Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.2.1.13 (glyceraldehyde-3-phosphate dehydrogenase)
 6,511 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although intrauterine growth retardation (IUGR) is a major risk factor for increased neonatal mortality and morbidity, the mechanisms behind it are not clear. We analyzed cytokine gene expression and gene polymorphisms in infants with and without IUGR in Pakistan, where IUGR is very common. 45 IUGR and 55 control mother/infant pairs were studied. mRNA for IL-10, IL-8, TNF-alpha, TGF-beta, IL-6, IL-4, IL-1beta, IL-12, IFN-gamma and GAPDH was quantified with RT-PCR from placenta. Cytokine and cytokine receptor gene polymorphisms for -1087IL10, -308TNFA, -174IL6, +915TGFB1, intron 2 IL1RN, +36TNFR1, 150V IL4RA and -159CD14 were determined from genomic DNA. The serum levels of IL-1beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha and TGF-beta were measured. There was a significant decrease of IL-10 and IL-12, but increase of TGF-beta in the decidua and similarly decrease of IL-10, but increase of TGF-beta in the trophoblasts of the IUGR placentas compared with the non-IUGR placentas. We found significantly lower levels of IL-1beta in serum from the mothers of the IUGR infants and of TGF-beta in serum of the infants with IUGR compared with the non-IUGR infants. We note that the IL-10 mRNA expression in the decidua was down-regulated, but the TGF-beta mRNA up-regulated in IUGR placentas of mothers from a population with multiple risk factors for IUGR. We propose that the low IL-10 in the placenta may be involved in the pathogenesis of IUGR and might possibly be treatable.
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PMID:Cytokines in the placenta of Pakistani newborns with and without intrauterine growth retardation. 1643 88

The cholinergic anti-inflammatory pathway has not yet been studied in splanchnic artery occlusion (SAO) shock. We investigated whether electrical stimulation (STIM) of efferent vagus nerves suppresses the inflammatory cascade in SAO shock. Animals were subjected to clamping of the splanchnic arteries for 45 min, followed by reperfusion. This surgical procedure resulted in an irreversible state of shock (SAO shock). Sham-operated animals were used as controls. Two minutes before the start of reperfusion, rats were subjected to bilateral cervical vagotomy (VGX) or sham surgical procedures. Application of constant voltage pulses to the caudal vagus ends (STIM: 5 V, 2 ms, 6 Hz for 15 min, 5 min after the beginning of reperfusion) increased survival rate (VGX + SAO + Sham STIM = 0% at 4 h of reperfusion; VGX + SAO + STIM = 90% at 4 h of reperfusion), reverted the marked hypotension, inhibited IkappaBalpha liver loss, blunted the augmented nuclear factor-kappaB activity, decreased hepatic tumor necrosis factor (TNF)-alpha mRNA (VGX + SAO + Sham STIM = 1.0 +/- 1.9 TNF-alpha/glyceraldehyde-3-phosphate dehydrogenase ratio; VGX + SAO + STIM = 0.3 +/- 0.2 TNF-alpha/glyceraldehyde-3-phosphate dehydrogenase ratio), reduced plasma TNF-alpha (VGX + SAO + Sham STIM = 118 +/- 19 pg/mL; VGX + SAO + STIM = 39 +/- 8 pg/mL), ameliorated leukopenia, and decreased leukocyte accumulation, as revealed by means of myeloperoxidase activity in the ileum (VGX + SAO + Sham STIM = 7.9 +/- 1 U/g tissue; VGX + SAO + STIM = 3.1 +/- 0.7 U/g tissue) and in the lung (VGX + SAO + Sham STIM = 8.0 +/- 1.0 U/g tissue; VGX + SAO + STIM = 3.2 +/- 0.6 U/g tissue). Chlorisondamine, a nicotinic receptor antagonist, abated the effects of vagal stimulation. Our results show a parasympathetic inhibition of nuclear factor-kappaB and TNF-alpha in SAO shock.
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PMID:Activation of the cholinergic anti-inflammatory pathway reduces NF-kappab activation, blunts TNF-alpha production, and protects againts splanchic artery occlusion shock. 1668 15

This study was designed to determine the relative levels of gene transcription of selected pathogens and cytokines in the brain and spinal cord of 12 horses with equine protozoal myeloencephalitis (EPM), 11 with equine herpesvirus type 1 (EHV-1) myeloencephalopathy, and 12 healthy control horses by applying a real time pcr to the formalin-fixed and paraffin-embedded tissues. Total rna was extracted from each tissue, transcribed to complementary dna (cDNA) and assayed for Sarcocystis neurona, Neospora hughesi, EHV-1, equine GAPDH (housekeeping gene), tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10 AND IL-12 p40. S neurona cdna was detected in the neural tissue from all 12 horses with EPM, and two of them also had amplifiable cDNA of N hughesi. The relative levels of transcription of protozoal cdna ranged from 1 to 461 times baseline (mean 123). All the horses with ehv-1 myeloencephalopathy had positive viral signals by PCR with relative levels of transcription ranging from 1 to 1618 times baseline (mean 275). All the control horses tested negative for S neurona, N hughesi and EHV-1 cdna. The cytokine profiles of each disease indicated a balance between pro- and anti-inflammatory markers. In the horses with epm the pro-inflammatory Th1 cytokines (IL-8, TNF-alpha and IFN-gamma) were commonly expressed but the anti-inflammatory Th2 cytokines (IL-4, IL-6 AND IL-10) were absent or rare. In the horses with ehv-1 the proinflammatory cytokine IL-8 was commonly expressed, but IL-10 and IFN-gamma were not, and TNF-alpha was rare. Tissue from the control horses expressed only the gene GAPDH.
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PMID:Cytokine gene signatures in neural tissue of horses with equine protozoal myeloencephalitis or equine herpes type 1 myeloencephalopathy. 1696 13

In this review, the impacts of mitochondrial reactive oxygen species (ROS) on diabetes and its complications are described. In endothelial cells, high-glucose treatment increases mitochondrial ROS and normalization of the ROS production by inhibitors of mitochondrial metabolism, or by overexpression of UCP-1 or MnSOD, prevents glucose-induced activation of PKC, formation of AGE, and accumulation of sorbitol, all of which are believed to be the main molecular mechanisms of diabetic complications. Glomerular hyperfiltration, one of the characteristics of early diabetic nephropathy, may be caused by mitochondrial ROS through activation of COX-2 gene transcription, followed by PGE2 overproduction. In pancreatic beta cells, hyperglycemia also increases mitochondrial ROS, which suppresses the first phase of glucose-induced insulin secretion, at least in part, through the suppression of GAPDH activity. In liver cells, similar to that in hyperglycemia, TNF-alpha increases mitochondrial ROS, which in turn activates apoptosis signal-regulating kinase 1 (ASK1) and c-jun NH2-terminal kinases (JNK), increases serine phosphorylation of IRS-1, and decreases insulin-stimulated tyrosine phosphorylation of IRS-1, leading to insulin resistance. These results suggest the importance of mitochondrial ROS in the pathogenesis of diabetes mellitus and its complications through modification of various cellular events in many tissues, including vessels, kidney, pancreatic beta cells, and liver.
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PMID:Impact of mitochondrial ROS production in the pathogenesis of diabetes mellitus and its complications. 1718 77

The aim of the studies was to identify the regulatory mechanisms that act at different levels of the ongoing immune response in BALB/c mice infected with intestinal nematode H. polygyrus. The role of TGF-beta during the course of H. polygyrus infection and an immunosuppressive action of the nematode against eosinophil response in allergic pulmonary inflammation has been studied. An attempt to identify the immunoregulatory proteins of the parasite has been performed as well. The obtained results proved: (1) for the first time the direct role of TGF-beta in the regulation of the immune response during helminth infections. Neutralization of TGF-beta in vivo increased concentration of IL-12, TNF-alpha and IL-10 in serum of infected mice and restored the control number of eosinophils in the intestinal mucosa. The mobilization of the immune response after neutralization of TGF-beta led to persistent decrease of nematode egg production and faster rejection of the worm from mouse intestine; (2) for the first time it was shown that the reduction of eosinophil number was due to the lower production of eotaxin and reduced expression of CCR3 receptor, playing an essential role in the chemotaxis of these leukocytes in Ova-related asthma; (3) significant decrease of T cell proliferation by one of the H. polygyrus protein fraction. With the use of mass spectrometry seven proteins have been identified: two heat shock proteins, disulfide isomerase, calreticulin, calumenin, fructose-bisphosphate aldolase, glyceraldehyde-3-phosphate dehydrogenase. From the bibliographic data it may be supposed that calreticulin could mediate the downregulation of lymphocytes proliferation. The fraction with calreticulin stimulated also production of specific IgE.
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PMID:[Regulation of the immune response in BALb/c mice infected with Heligmosomoides polygyrus]. 1791 15

Curdlan modified polyurethane was created by physically entrapping the former on TecoflexTM surface. ATR-FT-IR, SEM-EDAX and AFM analysis revealed the formation of stable thin curdlan layer on the film. Contact-angle measurements showed that the modified film was highly hydrophilic. Confocal laser scanning microscopy showed the existence of entrapped layer of approximately 20-25 microm in depth. Surface entrapment of curdlan minimized both protein adsorption and mouse L929 fibroblast cell adhesion relative to the control. Surface induced cellular inflammatory response was determined from the expression levels of proinflammatory cytokine TNF-alpha, by measuring their mRNA profiles in the cells using real time polymerase chain reaction (RT-PCR) normalized to the housekeeping gene GAPDH. The inflammatory response was suppressed on the modified substrate as expression of TNF-alpha mRNA was found to be up regulated on TecoflexTM, while it was significantly lower on curdlan substrate. The adhesion of S. aureus decreased by 62% on curdlan modified surface. Using such simple surface entrapment process, it will be possible to develop well-defined surface modifications that promote specific cell interactions and perhaps better performance in the long-term as implant.
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PMID:TecoflexTM functionalization by curdlan and its effect on protein adsorption and bacterial and tissue cell adhesion. 1909 93

Neospora caninum is one of the main causes of abortion and natimortality in cattle. Host immune defense is capable to inhibit tachyzoite activity during acute infection, but there is no action against bradyzoites in tissue cysts. Activation and modulation of this response is controlled by cell mediators. The real-time RT-PCR technique was employed to detect some of those mediators during N. caninum infection. Holstein and Nelore calves intramuscularly infected with tachyzoites and uninfected controls were slaughtered at the sixth day post-infection and popliteal lymph node, liver and brain cortex samples were analyzed. Real-time RT-PCR detected gene expression in all tissues. No significant variation of GAPDH gene expression was detected among groups, its amplification efficiency was similar to the other genes tested and it was used as the endogenous control for the analysis. Comparisons between infected and uninfected groups allowed the relative gene expression quantification. IFN-gamma and TNF-alpha genes showed increased expression in some samples. iNOS and TGF-beta1 genes had some non-significant variations and IL-4 and IL-10 stayed practically unaltered.
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PMID:[Use of the real time RT-PCR for immune related gene expression quantitation in experimentally infected Neospora caninum bovine calves]. 1950 Apr 54

Sulfobetaine-modified poly(ethylene terephthalate) (PET) systems were created by physically entrapping the zwitterionic species on the PET surface. The presence of the sulfobetiane molecules on these surfaces were verified by ATR-FTIR and SEM-EDAX analysis, while wettability of the films was investigated by water contact angle measurements. The blood compatibility of the modified films was evaluated by platelet adhesion in human platelet-rich plasma (PRP). The adhesion and inflammatory response of Mouse RAW 264.7 macrophage cells were studied. The surface induced cellular inflammatory response was determined by quantifying the expression levels of proinflammatory cytokines namely TNF-alpha and IL-1beta by measuring their mRNA profiles in the cells using real time polymerase chain reaction normalized to the housekeeping gene GAPDH. L-929 fibroblast cells were used to assess the propensity of the materials to support the fibroblast cell adhesion. A lower platelet adhesion and activation were observed on the sulfobetaine-modified PET film incubated in PRP after 2h when compared to control. The modified film reduced cellular adhesion events ( p<0.05) with respect to the base material, which could be linked to the reduced protein adsorption observed on this surface. The cellular inflammatory response was suppressed on sulfobetaine-modified substrate. Expression levels of pro-inflammmatory cytokines (TNF-alpha and IL-1beta) was found to be upregulated on bare PET, while it was significantly lower on modified PET ( p<0.001). Thus the sulfobetaine entrapment process can be applied on PET in order to achieve low biointeractions and reduced inflammatory host response for various biomedical and biotechnological applications.
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PMID:The biocompatibility of sulfobetaine engineered poly (ethylene terephthalate) by surface entrapment technique. 1974 1

Bacterial translocation in patients with cirrhosis induces a marked proinflammatory activity that may be different against viable bacteria or bacterial products. The aim of this study is to identify new markers of bacterial translocation by investigating bacterial-driven peptides and correlate their presence with the inflammatory response. Patients with cirrhosis and ascites were included. An analysis by two-dimensional polyacrylamide gel electrophoresis of ascitic fluid total protein from patients (n = 47) and from frequently detected bacterial strains was performed. Two-dimensional maps were digitally compared. The identification of possible markers was performed by mass spectrometry. TNF-alpha, IFN-gamma, IL-12, nitric oxide, and proteins of the complement and lipopolysaccharide-binding protein levels were measured in ascitic fluid samples of patients by enzyme-linked immunosorbent assay. Patients were distributed according to the presence (group I, n = 16) and absence (group II, n = 31) of serum and ascitic fluid bacterial DNA. Among clinical and analytical differences between groups, only mean arterial pressure was significantly higher in patients from group II. Identified bacterial peptides were associated with bacterial protection against immune defenses and included glyceraldehyde-3-phosphate dehydrogenase A, Porin OmpC, and HSP60. Eight patients from group I also showed bacterial peptides, whereas none from group II did. All studied mediators of immune activation were significantly higher in patients with bacterial DNA than in patients without bacterial DNA. TNF-alpha, IFN-gamma, and proteins of the complement were significantly increased in patients with bacterial peptides versus those without bacterial peptides. Bacterial peptide translocation is present in the ascitic fluid of a subgroup of patients with advanced cirrhosis and is associated with an increased immune response.
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PMID:Proteomic evidence of bacterial peptide translocation in afebrile patients with cirrhosis and ascites. 2008 63

Aging-related, nonresolving inflammation in both the central nervous system (CNS) and periphery predisposes individuals to the development of neurodegenerative disorders (NDDs). Inflammasomes are thought to be especially relevant to immune homeostasis, and their dysregulation contributes to inflammation and NDDs. However, few agents have been clinically shown to reduce NDD incidence by targeting inflammasomes. Our study indicated that NLRP3 (NLR family, pyrin domain containing 3) inflammasome is involved in Parkinson disease (PD) progression in patients and various murine models. In addition, the small molecule kaempferol (Ka) protected mice against LPS- and SNCA-induced neurodegeneration by inhibiting NLRP3 inflammasome activation as evidenced by the fact that Ka reduced cleaved CASP1 expression and disrupted NLRP3-PYCARD-CASP1 complex assembly with concomitant decreased IL1B secretion. Mechanically, Ka promoted macroautophagy/autophagy in microglia, leading to reduced NLRP3 protein expression, which in turn deactivated the NLRP3 inflammasome. Intriguingly, ubiquitination was involved in Ka-induced autophagic NLRP3 degradation. These findings were further confirmed in vivo as knockdown of Atg5 expression or autophagy inhibitor treatment significantly inhibited the Ka-mediated NLRP3 inflammasome inhibition and neurodegeneration amelioration. Thus, we demonstrated that Ka promotes neuroinflammatory inhibition via the cooperation of ubiquitination and autophagy, suggesting that Ka is a promising therapeutic strategy for the treatment of NDDs. Abbreviations: 3-MA: 3-methyladenine; AAV: adeno-associated virus; ACTB: actin, beta; AIF1/IBA1: allograft inflammatory factor 1; ATG5: autophagy related 5; ATG7: autophagy related 7; BafA1: bafilomycin A1; BECN1: beclin 1, autophagy related; CASP1: caspase 1; CNS: central nervous system; CQ: chloroquine; DA neurons: dopaminergic neurons; DAMPS: damage-associated molecular patterns; DAPI: 4',6-diamidino-2-phenylindole; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; GFAP: glial fibrillary acidic protein; IP: immunoprecipitation; i.p.: intraperitoneally; Ka: kaempferol; KD: knockdown; KO: knockout; LPS: lipopolysaccharide; IL1B: interleukin 1 beta; IL6: interleukin 6; Ly: lysate; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NC: negative control; NDD: neurodegenerative diseases; NLRP3: NLR family, pyrin domain containing 3; OE: overexpression; PD: Parkinson disease; poly-Ub: poly-ubiquitin; PTM: post-translational modification; PYCARD/ASC: PYD and CARD domain containing; Rapa: rapamycin; RFP: red fluorescent protein; SN: supernatant; SNCA: synuclein alpha; SNpc: substantia nigra pars compacta; SQSTM1: sequestosome 1; TH: tyrosine hydroxylase; TNF/TNF-alpha: tumor necrosis factor; Ub: ubiquitin; WT: wild type.
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PMID:Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiquitination and autophagy: implications for Parkinson disease. 3096 61


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