Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel combination of methods, two-dimensional liquid-phase electrophoresis (2D-LPE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS), have been used for the analysis of intact brain-specific proteins in cerebrospinal fluid (CSF). 2D-LPE is especially useful for isolating proteins present in low concentrations in complex biological samples. The proteins are separated in the first dimension by liquid-phase isoelectric focusing (IEF) in the Rotofor cell and in the second dimension by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) in the Preparative cell. The removal of SDS by chloroform/methanol/water, followed by sample preparation with the addition of n-octylglucoside, easily interfaced 2D-LPE with MALDI-TOFMS for analysis of intact proteins. Further characterization by proteolytic digestion is also demonstrated. The knowledge of both the molecular weights of the protein and of the proteolytic fragments obtained by peptide mapping increases specificity for protein identification by searching in protein sequence databases. Two brain-specific proteins in human CSF, cystatin C and transthyretin, were isolated in sufficient quantity for determination of the mass of the whole proteins and their tryptic digest by MALDI-TOFMS. This approach simplified the interface between electrophoresis and MALDI-TOFMS.
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PMID:Analysis of intact proteins from cerebrospinal fluid by matrix-assisted laser desorption/ionization mass spectrometry after two-dimensional liquid-phase electrophoresis. 1058 93

Scid mice are defective in the ability to repair DNA double strand breaks and, as a consequence, their cells are radiosensitive. Further, they have been shown to be prone to develop thymic lymphomas (TLs) after small doses of ionizing radiation. Little is known, however, on the role of scid mutation in chemical carcinogenesis. To determine if scid mutation increased predisposition to chemical carcinogenesis, we examined both the susceptibility of scid mice to N-ethyl-N-nitrosourea (ENU)-induced lymphomagenesis and the involvement of ras gene activation. Adult female mice at 8 weeks of age were given ENU in their drinking water at 400 ppm for 2-10 weeks. Contrary to expectations, we observed a two to three-fold reduction in TL development in the scid mice. The highest incidence was achieved by ENU treatment for 8 weeks for scid and wild-type C.B-17 mice, of 42 and 85%, respectively (P<0.05). We investigated whether this was attributable to the usage of the ras mutation pathway. There was, however, no significant difference in the frequency and spectrum of K-ras mutation between the scid and wild-type C.B-17 mice. Most of the K-ras mutations were either GGT to GAT transition in codon 12 (11/23: 48%) or CAA to CCA transversion in codon 61 (8/23: 35%) that was independent of scid background. The incidence of N-ras mutation was very low. These results indicate that scid mice are less susceptible to ENU-induced lymphomagenesis and ras gene mutation frequently occurs in both scid and wild-type C.B-17 mice.
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PMID:Reduced sensitivity to and ras mutation spectrum of N-ethyl-N-nitrosourea-induced thymic lymphomas in adult C.B-17 scid mice. 1151 30

The efficiency of chemotherapy of Lewis lung carcinoma with cyclophosphamide was affected by administration of the water-soluble yeast polysaccharide derivative--carboxymethylated (1 --> 3)-beta-D-glucan (CMG)-a well-known macrophage stimulator. It was found that while cyclophosphamide showed 57% growth inhibition of the intramuscular tumor implants in comparison with the control group, its combined administration with CMG led to 75-90% inhibition. Similarly, increased inhibition of occurrence of lung metastases (up to 92-94%) was observed using the combined application of the two compounds. The stimulatory effect of CMG is not associated with the changed cellularity of peripheral blood, but is rather due to the obviously increased concentration of the intracellular inhibitor of cysteine proteases-stefin A and cystatin C in tumor tissue.
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PMID:Increased efficiency of Lewis lung carcinoma chemotherapy with a macrophage stimulator--yeast carboxymethyl glucan. 1209 68

A series of azapeptides as potential inhibitors of cysteine proteases were synthesized. Their structures, based on the binding center of cystatins, contain an azaglycine residue (Agly) in place of the evolutionarily conserved glycine residue in the N-terminal part of the enzyme binding region of cystatins. Incorporation of Agly should lead to deactivation of the acyl-enzyme complex formed against nucleophilic attack by water molecules in the final step of peptide bond hydrolysis. The majority of synthesized azapeptides shows high inhibitory potency toward the investigated cysteine proteases, papain, cathepsin B, and cathepsin K. One of them, Z-Arg-Leu-Val-Agly-Ile-Val-OMe (compound 17), which contains in its sequence the amino acid residues from the N-terminal binding segment as well as the hydrophobic residues from the first binding loop of human cystatin C, proved to be a highly potent and selective inhibitor of cathepsin B. It inhibits cathepsin B with a K(i) value of 0.088 nM. To investigate the influence of the structure of compound 17 for its inhibitory properties, we determined its conformation by means of NMR studies and theoretical calculations. The Z-Arg-Leu-Val-Agly fragment, covalently linked to Cys29 of cathepsin B, was also developed and modeled, in the catalytic pocket of the enzyme, through a molecular dynamics approach, to analyze ligand-protein interactions in detail. Analysis of the simulation trajectories generated using the AMBER force field provided us with atomic-level understanding of the conformational variability of this inhibitor, which is discussed in the context of other experimental and theoretical data.
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PMID:Azapeptides structurally based upon inhibitory sites of cystatins as potent and selective inhibitors of cysteine proteases. 1221 61

Characterization of functional properties of Sphagnum magellanicum fiber were investigated. Water absortion (WAC) and water retention (WRC) capacities, swelling capacity (SC); organic molecule absortion capacity (OMAC) and cationic interchange capacity (CIC) were evaluated, as well as its incorporation as fiber source to bakery produts. Diferent particles sizes were selected to evaluate their effects on the functional properties of moss fiber: T1(1.4 mm);T2(1.0 mm); T3(0.42 mm); T4(0.18 mm). Best results of CAA, CRA; SC and OMRC were obtained with T3, whereas best values of CIC were attained with T1. An optimized formulation of fiber enriched bread was developed analizing simultaneously the effect of four independent variables (yeast, moss fiber, fluffy agent and shortening) on the sensory quality of products. Shelf life studies were carried out by storing samples of fiber enriched breads at 20 degrees C and 6 degrees C. At the end of the study, refrigerated samples showed better sensory quality stability.
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PMID:[Functional properties of Sphagnum magellanicum fiber and its direct use in formulation of bakery products]. 1512 83

In this study, a homology model of carp ovum cystatin was constructed based on the crystal structure of chicken egg white cystatin. The results of amino acid sequence alignment indicate that these two proteins exhibit 36.11% of sequence identity. The resultant homology model reveals that carp ovum cystatin shares similar folds as chicken egg white cystatin, particularly in the conserved regions of Q48-V49-G52 and P98-W99 and the locations of two disulfide bonds, C67-C76 and C90-C110. However, the results of 1 ns molecular dynamics simulations show that carp ovum cystatin exhibits less structural integrity than chicken egg white cystatin in explicit water at 300 K. The relatively hydrophilic Met62 of carp ovum cystatin, corresponding to the hydrophobic Leu68 of human cystatin C and Ile66 of chicken egg white cystatin, may destabilize the hydrophobic core and form a dimeric structure more easily through domain swapping. A total of 16 positively charged residues are equally distributed on the surface of carp ovum cystatin, resulting in agglutination with the negatively charged spermatozoa via electrostatic interaction. Thus, carp ovum cystatin is considered to be important in preventing carp eggs from polyspermy.
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PMID:Homology model and molecular dynamics simulation of carp ovum cystatin. 1608 Jul 17

The neurovascular unit (NVU) comprises cerebral blood vessels and surrounding astrocytes, neurons, perivascular microglia and pericytes. Astrocytes associated with the NVU are responsible for maintaining cerebral blood flow and ionic and osmotic balances in the brain. A significant proportion of individuals with Alzheimer's disease (AD) have vascular amyloid deposits (cerebral amyloid angiopathy, CAA) that contribute to the heterogeneous nature of the disease. To determine whether NVU astrocytes are affected by the accumulation of amyloid at cerebral blood vessels we examined astrocytic markers in four transgenic mouse models of amyloid deposition. These mouse models represent mild CAA, moderate CAA with disease progression to tau pathology and neuron loss, severe CAA and severe CAA with disease progression to tau pathology and neuron loss. We found that CAA and disease progression both resulted in distinct NVU astrocytic changes. CAA causes a loss of apparent glial fibrillary acidic protein (GFAP)-positive astrocytic end-feet and loss of water channels (aquaporin 4) localized to astrocytic end feet. The potassium channels Kir4.1, an inward rectifying potassium channel, and BK, a calcium-sensitive large-conductance potassium channel, were also lost. The anchoring protein, dystrophin 1, is common to these channels and was reduced in association with CAA. Disease progression was associated with a phenotypic switch in astrocytes indicated by a loss of GFAP-positive cells and a gain of S100 beta-positive cells. Aquaporin 4, Kir4.1 and dystrophin 1 were also reduced in autopsied brain tissue from individuals with AD that also display moderate and severe CAA. Together, these data suggest that damage to the neurovascular unit may be a factor in the pathogenesis of Alzheimer's disease.
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PMID:Vascular amyloid alters astrocytic water and potassium channels in mouse models and humans with Alzheimer's disease. 1935 89

Haloacetic acids, disinfection byproducts (DBPs) formed during drinking water chlorination process are carcinogens. The efficacy of nanofiltration (NF) was examined for the removal of five regulated haloacetic acids (HAA5): chloro-, dichloro-, and trichloro-acetic acid (CAA, DCAA, and TCAA); bromo-, and dibromo-acetic acid (BAA, and DBAA) in synthetic water. NF with the dense negatively charged membrane (ES 10), is the most efficient in removing HAA5 than the loose negatively charged membrane (NTR 7410) and neutral surface membrane (NTR 729HF), due to the greater electrostatic repulsion (Donan exclusion) and sieve effect. Excellent HAA5 removal efficiency of 90%-100% could be obtained even at a low pressure of 1 x 10(5) Pa with ES 10. Changes in cross-flow velocity did not effect the performance of membranes with a small pore size such as ES 10 and NTR 729HF. The increase in HAA5 concentration exhibited the adverse effect on the performance of three membranes by strengthening the concentration polarization, which was the driving force for the diffusion of HAA anions across the membrane.
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PMID:Removal of haloacetic acids by nanofiltration. 1940 6

Recently, we showed that mechanical stress on scleractinian (stony) corals caused a rapid release of antibacterial material (referred to as coral antibacterial activity, or CAA), which killed various bacterial species, including the coral pathogen Vibrio coralliilyticus. We now report on studies on the regulation of CAA release from stressed scleractinian corals. Corals can repeatedly release highly active CAA as a result of sequential stress inductions. Coral fragments were transferred 19 times from one beaker into another with a stress induction each time after 10 min. There was a decrease in the level of antibacterial activity released during the first four to five transfers. After the fifth transfer, the corals kept releasing CAA for the rest of the experiment with no significant decrease. Apparently, the release of CAA is downregulated by feedback inhibition, depending on the concentration of CAA in the surrounding water. By separating CAA-treated V. coralliilyticus from the surrounding water, it was shown that CAA was bound irreversibly to bacterial cells in a stoichiometric manner. Approximately 4 x 10(2) bacterial cells were sufficient to bind 1 U of CAA. Resident coral bacteria were more resistant to CAA than bacteria isolated from seawater, suggesting an ecological role for CAA. CAA release was obtained from corals after removal of the mucus layer, and the mucus itself contained antibacterial activity.
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PMID:Regulation of release of antibacterials from stressed scleractinian corals. 1947 57

Enzymes catalyzing the conversion of organohalogen compounds are useful in the chemical industry and environmental technology. Here we report the occurrence of a new reduced flavin adenine dinucleotide (FAD) (FADH(2))-dependent enzyme that catalyzes the removal of a halogen atom from an unsaturated aliphatic organohalogen compound by the addition of a water molecule to the substrate. A soil bacterium, Pseudomonas sp. strain YL, inducibly produced a protein named Caa67(YL) when the cells were grown on 2-chloroacrylate (2-CAA). The caa67(YL) gene encoded a protein of 547 amino acid residues (M(r) of 59,301), which shared weak but significant sequence similarity with various flavoenzymes and contained a nucleotide-binding motif. We found that 2-CAA is converted into pyruvate when the reaction was carried out with purified Caa67(YL) in the presence of FAD and a reducing agent [NAD(P)H or sodium dithionite] under anaerobic conditions. The reducing agent was not stoichiometrically consumed during this reaction, suggesting that FADH(2) is conserved by regeneration in the catalytic cycle. When the reaction was carried out in the presence of H(2)(18)O, [(18)O]pyruvate was produced. These results indicate that Caa67(YL) catalyzes the hydration of 2-CAA to form 2-chloro-2-hydroxypropionate, which is chemically unstable and probably spontaneously dechlorinated to form pyruvate. 2-Bromoacrylate, but not other 2-CAA analogs such as acrylate and methacrylate, served as the substrate of Caa67(YL). Thus, we named this new enzyme 2-haloacrylate hydratase. The enzyme is very unusual in that it requires the reduced form of FAD for hydration, which involves no net change in the redox state of the coenzyme or substrate.
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PMID:2-haloacrylate hydratase, a new class of flavoenzyme that catalyzes the addition of water to the substrate for dehalogenation. 2065 77


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