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1.
An analytical method for determining paraoxonase activity against sarin, soman and VX was established. We used capillary electrophoresis to measure directly the hydrolysis products: alkyl methylphosphonates. After enzymatic reaction of human serum paraoxonase (PON1) with nerve gas, substrate was removed with dichloromethane, and alkyl methylphoshphonates were quantified by capillary electrophoresis of reversed osmotic flow using cationic detergent and sorbic acid. This method was applied to the characterization of human serum PON1 polymorphism for nerve gas hydrolytic activity in the coding region (Q192R). PON1-192 and PON1-55 genotypes were determined by their gel electrophoretic fragmentation pattern with restriction enzymes after polymerase chain reaction (PCR) of blood leukocyte genomic DNA. Frequencies of genotypes among 63 members of our institutes with PON1-192 and PON1-55 were 9.5% (192QQ), 30.1% (192QR) and 44.4% (192RR), and 82.5% (55LL), 17.5% (55LM) and 0% (55MM), respectively. 192Q and 192R enzymes were purified from the respective genotype human plasma, using blue agarose affinity chromatography and diethyl amino ethane (DEAE) anion exchange chromatography. Vmax and Km were measured using Lineweaver-Burk plots for hydrolytic activities against sarin, soman and VX at pH 7.4 and 25 °C. For sarin and soman, the Vmax for 192Q PON1 were 3.5- and 1.5-fold higher than those for 192R PON1; and kcat/Km for 192Q PON1 were 1.3- and 2.8-fold higher than those for 192R PON1. For VX, there was little difference in Vmax and kcat/Km between 192Q and 192R PON1, and VX hydrolyzing activity was significantly lower than those for sarin and soman. PON1 hydrolyzed sarin and soman more effectively than paraoxon. 相似文献
2.
L. Cozzi J. Campolo M. Parolini R. De Maria M. C. Patrosso A. Marocchi O. Parodi S. Penco 《Molecular and cellular biochemistry》2013,374(1-2):233-238
Increased oxidative stress is known to play a role in the pathogenesis of atherosclerosis, and polymorphisms in genes encoding for enzymes involved in modulation of oxidant stress, such as paraoxonases (PONs), provide a potentially powerful approach to study the risk of disease susceptibility. Aim of our study is to investigate the possible association among PONs polymorphisms, clinical and metabolic factors, and atherothrombotic events in an Italian population. We evaluated in 105 subjects, with or without atherosclerotic risk factors, the presence of PON1 L55M, PON1 Q192R, and PON2 S311C genetic variants, as well as lipid profile, the concentration of aminothiols (blood reduced glutathione, plasma total glutathione, homocysteine, cysteine, cysteinyl glycine), and malondialdehyde as markers of lipid peroxidation. Clinical, biochemical, and genetic variables were correlated with a history of atherothrombosis. Previous atherothrombotic events were found in 42 patients (40 %): myocardial infarction in 24, stroke or transient ischemic attack in 18. By multiple logistic regression analysis, hypertension (OR = 5.538; 95 % CI 2.202–13.902, P < 0.001), HDL-cholesterol concentration (OR = 0.947; 95 % CI 0.910–0.985, P = 0.007), and the presence of C allele in PON2 gene (OR = 3.595; 95 % CI 1.247–10.361, P = 0.018) were independently associated with atherothrombotic events. Our study sheds light on the role of PON2 as a possible cofactor in determining the risk of events together with the well-known risk markers HDL-cholesterol and hypertension. 相似文献
3.
Paraoxonase is an HDL-associated enzyme that plays a preventive role against oxidative stres. Previous studies suggested that
involved an amino acid substitution at position 192 gives rise to two alloenzymes with a low activity (Q allele) and a high
activity (R allele) towards paraoxon. There also exists a second polymorphism of the human PON1 gene affecting amino acid 55, giving rise to a leucine (L-allele) substitution for methionine (M-allele). PON1 gene polymorphisms were studied in 50 patients with osteosarcoma and 50 healthy controls. Paraoxonase genotypes were determined
by PCR–RFLP. We found a reduction in the frequency of PON1 192 R allele in patients (P = 0.015). Besides, PON1 192 wild type QQ genotype (P = 0.015) and PON1 55 wild type L allele (P = 0.001) were higher in patients compared to healthy controls. PON1 192 QQ genotype was associated with osteosarcoma in multivariate
logistic regression analysis. Our findings have suggested that PON1 192 wild type genotypes may be associated with a risk
of developing osteosarcoma. 相似文献
4.
CONTEXT:
The human serum paraoxonase 1 (PON1) is calcium-dependent esterase and associates with the high density serum lipoproteins. PON1 plays a major role in oxidation of high density lipoprotein and low density lipoprotein and prevention of atherogenesis in coronary heart disease. PON1Q and R allele hydrolyses number of substrates like paraoxon (PO) (diethyl p-nitrophenyl phosphate) and phenylacetate.AIMS:
The aim of the study is to the determination of Q192R polymorphism of PON1 by using non-toxic substrate p-nitrophenylacetate and compares it with the phenotype determined by using PO as substrate.MATERIALS AND METHODS:
The study group consists of 60 healthy normal patients. Paraoxonase activity was measured using the procedure described by Eckerson (Reference method) and for phenotyping; the ratio of hydrolysis of PO in the presence of 1 M NaCl (salt-stimulated PON1, SALT) to the hydrolysis of phenylacetate (PA) is calculated. In new method (Haagen et al.) arylesterase activity measured using p-nitrophenylacetate and for phenotyping arylesterase, the ratio of inhibition of enzymatic hydrolysis of p-nitrophenylacetate (substrate) by phenyl acetate to non-inhibited hydrolysis of p-nitrophenylacetate (inhibited arylesterase activity (IA-IA0)/non-inhibited arylesterase activity (NIA).RESULTS:
It was found that paraoxonase activity is trimodally distributed in both the methods. There is no significant difference in the distribution of PON1 phenotypes of both reference method and new method being frequencies 0.946 and 0.376 respectively and there was no significant difference for phenotypic polymorphism for an individual by both methods (χ2= 0.15 and P = 0.9262).CONCLUSION:
The Q192R polymorphism of PON1 by using non-toxic substrate p-nitrophenylacetate showed trimodal distribution of QQ (homozygous), QR (heterozygous), and RR (homozygous) phenotype and it is comparable with reference method. This method can be used for PON1 phenotype in different pathological and complex disease conditions. 相似文献5.
Paraoxonase 1 gene polymorphism 192Q/R in old men and long-livers from Tatars ethnic group 总被引:1,自引:0,他引:1
Pauk VV Tuktarova IA Nasibullin TR Zueva LP Adel'guzhina AKh Khusnutdinova EK Mustafina OE 《Molekuliarnaia biologiia》2007,41(4):601-607
Comparison in genotype and allele frequencies of people groups of younger (from 1 till 20 years), middle (21-55 years), elderly (56-74 years), senile (75-89 years) age and long-livers (90-109 years) have been performed (only 1116 person) with the purpose of analysis of molecular-genetic bases of ageing and longevity of the person. Allele variants of PON1 gene have been identified by polymerase chain reaction in a combination with restriction analysis. In the general sample of Tatars genotypes PON1*Q/*Q, PON1*Q/*R and PON1*R/*R are revealed with frequencies of 46.15, 44.35 and 9.5%, alleles PON1*Q and PON1*R are found with frequencies of 68.32 and 31.68% accordingly. Statistically significant distinctions on frequencies of genotypes and alleles between separate age groups are found. It has appeared, that frequency of PON1*R allele (28.46%) is lowered among old men in comparison with those among persons of younger age (37.42%, P = 0.009). However essentially above in group of long-livers, than in group of old men, frequencies allele PON1*R (P = 0.005) and genotype PON1*R/*R (P = 0.01). 相似文献
6.
Paraoxonase (PON1) 55 and 192 polymorphism and its effects to oxidant-antioxidant system in turkish patients with type 2 diabetes mellitus 总被引:3,自引:0,他引:3
Agachan B Yilmaz H Ergen HA Karaali ZE Isbir T 《Physiological research / Academia Scientiarum Bohemoslovaca》2005,54(3):287-293
Paraoxonase (PON1) is a serum enzyme with an antioxidant function, protecting the low density lipoproteins (LDL) from oxidative modifications. Because diabetic patients are at greater risk of oxidative stress, we investigated the effect of PON1 55 methione (M)/leucine (L) and PON1 192 glutamine (A)/arginine (B) polymorphisms on oxidant-antioxidant system in 213 individuals with type 2 diabetes mellitus and 116 non-diabetic control subjects from Turkish population were included in the study. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the PON1 genotypes. Thiobarbituric acid reactive substances (TBARS), conjugated dienes levels in the serum and glutathione (GSH) levels in whole blood were measured spectrophotometrically. In both groups PON1 192 AA and PON1 55 MM genotypes had higher TBARS, conjugated dienes levels and lower GSH levels, whereas PON1 192 BB and PON1 55 LL genotypes had lower TBARS, conjugated diene levels and higher GSH level than other genotypes. We thus conclude that PON1 192 BB and PON1 55 LL alleles have protective effect against oxidative stress. 相似文献
7.
《Redox report : communications in free radical research》2013,18(3):113-119
AbstractOver the last few years, a relative decline of the morbidity and mortality of human immunodeficiency virus (HIV) infection in industrialised countries has been observed due to the use of a potent combined therapy known as high active antiretroviral therapies (HAARTs). It has led to a decrease of viral load and a quantitative and qualitative improvement of immune function in patients, especially CD4+ T-lymphocyte count, having as a consequence a decrease of infectious complications and a global clinical improvement. Besides the positive effects of HAARTs on immune and metabolic alterations during HIV infection, it has been reported that the commonly used drugs AZT, ddI, and ddC are toxic to hepatocytes. Recent reports continue to point to the mitochondria as targets for toxicity. The prevalence of these symptoms is continued during acquired immunodeficiency syndrome (AIDS). The effects of oxidative stress occurring as a consequence of mitochondrial toxicity may amplify some of the pathophysiological and phenotypic events during infection. Mitochondrial stabilisation and antioxidative strategies are possible new therapeutic aims since the antiretroviral treatment is prolonged with increased longevity from AIDS, which has become a more manageable chronic illness. The aim of the present review article is to summarize the current knowledge about mitochondrial dysfunction during HAART and its consequence for patients with chronic treatment. Oxidative stress may serve as one pathway for cellular damage in AIDS and its treatment. One important future goal is to prevent or attenuate the side effects of HAART so that improved disease management can be achieved. 相似文献
8.
Mohammed A. Hassan Omar S. Al-Attas Tajamul Hussain Nasser M. Al-Daghri Majed S. Alokail Abdul K. Mohammed Benjamin Vinodson 《Molecular and cellular biochemistry》2013,380(1-2):121-128
Paraoxonase-1 (PON1) is a HDL-bound antioxidant enzyme that protects LDL from oxidative modification. Discovery of the antioxidant properties of PON1 led to extensive research on its role in the initiation and progression of atherosclerosis. The Q192R (rs662; A/G) polymorphism, which results in the glutamine to arginine substitution at position 192, of the PON1 gene has been linked to increased atherosclerosis risk in several but not all population studies. Besides genetic factors, environmental variables and ethnicity have been implicated as factors responsible for the ambiguity in relating the PON1 gene with atherosclerotic risk. Here, we tested the association of the Q192R polymorphism with coronary artery disease (CAD) in Saudi ethnic subjects taking environmental factors into consideration. The genomic DNA samples from 121 angiographically confirmed CAD cases and 108 normal healthy control subjects were genotyped by PCR–RFLP analysis. The distribution of QQ, QR, and RR genotypes was significantly different between cases and controls (p < 0.005). The RR genotype was associated with CAD risk independently of several established risk factors including age, gender, smoking, obesity, and diabetes (OR 2.2, 1.4–7.4, p < 0.01). Genotype-based stratification of demographic and biochemical data revealed that the RR genotype has proatherogenic properties. This study, thus, identifies the Q192R polymorphism as an additional risk factor for CAD in the Saudi population and suggests that it may have prognostic value. The negative effect of this genetic variant is presumably due to the diminished ability of the RR variant genotype of PON1 to blunt LDL oxidation. 相似文献
9.
Mahesh Harishchandra Hampe Mukund Ramchandra Mogarekar 《Indian journal of human genetics》2014,20(1):51-58
AIMS AND OBJECTIVES:
The present study was evaluated the atheroprotective potential of paraoxonase1 (PON1) and its Q192R polymorphism, to determine whether this polymorphism, which is responsible for differential PON1 activity plays any role in the pathogenesis, severity and extent of coronary artery disease (CAD).MATERIALS AND METHODS:
This hospital-based cross-sectional study investigated 60 diagnosed cases of CAD and 60 age and gender matched controls. All were assessed for serum PON1 activity, PON1 Q192R polymorphism and for classical cardiovascular risk factors. Individual serum phenotyping for PON1 Q192R polymorphism was determined by double substrate hydrolysis assay. Severity of CAD was assessed by the length of intensive cardiac care unit (ICCU) stay.RESULTS:
Serum PON1 activity is significantly reduced in cases of CAD (92.6 ± 31.13 IU/L when compared with controls (105.26 ± 32.53 IU/L). Furthermore, serum arylesterase activity is reduced in CAD patients (90.31 ± 23.26 kU) when compared with the control subjects (101.61 ± 28.68 kU). Serum PON1 and arylesterase activities are significantly negatively correlated with the length of ICCU stay (r = −393 and r = −374 respectively). There is no significant difference in the occurrence of CAD and length of ICCU stay among the PON1 phenotypes (P = 0.92). Logistic regression analysis after adjustment of established risk factors revealed no significant association between CAD risk and PON1 Q192R polymorphism (odds ratios: 1.179 [95% confidence intervals: 0.507-2.744], P = 0.702).SUMMARY AND CONCLUSIONS:
The current study demonstrates that the activity of the PON1 enzyme may be more important factor than the PON1 Q192R polymorphism in the severity and extent of CAD. 相似文献10.
Y. Yamasaki Ken’ya Sakamoto Hirotaka Watada Yoshitaka Kajimoto Masatsugu Hori 《Human genetics》1997,101(1):67-68
The high-density-lipoprotein-associated enzyme paraoxonase, which has a role in the detoxification of organophosphorus compounds,
is known to be polymorphic in humans. The Arg192 isoform of paraoxonase hydrolyzes paraoxon more rapidly than the Gln192 isoform. However, with respect to the hydrolysis of toxic nerve agents, such as diazoxon, soman, and sarin, the Arg192 isoform displays a lower activity than the other isoform. To evaluate the possibility that the genetic polymorphism was involved
in the aggravated extent of human injury in the sarin gas poisoning incident in the Tokyo subway in March 1995, we investigated
the prevalance of this polymorphism in the Japanese population. We found that the Arg192 allele is more common in the Japanese (allele frequency: 0.66) than in people of other races (ranging 0.24–0.31). In the
Japanese, 135 out of the 326 subjects (41.4%) investigated were homozygous for the Arg192 allele, which shows a very low hydrolysis activity for sarin. Thus, there seems to be a racial difference in vulnerability
to toxic nerve agents, such as sarin. The dominance of the Arg192 allele in the Japanese population probably worsened the tragedy of March 1995 in the Tokyo subway.
Received: 5 April 1997 / Accepted: 10 June 1997 相似文献
11.
Geetika Aggarwal Rameshwar Prajapati Rajan K. Tripathy Priyanka Bajaj A. R. Satvik Iyengar Abhay T. Sangamwar Abhay H. Pande 《PloS one》2016,11(2)
Human paraoxonase 1 (h-PON1) is a serum enzyme that can hydrolyze a variety of substrates. The enzyme exhibits anti-inflammatory, anti-oxidative, anti-atherogenic, anti-diabetic, anti-microbial and organophosphate-hydrolyzing activities. Thus, h-PON1 is a strong candidate for the development of therapeutic intervention against a variety conditions in human. However, the crystal structure of h-PON1 is not solved and the molecular details of how the enzyme hydrolyzes different substrates are not clear yet. Understanding the catalytic mechanism(s) of h-PON1 is important in developing the enzyme for therapeutic use. Literature suggests that R/Q polymorphism at position 192 in h-PON1 dramatically modulates the substrate specificity of the enzyme. In order to understand the role of the amino acid residue at position 192 of h-PON1 in its various hydrolytic activities, site-specific mutagenesis at position 192 was done in this study. The mutant enzymes were produced using Escherichia coli expression system and their hydrolytic activities were compared against a panel of substrates. Molecular dynamics simulation studies were employed on selected recombinant h-PON1 (rh-PON1) mutants to understand the effect of amino acid substitutions at position 192 on the structural features of the active site of the enzyme. Our results suggest that, depending on the type of substrate, presence of a particular amino acid residue at position 192 differentially alters the micro-environment of the active site of the enzyme resulting in the engagement of different subsets of amino acid residues in the binding and the processing of substrates. The result advances our understanding of the catalytic mechanism of h-PON1. 相似文献
12.
Bahar Toptaş Özlem Kurt Hülya Yılmaz Aydoğan Ilhan Yaylim Ümit Zeybek Ayse Can Bedia Agachan Mehmet Uyar M. Kerem Özyavuz Turgay İsbir 《Molecular biology reports》2013,40(11):6519-6524
There is increasing evidence of a biochemical link between oxidative stress and bone metabolism. Oxidative stress has been shown to be involved in bone resorption as it causes loss of bone mineral density (BMD). Paraoxonase 1 (PON1), can prevent these effects of the oxidative stress on bone formation. It has been suggested that the PON1 gene as possibly implicated in reduced BMD in bone fragility cases. It has been hypothesized that PON1 gene polymorphisms may influence both the risk of osteoporosis and osteopenia occurrence and prognosis. The aim of our study is to evaluate the relationship between PON1 polymorphisms and bone fragility development. Seventy-four osteoporotic, 121 osteopenic and 79 nonosteoporotic postmenopausal women were recruited. For detection of the polymorphisms, polymerase chain reaction-restriction fragment length polymorphism techniques have been used. BMD was measured at the lumbar spine and hip by dual-energy X-ray absorptiometry. Distributions of PON1 (PON 192 and PON 55) polymorphisms in study groups were not significantly different. But, there was medium strength connection between in the osteopenic with control groups regarding PON1 55–PON1 192 haplotypes and we found a power strength connection between in the osteoporosis with control groups regarding PON1 55–PON1 192 haplotypes. Furthermore, subjects with PON1 192RR and PON1 55LL genotypes had lower PON activity values of osteoporotic subject compared to healthy control and this difference was statistically significant (p < 0.05). This result suggest that PON1 genotypes could be higher risk for osteoporosis, as determined by reduced BMD. 相似文献
13.
Mestre-Alfaro A Ferrer MD Banquells M Riera J Drobnic F Sureda A Tur JA Pons A 《Free radical research》2012,46(6):799-808
The aim of this study was to determine the effects of whole body heat in combination with exercise on the oxidative stress and acute phase immune response. Nine male endurance-trained athletes voluntarily performed two running bouts of 45 minutes at 75-80% of VO(2max) in a climatic chamber in two conditions: cold and hot humid environment. Leukocyte, neutrophil and basophil counts significantly rose after exercise in both environments; it was significantly greater in the hot environment. Lymphocyte and neutrophil antioxidant enzyme activities and carbonyl index significantly increased or decreased after exercise only in the hot environment, respectively. The lymphocytes expression of catalase, Hsp72 and CuZn-superoxide dismutase was increased in the hot environment and Sirt3 in the cold environment, mainly during recovery. In conclusion, the increased core body temperature results in the acute phase immune response associated to intense exercise and in the immune cell adaptations to counteract the oxidative stress situation. 相似文献
14.
《Free radical research》2013,47(6):799-808
AbstractThe aim of this study was to determine the effects of whole body heat in combination with exercise on the oxidative stress and acute phase immune response. Nine male endurance-trained athletes voluntarily performed two running bouts of 45 minutes at 75–80% of VO2max in a climatic chamber in two conditions: cold and hot humid environment. Leukocyte, neutrophil and basophil counts significantly rose after exercise in both environments; it was significantly greater in the hot environment. Lymphocyte and neutrophil antioxidant enzyme activities and carbonyl index significantly increased or decreased after exercise only in the hot environment, respectively. The lymphocytes expression of catalase, Hsp72 and CuZn-superoxide dismutase was increased in the hot environment and Sirt3 in the cold environment, mainly during recovery. In conclusion, the increased core body temperature results in the acute phase immune response associated to intense exercise and in the immune cell adaptations to counteract the oxidative stress situation. 相似文献
15.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):758-764
Some enzymes are known to be drug target inhibitions of which can be critical for organisms. PON has a critical role to prevent atherogenesis by inhibiting lipid peroxidation. It is well known that paraoxonase 1 (PON1) plays an important function on high-density lipoprotein (HDL) structure to prevent lipid oxidation not only of low-density lipoprotein, but also of HDL itself. We investigated in vitro effects of some medical drugs on PON1 activity from human serum. Ki constants for oxytetracycline hydrochloride, netilmycin sulfate, lincomycin hydrochloride, clindamycin phosphate, and streptomycin sulfate were found as 0.2, 3.73, 18.30, 35.80, and 56.30 mM, respectively. Our results indicate that these commonly used drugs inhibit the activity of the enzyme at very low doses with different inhibition mechanisms. 相似文献
16.
PURPOSE OF REVIEW: To provide up-to-date information on the most recent advances in the epidemiology, biochemistry and molecular biology of the antiatherosclerotic enzyme paraoxonase 1. RECENT FINDINGS: Case-control and prospective studies published during the period covered by this review have indicated that paraoxonase 1 'status' (i.e. activity and/or concentration) was a more important coronary heart disease risk factor than the paraoxonase 1 genetic polymorphisms. New findings on the role of paraoxonase 1 in homocysteine metabolism are reviewed, as are advances in the nutritional and pharmacological regulation of paraoxonase 1. The recent controversy over whether paraoxonase 1 or platelet-activating factor acetylhydrolase is responsible for the antioxidant activity of high-density lipoprotein is also addressed. SUMMARY: In the light of recent findings, we believe that genetic epidemiological studies of the paraoxonase 1 polymorphisms in relation to coronary heart disease should no longer be undertaken unless they are very large and prospective in nature. More research should be undertaken to discover the biochemical mechanisms underlying the mode of action of paraoxonase 1 and the factors which modulate its activity and/or concentration. SPONSORSHIP: Bharti Mackness is funded by the International HDL Research Awards Programme. All authors receive research funding from the British Heart Foundation and Diabetes UK. 相似文献
17.
Scacchi R Corbo RM Rickards O De Stefano GF 《Human biology; an international record of research》2003,75(3):365-373
The physiological role of human paraoxonase (PON), a serum enzyme that hydrolyzes organophosphate insecticides and nerve agents, is not clear. Of the three genes in the paraoxonase gene family, PON1 shows a polymorphism, Gln 192 --> Arg, governed by two common alleles named *Q and *R. These determine two different isoforms associated, respectively, with lower and higher activity towards paraoxon, a toxic metabolic product of the insecticide parathion. The *R allele has often been found associated with an increased risk of coronary heart disease. As human populations tend towards greater exposure to environmental changes, including changes in dietary habits and contact with insecticides or other toxic substances, health risks will change as well. In studying the prevention of these newly emerging risks, it could be important to know the distribution of the two alleles in the various world populations. In this paper we report on the genotype and allele frequencies of this polymorphism in different populations, most of which have never been examined for this polymorphism. Samples were taken from mainland Italy, Sardinia, Ethiopia, Benin, and Ecuador. The *R allele frequencies for the samples were: 0.313, 0.248, 0.408, 0.612, and 0.789, respectively. The data show a large variability in allele frequencies, and, in particular, that PON1 allele distribution depends on membership to different geographic populations. 相似文献
18.
Otocka-Kmiecik A Lewandowski M Stolarek R Szkudlarek U Nowak D Orlowska-Majdak M 《Redox report : communications in free radical research》2010,15(6):275-281
The purpose of this study was to elucidate the participation of plasma PON1 (paraoxonase activity [PON] and arylesterase activity [ARE]) in antioxidant defense in response to a single bout of maximal exercise. PON, ARE, lipid profile, lipid peroxidation (thiobarbituric acid reactive substances [TBARS]), total antioxidant status (ferric reducing ability of plasma [FRAP]), concentration of uric acid [UA], and total bilirubin (TBil) were determined in the plasma before, at the bout and 2 h after maximal exercise on a treadmill in young sportsmen. Chosen physiological parameters also were controlled during maximal exercise. Following maximal exercise, the unaltered level of TBARS and increased FRAP were registered. ARE increment was the highest (37.6%) of all measured variables but lasted for a short time. UA increment was lower than ARE but long-lasting and correlated with FRAP. PON activity increment was associated with the combined effect of body weight, lean, body mass index (BMI) and basal metabolic rate (BMR). We conclude that PON1 is a co-factor of the first line of antioxidant defense during maximal exercise. Its activity is associated with body composition and not the physical fitness of the subjects. 相似文献
19.
20.
Zehra Hashim Amber Ilyas Ammara Saleem Asmat Salim Shamshad Zarina 《Free radical biology & medicine》2009,46(8):1089-1095
Paraoxonase 1 (PON1) is a high-density lipoprotein-associated enzyme that is believed to be involved in the protection against oxidative stress. There is evidence that paraoxonase activity is reduced in patients with diabetes and cataract. In the current study, we analyzed mRNA expression of PON1 as well as other members of the paraoxonase family, PON2 and PON3, in human cataractous lens samples. Our results indicate that only PON1 is expressed at the gene and protein levels in human lens tissues. We quantified MDA levels and measured PON1 (paraoxonase/arylesterase) enzymatic activities in subjects suffering from cataract due to aging and diabetes. Decreased PON1 activity was more pronounced in diabetic patients (p < 0.001) compared to senile subjects, which may be due to glycation and increased oxidative insult. To examine the structural alterations that occur in response to glycation, we constructed a three-dimensional model of PON1 and its glycated variant. Glycation at Lys70 and Lys75 is predicted to cause hindrance in binding of substrate to the active site of the enzyme. 相似文献