Paraoxonase-1(PON1)is an important enzyme in various pathologies such as pesticide poisoning,diabetes,atherosclerosis,neuronal disorders,and cancer,due to its multifunctional activity since it acts on different metabo...Paraoxonase-1(PON1)is an important enzyme in various pathologies such as pesticide poisoning,diabetes,atherosclerosis,neuronal disorders,and cancer,due to its multifunctional activity since it acts on different metabolites.However,one of its main functions is the hydrolysis of organophosphate(OP)compounds from pesticides that cause fatal poisoning at the level of the central nervous system(CNS).The objective of this review was to investigate whether the structure,genetics,and function of PON1 affect the metabolism of organophosphate pesticides or other abnormalities.Information was selected from articles in the database PubMed–NCBI(https://www.ncbi.nlm.nih.gov/pubmed/)with a publication date between 2011 and 2019.The enzymatic activity of PON1 can be modified depending on its chemical structure since there are different genetic polymorphisms that change PONI morphologies or the levels of expression in the bloodstream.This leads to differences in susceptibilities to organophosphate pesticide poisoning.The results of this review reveal that phenotypic variants of PON1 have differences in affinities for OP substrates.展开更多
Background：Paraoxonase 1（PON1） is an antioxidant enzyme that protects high-density lipoprotein（HDL） and low-density lipoprotein against oxidation.Limited studies have addressed the influenc of exercise on PON1 ac...Background：Paraoxonase 1（PON1） is an antioxidant enzyme that protects high-density lipoprotein（HDL） and low-density lipoprotein against oxidation.Limited studies have addressed the influenc of exercise on PON1 activity and its relationship with PON1 phenotypes.We investigated relationships between PON1-192 phenotypes,PON1 activity,aerobic exercise,and blood lipid and lipoprotein concentrations in middle-aged women.Methods：An exercise group（n=50） engaging in regular aerobic exercise and a control group（n=41） were selected from a subset of 300 Caucasian women that met the inclusion criteria.Serum PON1,salt-stimulated PON1（SSPON1）,and arylesterase（ARE） activities;cholesterol levels and ARE activities of total HDL and HDL subgroups（HDLs）（supernatants obtained by polyethylene glycol）;and blood lipid and lipoprotein concentrations were determined by standardized enzymatic methods.PON1-192 QQ（low activity）,QR（moderate activity）,and RR（high activity） phenotype groups were define using serum SSPON1/ARE activity ratios.The R-carries（RC） phenotype group consisted of the QR and RR groups combined.Results：All lipid and lipoprotein concentrations were greater in the exercise group than in the control group.Regardless of phenotype,no significan differences were observed between the exercise and control groups in terms of serum PON1,SSPON1,or ARE activity associated with HDLs（p〉 0.05）,whereas PON1 activities in QQ-phenotyped women in the exercise group were significant y higher than those in the control group（p〈0.01）,but not the RC group.A statistically significan interaction between PON1 phenotypes（QQ and RC groups） and exercise（exercise and control groups） on PON1 activity was found.Conclusion：These results showed that a regular aerobic exercise program can improve PON1 activity depending on PON1-192 phenotype,but not on lipid and lipoprotein levels,in middle-aged Turkish women.展开更多
目的:探讨对氧磷酶1基因(PON1基因)rs854560、rs757158两位点与广西地区女性人群乳腺癌(BC)的遗传易感性关系。方法:选取广西地区64例无血缘关系并排除癌症家族史的女性健康体检者(对照组)、60例排除其他肿瘤和遗传病的女性BC患者入组(B...目的:探讨对氧磷酶1基因(PON1基因)rs854560、rs757158两位点与广西地区女性人群乳腺癌(BC)的遗传易感性关系。方法:选取广西地区64例无血缘关系并排除癌症家族史的女性健康体检者(对照组)、60例排除其他肿瘤和遗传病的女性BC患者入组(BC组)。所有参与者清晨空腹采集2 mL EDTA-K2抗凝静脉血样本,从两组的全血样本中提取全基因组DNA。检测两组的PON1基因rs854560和rs757158 SNP位点。比较两组间的PON1基因rs854560和rs757158两位点基因型及等位基因分布频率的差异性,通过校正年龄、吸烟史、饮酒史、民族因素的logistic回归分析筛选独立的易感与保护基因型和等位基因,用比值比(OR)、95%可信区间(95%CI)表示患病的相对风险性,并运用SHEsis在线软件对各组中PON1两个SNP位点进行单倍型构建分析。结果:与对照组比较,BC组年龄、饮酒、吸烟均有显著差异(P<0.05),而体质量指数、民族构成比均无显著差异(P>0.05)。PON1基因rs854560和rs757158基因型和等位基因在两组间分布频率比较差异均无统计学意义(P>0.05),PON1基因rs854560和rs757158基因型和等位基因与BC无相关性(P>0.05),且构建的单倍型AT增加1.662倍BC患病风险(P<0.05)。结论:年龄、饮酒、吸烟是BC的危险因素,PON1基因rs854560、rs757158两位点与广西地区女性人群BC及各分子分型之间的患病风险均无关联,PON1基因rs854560和rs757158两位点构建的单倍体AT与BC的发病风险有关,单倍体AT增加BC的患病风险,单倍体AT可能是导致广西地区女性人群BC患病风险的遗传危险因素。展开更多
BACKGROUND: Paraoxonase 1(PON1) is an ester hydro- lase in serum and in the liver. Studies have suggested that PON1 measurement to the current battery of tests may im- prove the evaluation of chronic liver diseases. T...BACKGROUND: Paraoxonase 1(PON1) is an ester hydro- lase in serum and in the liver. Studies have suggested that PON1 measurement to the current battery of tests may im- prove the evaluation of chronic liver diseases. The aim of this study was to investigate the clinical significance of mo- nitoring the level of serum PON1 activity in liver transplan- tation patients. METHODS: A series of biochemical indexes were moni- tored in preoperative, operative and postoperative serum samples of 17 liver-transplanted patients. The change of se- rum PON1 level and its relations with other biochemical in- dexes were analyzed. RESULTS: PON1 was distributed normally in the healthy population and its reference value ranged from 45.5 to 265.8 U/mL. The PON1 level of all patients was lower than that of control group significantly (P<0.001); the level be- gan to elevate continuously 5 minutes after opening of the portal vein and was higher than that 90 minutes after open- ing of the portal vein ( P <0.05). Two days after operation it was still higher than the normal. The levels of serum ALT and AST elevated more significantly after opening of the portal vein than before operation and they were higher than the normal values till 2 days after the operation. CONCLUSIONS: The level of PON1 in serum may be taken as one of the effective indexes to assess whether the implant is alive and to monitor liver function of the patient together with other tests.展开更多
Background: Paraoxonase 1 (PON1) is reported to have an antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or (type A)/arginine (Arg) or (type B) polymorphism at position 192 of P...Background: Paraoxonase 1 (PON1) is reported to have an antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or (type A)/arginine (Arg) or (type B) polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported. Objectives: To investigate the relationship between PON1 gene (Gln192-Arg) poly-morphism and the presence, extent and severity of CAD in type 2 DM. Methods: The study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into 4 groups;Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) non diabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1 (Gln192-Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion. Results: The frequency of Gln allele (Type A) was significantly higher in group I and group II compared to group III and group IV (62.5%, 60% vs 38.3%, 31.25% respectively, p 100 mg/dL [OR 4.31, CI (1.25 - 12.5), P < 0.001], high density lipoprotein (HDL) cholesterol <40 mg/dL [OR 5.11, CI (1.79 - 16.33), P < 0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67 - 13.57), P < 0.001] were significantly independent predictors of CAD. Conclusion: Arg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and it is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.展开更多
Introduction Single nucleotide polymorphisms （SNPs） are the most abundant DNA markers in the human genome occurring at a frequency of one in every 500--1000 nucleotides. A variety of methods have been used for the ...Introduction Single nucleotide polymorphisms （SNPs） are the most abundant DNA markers in the human genome occurring at a frequency of one in every 500--1000 nucleotides. A variety of methods have been used for the analysis of single nucleotide polymorphisms, including restriction fragment length polymorphism （RFLP）, direct sequencing by using laser-induced fluorescence detectionTM, fluorescence energy transfer, MALDI-TOF MS combined with primer extension or invasive cleavage, and fluorescence polarization. During the past two decades, mass spectrometry has become a very popular tool in the analysis of biomolecules and is perfectly suited to the analysis of single nucleotide polymorphisms （SNPs） due to its speed, low cost, and accuracy. In this work, we used MALDI TOF mass spectrometry to detect the fragments of restriction endonuclease hydrolysis of PCR products flanking a SNP located at paraoxonase 1（Q192R）. Compared with electrophoresis, this method requires less time of analysis and possess a higher accuracy.展开更多
PON 1 （Paraoxonase 1） has been proposed as an efficient catalytic bioscavenger to combat against OP （organophosphate） and CWNA （chemical warfare nerve agent） toxicity. Unlike stoichiometric bioscavengers such as...PON 1 （Paraoxonase 1） has been proposed as an efficient catalytic bioscavenger to combat against OP （organophosphate） and CWNA （chemical warfare nerve agent） toxicity. Unlike stoichiometric bioscavengers such as butyrylcholinesterase, catalytic bioscavengers are cost effective with the advantage of eliminating all the OPs/CWNAs at low doses. Analysis of catalytic bioscavenger efficacy of PONI showed promising results by various group of researchers. Still, there are large numbers of grey areas which are not addressed so far. One of the major areas of interest is the pharmacokinetic analysis of infused PON 1 in multiple animal models. It is shown that previous studies in mice significantly increased half-life of PONI, while recent studies in guinea pigs from our group showed reduced half-life of PON1. Similar results were reported by other research groups in guinea pigs and non-human primates. The short half-life of exogenously administered PON1 in multiple animal models may be due to poor association of PON1 with its endogenous carrier, high density lipoprotein or lower doses of PON 1 or a reflection of species difference. These observations warrant the significance of thorough pharmacokinetic analysis of infused PON 1 and the development of alternative approaches for successful utility of PON 1 as an efficient medical countermeasure against OP/CWNA toxicity.展开更多
文摘Paraoxonase-1(PON1)is an important enzyme in various pathologies such as pesticide poisoning,diabetes,atherosclerosis,neuronal disorders,and cancer,due to its multifunctional activity since it acts on different metabolites.However,one of its main functions is the hydrolysis of organophosphate(OP)compounds from pesticides that cause fatal poisoning at the level of the central nervous system(CNS).The objective of this review was to investigate whether the structure,genetics,and function of PON1 affect the metabolism of organophosphate pesticides or other abnormalities.Information was selected from articles in the database PubMed–NCBI(https://www.ncbi.nlm.nih.gov/pubmed/)with a publication date between 2011 and 2019.The enzymatic activity of PON1 can be modified depending on its chemical structure since there are different genetic polymorphisms that change PONI morphologies or the levels of expression in the bloodstream.This leads to differences in susceptibilities to organophosphate pesticide poisoning.The results of this review reveal that phenotypic variants of PON1 have differences in affinities for OP substrates.
基金supported by the Ege University Scientifi Research Projects Directorate(2006-BESYO-004)
文摘Background：Paraoxonase 1（PON1） is an antioxidant enzyme that protects high-density lipoprotein（HDL） and low-density lipoprotein against oxidation.Limited studies have addressed the influenc of exercise on PON1 activity and its relationship with PON1 phenotypes.We investigated relationships between PON1-192 phenotypes,PON1 activity,aerobic exercise,and blood lipid and lipoprotein concentrations in middle-aged women.Methods：An exercise group（n=50） engaging in regular aerobic exercise and a control group（n=41） were selected from a subset of 300 Caucasian women that met the inclusion criteria.Serum PON1,salt-stimulated PON1（SSPON1）,and arylesterase（ARE） activities;cholesterol levels and ARE activities of total HDL and HDL subgroups（HDLs）（supernatants obtained by polyethylene glycol）;and blood lipid and lipoprotein concentrations were determined by standardized enzymatic methods.PON1-192 QQ（low activity）,QR（moderate activity）,and RR（high activity） phenotype groups were define using serum SSPON1/ARE activity ratios.The R-carries（RC） phenotype group consisted of the QR and RR groups combined.Results：All lipid and lipoprotein concentrations were greater in the exercise group than in the control group.Regardless of phenotype,no significan differences were observed between the exercise and control groups in terms of serum PON1,SSPON1,or ARE activity associated with HDLs（p〉 0.05）,whereas PON1 activities in QQ-phenotyped women in the exercise group were significant y higher than those in the control group（p〈0.01）,but not the RC group.A statistically significan interaction between PON1 phenotypes（QQ and RC groups） and exercise（exercise and control groups） on PON1 activity was found.Conclusion：These results showed that a regular aerobic exercise program can improve PON1 activity depending on PON1-192 phenotype,but not on lipid and lipoprotein levels,in middle-aged Turkish women.
基金supported by grants from The National Natural Science Foundation of China(81200985,81071005)Natural Science Foundation of Hunan Province,China(11JJ3117)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry(2011508)~~
文摘目的:探讨对氧磷酶1基因(PON1基因)rs854560、rs757158两位点与广西地区女性人群乳腺癌(BC)的遗传易感性关系。方法:选取广西地区64例无血缘关系并排除癌症家族史的女性健康体检者(对照组)、60例排除其他肿瘤和遗传病的女性BC患者入组(BC组)。所有参与者清晨空腹采集2 mL EDTA-K2抗凝静脉血样本,从两组的全血样本中提取全基因组DNA。检测两组的PON1基因rs854560和rs757158 SNP位点。比较两组间的PON1基因rs854560和rs757158两位点基因型及等位基因分布频率的差异性,通过校正年龄、吸烟史、饮酒史、民族因素的logistic回归分析筛选独立的易感与保护基因型和等位基因,用比值比(OR)、95%可信区间(95%CI)表示患病的相对风险性,并运用SHEsis在线软件对各组中PON1两个SNP位点进行单倍型构建分析。结果:与对照组比较,BC组年龄、饮酒、吸烟均有显著差异(P<0.05),而体质量指数、民族构成比均无显著差异(P>0.05)。PON1基因rs854560和rs757158基因型和等位基因在两组间分布频率比较差异均无统计学意义(P>0.05),PON1基因rs854560和rs757158基因型和等位基因与BC无相关性(P>0.05),且构建的单倍型AT增加1.662倍BC患病风险(P<0.05)。结论:年龄、饮酒、吸烟是BC的危险因素,PON1基因rs854560、rs757158两位点与广西地区女性人群BC及各分子分型之间的患病风险均无关联,PON1基因rs854560和rs757158两位点构建的单倍体AT与BC的发病风险有关,单倍体AT增加BC的患病风险,单倍体AT可能是导致广西地区女性人群BC患病风险的遗传危险因素。
文摘BACKGROUND: Paraoxonase 1(PON1) is an ester hydro- lase in serum and in the liver. Studies have suggested that PON1 measurement to the current battery of tests may im- prove the evaluation of chronic liver diseases. The aim of this study was to investigate the clinical significance of mo- nitoring the level of serum PON1 activity in liver transplan- tation patients. METHODS: A series of biochemical indexes were moni- tored in preoperative, operative and postoperative serum samples of 17 liver-transplanted patients. The change of se- rum PON1 level and its relations with other biochemical in- dexes were analyzed. RESULTS: PON1 was distributed normally in the healthy population and its reference value ranged from 45.5 to 265.8 U/mL. The PON1 level of all patients was lower than that of control group significantly (P<0.001); the level be- gan to elevate continuously 5 minutes after opening of the portal vein and was higher than that 90 minutes after open- ing of the portal vein ( P <0.05). Two days after operation it was still higher than the normal. The levels of serum ALT and AST elevated more significantly after opening of the portal vein than before operation and they were higher than the normal values till 2 days after the operation. CONCLUSIONS: The level of PON1 in serum may be taken as one of the effective indexes to assess whether the implant is alive and to monitor liver function of the patient together with other tests.
文摘Background: Paraoxonase 1 (PON1) is reported to have an antioxidant and cardioprotective properties. Recently, an association of glutamine (Gln) or (type A)/arginine (Arg) or (type B) polymorphism at position 192 of PON1 gene has been suggested with coronary artery disease (CAD) among patients with diabetes mellitus (DM). However, conflicting results have also been reported. Objectives: To investigate the relationship between PON1 gene (Gln192-Arg) poly-morphism and the presence, extent and severity of CAD in type 2 DM. Methods: The study comprised 180 patients recruited from those undergoing coronary angiography for suspected CAD, who were divided according to the presence or absence of CAD and DM into 4 groups;Group I (n = 40 patients) nondiabetic subjects without CAD, Group II (n = 45 patients) diabetic patients without CAD, Group III (n = 47 patients) non diabetic patients with CAD and Group IV (n = 48 patients) diabetic patients with CAD. PON1 (Gln192-Arg) genotype was assessed using polymerase chain reaction (PCR) followed by AlwI digestion. Results: The frequency of Gln allele (Type A) was significantly higher in group I and group II compared to group III and group IV (62.5%, 60% vs 38.3%, 31.25% respectively, p 100 mg/dL [OR 4.31, CI (1.25 - 12.5), P < 0.001], high density lipoprotein (HDL) cholesterol <40 mg/dL [OR 5.11, CI (1.79 - 16.33), P < 0.001] and PON1 192 Arg allele [OR 4.62, CI (1.67 - 13.57), P < 0.001] were significantly independent predictors of CAD. Conclusion: Arg allele of PON1 192 gene polymorphism is an independent risk factor for CAD and it is associated not only with the presence of CAD but also with its extent and severity and its impact is clearly more pronounced in diabetic patients.
文摘Introduction Single nucleotide polymorphisms （SNPs） are the most abundant DNA markers in the human genome occurring at a frequency of one in every 500--1000 nucleotides. A variety of methods have been used for the analysis of single nucleotide polymorphisms, including restriction fragment length polymorphism （RFLP）, direct sequencing by using laser-induced fluorescence detectionTM, fluorescence energy transfer, MALDI-TOF MS combined with primer extension or invasive cleavage, and fluorescence polarization. During the past two decades, mass spectrometry has become a very popular tool in the analysis of biomolecules and is perfectly suited to the analysis of single nucleotide polymorphisms （SNPs） due to its speed, low cost, and accuracy. In this work, we used MALDI TOF mass spectrometry to detect the fragments of restriction endonuclease hydrolysis of PCR products flanking a SNP located at paraoxonase 1（Q192R）. Compared with electrophoresis, this method requires less time of analysis and possess a higher accuracy.
文摘PON 1 （Paraoxonase 1） has been proposed as an efficient catalytic bioscavenger to combat against OP （organophosphate） and CWNA （chemical warfare nerve agent） toxicity. Unlike stoichiometric bioscavengers such as butyrylcholinesterase, catalytic bioscavengers are cost effective with the advantage of eliminating all the OPs/CWNAs at low doses. Analysis of catalytic bioscavenger efficacy of PONI showed promising results by various group of researchers. Still, there are large numbers of grey areas which are not addressed so far. One of the major areas of interest is the pharmacokinetic analysis of infused PON 1 in multiple animal models. It is shown that previous studies in mice significantly increased half-life of PONI, while recent studies in guinea pigs from our group showed reduced half-life of PON1. Similar results were reported by other research groups in guinea pigs and non-human primates. The short half-life of exogenously administered PON1 in multiple animal models may be due to poor association of PON1 with its endogenous carrier, high density lipoprotein or lower doses of PON 1 or a reflection of species difference. These observations warrant the significance of thorough pharmacokinetic analysis of infused PON 1 and the development of alternative approaches for successful utility of PON 1 as an efficient medical countermeasure against OP/CWNA toxicity.
