Paraoxonase-1 (PON1) is an esterase and lactonase synthesized by the liver and found in the circulation associated with high-density lipoproteins. The physiological function of PON1 seems to be to degrade specific oxi...Paraoxonase-1 (PON1) is an esterase and lactonase synthesized by the liver and found in the circulation associated with high-density lipoproteins. The physiological function of PON1 seems to be to degrade specific oxidized cholesteryl esters and oxidized phospholipids in lipoproteins and cell membranes. PON1 is, therefore, an antioxidant enzyme. Alterations in circulating PON1 levels have been reported in a variety of diseases involving oxidative stress including chronic liver diseases. Measurement of serum PON1 activity has been proposed as a potential test for the evaluation of liver function. However, this measurement is still restricted to research and has not been extensively applied in routine clinical chemistry laboratories. The reason for this restriction is due to the problem that the substrate commonly used for PON1 measurement, paraoxon, is toxic and unstable. The recent development of new assays with non-toxic substrates makes this proposal closer to a practical development. The present editorial summarizes PON1 biochemistry and function, its involvement with chronic liver impairment, and some aspects related to the measurement of PON1 activity in circulation.展开更多
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
目的探索酮还原酶家族1成员C3(aldo-keto reductase family 1 member C3,AKR1C3)对乳腺癌恶性细胞生物学行为的干预作用及对程序性细胞死亡蛋白/程序性死亡-配体1(programmed cell death protein1/programmed death-ligand1,PD-1/PD-L)...目的探索酮还原酶家族1成员C3(aldo-keto reductase family 1 member C3,AKR1C3)对乳腺癌恶性细胞生物学行为的干预作用及对程序性细胞死亡蛋白/程序性死亡-配体1(programmed cell death protein1/programmed death-ligand1,PD-1/PD-L)通路的影响。方法把MCF-7人乳腺癌细胞中NC组和AKR1C3组分别转染空质粒和AKR1C3质粒,采用MTT法检测转染后24 h、48 h、72 h细胞活力;采用流式细胞技术测定各组细胞的存活率以及早期、晚期凋亡比例;通过Transwell实验对各组细胞的迁移和侵袭能力进行检测;通过Western blot检测各组细胞PD-1、PD-L1、蛋白激酶B(protein kinase b,AKT)蛋白表达水平。使用C57BL/6小鼠构建荷瘤模型,将采用人乳腺癌MCF-7细胞转染NC质粒和AKR1C3质粒进行细胞荷瘤,每3 d测量瘤体积,持续21 d,绘制两组小鼠肿瘤生长曲线,并于实验终点测量肿瘤质量。结果相较于NC组,AKR1C3组细胞活力降低(P<0.05),并且具有时间依赖效应(P<0.05),迁移和侵袭能力降低(P<0.05),早期凋亡和晚期凋亡比例升高(P<0.05),PD-1、PD-L1、AKT蛋白表达水平降低(P<0.05)。动物实验表明,AKR1C3组小鼠肿瘤体积降低,肿瘤质量下降(P<0.05)。结论AKR1C3可以抑制人乳腺癌细胞恶性生物学行为,抑制PD-1/PDL1信号通路蛋白表达。展开更多
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)~~
基金Supported by Fondo de Investigación Sanitaria,FIS 00/0232,02/0430, 05/1607the Instituto de Salud Carlos Ⅲ, C03/02,C03/08,G03/015the Generalitat de Catalunya,FI 05/00068
文摘Paraoxonase-1 (PON1) is an esterase and lactonase synthesized by the liver and found in the circulation associated with high-density lipoproteins. The physiological function of PON1 seems to be to degrade specific oxidized cholesteryl esters and oxidized phospholipids in lipoproteins and cell membranes. PON1 is, therefore, an antioxidant enzyme. Alterations in circulating PON1 levels have been reported in a variety of diseases involving oxidative stress including chronic liver diseases. Measurement of serum PON1 activity has been proposed as a potential test for the evaluation of liver function. However, this measurement is still restricted to research and has not been extensively applied in routine clinical chemistry laboratories. The reason for this restriction is due to the problem that the substrate commonly used for PON1 measurement, paraoxon, is toxic and unstable. The recent development of new assays with non-toxic substrates makes this proposal closer to a practical development. The present editorial summarizes PON1 biochemistry and function, its involvement with chronic liver impairment, and some aspects related to the measurement of PON1 activity in circulation.
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.
