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Objective: To determine whether term fetal membranes from transabdominal cerclage (TAC) patients have favorable characteristics compared with membranes from patients without TAC.Methods: A prospective study of consecutive pregnant women who had undergone TAC and were delivered by elective cesarean after 37 weeks before the onset of labor at Cliniques universitaires Saint-Luc, Brussels, between January 2015 and June 2016. Membranes were collected from two areas: overlying the cervix and located far from the cervix. Membrane thickness, 15-hydroxyprostaglandin dehydrogenase (PGDH), toll-like receptor-2 (TLR2) expression, and senescence were measured and compared between the TAC group and a control group without TAC enrolled using the same study criteria.Results: In the cervical area of the TAC group, the chorion was significantly thicker (P=0.003). PGDH and TLR2 expression were also significantly increased in the cervical area of the TAC group (P=0.021 and P=0.043, respectively). Senescence was significantly decreased in the TAC group (P=0.001).Conclusion: A significant relationship between chorion thickening and increase in PGDH and TLR2 expression and decrease in senescence was reported in the cervical area of membranes in the TAC group. These membrane changes could prevent triggering of parturition and may account for favorable outcomes and clinical success in pregnancies with TAC. [ABSTRACT FROM AUTHOR]

Abstract: Enzyme polymorphism in phosphogluconate dehydrogenase (Pgdh) is a striking example of single gene polymorphism involved in sexual conflict in bulb mite Rhizoglyphus robini. Males homozygous for the S Pgdh allele were shown to achieve higher reproductive success than FF homozygous males, while negatively influencing fecundity of their female partners. Here, we investigate proximate mechanisms responsible for the increased reproductive success of SS males and find that the S allele is associated with shorter time until copulation, higher copulation frequency and increased sperm production. We also show that Pgdh alleles are probably codominant, with SS males gaining the highest reproductive success, FF males – the lowest – and FS‐heterozygous males taking an intermediate position in all fitness parameters differentiating males of different genotypes. Additionally, we confirm the negative effect that S‐bearing males impose on the fecundity of females they mate with, showing a clear pattern of interlocus sexual conflict. We discuss that this effect is probably associated with increased copulation frequency. Whereas, contrary to what we have predicted, the S allele does not cause increased general male mobility, we speculate that the S allele‐bearing males are more efficient in forcing copulation and/or detecting females. [ABSTRACT FROM AUTHOR]

Release of arachidonic acid (AA) by cytoplasmic phospholipase A2 (cPLA2), followed by metabolism through cyclooxygenase-2 (COX-2) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH), results in the formation of the eicosanoids 11-oxo- and 15-oxo-eicosatetraenoic acid (oxo-ETE). Both 11-oxo- and 15-oxo-ETE have been identified in human biospecimens but their function and further metabolism is poorly described. The oxo-ETEs contain an α,β-unsaturated ketone and a free carboxyclic acid, and thus may form Michael adducts with a nucleophile or a thioester with the free thiol of Coenzyme A (CoA). To examine the potential for eicosanoid-CoA formation, which has not previously been a metabolic route examined for this class of lipids, we applied a semi-targeted neutral loss scanning approach following arachidonic acid treatment in cell culture and detected inducible long-chain acyl-CoAs including a predominant AA-CoA peak. Interestingly, a series of AA-inducible acyl-CoAs at lower abundance but higher mass, likely corresponding to eicosanoid metabolites, was detected. Using a targeted LC–MS/MS approach we detected the formation of CoA thioesters of both 11-oxo- and 15-oxo-ETE and monitored the kinetics of their formation. Subsequently, we demonstrated that these acyl-CoA species undergo up to four double bond reductions. We confirmed the generation of 15-oxo-ETE-CoA in human platelets via LC-high resolution MS. Acyl-CoA thioesters of eicosanoids may provide a route to generate reducing equivalents, substrates for fatty acid oxidation, and substrates for acyl-transferases through cPLA2-dependent eicosanoid metabolism outside of the signaling contexts traditionally ascribed to eicosanoid metabolites. [ABSTRACT FROM AUTHOR]

Serine biosynthesis defects can present in a broad phenotypic spectrum ranging from Neu-Laxova syndrome, a lethal disease with multiple congenital anomalies at the severe end, to an infantile disease with severe psychomotor retardation and seizures as an intermediate phenotype, to a childhood disease with intellectual disability at the mild end. In this report we present 6 individuals from 3 families with infantile phosphoglycerate dehydrogenase (PGDH) deficiency who presented with psychomotor delay, growth failure, microcephaly, and spasticity. The phenotype was variable with absence of seizures in 2 sisters in family 1 and 1 infant in family 2 and seizures with pronounced happy affect in 3 sisters in family 3. The initiation of serine treatment had pronounced effect on seizures and spasticity in the sisters in family 3, but minimal developmental effects on the children in families 1 and 2. With such phenotypic variability, the diagnosis of PGDH deficiency can be challenging. [ABSTRACT FROM AUTHOR]

The direct fermentative production of l-serine from renewable biomass using Corynebacterium glutamicum is attracting increasing attention. In this study, wild-type C. glutamicum SYPS-062 produced up to 6.65 ± 0.23 g/L l-serine; to further improve l-serine production, the serA gene was cloned, and the C-terminal domain of 3-phosphoglycerate dehydrogenase (PGDH) from this strain was truncated. When expressed in Escherichia coli, the resultant mutein SerAΔ197 showed a specific PGDH activity of 1.092 ± 0.05 U/mg protein, representing a decrease of 25.87 % from that encoded by serA, and was no longer sensitive to high concentrations of l-serine. When serA was overexpressed in C. glutamicum SYPS-062, the activity of PGDH in C. glutamicum pJC1- tac- serA increased by 47.72 %, and the resultant strain C. glutamicum pJC1- tac- serA could accumulate 7.69 ± 0.22 g/L l-serine. Furthermore, when serA was overexpressed in C. glutamicum SYPS-062 ΔsdaA, the resultant strain could accumulate 8.84 ± 0.23 g/L l-serine at 102 h, and the yield of l-serine on cells (Y p/x) improved by 60 % when compared with that noted in the control. These results demonstrate that l-serine production in C. glutamicum SYPS-062 could be improved by overexpressing a C-terminal truncation of PGDH in combination with other genetic modifications. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a pathological state presenting at the progressive stage of heterogeneous interstitial lung disease (ILD). The current understanding of the molecular mechanisms involved is incomplete. This clinical toxicology study focused on the pulmonary fibrosis induced by paraquat (PQ), a widely-used herbicide. Using proteo-transcriptome analysis, we identified differentially expressed proteins (DEPs) derived from the initial development of fibrosis to the dissolved stage and provided further functional analysis. We established a mouse model of progressive lung fibrosis via intratracheal instillation of paraquat. To acquire a comprehensive and unbiased understanding of the onset of pulmonary fibrosis, we performed time-series proteomics profiling (iTRAQ) and RNA sequencing (RNA-Seq) on lung samples from paraquat-treated mice and saline control. The biological functions and pathways involved were evaluated through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis. Correlation tests were conducted on comparable groups 7 days and 28 days post-exposure. Differentially expressed proteins and genes following the same trend on the protein and mRNA levels were selected for validation. The functions of the selected molecules were identified in vitro. The protein level was overexpressed by transfecting gene-containing plasmid or suppressed by transfecting specific siRNA in A549 cells. The levels of endothlial-mesenchymal transition (EMT) markers, including E-cadherin, vimentin, FN1, and α-SMA, were determined via western blot to evaluate the fibrotic process. We quantified 1358 DEPs on day 7 and 426 DEPs on day 28 post exposure (Fold change >1.2; Q value < 0.05). The top 5 pathways – drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450, complement and coagulation cascades, chemical carcinogenesis, protein digestion and absorption — were involved on both day 7 and day 28. Several pathways, including tight junction, focal adhesion, platelet activation, and ECM-receptor interaction, were more enriched on day 28 than on day 7. Integrative analysis of the proteome and transcriptome revealed a moderate correlation of quantitative protein abundance ratios with RNA abundance ratios (Spearman R = 0.3950 and 0.2477 on days 7 and 28, respectively), indicating that post-transcriptional regulation plays an important role in lung injury and repair. Western blot identified that the protein expressions of FN1, S100A4, and RBM3 were significantly upregulated while that of CYP1A1, FMO3, and PGDH were significantly downregulated on day 7. All proteins generally recovered to baseline on day 28. qPCR showed the mRNA levels of Fn1, S100a4, Rbm3, Cyp1a1, Fmo3, and Hpgd changed following the same trend as the levels of their respective proteins. Further, in vitro experiments showed that RBM3 was upregulated while PGDH was downregulated in an EMT model established in human lung epithelial A549 cells. RBM3 overexpression and PGDH knockout could both induce EMT in A549 cells. RBM3 knockout or PGDH overexpression had no reverse effect on EMT in A549 cells. Our proteo-transcriptomic study determined the proteins responsible for fibrogenesis and uncovers their dynamic regulation from lung injury to repair, providing new insights for the development of biomarkers for diagnosis and treatment of fibrotic diseases. [ABSTRACT FROM AUTHOR]

In the l -Serine biosynthesis, D-3-phosphoglycerate dehydrogenase (PGDH) catalyzes the inter-conversion of D-3-phosphoglycerate to phosphohydroxypyruvate. PGDH belongs to 2-hydroxyacid dehydrogenases family. We have determined the crystal structures of PGDH from Sulfolobus tokodaii ( St PGDH) and Pyrococcus horikoshii ( Ph PGDH) using X-ray diffraction to resolution of 1.77 Å and 1.95 Å, respectively. The PGDH protomer from both species exhibits identical structures, consisting of substrate binding domain and nucleotide binding domain. The residues and water molecules interacting with the NAD are identified. The catalytic triad residues Glu-His-Arg are highly conserved. The residues involved in the dimer interface and the structural features responsible for thermostability are evaluated. Overall, structures of PGDHs with two domains and histidine at the active site are categorized as type III H and such PGDHs structures having this type are reported for the first time. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To investigate the protective effects of 18β-glycyrrhetinic acid (GA) on lipopolysaccharide (LPS)-induced injury in the intestinal epithelial cell line (IEC-6). Methods: IEC-6 cells were treated by LPS (100 μg·mL−1) with or without GA (0. 1, 1.0 or 10 μmol·L−1) for 24 h. The inflammatory cytokines in the cultured medium, TNF-α and IL-6, were measured by ELISA. The supernatant nitric oxide (NO) production was detected by nitrite assay. Reactive oxygen species (ROS) were estimated by flow cytometry. Epithelial tight junction was determined by transepithelial resistance (TER), and protein levels were measured by Western blotting. Results: With GA treatment, LPS-stimulated TNF-α and IL-6 were inhibited, ROS and NO were decreased, the transepithelial permeability was recovered, ZO-1 (tight junction related protein) was reversed, the protein level of cyclooxygenase-2 (COX-2) was down-regulated, and 15-hydroxyprostaglandin dehydrogenase (PGDH) was up-regulated. Conclusions: These results suggest that GA has the protective capacity to attenuate LPS-induced injury in intestinal epithelial cells and protect the epithelial tight junction. The underlying mechanism was related to a decrease in proinflammatory factor and regulating COX-2 and PGDH. [Copyright &y& Elsevier]

Prostaglandins are key components of the parturition cascade; however, the mechanisms that regulate prostaglandin concentrations in the uterus during pregnancy are largely unknown. The purpose of this study was to determine the intrauterine expression of the chief prostaglandin-inactivating enzyme, 15-hydroxyprostaglandin dehydrogenase (PGDH), during gestation and labor in the guinea pig, an animal model in which the endocrine control of pregnancy and parturition is analogous to that of women. PGDH messenger RNA (mRNA) abundance decreased significantly in the visceral yolk sac membrane (VYS, the anatomical equivalent of the human chorion laeve) and the amnion throughout the last third of pregnancy. PGDH protein was robustly expressed in the VYS epithelium and mesoderm, correlated strongly with PGDH mRNA levels and exhibited a nadir at term prior to labor onset. PGDH protein was not detected in the amnion. PGDH mRNA and protein levels in the placenta and myoendometrium were variable throughout late gestation. In the placenta, PGDH protein was concentrated in the parietal yolk sac membrane (PYS) lining the placental surface and in placental blood vessels. We observed strong expression of PGDH protein in the endometrial epithelium with comparably little expression in the myometrium. These data indicate that metabolic inactivation of prostaglandins in the pregnant guinea pig uterus takes place in the VYS, PYS, and endometrium. Decreased PGDH expression in the fetal membranes may contribute to the increase in intrauterine prostaglandin concentrations at term, stimulating the onset of labor. [ABSTRACT FROM AUTHOR]

Most legume phylogenies have relied heavily on plastid gene datasets, with or without nuclear ribosomal DNA ITS data, but the sequences of nuclear genes and gene-spanning regions offer certain advantages. We tested the phylogenetic utility of five nuclear loci across the species-rich legume clade Hologalegina: PGDH, TRPT, HRIP, RNAR, and CNGC4 (CNGC4-like protein). Our objective was to determine whether any of these nuclear loci could be beneficial at resolving lower-level phylogenetic relationships in this clade, with a particular interest in finding markers that might work at the species level. While the phylogenetic utility of these nuclear loci is unknown outside of Hologalegina, we determined that two of the loci, PGDH and TRPT, are useful for phylogenetic analyses within Hologalegina, depending upon the desired scale of resolution. [ABSTRACT FROM AUTHOR]

Myometrial quiescence is a key factor in all species to accomplish a successful gestation. PGs play a crucial role in mediating parturition events, and their synthesis and metabolism are regulated by cyclooxygenases (COXs) and NAD+-dependent 15-hydroxy-PG dehydrogenase (PGDH), respectively.Progesterone (P4) is the hormone responsible for maintaining uterine smooth muscle quiescence during pregnancy. In this work, we have studied the effect of P4 on the activity of COXs and PGDH, the uterine enzymes involved in the biosynthesis and metabolism of prostanoids in the rat.We found that during pregnancy PGF2α production and also protein levels of COX-1 and COX-2 were decreased.The exogenous administration of P4 significantly inhibited the uterine production of PGF2α and also the protein level of COX-2.PGF2α, metabolism was assessed by PGDH activity, which resulted high during pregnancy and increased as a result of P4 administration.These results indicate that PGs levels were negatively modulated by P4, which could be exerting its effect by increasing PGs metabolism through stimulation on PGDH activity and an inhibition on COX and that is a major mechanism for maintain uterine quiescence in pregnancy. [Copyright &y& Elsevier]

• Phosphoglycerate dehydrogenases (PGDH) have been related to serine biosynthesis through the phosphorylated pathway. • In Arabidopsis, PGDH1 and PGDH2 co-operate in serine metabolism. • PGDH3 may have additional functions in photosynthetic cells unrelated to serine biosynthesis. Unlike animals, plants possess diverse L-serine (Ser) biosynthetic pathways. One of them, the Phosphorylated Pathway of Serine Biosynthesis (PPSB) has been recently described as essential for embryo, pollen and root development, and required for ammonium and sulfur assimilation. The first and rate limiting step of PPSB is the reaction catalyzed by the enzyme phosphoglycerate dehydrogenase (PGDH). In Arabidopsis, the PGDH family consists of three genes, PGDH1 , PGDH2 and PGDH3. PGDH1 is characterized as being the essential gene of the family. However, the biological significance of PGDH2 and PGDH3 remains unknown. In this manuscript, we have functionally characterized PGDH2 and PGDH3. Phenotypic, metabolomic and gene expression analysis in PGDH single, double and triple mutants indicate that both PGDH2 and PGDH3 are functional, affecting plant metabolism and development. PGDH2 has a stronger effect on plant growth than PGDH3, having a partial redundant role with PGDH1. PGDH3 , however, could have additional functions in photosynthetic cells unrelated to Ser biosynthesis. [ABSTRACT FROM AUTHOR]

It is quite important to understand the basic principle embedded in the main metabolism for the interpretation of the fermentation data. For this, it may be useful to understand the regulation mechanism based on systems biology approach. In the present study, we considered the perturbation analysis together with computer simulation based on the models which include the effects of global regulators on the pathway activation for the main metabolism of Escherichia coli. Main focus is the acetate overflow metabolism and the co-fermentation of multiple carbon sources. The perturbation analysis was first made to understand the nature of the feed-forward loop formed by the activation of Pyk by FDP (F1,6BP), and the feed-back loop formed by the inhibition of Pfk by PEP in the glycolysis. Those together with the effect of transcription factor Cra caused by FDP level affected the glycolysis activity. The PTS (phosphotransferase system) acts as the feed-back system by repressing the glucose uptake rate for the increase in the glucose uptake rate. It was also shown that the increased PTS flux (or glucose consumption rate) causes PEP/PYR ratio to be decreased, and EIIA-P, Cya, cAMP-Crp decreased, where cAMP-Crp in turn repressed TCA cycle and more acetate is formed. This was further verified by the detailed computer simulation. In the case of multiple carbon sources such as glucose and xylose, it was shown that the sequential utilization of carbon sources was observed for wild type, while the co-consumption of multiple carbon sources with slow consumption rates were observed for the ptsG mutant by computer simulation, and this was verified by experiments. Moreover, the effect of a specific gene knockout such as Δpyk on the metabolic characteristics was also investigated based on the computer simulation., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Substantial evidence supports important independent roles for lymphangiogenic growth factor signaling and prostaglandins in the metastatic spread of cancer. The significance of the lymphangiogenic growth factors, vascular endothelial growth factor (VEGF)-C and VEGF-D, is well established in animal models of metastasis, and a strong correlation exits between an increase in expression of VEGF-C and VEGF-D, and metastatic spread in various solid human cancers. Similarly, key enzymes that control the production of prostaglandins, cyclooxygenases (COX-1 and COX-2, prototypic targets of Non-steroidal anti-inflammatory drugs (NSAIDs)), are frequently over-expressed or de-regulated in the progression of cancer. Recent data have suggested an intersection of lymphangiogenic growth factor signaling and the prostaglandin pathways in the control of metastatic spread via the lymphatic vasculature. Furthermore, this correlates with current clinical data showing that some NSAIDs enhance the survival of cancer patients through reducing metastasis. Here, we discuss the potential biochemical and cellular basis for such anti-cancer effects of NSAIDs through the prostaglandin and VEGF signaling pathways.

The phosphogluconate dehydrogenase (Pgdh) locus is the only polymorphic allozyme locus observed among 37 loci examined in all four populations of a New Mexico state Endangered species, the White Sands pupfish (Cyprinodon tularosa). We report evidence suggesting that this polymorphism may be associated with salinity. Salinity levels vary widely within and between habitats occupied by White Sands pupfish. The frequency of the Pgdh 100 allozyme was correlated with salinity but not with temperature. Frequency of Pgdh 100 differed between low (3.76 parts per thousand (ppt)) and high (9.23 ppt) salinity sites at Malpais Spring despite no obvious barriers to fish movement. Frequencies of Pgdh 100 in two introduced populations differed from that of the presumptive founding stock and correlated with salinity in the current habitats., (© 1998 The Society for the Study of Evolution.)