Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bach2 is a B cell-specific transcription repressor whose deficiency in mice causes a reduced class switch recombination and a reduced somatic hypermutation of immunoglobulin genes. Little is known about the direct target genes of Bach2 in B cells. By analyzing various B cell and plasma cell lines, we showed that the expression patterns of Bach2 and Blimp-1 (B lymphocyte-induced maturation protein 1), a master regulator of plasma cell differentiation, are mutually exclusive. The reporter gene of the Blimp-1 gene (Prdm1) was repressed by the overexpression of Bach2 in B cell lines. The heterodimer of Bach2/MafK bound to the Maf recognition element located upstream of the Prdm1 promoter in an electrophoretic mobility shift assay. The binding of MafK in B cells to the Prdm1 Maf recognition element was confirmed by chromatin immunoprecipitation assays. When MafK was purified from the BAL17 B cell line, a significant portion of it was present as a heterodimer with Bach2, with no apparent formation of MafK homodimer. These results strongly suggest that Bach2 represses the expression of Blimp-1 together with MafK in B cells prior to plasma cell differentiation. Accordingly, the knockdown of Bach2 mRNA using short hairpin RNA in BAL17 cells resulted in higher levels of Prdm1 expression after the stimulation of B cell receptor by surface IgM cross-linking. Induction of Prdm1 was more robust and faster in primary Bach2-deficient B cells than in wild-type control B cells upon lipopolysaccharide stimulation. Therefore, the Prdm1 regulation in B cells involves the repression by Bach2, which may be cancelled upon terminal plasma cell differentiation.
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PMID:Plasmacytic transcription factor Blimp-1 is repressed by Bach2 in B cells. 1704 16

Interleukin-12 (IL-12) p70 is an important cytokine secreted by antigen-presenting cells in response to antigenic stimulation; it is a heterodimer of p35 and p40 subunits. Here, we report a new, highly sensitive, and reliable method that employs fluorometric sandwich ELISA for quantification of the mouse IL-12 (moIL-12) p70 protein. Our method could quantify moIL-12 p70 in the range of approximately 0.5 to 500 pg/ml. In the assay, no signals were produced by the moIL-12 p40 monomer, homodimer [(p40)2], or mouse IL-23 even up to a concentration of 500 pg/ml; this ensures that our assay has a high specificity for moIL-12 p70. To demonstrate that our method can determine natural moIL-12 in real physiological/pathological samples, we monitored the moIL-12 p70 secretion from peritoneal exudative cells after lipopolysaccharide (LPS) stimulation. IL-12 p70 secretion as early as 3h after LPS stimulation was reliably detected due to the high sensitivity of the method.
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PMID:A sensitive and reliable quantification method for mouse interleukin-12 p70 based on fluorometric sandwich ELISA (FS-ELISA). 1714 87

The confirmed advantageous effects of oxygen/ozone therapy in several clinical conditions stimulated experimental studies on effects of the therapy in rats with an induced septic shock. The studies were conducted on adult male rats of Wistar strain. Four groups of the animals, each of 15 rats, included: I--control group, (C); II--animals intraperitoneally administered with O(2)/O(3) (CO), III--rats given of Escherichia coli endotoxin (lipopolysaccharide-LPS) (CL), IV--rats administered with the lipopolysaccharide plus administered with the oxygen/ozone mixture (OL). Activities of catalase and superoxide dismutase and of free radical reactions were estimated. The exposure to LPS augmented activities of SOD and of catalase in liver, lungs and heart. In all the examined organs LPS induced significant changes in levels of free radicals. Except of the lungs, parallel administration of the rats with LPS and ozone/oxygen revoked development of the alterations. The obtained results point to a strong, stabilizing and regenerative effect of ozonotherapy.
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PMID:Ozonotherapy in an induced septic shock. I. Effect of ozonotherapy on rat organs in evaluation of free radical reactions and selected enzymatic systems. 1737 41

NF-kappaB family of transcription factors are involved in numerous cellular processes, including differentiation, proliferation, and inflammation. It was reported that hydroxycinnamic acid derivatives (HADs) are inhibitors of NF-kappaB activation. Rice bran oil contains a lot of phytosteryl ferulates, one of HADs. We have investigated effects of phytosteryl ferulates on NF-kappaB activation in macrophage. Cycloartenyl ferulate (CAF), one of phytosteryl ferulates, significantly reduced lipopolysaccharide (LPS)-induced NO production and mRNA expression of inducible NO synthase and cyclooxygenese-2 but upregulated SOD activity. Electrophoresis mobility shift assay revealed that CAF inhibited DNA-binding of NF-kappaB. CAF and phytosteryl ferulates probably have potentially anti-inflammatory properties.
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PMID:Anti-inflammatory effects of hydroxycinnamic acid derivatives. 1749 10

Sphingolipid biosynthesis commences with the condensation of L-serine and palmitoyl-CoA to produce 3-ketodihydrosphingosine (KDS). This reaction is catalysed by the PLP-dependent enzyme serine palmitoyltransferase (SPT; EC 2.3.1.50), which is a membrane-bound heterodimer (SPT1/SPT2) in eukaryotes such as humans and yeast and a cytoplasmic homodimer in the Gram-negative bacterium Sphingomonas paucimobilis. Unusually, the outer membrane of S. paucimobilis contains glycosphingolipid (GSL) instead of lipopolysaccharide (LPS), and SPT catalyses the first step of the GSL biosynthetic pathway in this organism. We report here the crystal structure of the holo-form of S. paucimobilis SPT at 1.3 A resolution. The enzyme is a symmetrical homodimer with two active sites and a monomeric tertiary structure consisting of three domains. The PLP cofactor is bound covalently to a lysine residue (Lys265) as an internal aldimine/Schiff base and the active site is composed of residues from both subunits, located at the bottom of a deep cleft. Models of the human SPT1/SPT2 heterodimer were generated from the bacterial structure by bioinformatics analysis. Mutations in the human SPT1-encoding subunit have been shown to cause a neuropathological disease known as hereditary sensory and autonomic neuropathy type I (HSAN1). Our models provide an understanding of how these mutations may affect the activity of the enzyme.
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PMID:The structure of serine palmitoyltransferase; gateway to sphingolipid biosynthesis. 1755 74

Peroxynitrite (ONOO-), formed from a reaction of superoxide and nitric oxide, is one of the most potent cytotoxic species known to oxidize cellular constituents including essential proteins, lipids, and DNA. ONOO- induces cellular and tissue injury, resulting in several human diseases such as Alzheimer's disease, atherosclerosis, and stroke. Due to the lack of endogenous enzymes responsible for ONOO- scavenging activity, finding a specific ONOO- scavenger is of considerable importance. In this study, the ability of trypsin inhibitor (TI), isolated from sweet potato storage roots (SPTI), to scavenge *ON and ONOO- was investigated. The data obtained show that TI generated a dose-dependent inhibition on production of nitrite and superoxide radicals. The IC50 value of TI on superoxide radical was 143.2 +/- 4.29 microg/mL. SOD activity staining was used to confirm SOD activity of SPTI. SPTI also caused a dose-dependent inhibition of the oxidation of dihydrorhodamine 123 (DHR) by peroxynitrite. A calculated IC50 value of 809.1 +/- 32.36 microg/mL was obtained on the inhibition of peroxynitrite radical. Spectrophotometric analyses revealed that TI suppressed the formation of ONOO--mediated tyrosine nitration through an electron donation mechanism. In further studies, TI also showed a significant ability to inhibit nitration of bovine serum albumin (BSA) in a dose-dependent manner. In vivo TI inhibited lipopolysaccharide-induced nitrite production in macrophages in a concentration-dependent manner with an IC50 value of 932.8 +/- 29.85 microg/mL. The present study suggested that TI had an efficient reactive nitrogen species scavenging ability. TI might be a potential effective NO and ONOO- scavenger useful for the prevention of NO- and ONOO--involved diseases.
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PMID:Inhibition of reactive nitrogen species in vitro and ex vivo by trypsin inhibitor from sweet potato 'Tainong 57' storage roots. 1760 66

Multidrug resistance of pathogenic microorganisms and mammalian tumors can be associated with the overexpression of multidrug transporters. These integral membrane proteins are capable of extruding a wide range of structurally unrelated compounds from the cell. Among the different classes of multidrug transporters are the ATP binding cassette (ABC) transporters, which are dependent on the binding and hydrolysis of ATP. In the past five years, many researchers have built homology models of ABC extrusion systems using the atomic coordinates of crystallized MsbA, a lipopolysaccharide transporter in Gram-negative bacteria. Likewise, we have previously used the Vibrio cholera MsbA structure as a template in the modeling of the multidrug transporter LmrA from Lactococcus lactis. In view of the recently discovered inaccuracies in the MsbA structure, we have remodelled LmrA using the atomic coordinates of the MsbA homologue Sav1866 from Staphylococcus aureus. To compare and test our MsbA-based and Sav1866-based LmrA models we performed cysteine cross-linking at three key positions in LmrA. The pattern of cross-linking at these positions was consistent with the overall topology of transmembrane helices in Sav1866, suggesting that its crystal structure might be physiologically relevant. We recently identified E314 as a residue important in proton conduction by LmrA. The predicted location of this residue at the interface between the two half-transporters in the Sav1866-based homodimer, within the inner leaflet of the phospholipid bilayer, provides a new structural basis for the role of E314 in LmrA-mediated transport.
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PMID:New structure model for the ATP-binding cassette multidrug transporter LmrA. 1762 17

A common gene variant in the heparin-binding domain (HBD) of extracellular superoxide dismutase (ECSOD) may predispose human carriers to ischaemic heart disease. We have demonstrated that the HBD of ECSOD is important for ECSOD to restore vascular dysfunction produced by endotoxin. The purpose of this study was to determine whether the gene variant in the HBD of ECSOD (ECSOD(R213G)) protects against endothelial dysfunction in a model of inflammation. We constructed a recombinant adenovirus that expresses ECSOD(R213G). Adenoviral vectors expressing ECSOD, ECSOD(R213G) or beta-galactosidase (LacZ, a control) were injected i.v. in mice. After 3 days, at which time the plasma SOD activity is maximal, vehicle or endotoxin (lipopolysaccharide or LPS, 40 mg kg(-1)) was injected i.p. Vasomotor function of aorta in vitro was examined 1 day later. Maximal relaxation to sodium nitroprusside was similar in aorta from normal and LPS-treated mice. Maximal relaxation to acetylcholine (10(-5)) was impaired after LPS and LacZ (63 +/- 3%, mean +/- s.e.m.) compared to normal vessels (83 +/- 3%) (P < 0.05). Gene transfer of ECSOD improved (P < 0.05) relaxation in response to acetylcholine (76 +/- 5%) after LPS, whereas gene transfer of ECSOD(R213G) had no effect (65 +/- 4%). Superoxide was increased in aorta (measured using lucigenin and hydroethidine) after LPS, and levels of superoxide were significantly reduced following ECSOD but not ECSOD(R213G). Thus, ECSOD reduces superoxide and improves relaxation to acetylcholine in the aorta after LPS, while the ECSOD variant R213G had minimal effect. These findings suggest that, in contrast to ECSOD, the common human gene variant of ECSOD fails to protect against endothelial dysfunction produced by an inflammatory stimulus.
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PMID:Effects of a common human gene variant of extracellular superoxide dismutase on endothelial function after endotoxin in mice. 1771 13

Time-series changes in transcript abundance of nine genes encoding important immune proteins in haemocytes or hepatopancreas of Pacific white shrimp Litopenaeus vannamei fed daily in a 1-week feeding trial diets containing three levels (0%, 0.2% or 1%) of beta-1,3-glucan from Schizophyllum commune were quantified by real-time PCR. As a whole, the immune modulation elicited by beta-glucan is bimodal, one swift reaction of up- or down-regulation occurred within 24h and a delayed regulation was commenced as late as 3-7days. Haemocyanin, crustin, prophenoloxidase (proPO) and transglutaminase (TGase) did not respond to the glucan treatment. While penaeidin 3 (Litvan PEN3) was swiftly down-regulated (0-24h), lysozyme and cytosolic manganese superoxide dismutase (cMnSOD) were swiftly up-regulated (0-24h). In contrast, the two pattern recognition proteins (PRPs), beta-glucan binding protein-high density lipoprotein (BGBP-HDL) and lipopolysaccharide/beta-glucan binding protein (LGBP), showed a delayed up-regulation. Their expressions were not maximized until as late as 72h or 7days, respectively, which coincide with the initiation of reported immune enhancement (6-24days) of PO and SOD activity, phagocytosis and superoxide anion production in penaeid shrimp receiving glucan-containing diet. These immune responses could be the downstream effects of the two PRP gene up-regulation that predispose the shrimp to a state of high immune responsiveness. Increased dosage of beta-glucan from 2 to 10gkg(-1) diet did not affect the expressions of the genes, indicating the sufficiency of beta-glucan supplementation at 2gkg(-1) diet.
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PMID:Differential time-series expression of immune-related genes of Pacific white shrimp Litopenaeus vannamei in response to dietary inclusion of beta-1,3-glucan. 1802 7

Injection of D-galactosamine and lipopolysaccharide (DGaIN/LPS) is useful as an experimental model of acute hepatic damage. Juvenile rats were used for investigation. The hepatoprotective activity of aqueous garlic (Allium sativum) extract (AGE) at a dose of 300 mg/kg body weight for 14 days, intraperitoneal (i.p.) prior to the induction of DGalN/LPS, was investigated against DGalN/LPS-induced hepatitis in rats. DGalN/LPS (300 mg/kg body weight/30 microg/kg body weight, i.p.), induced hepatic damage that was manifested by a significant increase in the activities of marker enzymes [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (gamma GT)], bilirubin, lipid peroxides (LPO), tumor necrosis factor (TNF-alpha) and myeloperoxidase (MPO) activity level in serum. Also, the lipid profile in serum and liver homogenate including total cholesterol, triglycerides, free fatty acids and phospholipids were significantly deteriorated. The antioxidant enzyme activities (superoxide dismutase, SOD; reduced glutathione, GSH; catalase, CAT and glutathione peroxidase, GPX) in liver homogenate were significantly decreased in the DGalN/LPS. Pretreatment of rats with AGE reversed these altered parameters near to normal control values. Results of this study revealed that AGE could afford a significant protection in the alleviation of DGalN/LPS-induced hepatic damage.
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PMID:Aqueous garlic extract attenuates hepatitis and oxidative stress induced by galactosamine/lipoploysaccharide in rats. 1857 Feb 25


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