ABSTRACT
Background The metabolites and metabolic pathways of hand-arm vibration syndrome have not yet been elucidated. Objective To investigate the effect of local vibration on endogenous metabolites in rat serum by metabolomic analysis, to preliminarily explore the potential metabolic pathway of endogenous metabolites, so as to provide evidence for further research on the mechanism of hand-arm vibration syndrome. Methods Thirty-two SPF male SD rats, (211.3±11.1) g, 7−8 weeks of age, were selected and randomly divided into three groups: control group (14 rats, without vibration), 7 d vibration group (9 rats, continuously vibration for 7 d), and 14 d vibration group (9 rats, continuous vibration for 14 d). The vibration rats were vibrated every day for 4 h, the frequency weighted acceleration was 4.9 m·s−2, the vibration frequency was 125 Hz, and the vibration direction was one-way vertical vibration. The control group had the same conditions except not contacting vibration. After the vibration exposure, the blood samples taken from the abnormal aorta of rats were collected, and the changes of rat serum metabolome were analyzed by ultra-performance liquid chromatography-tandem time-of-flight mass spectrometry. Principal components analysis (PCA) was used to explore changes in rat serum metabolic profile, and orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to screen out differential metabolites. Combined with online databases, a metabolic pathway enrichment analysis of differential metabolites was performed. Results The PCA analysis showed that compared with the control group, the rat serum metabolic profiles in the 7 d group and the 14 d group were clearly differentiated, and the rat serum metabolic profiles in the 7 d group and the 14 d group partially overlapped. The OPLS-DA analysis showed significant differences between groups. The main parameters were: model interpretation rate R2Y=0.914, model predictive ability Q2=0.58. The OPLS-DA analysis screened out 26 and 119 differential metabolites from the 7 d group and the 14 d group respectively, and there were 24 common differential metabolites between the 7 d group and the 14 d group. The metabolomic pathway analysis showed that local vibration-induced changes in rat serum metabolism were mainly related to arachidonic acid metabolism in the 14 d group, among which the metabolites with significant effects were arachidonic acid, prostaglandin E2, and prostaglandin D2. Conclusion Local vibration could affect the normal metabolism in rats, and the metabolic pathway with significant influence is arachidonic acid metabolism after a 14 d exposure and the involved metabolites are arachidonic acid, prostaglandin E2, and prostaglandin D2.
ABSTRACT
La proteína beta trace (PBT), también llamada Prostaglandina D2 Sintasa de tipo lipocalina, es una glicoproteína de peso molecular entre 23 y 29 kDa que convierte la prostaglandina H2 en prostaglandina D2. La misma está asociada a diferentes entidades clínicas. Por sus características moleculares puede ser un indicador útil de la alteración precoz en la filtración glomerular; por el aumento de su síntesis y su concomitante elevación en suero, un predictor de riesgo cardiovascular; y por su alta concentración en líquido cefalorraquídeo (LCR), un biomarcador de fístula de LCR. Puede medirse en distintos líquidos biológicos, como suero, orina y LCR. El objetivo de esta revisión fue actualizar los conocimientos de esta proteína para evaluar su utilidad en distintas áreas de la Medicina. La trascendencia de PBT en el campo de la bioquímica como posible biomarcador dependerá de la patología de base del paciente.
The beta trace protein (BTP), also called Prostaglandin D2 Synthase lipocalin type PGDS, is a glycoprotein between 23 and 29 kDa of low molecular weight that converts prostaglandin H2 in prostaglandin D2. BTP is a protein that has multiple clinical associations. Due to the characteristics of the molecule, it may indicate an early alteration in glomerular filtration; by the serum increase of its synthesis, it is a predictor of cardiovascular risk, and for its high concentration in cerebrospinal fluid (CSF), it is a marker of leakage. This protein can be measured in different biological fluids such as serum, urine, and CSF. The objective of this review is to update the knowledge about this protein as a biomarker. The significance of BTP in the field of biochemistry as a possible biomarker will depend on the patient's underlying pathology.
A proteína beta trace (PBT), também chamada de Prostaglandina D2, sintase de lipocalina é uma glicoproteína de peso molecular entre 23 e 29 kDa, que converte prostaglandina H2 em prostaglandina D2. PBT é uma proteína que está associada a várias entidades clínicas. Devido às características moleculares, pode ser uma indicação útil da alteração precoce na filtração glomerular, devido ao aumento de sua síntese e sua concomitante elevação em soro, um preditor de risco cardiovascular e, devido à sua alta concentração no líquido cefalorraquidiano (LCR), é um biomarcador da fístula LCR. É uma proteína que pode ser medida em diferentes fluidos biológicos, como soro, urina e LCR, e o objetivo desta revisão foi atualizar os conhecimentos desta proteína para avaliar sua utilidade em diversas áreas da medicina. A importância de PBT no campo da bioquímica como possível biomarcador dependerá da patologia subjacente do paciente.
ABSTRACT
Prostaglandin D₂ (PGD₂) may act against myocardial ischemia-reperfusion (I/R) injury and play an anti-inflammatory role in the heart. Although the effect of PGD₂ in regulation of ANP secretion of the atrium was reported, the mechanisms involved are not clearly identified. The aim of the present study was to investigate whether PGD₂ can regulate ANP secretion in the isolated perfused beating rat atrium, and its underlying mechanisms. PGD₂ (0.1 to 10 µM) significantly increased atrial ANP secretion concomitantly with positive inotropy in a dose-dependent manner. Effects of PGD₂ on atrial ANP secretion and mechanical dynamics were abolished by AH-6809 (1.0 µM) and AL-8810 (1.0 µM), PGD₂ and prostaglandin F2α (PGF2α) receptor antagonists, respectively. Moreover, PGD₂ clearly upregulated atrial peroxisome proliferator-activated receptor gamma (PPARγ) and the PGD₂ metabolite 15-deoxy-Δ12,14-PGJ₂ (15d-PGJ₂, 0.1 µM) dramatically increased atrial ANP secretion. Increased ANP secretions induced by PGD₂ and 15d-PGJ₂ were completely blocked by the PPARγ antagonist GW9662 (0.1 µM). PD98059 (10.0 µM) and LY294002 (1.0 µM), antagonists of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling, respectively, significantly attenuated the increase of atrial ANP secretion by PGD₂. These results indicated that PGD₂ stimulated atrial ANP secretion and promoted positive inotropy by activating PPARγ in beating rat atria. MAPK/ERK and PI3K/Akt signaling pathways were each partially involved in regulating PGD₂-induced atrial ANP secretion.
Subject(s)
Animals , Rats , Atrial Natriuretic Factor , Heart , Mitogen-Activated Protein Kinases , Peroxisomes , Phosphotransferases , PPAR gamma , Protein KinasesABSTRACT
OBJECTIVE@#To preliminarily investigate the possible role of prostaglandin D2 (PGD2) in malaria infections.@*METHODS@#Blood and urinary samples (n = 120 each) were collected from Thai patients with Plasmodium falciparum (P. falciparum) with moderate (n = 26) and high (n = 4) parasitemia, patients with Plasmodium vivax (P. vivax) (n = 30), patients with fever associated with other infections (n = 30), and healthy subjects (n = 30). PGD2 concentrations in plasma and urinary samples of healthy subjects, patients with fever associated with other infections and patients with malaria were determined using Prostaglandin D2-MOX express EIA kit (Cayman Chemical, USA).@*RESULTS@#The possible association between PGD2 and malaria infections is clearly demonstrated with PGD2 concentration in urine. The urinary PGD2 concentrations were relatively high (about 5-fold) in patients with P. falciparum with moderate parasitemia and P. vivax infections compared with other groups. Furthermore, the concentration in patients with P. falciparum with moderate parasitemia and P. vivax infection were significantly higher than that in healthy subjects and patients with fever associated with other infections.@*CONCLUSIONS@#Urinary PGD2 concentrations may offer a more dependable and useful tool for predicting malaria severity. Confirmation is this preliminary finding is required with a larger sample size.
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Objective To evaluate the effect of 15-deoxy-△12,14-prostaglandin J2 (15d-PGJ2) on endotoxin-induced acute lung injury (ALI) in rats.Methods Forty healthy male Sprague-Dawley rats, aged 3-5 months, weighing 220-250 g, were randomly divided into 4 groups (n =10 each) using a random number table: control group (group C), 15d-PGJ2 group, lipopolysaccharide (LPS) group, and LPS +15d-PGJ2 group.In group 15d-PGJ2, 15d-PGJ20.3 mg/kg was injected via the tail vein, while the equal volume of normal saline was given in group C.In LPS and LPS+15d-PGJ2 groups, ALI was produced with LPS 6 mg/kg injected through the tail vein, and then the equal volume of normal saline and 15d-PGJ2 0.3 mg/kg were injected, respectively.At 4 h after LPS injection, blood samples were drawn from the abdominal aorta for blood gas analysis, and arterial oxygen partial pressure (PaO2) was recorded.The rats were then sacrificed, lungs were removed for microscopic examination, and for determination of wet/dry lung weight ratio (W/D ratio), TNF-α, IL-8 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) contents (by enzyme-linked immunosorbent assay) , and nuclear factor kappa B (NF-κB) p65 and IκB-α expression (by Western blot).Results Compared with group C, no significant change was found in PaO2, W/D ratio, contents of TNF-α, IL-8 and CINC-1, and expression of NF-κB p65 and IκB-α in group 15d-PGJ2 (P＞0.05), and PaO2 was significantly decreased, W/D ratio and contents of TNF-α,IL-8 and CINC-1 were increased, the expression of NF-κB p65 was up-regulated, and the expression of IκB-α was down-regulated in LPS and LPS+ 15d-PGJ2 groups (P＜0.05).Compared with group LPS,PaO2 was significantly increased, W/D ratio and contents of TNF-α, IL-8 and CINC-1 were decreased, the expression of NF-κB p65 was down-regulated, and the expression of IκB-α was up-regulated (P＜0.05),and the pathological changes were attenuated in group LPS+ 15d-PGJ2.Conclusion 15d-PGJ2 can mitigate endotoxin-induced ALI in rats.
ABSTRACT
Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent LTC4 and cyclooxygenase-2-dependent PGD2 through the inhibition of intracellular calcium influx/phospholipase Cgamma1, cytosolic phospholipase A2/mitogen-activated protein kinases and/or nuclear factor-kappaB pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.
Subject(s)
Animals , Mice , Calcium , Cytosol , Eicosanoids , Inflammation , Leukotriene C4 , Mast Cells , Mitogen-Activated Protein Kinases , Phospholipases , Prostaglandin D2 , Protein KinasesABSTRACT
Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2) and 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular Ca2+ influx via phospholipase Cgamma1 (PLCgamma1) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappaB (NF-kappaB) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum LTC4, PGD2, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.
Subject(s)
Animals , Mice , Administration, Oral , Anaphylaxis , Arachidonate 5-Lipoxygenase , Curcuma , Curcumin , Cyclooxygenase 2 , Histamine , Immunoglobulin E , Immunoglobulins , Leukotriene C4 , Mast Cells , Mitogen-Activated Protein Kinases , Phospholipases , Phosphorylation , Prostaglandin D2ABSTRACT
Curcumin is naturally occurring polyphenolic compound found in turmeric and has many pharmacological activities. The present study was undertaken to evaluate anti-allergic inflammatory activity of curcumin, and to investigate its inhibitory mechanisms in immunoglobulin E (IgE)/Ag-induced mouse bone marrow-derived mast cells (BMMCs) and in a mouse model of IgE/Ag-mediated passive systemic anaphylaxis (PSA). Curcumin inhibited cyclooxygenase-2 (COX-2) dependent prostaglandin D2 (PGD2) and 5-lipoxygenase (5-LO) dependent leukotriene C4 (LTC4) generation dose-dependently in BMMCs. To probe the mechanism involved, we assessed the effects of curcumin on the phosphorylation of Syk and its downstream signal molecules. Curcumin inhibited intracellular Ca2+ influx via phospholipase Cgamma1 (PLCgamma1) activation and the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappaB (NF-kappaB) pathway. Furthermore, the oral administration of curcumin significantly attenuated IgE/Ag-induced PSA, as determined by serum LTC4, PGD2, and histamine levels. Taken together, this study shows that curcumin offers a basis for drug development for the treatment of allergic inflammatory diseases.
Subject(s)
Animals , Mice , Administration, Oral , Anaphylaxis , Arachidonate 5-Lipoxygenase , Curcuma , Curcumin , Cyclooxygenase 2 , Histamine , Immunoglobulin E , Immunoglobulins , Leukotriene C4 , Mast Cells , Mitogen-Activated Protein Kinases , Phospholipases , Phosphorylation , Prostaglandin D2ABSTRACT
PURPOSE: The mast cell plays a pivotal role in the human immune response. Crosslinking of 2 IgE molecules bound to the high affinity IgE receptor (FcepsilonRI) on the surface of the mast cell results in mast cell degranulation and the release of several proinflammatory mediators. Patients with type-I allergy have increased levels of IgE in the blood compared to healthy individuals. METHODS: In a 6-week culture system of stem cells to human mast cells we investigated the effect of the concentration of IgE. The mast cells were cultured with different concentrations of IgE for the last 10 days of the maturation period. It was observed how the IgE concentration affects the histamine release, FcepsilonRI density on the mast cell surface and the concentration of other mediators. RESULTS: A clear correlation between IgE concentration in culture medium and the release of histamine upon activation was observed. It showed a bell-shaped dose response curve, with maximal response around an IgE-concentration of 250 ng/mL. Furthermore, the sensitivity of the mast cells and surface density of FcepsilonRI on mast cell surface was also influenced by the IgE concentration in the culture medium. CONCLUSIONS: IgE in the culture medium during the last 10 days of mast cell maturation influences the release of the preformed mediator histamine after mast cell activation and the density of FcepsilonRI on the mast cell surface. The release of the de novo synthetized mediator prostaglandin D2 and the expression of chymase and tryptase are not influenced by IgE in culture medium.
Subject(s)
Humans , Chymases , Histamine , Histamine Release , Hygiene Hypothesis , Hypersensitivity , Immunoglobulin E , Mast Cells , Prostaglandin D2 , Stem Cells , TryptasesABSTRACT
PURPOSE: The mast cell plays a pivotal role in the human immune response. Crosslinking of 2 IgE molecules bound to the high affinity IgE receptor (FcepsilonRI) on the surface of the mast cell results in mast cell degranulation and the release of several proinflammatory mediators. Patients with type-I allergy have increased levels of IgE in the blood compared to healthy individuals. METHODS: In a 6-week culture system of stem cells to human mast cells we investigated the effect of the concentration of IgE. The mast cells were cultured with different concentrations of IgE for the last 10 days of the maturation period. It was observed how the IgE concentration affects the histamine release, FcepsilonRI density on the mast cell surface and the concentration of other mediators. RESULTS: A clear correlation between IgE concentration in culture medium and the release of histamine upon activation was observed. It showed a bell-shaped dose response curve, with maximal response around an IgE-concentration of 250 ng/mL. Furthermore, the sensitivity of the mast cells and surface density of FcepsilonRI on mast cell surface was also influenced by the IgE concentration in the culture medium. CONCLUSIONS: IgE in the culture medium during the last 10 days of mast cell maturation influences the release of the preformed mediator histamine after mast cell activation and the density of FcepsilonRI on the mast cell surface. The release of the de novo synthetized mediator prostaglandin D2 and the expression of chymase and tryptase are not influenced by IgE in culture medium.
Subject(s)
Humans , Chymases , Histamine , Histamine Release , Hygiene Hypothesis , Hypersensitivity , Immunoglobulin E , Mast Cells , Prostaglandin D2 , Stem Cells , TryptasesABSTRACT
Astrocytes are the most abundant cells in the central nervous system that play roles in maintaining the blood-brain-barrier and in neural injury, including cerebral malaria, a severe complication of Plasmodium falciparum infection. Prostaglandin (PG) D2 is abundantly produced in the brain and regulates the sleep response. Moreover, PGD2 is a potential factor derived from P. falciparum within erythrocytes. Heme oxygenase-1 (HO-1) is catalyzing enzyme in heme breakdown process to release iron, carbon monoxide, and biliverdin/bilirubin, and may influence iron supply to the P. falciparum parasites. Here, we showed that treatment of a human astrocyte cell line, CCF-STTG1, with PGD2 significantly increased the expression levels of HO-1 mRNA by RT-PCR. Western blot analysis showed that PGD2 treatment increased the level of HO-1 protein, in a dose- and time-dependent manner. Thus, PGD2 may be involved in the pathogenesis of cerebral malaria by inducing HO-1 expression in malaria patients.
Subject(s)
Animals , Humans , Astrocytes/enzymology , Blotting, Western , Cell Line , Gene Expression Profiling , Heme Oxygenase-1/biosynthesis , Malaria, Cerebral/pathology , Malaria, Falciparum/complications , Plasmodium falciparum/pathogenicity , Prostaglandins/metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
AIM: To investigate the effect of prostanoid DP receptors (DPR) on sleep-wake regulation in mice. METHODS: Under pentobarbital anesthesia, mice were chronically implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes for polysomnographic recordings. The spontaneous sleep-wake cycles were monitored continuously by EEG/EMG recording system for 24 h beginning at 800 p.m. and analyzed by SLEEPSIGN software in DPR knock out (KO) and wild type (WT) mice. RESULTS: DPR-KO mice exhibited a similar circadian rhythm of sleep-wake cycles to WT mice. The amounts of rapid eye movement (REM) sleep or non-REM (NREM) sleep during both the light and dark periods were identical between the DPR-KO and WT mice. Whereas, an increase in the episode number of wakefulness and a shortage in the duration of NREM sleep were found in DPR-KO mice during the light period compared with WT mice. Moreover, DPR-KO mice showed lower activity in delta-wave component in NREM sleep and higher activity in theta-wave component in REM sleep than WT mice. CONCLUSION: DPR plays a crucial role in mediating the prostaglandin D2-induced sleep. Deficiency of DPR results in the low intensity and fragmented diurnal NREM sleep and the high vigilance REM sleep, with the normal circadian rhythm of sleep in mice.
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Objective To investigate the expression of peroxisome proliferators-activated receptor ? (PPAR?) in trophoblast and relation between PPAR? ligands and trophoblast invasion.Methods We examined the expression of PPAR? by immunohistochemistry,immunocytochemistry and real time quantitative PCR.We next examined,using the cytotrophoblast culture model,the biological role of PPAR? ligands in vitro.Results PPAR? was mainly localized in the nuclei of villous cytotrophoblast and extravillous cytotrophoblast of cell islands and cell columns.In villous tissue and cultured trophoblast from early first trimester,the level of expression of PPAR? mRNA and protein was 36.0?5.1,13.4?3.1 and 1.35?0.08,1.13?0.11;from late first trimester it was 23.3?5.5,6.1?1.3 and 1.17?0.03,0.86 ?0.05,and the expression of PPAR? was obviously decreased (P