Acetylhydrolase Activity Research Articles

Platelet Activating Factor Acetylhydrolase (PAF-AH) activity : could it have a role on coagulation in covid-19 patients?

Objective: Abnormal immune inflammatory response and cytokine storm play an important role on the aspect of increasing mortality in Covid-19. We aimed to investigate whether the Platelet Activating Factor Acetylhydrolase activity (PAF-AH) and hematological parameters have prognostic and predictive value in determining the disease severity.
 Methods: A total of 84 Covid-19 patients, 52 of whom were hospitalized in the ward and 32 in the intensive care unit (ICU), and 38 control patients were included in this study. 
 Results: Lymphocyte and serum albumin levels were significantly lower (p < .001) and age, neutrophils, CRP, procalcitonin, LDH, INR, D-dimer levels were significantly higher (p < .001) in Covid-19 patients compared to the control group. ICU patients had significantly lower (p < .001) lymphocyte, albumin values and significantly higher (p < .001) age, leukocyte, neutrophils, CRP, INR, aPTT, D-dimer levels compared to ward patients. PAF-AH activity was significantly increased in ICU patients compared to the control group (p < .05). A positive correlation was found between PAF-AH and D-Dimer in the ICU group.
 Conclusion: We found increased PAF-AH activity in patients with Covid-19. It’s important to spot the PAF-AH activity in cardiovascular events that develop due to coagulation problems, which are likely to be seen on these patients in the future.

Identification and In Silico Simulation on Inhibitory Platelet-Activating Factor Acetyl Hydrolase Peptides from Dry-Cured Pork Coppa

The unique processing technology of dry-cured meat products leads to strong proteolysis, which produces numerous peptides. The purpose of this investigation was the systematic isolation, purification, and identification of potentially cardioprotective bioactive peptides from dry-cured pork coppa during processing. According to the results of anti-platelet-activating factor acetyl hydrolase activity and radical scavenging ability in vitro, the inhibitory effect of M1F2 in purified fractions on cardiovascular inflammation was higher than that of M2F2. The peptide of M1F2 was identified by nano-liquid chromatography-tandem mass spectrometry. A total of 30 peptides were identified. Based on bioinformatics methods, including in silico analysis and molecular docking, LTDKPFL, VEAPPAKVP, KVPVPAPK, IPVPKK, and PIKRSP were identified as the most promising potential platelet-activating factor acetyl hydrolase inhibitory peptides. Overall, bioactive peptides produced during dry-cured pork coppa processing demonstrate positive effects on human health.

Electronegative LDL Is Associated with Plaque Vulnerability in Patients with Ischemic Stroke and Carotid Atherosclerosis

Owing to the high risk of recurrence, identifying indicators of carotid plaque vulnerability in atherothrombotic ischemic stroke is essential. In this study, we aimed to identify modified LDLs and antioxidant enzymes associated with plaque vulnerability in plasma from patients with a recent ischemic stroke and carotid atherosclerosis. Patients underwent an ultrasound, a CT-angiography, and an 18F-FDG PET. A blood sample was obtained from patients (n = 64, 57.8% with stenosis ≥50%) and healthy controls (n = 24). Compared to the controls, patients showed lower levels of total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B (apoB), apoA-I, apoA-II, and apoE, and higher levels of apoJ. Patients showed lower platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase-1 (PON-1) enzymatic activities in HDL, and higher plasma levels of oxidized LDL (oxLDL) and electronegative LDL (LDL(-)). The only difference between patients with stenosis ≥50% and <50% was the proportion of LDL(-). In a multivariable logistic regression analysis, the levels of LDL(-), but not of oxLDL, were independently associated with the degree of carotid stenosis (OR: 5.40, CI: 1.15-25.44, p < 0.033), the presence of hypoechoic plaque (OR: 7.52, CI: 1.26-44.83, p < 0.027), and of diffuse neovessels (OR: 10.77, CI: 1.21-95.93, p < 0.033), indicating that an increased proportion of LDL(-) is associated with vulnerable atherosclerotic plaque.

Platelet-activating factor acetylhydrolase is a biomarker of severe anaphylaxis in children.

There is limited ability to predict the severity of allergic reactions in children. Data derived predominantly from adults have implicated the platelet-activating factor pathway as a potential contributor to severe anaphylaxis. In this study, we sought to prospectively assess involvement of key components of the platelet-activating factor pathway in pediatric patients with anaphylaxis. Forty-six pediatric patients (<18years) presenting with acute anaphylaxis were assessed. Anaphylaxis severity was graded and serum anaphylaxis markers were measured acutely and in 36 children who returned for follow-up >4weeks after their acute presentation. These markers were compared with pediatric laboratory reference sera. Severe anaphylaxis was experienced by 12/46 (26%) and mild-moderate anaphylaxis in 34/46 (74%) children. Platelet-activating factor acetylhydrolase (PAF-AH) activity was inversely associated with severe anaphylaxis: 9/12 children with severe anaphylaxis had reduced PAF-AH activity as compared with 14/34 with mild-moderate anaphylaxis (p < .05). Furthermore, 3/3 children who required intensive care had markedly reduced mean PAF-AH (nmol/ml/min) (13.73, 95%CI: 7.42-20.03) versus 20/23 who required ward/emergency department care (17.81, 95%CI: 16.80-18.83; p < .05). In children with anaphylaxis, PAF-AH during acute anaphylaxis was unchanged relative to the child's basal levels (mean, 17.26, 95%CI: 16.10-18.42 vs 17.50, 95%CI: 16.21-18.78, p = .63) and was lower than healthy pediatric controls (mean 19.21; 95%CI:18.21-20.21; p < .05). Decreased serum PAF-AH activity is a biomarker of severe anaphylaxis. Levels of this enzyme do not change from basal levels during acute anaphylaxis. Our results show that PAF-AH is a biomarker of anaphylaxis severity in children. This key regulatory enzyme may modulate susceptibility to severe anaphylaxis.

Metabolomic profiling revealed altered lipid metabolite levels in childhood food allergy

The pathophysiology of childhood food allergy (FA) and its natural history are poorly understood. Clarification of the underlying mechanism may help identify novel biomarkers and strategies for clinical intervention in children with FA. This study aimed to identify metabolites associated with the development and resolution of FA. The metabolomic profiles of 20 children with FA and 20 healthy controls were assessed by liquid chromatography-tandem mass spectrometry. Comparative analysis was performed to identify metabolites associated with FA and FA resolution. For subjects with FA, serum samples were collected at the time of diagnosis and after resolution to identify the changes in metabolite levels. The selected metabolites were then quantified in a quantification cohort to validate the results. Finally, genome-wide association analysis of the metabolite levels was performed. The study demonstrated a significantly higher level of sphingolipid metabolites and a lower level of acylcarnitine metabolites in children with FA than those in healthy controls. At diagnosis, subjects with resolving FA had a significantly high level of omega-3 metabolites and a low level of platelet-activating factors compared to persistent FA. However, the level of omega-3 metabolites decreased in children with resolving FA but increased in children with persistent FA during the same time. The quantification data of omega-3-derived resolvins, platelet-activating factor, and platelet-activating factor acetylhydrolase activity further supported these results. The lipid metabolite profile is closely related to childhood FA and FA resolution. This study suggests potential predictive biomarkers and provides insight into the mechanisms underlying childhood FA.

Clinical significance of plasma PAF acetylhydrolase activity measurements as a biomarker of anaphylaxis: Cross-sectional study.

IntroductionPlatelet-activating factor (PAF) has a direct role as a mediator in the pathogenesis of various disorders with an inflammatory component, including those with allergic aetiology. The peripheral blood concentration of PAF is dynamically regulated by plasma PAF acetylhydrolase (PAF-AH). Previous research suggest that low activity of plasma PAF-AH could be a predictive marker for increased severity of some types of allergic hypersensitivity reactions–especially anaphylaxis. The purpose of the study was to evaluate the association between plasma PAF-AH activity and severity in patients with anaphylactic reactions following a wasp or bee sting.Materials and methodsThe study group of 89 patients was divided into two subgroups depending on the increasing severity of the most severe anaphylactic reaction in the past, which was assessed according to the Müller’s scale. The first subgroup included participants with a history of hypersensitivity reactions up to grade II. The second subgroup consisted of patients who have experienced at least one grade III or IV reactions in the past. A control group of 20 people was established. Plasma PAF-AH activity was measured using a colorimetric method.ResultsIt has been observed that plasma activity of platelet-activating factor acetylhydrolase was significantly lower in patients with anaphylaxis history compared to the control group with negative atopic history (on average 21.38 nmol/min/ml for the control group, 9.47 nmol/min/ml for the first subgroup and 10.16 nmol/min/ml for the second subgroup, in both cases p < 0.0001).ConclusionThe plasma activity of PAF-AH is a promising parameter that can help to distinguish a group of patients not threatened with development of anaphylaxis and not requiring laborious or expensive prophylactic procedures.

Kupffer cell release of platelet activating factor drives dose limiting toxicities of nucleic acid nanocarriers

This work establishes that Kupffer cell release of platelet activating factor (PAF), a lipidic molecule with pro-inflammatory and vasoactive signaling properties, dictates dose-limiting siRNA nanocarrier-associated toxicities. High-dose intravenous injection of siRNA-polymer nano-polyplexes (si-NPs) elicited acute, shock-like symptoms in mice, associated with increased plasma PAF and consequently reduced PAF acetylhydrolase (PAF-AH) activity. These symptoms were completely prevented by prophylactic PAF receptor inhibition or Kupffer cell depletion. Assessment of varied si-NP chemistries confirmed that toxicity level correlated to relative uptake of the carrier by liver Kupffer cells and that this toxicity mechanism is dependent on carrier endosome disruptive function. 4T1 tumor-bearing mice, which exhibit increased circulating leukocytes, displayed greater sensitivity to these toxicities. PAF-mediated toxicities were generalizable to commercial delivery reagent in vivo-jetPEI® and an MC3 lipid formulation matched to an FDA-approved nanomedicine. These collective results establish Kupffer cell release of PAF as a key mediator of siRNA nanocarrier toxicity and identify PAFR inhibition as an effective strategy to increase siRNA nanocarrier tolerated dose.

Evaluation of maternal plasma platelet activating factor acetylhydrolase activity and mRNA expression in pre-eclampsia: a case control study

Preeclampsia (PE) remains a leading cause of maternal morbidity and mortality all over the world. However, its aetiology and pathophysiology remain elusive. Platelet activating factor (PAF) is produced in response to oxidative stress and is a potent hypotensive agent. PAF acetylhydrolase (PAF-AH) inactivates PAF and is seen to decrease in normotensive women. The role of PAF-AH in preeclampsia has been in investigational literature, so far. The few studies done have shown a positive association of elevated levels of PAF-AH with preeclampsia. However, this marker has not been studied in the Indian population to-date and such studies are needed to elucidate the pathogenesis of this condition. Our study aimed to determine the PAF-AH activity by spectrophotometric assay in maternal plasma of 73 PE patients versus 73 normotensive controls and plasma PAF-AH mRNA expression to know the aberration of PAF-AH activity at the genetic level. Relative mRNA expression was calculated by Δ DCT method and a fold change was calculated by 2–ΔDCT. We found that the mean plasma PAF-AH activity levels among cases was significantly higher than the normotensive controls. However, the mRNA expression of the PAF-AH gene was similar between the cases and controls, as well as between severe and non-severe preeclampsia (true fold change =1). To conclude, PAF-AH appears to be increased in women with preeclampsia and hence may contribute to pathophysiology and severity. However, a larger sample size will be required to reiterate this association. Recently, PAF-AH inhibitors such as Darapladib has been tested as a therapeutic option in atherosclerosis. After studying the role of PAF-AH in the pathogenesis of PE, PAF-AH inhibitors may be used as a therapeutic tool in the future in PE. IMPACT STATEMENT What is already known on this subject? Platelet activating factor (PAF) is produced in response to oxidative stress and is a potent hypotensive agent. PAF acetylhydrolase (PAF-AH) hydrolyses and inactivates PAF and is seen to decrease in normotensive women. The role of platelet activating factor-acetylhydrolase (PAF-AH) in preeclampsia has been investigational so far. Few studies done have shown a positive association of elevated levels of PAF-AH in preeclamptic women. What do the results of this study add? Our study aimed to determine the activity of PAF-AH in maternal plasma of PE patients versus normal pregnancy and plasma PAF-AH mRNA expression to know the aberration of PAF-AH activity at the level of the gene. We found that plasma PAF-AH activity among preeclamptics was significantly higher than in the controls with a possible role in early-onset preeclampsia (<32 weeks), in the Indian population. This marker has never been studied in this population earlier. The results of our study re-emphasised its role in the pathogenesis of preeclampsia. What are the implications of these findings for clinical practice and/or further research? Such studies are important to not only give us a greater understanding of the various pathways involved in this multifactorial dreaded condition, but can also offer us a marker for early identification of women at risk. Recently, PAF-AH inhibitors like Darapladib has been tested as a therapeutic option in atherosclerosis. After studying the role of PAF-AH in the pathogenesis of PE, PAF-AH inhibitors may be used as a therapeutic tool in the future in PE.

Mediterranean Diet and Atherothrombosis Biomarkers: A Randomized Controlled Trial

To assess whether following a Mediterranean diet (MedDiet) improves atherothrombosis biomarkers in high cardiovascular risk individuals. In 358 random volunteers from the PREvención con DIeta MEDiterránea trial, the 1-year effects on atherothrombosis markers of an intervention with MedDiet, enriched with virgin olive oil (MedDiet-VOO; n = 120) or nuts (MedDiet-Nuts; n = 119) versus a low-fat control diet (n = 119), and whether large increments in MedDiet adherence (≥3 score points, versus compliance decreases) and intake changes in key food items are associated with 1-year differences in biomarkers. Differences are observed between 1-year changes in the MedDiet-VOO intervention and control diet on the activity of platelet activating factor acetylhydrolase in high-density lipoproteins (HDLs) (+7.5% [95% confidence interval: 0.17; 14.8]) and HDL-bound α1 -antitrypsin levels (-6.1% [-11.8; -0.29]), and between the MedDiet-Nuts intervention and the control arm on non-esterified fatty acid concentrations (-9.3% [-18.1; -0.53]). Large MedDiet adherence increments are associated with less fibrinogen (-9.5% [-18.3; -0.60]) and non-esterified fatty acid concentrations (-16.7% [-31.7; -1.74]). Increases in nut, fruit, vegetable, and fatty fish consumption, and decreases in processed meat intake are linked to enhancements in biomarkers. MedDiet improves atherothrombosis biomarkers in high cardiovascular risk individuals.

Sesame lignans reduce LDL oxidative susceptibility by downregulating the platelet-activating factor acetylhydrolase.

Low-density lipoprotein (LDL) oxidative susceptibility is recognized as a risk factor for atherosclerosis. We previously reported that the ingestion of a supplement containing sesame lignans (sesamin/episesamin) for 4 weeks reduced LDL oxidative susceptibility in humans. To elucidate the mechanisms underlying this observation, 12-week-old New Zealand White rabbits were fed a fat/cholesterol-enriched diet (100 g/day) for 6 weeks followed by oral administration of vehicle (control) or sesame lignans (50 mg/kg) for 4 weeks with the fat/cholesterol-enriched diet. The results showed that the ingestion of sesame lignans prolonged LDL oxidation lag time, regardless of the existence of the anti-oxidative catechol metabolite of sesamin/episesamin in LDL. Plasma platelet-activating factor acetylhydrolase (PAF-AH) activity was significantly reduced by sesame lignans. The prolongation of LDL oxidation lag time was abolished by the addition of a PAF-AH inhibitor. The expression level of pro-inflammatory cytokines and macrophage infiltration observed in the liver following the feeding of the fat/cholesterol-enriched diet were also significantly reduced by sesame lignans. These results indicate that sesame lignans reduce LDL oxidative susceptibility by downregulating plasma PAF-AH activity via the reduction of inflammation in the liver induced by fat/cholesterol-enriched diets.

Hereditary angioedema attack: what happens to vasoactive mediators?

Hereditary angioedema is a disabling, life-threatening condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein (C1-INH-HAE) leading to bradykinin accumulation and recurrent episodes of edema attack. Vascular leakage is a complex process sustained by the coordinated production of several permeabilizing factors including vascular endothelial growth factors (VEGFs), angiopoietins (ANGPTs) and phospholipase A2 enzymes (PLA2). We previously reported that patients with C1-INH-HAE in remission have increased plasma levels of VEGFs, ANGPTs and secreted PLA2. In this study, we sought to analyze plasma levels of these mediators in 15 patients with C1-INH-HAE during the acute attack compared to remission. Plasma concentrations of VEGF-A, VEGF-C and VEGF-D were not altered during attack compared to remission. Moreover, VEGF-D concentrations were not altered also in remission phase compared to controls. Concentrations of ANGPT1, a vascular stabilizer, were increased during attacks compared to symptoms-free periods, whereas ANGPT2 levels were not altered. The ANGPT2/ANGPT1 ratio was decreased during angioedema attacks. Platelet activating factor acetylhydrolase activity was increased in patients with C1-INH-HAE in remission compared to controls and was decreased during angioedema attacks. Our results emphasize the complexity by which several vasoactive mediators are involved not only in the pathophysiology of C1-INH-HAE, but also during angioedema attacks and its resolution.

Risk factors and indicators of severe systemic insect sting reactions.

Hymenoptera venom allergy ranks among the top three causes of anaphylaxis worldwide, and approximately one-quarter of sting-induced reactions are classified as severe. Fatal sting reactions are exceedingly rare, but certain factors may entail a considerably higher risk. Delayed administration of epinephrine and upright posture are situational risk factors which may determine an unfavorable outcome of the acute anaphylactic episode and should be addressed during individual patient education. Systemic mastocytosis and senior age are major, unmodifiable long-term risk factors and thus reinforce the indication for venom immunotherapy. Vespid venom allergy and male sex likewise augment the risk of severe or even fatal reactions. Further studies are required to assess the impact of specific cardiovascular comorbidities. Available data regarding potential effects of beta-blockers and/or ACE inhibitors in coexisting venom allergy are inconclusive and do not justify recommendations to discontinue guideline-directed antihypertensive treatment. The absence of urticaria/angioedema during sting-induced anaphylaxis is indicative of a severe reaction, serum tryptase elevation, and mast cell clonality. Determination of basal serum tryptase levels is an established diagnostic tool for risk assessment in Hymenoptera venom-allergic patients. Measurement of platelet-activating factor acetylhydrolase activity represents a complementary approach but is not available for routine diagnostic use.

The effect of exenatide (a GLP-1 analog) and sitagliptin (a DPP-4 inhibitor) on plasma platelet-activating factor acetylhydrolase (PAF-AH) activity and concentration in normal and fructose-fed rats

Inflammation and oxidative stress are the two processes crucial in atherogenesis. Platelet-activating factor acetylhydrolase (PAF-AH), a plasma lipoprotein-associated enzyme, degrades pro-inflammatory lipids generated within oxidatively modified lipoproteins. Extensive evidence shows that incretin-based drugs, a new class of anti-diabetic agents, can provide cardiovascular protection that cannot be attributed to their glucose-lowering effects. The present study was undertaken to determine whether the antiatherogenic effects of the GLP-1(glucagon-like peptide-1) receptor agonist (exenatide) and DPP-4(dipeptidyl peptidase-4) inhibitors (sitagliptin) may occur via the regulation of platelet-activating factor acetylhydrolase (PAF-AH) activity/mass and inhibition of low-density lipoprotein (LDL) oxidation in the fructose-fed rats.Normal and fructose-fed rats (8 wk) were treated (4 wk) with sitagliptin (5 and 10 mg/kg p.o.) or with exenatide (5 and 10 µg/kg, s.c.). Plasma PAF-AH activity and phosphatidylcholine (PC) concentration were measured colorimetrically. Plasma PAF-AH concentration, oxidized LDL (oxLDL), hexanoyl-Lys adduct (HEL), lyso-PC, apolipoprotein A-I (apoA-I), apoB, platelet-activating factor (PAF), monocyte chemoattractant protein-1 (MCP-1) and endothelin-1 (ET-1) were measured by ELISA.The four-week exenatide (5 µg/kg, sc.) treatment of fructose fed-rats significantly increased plasma PAF-AH activity (+33%, P < 0.001) and decreased the level of circulating oxLDL (-42%, P < 0.05) and MCP-1 (-23%, P < 0.01). These changes were accompanied by the decrease in plasma PC/lyso-PC (-47%, P < 0.001) and apoB/apoA-I ratio (-75%, P < 0.001). The effect of exenatide on enzyme activity was associated with only a minor effect on metabolic parameters and was independent of weight reduction.Exenatide but not sitagliptin inhibits oxidative modification of LDL probably due to favorable effect on plasma PAF-AH activity.

Temporal-spatial characteristics of lipea gene expression in Cyprinus carpio and its correlation with fat deposition

PDF HTML阅读 XML下载 导出引用 引用提醒 鲤lipea基因表达的时空特征及与脂肪沉积相关性分析 DOI: 作者: 作者单位: 1. 上海海洋大学, 农业农村部淡水水产种质资源重点实验室, 上海 201306;2. 中国水产科学研究院黑龙江水产研究所, 淡水鱼类育种国家地方联合工程实验室, 黑龙江 哈尔滨 150070 作者简介: 党红阳(1995-),女,硕士研究生,研究方向为水产生物技术.E-mail:danghongyang95@163.com 通讯作者: 中图分类号: S965 基金项目: 国家自然科学基金项目（31302174）；中国水产科学研究院基本科研业务费（2015C04XK01）；国家水产种质资源共享服务平台项目（2018DKA30470）. Temporal-spatial characteristics of lipea gene expression in Cyprinus carpio and its correlation with fat deposition Author: Affiliation: 1. Key Laboratory of Freshwater Fishery Germplasm Resource, Ministry of Agriculture and Rural Affairs;Shanghai Ocean University, Shanghai 201306, China;2. National Local Joint Engineering Laboratory for Freshwater Fish Breeding, Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China Fund Project: 摘要 | 图/表 | 访问统计 | 参考文献 | 相似文献 | 引证文献 | 资源附件 | 文章评论 摘要:本文旨在克隆鲤（）基因，探究其时空表达特征及其与脂肪沉积的关系，以期为鲤脂肪沉积分子调控机制研究奠定理论基础。本实验采用RACE技术克隆获得鲤基因，其cDNA全长为3379 bp，包括230 bp的5'非翻译区（5'-UTR）、1067 bp的3'非翻译区（3'-UTR）和编码693个氨基酸的开放阅读框。多序列比对显示，鲤Oncorhynchus mykiss）的氨基酸序列相似性分别为88.17%、64.94%和63.35%，不同物种间序列差异主要集中在C-端的多肽序列上。蛋白质结构分析显示该蛋白含有3个功能域分别具有脂肪酶活性、乙酰基水解酶活性和水解酶活性。应用实时荧光定量PCR技术分析了在各组织中均有表达，腹腔脂肪中相对表达量最高，其次是腹部肌肉，血液中最少。随着胚胎的发育，表达量与背部肌肉脂肪含量呈正相关，但差异不显著（基因对鲤腹腔脂肪沉积可能具有抑制作用。本实验结果可为进一步解析鲤基因的功能和基因调控脂肪沉积分子机制研究提供参考。 Abstract:The objectives of this study were to investigate the expression pattern of Cyprinus carpio), to lay the foundation for studying and understanding the molecular regulation mechanism of fat deposition in common carp. In this study, a full-length cDNA sequence of gene in common carp was cloned by reverse transcription PCR and rapid-amplification of cDNA ends (RACE) technology, and the expression pattern of gene in different tissues of common carp and during its different developmental stages. cDNA of the gene of common carp was 3379 bp, with an open reading frame of 2079 bp, 5' untranslated region was 230 bp, 3' untranslated region was 1067 bp, encoding 693 amino acids. Multiple sequences alignment revealed that the amino acid sequences of Paralichthys olivaceus, and , respectively. It was determined that the sequence differences were mainly concentrated on the C-terminal polypeptide sequence between different species, and the structural analysis of proteins showed that the protein contains three functional domains with lipase activity, acetyl hydrolase activity, and hydrolase activity, respectively. Real-time quantitative PCR showed that the gene was expressed in all tested tissues, and the relative expression level was the highest in visceral fat, followed by abdominal muscles, and lowest in the blood. Its expression declined during the development of embryo; it was the highest in the 8-cell stage, followed by the late blastula stage. It was the lowest in the feeding period. The mRNA expression in different fat tissues negatively correlated with adipose tissue in the abdominal cavity; the highest and the lowest expression levels differed significantly (<0.01). The expression also positively correlated with dorsal muscle but it was not significant ( gene highlights its function and molecular regulation mechanism of fat development in common carp. 参考文献 相似文献 引证文献

Exercise intervention alters HDL subclass distribution and function in obese women

BackgroundObesity is associated with a change in high-density lipoprotein (HDL) function and subclass. Exercise training reduces cardiovascular risk in obese patients. We aimed to explore the effect of an exercise training stimulus on HDL functionality and subclass in obese women.MethodsThirty-two obese black South African women were randomly assigned to exercise (combined aerobic and resistance exercise) or control (no exercise) conditions for 12-weeks. Pre- and post-testing included venous blood sampling for analysis of lipid profile and HDL functionality, by measuring cellular cholesterol efflux capacity, reduction in endothelial vascular cell adhesion molecule (VCAM) expression (anti-inflammatory function), paraoxonase (PON) (antioxidative function) and platelet activating factor acetylhydrolase (PAF-AH) activities (anti-thrombotic function). PON-1 and PAF-AH expression were determined in serum and in isolated HDL using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system.ResultsExercise training resulted in a decrease in body mass index (− 1.0 ± 0.5% vs + 1.2 ± 0.6%, p = 0.010), PON activity (− 8.7 ± 2.4% vs + 1.1 ± 3.0%, p = 0.021), PAF-AH serum expression (− 22.1 ± 8.0% vs + 16.9 ± 9.8, p = 0.002), and the distribution of small HDL subclasses (− 10.1 ± 5.4% vs + 15.7 ± 6.6%, p = 0.004) compared to controls. Exercise did not alter HDL cellular cholesterol efflux capacity and anti-inflammatory function.ConclusionsThese results demonstrate the potential for exercise training to modify HDL subclass distribution and HDL function in obese women.Trial registrationClinical trials number: PACTR201711002789113.

Effects of apoC1 genotypes on the hormonal levels, metabolic profile and PAF-AH activity in Chinese women with polycystic ovary syndrome

BackgroundElevated serum levels of apolipoprotein (apo) C1 may be an early protein marker of metabolic abnormality in women with polycystic ovary syndrome (PCOS). It is not clear, however, whether there are any relationships between the apoC1 rs4420638A/G and -317deletion (H1)/insertion (H2) polymorphisms and PCOS. We investigated the relationship between these two variants and the risk of PCOS, evaluated the genotypic effects on clinical, hormonal and metabolic indexes and plasma platelet-activating factor acetylhydrolase (PAF-AH) activity, and defined the association of apoC1 gene variants with apoE ε2/ε3/ε4 polymorphisms.MethodsThis is a cross-sectional study of 877 women with PCOS and 761 controls. The apoC1 rs4420638A/G genotype was determined by a Taqman real-time PCR allelic discrimination assay. The apoC1–317H1/H2 and apoE ε2/ε3/ε4 genotypes were measured using PCR and restriction fragment length polymorphism analysis. The clinical, hormonal and metabolic parameters and PAF-AH activity were measured.ResultsThe frequencies of apoC1 rs4420638A/G and -317H1/H2 genotypes and alleles were similar between PCOS and control groups (P > 0.05). However, the rs4420638 G allele was related to increased serum luteinizing hormone, cholesterol and apoB levels, and the ratio of apoB to apoA1 (P < 0.05), and the -317H1H1 genotype was associated with a higher acne grade score and a higher ratio of apoB-PAF-AH to H-PAF-AH activity (P < 0.05) in patients with PCOS. We also demonstrated that the apoC1 rs4420638A/G and -317H1/H2 gene variants existed in moderate to reasonably high linkage disequilibrium with apoE ε2/ε3/ε4 polymorphisms in Chinese women.ConclusionThe apoC1 rs4420638A/G and -317H1/H2 gene variants might be involved in endocrine abnormalities of reproductive axis, metabolic abnormalities and chronic inflammation in PCOS, although no association was observed between the apoC1 genetic variants and the risk of PCOS in Chinese women.

Comparison of serum acetyl hydrolase (PAF-AH) and paraoxonase 1 (PON1) values between prostate cancer patients and a control group

The aim of the study was to measure platelet-activating factor acetyl hydrolase (PAF-AH) and paraoxonase (PON1) enzyme activity levels in patients with high Psa values to compare with healthy peers and also to determine the efficacy of these parameters in predicting pathologic results of patients with high Psa values. This study included 66 patients with Psa value > 4 ng/dl (Group 1) and 44 patients with Psa <4 ng/dl (Group 2) for a total of 110 patients. Parameters measured in serum of PON1, PAF-AH, and MDA were compared between the groups. Additionally the same parameters were compared between patients with prostate biopsy performed due to high Psa and diagnosed with cancer and the control group with normal Psa values. The PAF-AH activity in Group 1 was 125.17 ± 8.64 and in Group 2 was 120.08 ± 9.23 U/ml (p = 0.003). The PON1 activity was 63.12 ± 6.74 and 65.91 ± 7.77 U/ml in the groups, respectively (p = 0.04). Additionally, there were significant differences identified between the control group and PCa diagnosis group in terms of PAF-AH and PON1 activities (p = 0.004 and p = 0.02, respectively). The enzyme activity of PAF-AH and PON1 measured in serum of patients with high Psa value and patients with diagnosis of prostate cancer (PCa) were identified to have changed by a significant amount compared to healthy peers with normal Psa value. It was concluded that these parameters may be beneficial markers for use in assessment of patients with high Psa value.

The human asparaginase enzyme (ASPG) inhibits growth in leukemic cells.

The human protein ASPG is an enzyme with a putative antitumor activity. We generated in bacteria and then purified a recombinant GST-ASPG protein that we used to characterize the biochemical and cytotoxic properties of the human ASPG. We demonstrated that ASPG possesses asparaginase and PAF acetylhydrolase activities that depend on a critical threonine residue at position 19. Consistently, ASPG but not its T19A mutant showed cytotoxic activity in K562, NALM-6 and MOLT-4 leukemic cell lines but not in normal cells. Regarding the mechanism of action of ASPG, it was able to induce a significant apoptotic death in K562 cells. Taken together our data suggest that ASPG, combining different enzymatic activities, should be considered a promising anti-cancer agent for inhibiting the growth of leukemia cells.

Exploring the plasmatic platelet-activating factor acetylhydrolase activity in patients with anti-phospholipid antibodies

PurposeTo explore the role of plasmatic platelet-activating factor acetylhydrolase (PAF-AH), a marker of cardiovascular risk, in patients with anti-phospholipid antibodies (aPL).MethodsPAF-AH activity was assessed in a series of 167 unselected patients screened for aPL in a context of thrombotic events, risk of thrombosis or obstetric complications and in 77 blood donors.Results116/167 patients showed positive results for at least one aPL among IgG/IgM anti-prothrombin/phosphatidylserine (aPS/PT), anti-cardiolipin (aCL), anti-beta2-glycoprotein I (aβ2GPI) or lupus anticoagulant (LAC), while 51/167 patients resulted aPL-negative. LAC+ patients disclosed higher PAF-AH than LAC-negative (22.1 ± 6.4 nmol/min/ml vs. 19.5 ± 4.1 nmol/min/ml; p = 0.0032), and aPL-negative patients (p = 0.03). Patients presenting positive IgG aβ2GPI disclosed higher PAF-AH than patients with only IgM aβ2GPI-positive antibodies (23.1 ± 7.2 nmol/min/ml vs. 20.1 ± 5.3 nmol/min/ml; p = 0.035), as well as than patients showing only isolated LAC, aCL or aPS/PT (16.9 ± 3.8 nmol/min/ml; p = 0.003).ConclusionsPAF-AH plasmatic activity is particularly up-regulated in LAC+ and in aβ2GPI IgG+ patients, possibly representing an alternative prognostic biomarker for the therapeutic management of APS patients.

Association between ethnicity and obesity with high-density lipoprotein (HDL) function and subclass distribution.

BackgroundObesity and low high-density lipoprotein-cholesterol (HDL-C) levels are associated with cardiovascular risk. Surprisingly, despite a greater prevalence of obesity and lower HDL concentrations than white women, black South African women are relatively protected against ischaemic heart disease.MethodsWe investigated whether this apparent discrepancy may be related to different HDL function and subclass distribution in black and white, normal-weight and obese South African women (n = 40). HDL functionality was assessed by measuring paraoxonase (PON) activity, platelet activating factor acetylhydrolase (PAF-AH) activity, Oxygen Radical Absorbance Capacity (ORAC) and quantification of the expression of vascular cell adhesion molecule in endothelial cells. PON-1 and PAF-AH expression was determined in isolated HDL and serum using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system.ResultsPON activity was lower in white compared to black women (0.49 ± 0.09 U/L vs 0.78 ± 0.10 U/L, p < 0.05), regardless of PON-1 protein levels. Obese black women had lower PAF-AH activity (9.34 ± 1.15 U/L vs 13.89 ± 1.21 U/L, p <0.05) and HDL-associated PAF-AH expression compared to obese white women. Compared to normal-weight women, obese women had lower large HDL, greater intermediate and small HDL; an effect that was more pronounced in white women than black women. There were no differences in antioxidant capacity or anti-inflammatory function across groups.ConclusionsOur data show that both obesity and ethnicity are associated with differences in HDL functionality, while obesity was associated with decreases in large HDL subclass distribution. Measuring HDL functionality and subclass may, therefore, be important factors to consider when assessing cardiovascular risk.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-016-0257-9) contains supplementary material, which is available to authorized users.