C could be a risk factor for vascular disease in type 2 diabetic patients by virtue of its ability to modulate serum concentrations of the antioxidant enzyme. The low-expressor genotype (TT) was associated with significantly lower serum PON concentrations, and it was over-represented in type 2 diabetic patients with coronary heart disease (CHD) (TT vs. TC+CC: odds ratio [OR] 1.64 [95% CI 1.03-2.61], P < 0.05). The association of the low-expressor genotype with an increased risk of disease was independent of other risk factors, including the coding region Q191R polymorphism (OR 2.12 [95% CI 1.19-3.70], P = 0.01). However, an interaction of the promoter polymorphism with the Q191R polymorphism, which was previously identified as an independent risk factor, was observed. The low-expressor promoter allele (-107T) associated with the high-risk 191R allele showed a lower-than-expected level of risk (OR 2.21 vs. the expected 4.76). The data are consistent with the hypothesis that low expression of the antioxidant enzyme PON increases the risk of CHD. Moreover, the promoter polymorphism appears to have a modulating effect on risk that is associated with the coding region polymorphism Q191R. This study indicates a strong genetic component to the antioxidant capacity of HDLs.
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PMID:Promoter polymorphism T(-107)C of the paraoxonase PON1 gene is a risk factor for coronary heart disease in type 2 diabetic patients. 1092 42

Paraoxonase is a serum enzyme with an anti-oxidant function, protecting low density lipoproteins (LDL) from oxidative modifications. Diabetic patients are suggested to be at greater risk of oxidative stress, which may contribute to the significantly higher incidence of vascular disease in this population. Less efficient protection mechanisms may be one feature of the greater susceptibility to oxidation in diabetes. In this context, the present study examined the hypothesis that serum paraoxonase is reduced in type 1 (insulin-dependent) diabetic patients and that the reduction can affect the anti-oxidant capacity of HDL. Serum paraoxonase concentrations and activities were compared in type 1 patients and first degree, non-diabetic relatives with particular attention paid to the confounding effects of paraoxonase gene polymorphisms. In addition, the ability of HDL-paraoxonase to protect low density lipoproteins from oxidation was analysed in an in vitro system. Serum concentrations and enzyme activities of paraoxonase were significantly lower in type 1 patients compared to non-diabetic, first degree relatives. The differences were independent of promoter and coding region polymorphisms, which influence serum concentrations and activities of the enzyme. Overall, paraoxonase concentrations were a mean 13.3+/-4.5% lower (P<0.02) in type 1 patients. Specific activities did not differ between diabetic and non-diabetic groups. The concentration ratios of LDL cholesterol:paraoxonase (1.37+/-0.51 vs. 1.18+/-0.37, P=0.003) and apolipoprotein B:paraoxonase (0.84+/-0.33 vs. 0.71+/-0.40; P=0.012) were significantly higher in diabetic patients, consistent with a reduced capacity to protect LDL from oxidation. In vitro oxidation studies showed that a significantly higher level of lipid hydroperoxides was generated in LDL in the presence of HDL, containing paraoxonase levels equivalent to those of type 1 patients, compared to HDL containing paraoxonase levels equivalent to those of control subjects (mean difference 8.1%, P<0.05). The study demonstrates that serum concentrations of the antioxidant enzyme paraoxonase are significantly lower in type 1 (insulin-dependent) diabetic patients compared to non-diabetic, first-degree relatives, independently of known gene polymorphisms. Concentrations are reduced to an extent that can affect its anti-oxidant capacity. The results are consistent with the contention that modifications to serum paraoxonase in type 1 patients can increase risk of lipoprotein oxidation and, consequently, risk of vascular disease.
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PMID:Serum paraoxonase is reduced in type 1 diabetic patients compared to non-diabetic, first degree relatives; influence on the ability of HDL to protect LDL from oxidation. 1122 46

In vivo supplementation studies of the antioxidant alpha-tocopherol in human Type II diabetes have used surrogate, rather than direct, markers of oxidative damage/antioxidant protection and have used higher doses of alpha-tocopherol than used in coronary secondary prevention trials. We tested the hypothesis that oral alpha-tocopherol in a dosage regimen used in secondary prevention trials would reduce directly observed oxidatively induced single-strand breaks in lymphocyte DNA in Type II diabetes. We studied 40 people with Type II diabetes and 30 controls in a randomized, double-blind, placebo-controlled trial of 400 i.u. of oral alpha-tocopherol daily for 8 weeks. Lymphocyte DNA single-strand breaks and low-density lipoprotein (LDL) particle size and oxidizability were measured at baseline, after 8 weeks, and after 4 weeks washout. Polymorphisms in the gene for the antioxidant enzyme paraoxonase-1 gene (position 192) were measured. The diabetics had increased DNA oxidative susceptibility (P=0.008), without increased LDL oxidative susceptibility. There was a direct relationship between DNA oxidative susceptibility and baseline plasma alpha-tocopherol in the diabetes group alone (r=0.421, r(2)=0.177 and P=0.023), but DNA and LDL oxidative susceptibility were not influenced by alpha-tocopherol supplementation in either group in this regimen. Paraoxonase-1 gene polymorphisms did not contribute to LDL or DNA oxidative susceptibility or response to alpha-tocopherol. Increased DNA oxidative susceptibility, therefore, can occur in Type II diabetes without increased LDL oxidative susceptibility, but alpha-tocopherol supplementation in this regimen has no influence on DNA or LDL oxidative susceptibility in Type II diabetes or controls. Polymorphisms in the paraoxonase gene (position 192) are not associated with differences in oxidative susceptibility or responses to alpha-tocopherol.
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PMID:Increased DNA oxidative susceptibility without increased plasma LDL oxidizability in Type II diabetes: effects of alpha-tocopherol supplementation. 1152 40

Polymorphisms of the gene for the antioxidant enzyme, paraoxonase-1 (PON1), have been identified as risk factors for coronary disease (CHD), notably in diabetic patients. The polymorphisms have also been linked with other diabetic complications. The present study analyzed glucose metabolism as a function of PON1 polymorphisms in young healthy nondiabetic men from families with premature CHD and matched controls. The L55M PON1 polymorphism was independently associated with the glucose response to an oral glucose tolerance test. LL homozygotes had significantly impaired glucose disposal (P = 0.0007) compared with (LM+MM) genotypes. It was particularly marked for subjects from high CHD risk families and differentiated them from matched controls (P = 0.049). The area under the glucose curve (P = 0.0036) and the time to peak glucose value (P = 0.026) were significantly higher in the LL carriers, whereas the insulin response was slower (P = 0.013). Insulin resistance did not differ between L55M genotypes. There was a trend for reduced pancreatic beta-cell function as measured by glucose-induced insulin secretion (LL vs. LM vs. MM, 20.26 vs. 23.74 vs. 25.60; P = 0.077). The frequency of the L55 allele decreased significantly (P = 0.028) across regions defining a north-south European axis. No significant differences for the glucose response or case-control populations were observed as a function of the PON1 Q192R polymorphism. The study demonstrates an association between PON1 gene polymorphisms and glucose metabolism. The L55M-glucose interaction differentiated offspring of high CHD risk families, suggesting that it may be of particular relevance for vascular disease and possibly other diabetic complications.
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PMID:Paraoxonase-1 L55M polymorphism is associated with an abnormal oral glucose tolerance test and differentiates high risk coronary disease families. 1188 98

The antioxidative effects of naringenin (1) and its synthetic derivative, naringenin 7-O-cetyl ether (2), were tested. Male rats were fed a 1 g/100 g high-cholesterol diet for 6 weeks with supplements of either 1 or 2 (0.073 mmol/100 g diet) to study the effects on the antioxidant enzyme activities in the erythrocyte and liver. The erythrocyte catalase (CAT) and superoxide dismutase (SOD) activities were significantly higher in the compounds 1 or 2 supplemented groups than in the control group, whereas the hepatic SOD and CAT activities were significantly lower in the compound 2 supplemented group. The compounds 1 and 2 supplements to a high cholesterol diet lowered or tended to lower the plasma TBARS levels, that is, lipid peroxide products, while enhancing the plasma paraoxonase activity. These results indicate that the supplementation of 1 and 2 was effective in improving the antioxidant capacity of the erythrocyte and liver, plus the synthetic functional compound 2 appeared to be as potent as 1 in enhancing the antioxidant defense system.
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PMID:Supplementation of naringenin and its synthetic derivative alters antioxidant enzyme activities of erythrocyte and liver in high cholesterol-fed rats. 1198 21

We examined levels of malondialdehyde (MDA) (an end-product of lipid peroxidation) and paraoxonase (PON1) (an antioxidant enzyme) activity and PON1 phenotypes in people who were exposed to ionizing radiation for different time periods and doses. A total of 78 individuals (mean age 34 +/- 7 years) were included in the study. Fifty-one of them were radiology workers whereas the control group was composed of 27 healthy volunteers who had never worked in a radiology-related job. Paraoxon was used as substrate for measurement of PON1 activity levels (basal and NaCl-stimulated). Phenylacetate was used as substrate for measurement of arylesterase activity levels. Cumulative levels of serum NaCl-stimulated PON1/arylesterase activities were utilized for phenotypic differentiation. In radiology workers, three different phenotypes were determined based on paraoxonase/arylesterase ratio. The ratios were 1.09 +/- 0.30 for AA (homozygote low activity); 2.91 +/- 1.07 for AB (heterozygote activity) and 4.97 +/- 1.21 for BB (homozygote high activity). There was a statistically meaningful negative correlation between serum MDA levels and PON1 activity levels in all phenotypes (p < 0.05). PON1 activity levels were found to be 25-35% lower in people who were exposed to long-term ( > 5 years) radiation compared to controls. There was no statistically significant correlation between serum arylesterase activity and MDA levels in these subjects (r = -0.185, p > 0.05). PON1 activity levels were decreased whereas serum MDA levels were increased in individuals exposed to radiation for a long period. PON phenotypes of people employed in jobs which expose them to radiation should be determined and based on these findings they should be advised to avoid risk factors inducing oxidative stress, such as smoking, and to consume foods rich in vitamins and trace elements to increase their antioxidant capacity.
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PMID:Levels of paraoxonase and arylesterase activities and malondialdehyde in workers exposed to ionizing radiation. 1462 76

A remarkable reduction of plasma concentrations of high-density lipoproteins (HDL), especially of the HDL(2) subfraction, is one of the typical lipoprotein alterations found in patients with familial combined hyperlipidemia (FCHL). Fourteen FCHL patients received 4 capsules daily of Omacor (an omega-3 polyunsaturated fatty acid [omega3 FA] concentrate providing 1.88 g of eicosapentaenoic acid [EPA] and 1.48 g of docosahexaenoic acid [DHA] per day; Pronova Biocare, Oslo, Norway) or placebo for 8 weeks in a randomized, double-blind, crossover study. Plasma triglycerides were 44% lower, and LDL cholesterol and apoliporpotein (apo)B were 25% and 7% higher after Omacor than placebo. HDL cholesterol was higher (+8%) after Omacor than placebo, but this difference did not achieve statistical significance. Omacor caused a selective increase of the more buoyant HDL(2) subfraction; plasma HDL(2) cholesterol and total mass increased by 40% and 26%, respectively, whereas HDL(3) cholesterol and total mass decreased by 4% and 6%. Both HDL(2) and HDL(3) were enriched in cholesteryl esters and depleted of triglycerides after Omacor. No changes were observed in the plasma concentration of major HDL apolipoproteins, LpA-I and LpA-I:A-II particles, lecithin:cholesterol acyltransferase (LCAT), and cholesteryl ester transfer protein (CETP). The plasma concentration of the HDL-bound antioxidant enzyme paraoxonase increased by 10% after Omacor. Omacor may be helpful in correcting multiple lipoprotein abnormalities and reducing cardiovascular risk in FCHL patients.
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PMID:An omega-3 polyunsaturated fatty acid concentrate increases plasma high-density lipoprotein 2 cholesterol and paraoxonase levels in patients with familial combined hyperlipidemia. 1476 65

Plasma phospholipid transfer protein (PLTP) transfers phospholipids between lipoproteins and mediates HDL conversion. PLTP-overexpressing mice have increased atherosclerosis. However, mice do not express cholesteryl ester transfer protein (CETP), which is involved in the same metabolic pathways as PLTP. Therefore, we studied atherosclerosis in heterozygous LDL receptor-deficient (LDLR(+/-)) mice expressing both human CETP and human PLTP. We used two transgenic lines with moderately and highly elevated plasma PLTP activity. In LDLR(+/-)/huCETPtg mice, cholesterol is present in both LDL and HDL. Both are decreased in LDLR(+/-)/huCETPtg/huPLTPtg mice (>50%). An atherogenic diet resulted in high levels of VLDL+LDL cholesterol. PLTP expression caused a strong PLTP dose-dependent decrease in VLDL and LDL cholesterol (-26% and -69%) and a decrease in HDL cholesterol (-70%). Surprisingly, atherosclerosis was increased in the two transgenic lines with moderately and highly elevated plasma PLTP activity (1.9-fold and 4.4-fold, respectively), indicating that the adverse effect of the reduction in plasma HDL outweighs the beneficial effect of the reduction in apolipoprotein B (apoB)-containing lipoproteins. The activities of the antiatherogenic enzymes paraoxonase and platelet-activating factor acetyl hydrolase were both PLTP dose-dependently reduced ( approximately -33% and -65%, respectively). We conclude that expression of PLTP in this animal model results in increased atherosclerosis in spite of reduced apoB-containing lipoproteins, by reduction of HDL and of HDL-associated antioxidant enzyme activities.
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PMID:Elevation of plasma phospholipid transfer protein increases the risk of atherosclerosis despite lower apolipoprotein B-containing lipoproteins. 1499 44

We have evaluated the possible association of polycystic ovary syndrome (PCOS) with 15 genomic variants previously described to influence insulin resistance, obesity, and/or type 2 diabetes mellitus. Seventy-two PCOS patients and 42 healthy controls were genotyped for 15 variants in the genes encoding for paraoxonase (three variants), plasma cell differentiation antigen glycoprotein, human sorbin and SH3 domain containing 1, plasminogen activator inhibitor-1, peroxisome proliferator-activated receptor-gamma2, protein tyrosine phosphatase 1B (two variants), adiponectin (two variants), IGF1, IGF2, IGF1 receptor, and IGF2 receptor. Compared with controls, PCOS patients were more frequently homozygous for the -108T variant in paraoxonase (36.6% vs. 9.5%; P = 0.002) and homozygous for G alleles of the ApaI variant in IGF2 (62.9% vs. 38.1%; P = 0.018). Paraoxonase is a serum antioxidant enzyme and, because -108T alleles result in decreased paraoxonase expression, this increase in oxidative stress might result in insulin resistance. G alleles of the ApaI variant in IGF2 may increase IGF2 expression, and IGF2 stimulates adrenal and ovarian androgen secretion. In conclusion, the paraoxonase -108 C-->T variant and the ApaI polymorphism in the IGF2 gene are associated with PCOS and might contribute to increased oxidative stress, insulin resistance, and hyperandrogenism in this prevalent disorder.
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PMID:Association of the polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity. 1518 Oct 35

This study was conducted to determine the antioxidant effects of a Polygonatum extract compared with the major antioxidant, vitamin E, in rabbits fed a high-cholesterol diet. Rabbits were given a high-cholesterol (0.5%, wt/wt) diet with vitamin E (0.03%, wt/wt) or a Polygonatum extract (0.05%, wt/wt) for 8 weeks. The body weight gain (g/week) was only significantly increased only in the high-cholesterol-fed control group, yet the relative liver weight was significantly lower in the Polygonatum group compared with the other groups. The supplementation of vitamin E and Polygonatum extract led to an increase in the hepatic catalase (CAT) activity without any change in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. Hepatic total glutathione content was significantly higher in the Polygonatum group than in the other groups. The level of hepatic mitochondrial H(2)O(2) was significantly lower in the two supplemented groups compared with the control group, whereas the level of cytosolic H(2)O(2) was only significantly lower in the Polygonatum group than in the control group. The level of plasma thiobarbituric acid-reactive substances (TBARS) was only significantly lower in the vitamin E group, whereas the level of hepatic TBARS was slightly lower in the Polygonatum group than in the other groups. In the case of the high-density lipoprotein-related antioxidant enzyme, vitamin E supplementation produced the highest plasma paraoxonase (PON) activity compared with the other groups, although there was no difference in the hepatic PON activity among the groups. Meanwhile, the plasma vitamin E concentration was significantly higher in the vitamin E and Polygonatum groups than in the control group; however, plasma vitamin A concentration did not differ significantly between the groups. As regards the mRNA expressions of hepatic antioxidant enzymes, the vitamin E and Polygonatum extract supplementation had no effect on the SOD, CAT, GSH-Px, and PON mRNA expression. Accordingly, these results indicate that the Polygonatum extract had a positive effect on the antioxidant defense system based on decreasing the content of hepatic TBARS and hydrogen peroxide, increasing the CAT activity and total glutathione level in the liver, and sparing the plasma vitamin E. Thus, further studies on the functional components in Polygonatum extract and their biological efficacies are needed.
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PMID:Polygonatum rhizoma affects antioxidant defense systems without changing mRNA expression in diet-induced hypercholesterolemic rabbits. 1538 32


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