Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.25.1 (proteasome)
28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We are only beginning to understand the mechanisms involved in tactic sensing in the alpha-subgroup of bacteria. It is clear, however, from recent developments that although the central chemosensory pathways are related to those identified in enteric species, the primary signals and the effect on flagellar behaviour are very different. The expression of chemoreceptors is under environmental control, and the strength of a response depends on the metabolic state of the cell. This is very different from enteric species which always respond to MCP-dependent chemoeffectors, and in which the expression of the receptors is constitutive. Chemotaxis in R. sphaeroides and S. meliloti is therefore more directly linked to the environment in which a cell finds itself. The integration of chemosensory pathways dependent on growth state may be much more suited to the fluctuating environment of these soil and water bacteria. There is still a great deal that needs to be understood about the mechanisms involved in motor control. The presence of at least two CheY homologues and the finding that the swimming speed of these bacteria can vary, and, in the case of S. meliloti, vary with chemosensory stimulation, suggests a different control mechanism at the flagellar motor where speed can be altered, or the motor stopped, with a full delta p still present. Why R. sphaeroides should have at least two functional sets of genes encoding homologues of the enteric chemosensory pathway remains to be determined. The major differences in sensory behaviour between the two alpha-subgroup species so far studied in detail and the differences from the enteric species suggests that many more variations of the chemosensory pathways will be found as more species are studied.
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PMID:Bacterial chemotaxis: Rhodobacter sphaeroides and Sinorhizobium meliloti--variations on a theme? 942 93

We isolated several species of bacteria from the surface water of a Japanese lake. Of the isolated bacteria, Pseudomonas aeruginosa was the only species which could degrade microcystin LR in vitro. Microcystin LR decreased to 4.5% of the spiked microcystin LR quantity in the P. aeruginosa culture, and was metabolized to (2S, 3S, 8S)-3-amino-2, 6, 8-trimethyl-10-phenyldeca-4E, 6E-dienoic acid (DmADDA). It was possible that P. aeruginosa hydrolysed nucleophilically the peptide bond of microcystin LR. We examined if pyochelin, pyocyanin and alkaline protease produced by P. aeruginosa affected the reduction of microcystin LR. In the result, DmADDA was produced from microcystin LR in the presence of 100 microM H2O2 and 100 microM each of pyochelin, pyocyanin or both. However, the production of DmADDA was slight (2 to 12 mole%). After treatment with P. aeruginosa alkaline protease, DmADDA was produced 75 mole% from microcystin LR. Therefore, we concluded that microcystin was degraded mainly by the action of P. aeruginosa alkaline protease.
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PMID:Microcystin LR degradation by Pseudomonas aeruginosa alkaline protease. 956 41

A procedure is presented for the preparation of thin layers of vitrified biological suspensions in the presence of ammonium molybdate, which we term cryo-negative staining. The direct blotting of sample plus stain solution on holey carbon supports produces thin aqueous films across the holes, which are routinely thinner than the aqueous film produced by conventional negative staining on a continuous carbon layer. Because of this, a higher than usual concentration of negative stain (ca. 16% rather than 2%) is required for cryo-negative staining in order to produce an optimal image contrast. The maintenance of the hydrated state, the absence of adsorption to a carbon film and associated sample flattening, together with reduced stain granularity, generates high contrast cryo-images of superior quality to conventional air-dry negative staining. Image features characteristic of unstained vitrified cryo-electron microscopic specimens are present, but with reverse contrast. Examples of cryo-negative staining of several particulate biological samples are shown, including bacteriophage T2, tobacco mosaic virus (TMV), bovine liver catalase crystals, tomato bushy stunt virus (TBSV), turnip yellow mosaic virus (TYMV), keyhole limpet hemocyanin (KLH) types 1 and 2, the 20S proteasome from moss and the E. coli chaperone GroEL. Densitometric quantitation of the mass-density of cryo-negatively stained bacteriophage T2 specimens before and after freeze-drying within the TEM indicates a water content of 30% in the vitreous specimen. Determination of the image resolution from cryo-negatively stained TMV rods and catalase crystals shows the presence of optical diffraction data to ca. 10 A and 11.5 A, respectively. For cryo-negatively stained vitrified catalase crystals, electron diffraction shows that atomic resolution is preserved (to better than 20 diffraction orders and less than 3 A). The electron diffraction resolution is reduced to ca. 10 A when catalase crystal specimens are prepared without freezing or when they are freeze-dried in the electron microscope. Thin vitrified films of TMV, TBSV and TYMV in the presence of 16% ammonium molybdate show a clear indication of two-dimensional (2-D) order, confirmed by single particle orientational analysis of TBSV and 2-D crystallographic analysis of TYMV. These observations are in accord with earlier claims that ammonium molybdate induces 2-D array and crystal formation from viruses and macromolecules during drying onto mica. Three-dimensional analysis of the TBSV sample using the tools of icosahedral reconstruction revealed that a significant fraction of the particles were distorted. A reconstruction from a subset of undistorted particles produced the characteristic T = 3 dimer clustered structure of TBSV, although the spikes are shortened relative to the structure defined by X-ray crystallography. The 20S proteasome, GroEL, catalase, bacteriophage T2, TMV, TBSV and TYMV all show no indication of sample instability during cryo-negative staining. However, detectable dissociation of the KLH2 oligomers in the presence of the high concentration of ammonium molybdate conforms with existing knowledge on the molybdate-induced dissociation of this molecule. This indicates that the possibility of sample-stain interaction in solution, prior to vitrification, must always be carefully assessed.
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PMID:Cryo-negative staining. 968 50

The effects of two proteasome inhibitors on neurite outgrowth from PC12h cells were investigated in terms of the mean length of the neurites and the frequency of occurrence of cells with long neurites. Benzyloxycarbonyl-leucyl-leucyl-leucinal (ZLLLal) and benzyloxycarbonyl-isoleucyl-t-butyl-glutamyl-leucinal (PSI) caused a significant elongation of PC12h cell neurites. Since ZLLLal is known to inhibit both calpain and proteasome activity, we examined the effects ofbenzyloxycarbonyl-leucyl-leucinal (ZLLal) which inhibits calpain activity to the same degree as ZLLLal, but which inhibits proteasome activity only weakly. ZLLal did not induce the significant elongation of neurites at any of the concentrations we studied. These results show that the inhibition of proteasome activity causes neurite elongation. We also quantified subcellular levels of multi-ubiquitin chains and free ubiquitin after treatments with PSI, ZLLLal and ZLLal. Treatment with ZLLal had no effects on levels of water- and urea-soluble multi-ubiquitin chains or of free ubiquitin either in the nucleus or in the cytoplasm. PSI and ZLLLal induced a large accumulation of water- and urea-soluble multi-ubiquitin chains and free ubiquitin in the nucleus. Similarly, PSI and ZLLLal increased cytoplasmic levels of urea-soluble multi-ubiquitin chains. On the contrary, PSI and ZLLLal had no effect on levels of water-soluble multi-ubiquitin chains or free ubiquitin in the cytoplasm. This is the first study to demonstrate subcellular differences in the accumulation of multi-ubiquitin chains and free ubiquitin during the neurite elongation induced by proteasome inhibitors.
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PMID:Proteasome inhibitors which induce neurite outgrowth from PC12h cells cause different subcellular accumulations of multi-ubiquitin chains. 981 55

Previous work has shown that chicken strains selected for growth (broilers) degrade muscle proteins less rapidly than those selected for egg laying. They also have decreased calpain and increased calpastatin content in breast muscle. This study aimed to test the hypothesis that these differences correlate with changes in the ATP- and ubiquitin-dependent proteolytic system. Chickens of a broiler strain (Ross 1) and a layer strain (ISABrown) were reared to the age of 4 wk under identical conditions with ad libitum access to feed and water. Mean fractional growth rates were 10.4%/d for broilers and 7.4%/d for layers. Feed intake measured in the last week of the trial was slightly greater in layer birds (.11 and .12 g x g body weight(-1) x d(-1) for broilers and layers respectively; P < .006). Polyubiquitin (UbI) messenger RNA was abundant in the muscles of these well-fed birds, but it showed little difference between strains. Muscle did not significantly express the UbII polyubiquitin gene. The ATP-dependent system conjugating ubiquitin to endogenous proteins had greatest activity in the gastrocnemius muscle of broiler birds but was not significantly different between breeds. Proteins cross-reactive with antisera to recombinant human proteasome regulatory subunits MSS1 (multicopy suppressor of SUG 1; S7) and TBP1 (tat binding protein 1; S6') were present in muscle homogenates from both strains of bird. The chick equivalent of TBP1 was more abundant in breast muscle of broiler birds than in leg muscle, or in either muscle of layers. Antiserum to recombinant yeast subunit mts2 (mitosis temperature sensitive gene 2; S4) did not react with any protein of the expected size but detected a 30-kDa peptide that was not associated with the 26S proteasome; this was found only in muscle from the layer strain. Hence, during normal growth of chickens, rates of protein degradation are not controlled by the expression of ubiquitin mRNA or the conjugation of ubiquitin. However, the composition of the 26S proteasome may be a regulatory factor.
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PMID:Ubiquitin gene expression and ubiquitin conjugation in chicken muscle do not reflect differences in growth rate between broiler and layer birds. 1043 15

The effect of passive immunotherapy with antisera against heat-killed Pseudomonas aeruginosa and three of its exo-enzymes (elastase, alkaline protease and exotoxin A) in gut-derived P. aeruginosa sepsis was evaluated. Mice were given a suspension of P. aeruginosa strain D4 in their drinking water, together with ampicillin (200 mg/kg) to disrupt the normal bacterial flora. Cyclophosphamide was then administered to induce translocation of P. aeruginosa that had colonised the gastrointestinal tract so that gut-derived septicaemia was produced. In this model, intraperitoneal administration of antiserum against heat-killed bacteria, 100 microl/mouse, twice a day for 3 consecutive days significantly increased the survival rate over that of mice treated with normal rabbit serum. Antiserum against elastase, alkaline protease, or a combination of these two antisera, failed to provide significant protection. In contrast, antiserum against exotoxin A significantly increased the survival rate over that of mice treated with normal rabbit serum. These results indicate that passive immunisation with antiserum against heat-killed bacteria and exotoxin A, but not with antiserum against either elastase or alkaline protease, protects mice against gut-derived sepsis caused by P. aeruginosa.
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PMID:Effect of passive immunotherapy on murine gut-derived sepsis caused by Pseudomonas aeruginosa. 1045 Oct

The multicatalytic proteinase complex (MPC, proteasome) is composed of 28 subunits organized into four rings surrounding a water-filled canal. The catalytic centers face the inner canal confining protein substrates to an enclosed space. Experimental findings obtained with MPC from archaebacteria suggest that degradation of proteins by the complex is processive and have led to the proposal that the lengths of the peptides formed during degradation depend on the distances between active sites in the catalytic chamber. To test whether these postulates are valid for the MPC from a higher organism, we examined the size distributions of products formed early versus late in the course of protein degradation using reduced carboxamidomethylated lysozyme (RCM-lysozyme) and MPC from bovine spleen and pituitary. The majority of final degradation products ranged in length from 6 to 20 amino acids without a clear predilection for peptides of a particular, uniform size. Our observations suggest that selection of cleavage sites is governed by the amino acid sequence specificity of the MPC catalytic sites rather than the distances between the active sites. Early in the course of degradation, peptides with masses between 5 and 10 kDa accumulated in more than 80-fold molar excess over the MPC, indicating dissociation of large, partially degraded intermediates. Initial cleavages occurred at distances between 10 and 44 amino acids from the N- or C-terminus of the molecule and often involved removal of a fragment from both the N- and C-termini of RCM-lysozyme. Our data indicate that degradation of proteins by MPCs from higher organisms involves a nonprocessive mechanism comprised of multiple, independent cleavages with dissociation of degradation intermediates. A general model for protein degradation by the MPC is discussed.
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PMID:Lysozyme degradation by the bovine multicatalytic proteinase complex (proteasome): evidence for a nonprocessive mode of degradation. 1054 80

Subtilisin Carlsberg, an alkaline protease from Bacillus licheniformis, was modified with polyoxyethylene (PEG) or aerosol-OT (AOT), and the solubility, conformation, and catalytic activity of the modified subtilisins in some organic media were compared under the same conditions. The solubility of modified subtilisins depended on the solubility of the modifier. On the other hand, the conformational changes depended on the solubility, rather than the property, of the modifier. When the modified subtilisin was dissolved in water-miscible polar solvents such as dimethylsulfoxide, acetonitrile, and tetrahydrofuran, significant conformational changes occurred. When modified subtilisin was dissolved in water-immiscible organic solvents, such as isooctane and benzene, the solvent did not induce significant conformational changes. The catalytic activity in the transesterification reaction of the N-acetyl-L-phenylalanine ethylester of the modified subtilisin in organic solvents was higher than that of native subtilisin. The high activity of modified subtilisin was thought to be due to a homogeneous reaction by the dissolved enzymes.
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PMID:Catalytic activity and conformation of chemically modified subtilisin Carlsberg in organic media. 1057 97

Granuloma formation in response to mycobacterial infections is associated with increased expression of inducible nitric oxide synthase (NOS2) within granuloma macrophages and increased levels of nitrate/nitrite in the sera of infected mice. Continuous treatment with 5 mm or 10 mm l-N6-(1-imino-ethyl)-lysine (L-NIL), a selective NOS2-inhibitor, in acidified drinking water for up to 7 weeks consistently reduced infection-induced nitrate/nitrite to background levels in mycobacteria-infected BALB/c mice. Oral treatment with 5 mm L-NIL initiated at the time of infection significantly exacerbated growth of Mycobacterium tuberculosis, but had no effect on Mycobacterium avium colony-forming unit development in the liver, spleen and lungs of intravenously infected mice. In order to examine the role of nitric oxide in mycobacteria-induced granulomatous inflammation in the absence of any effect on the bacterial load, M. avium-infected mice were treated with 5 mm L-NIL from day 1 through 38 and the development of granulomatous lesions in the liver was assessed by histology, immunohistology and reverse-transcription-polymerase chain reaction (RT-PCR). Computer- and video-assisted morphometry performed at 4 and 7 weeks post-infection showed that treatment with L-NIL led to markedly increased number, cellularity and size of granulomatous lesions in infected mice regardless of the virulence of the M. avium isolate used for infection. Immunohistology of the liver revealed that in mice treated with L-NIL, the numbers of CD3+ T cells, CD21/35+ B cells, CD11b+ macrophages and RB6-8C5+ granulocytes associated with granulomatous lesions was increased. RT-PCR of the liver showed that in L-NIL-treated mice infected with M. avium, mRNA levels of tumour necrosis factor, interleukin-12p40, interferon-gamma, interleukin-10 and interferon-gamma-inducible protein-10 (IP-10) were up-regulated, while mRNA levels of interleukin-4, monocyte chemotactic protein-1 (MCP-1) and MCP-5 were similar to those in untreated control infected mice. When M. avium-infected mice were treated with 5 mm L-NIL between the 5th and 12th weeks of infection, similar changes in granuloma number and size were found in the absence of any effect on the bacterial load. These findings demonstrate that nitric oxide regulates the number, size and cellular composition of M. avium-induced granulomas independently of antibacterial effects by modulating the cytokine profile within infected tissues.
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PMID:NOS2-derived nitric oxide regulates the size, quantity and quality of granuloma formation in Mycobacterium avium-infected mice without affecting bacterial loads. 1058 88

Oxidative stress plays a major role in the early stage of acute pancreatitis. This study assessed the effects of N-acetylcysteine (NAC), a reduced glutathione (GSH) provider and a direct scavenger of reactive oxygen intermediates, in the course of acute pancreatitis in mice. Acute pancreatitis (AP) was induced by intraperitoneal (i.p.) injections of cerulein. Mice received NAC (1,000 mg/kg, i.p.) every 3 h, starting either 1 h before the first cerulein injection (prophylactic group) or 1 h after the first cerulein injection (therapeutic group), or i.p. saline injections for controls. Severity of AP was evaluated by histology, serum hydrolase levels, and serum and intrapancreatic levels of MCP-1 and interleukin 6 (IL-6). Pancreatic conjugated dienes and intrapancreatic and intrahepatic GSH levels were measured to assess the local and systemic oxidative processes. Acute pancreatitis was also induced with a CDE diet in controls and mice receiving either both NAC ad libidum in drinking water and 1,000 mg/kg i.p. injection once daily. The severity of pulmonary lesions was assessed by arterial blood gases (pO2) and intrapulmonary myeloperoxidase (MPO content) measurements as well as the survival of mice. The severity of cerulein-induced AP was significantly decreased in the prophylactic group compared with the therapeutic and control groups. Prophylactic administration of NAC also decreased the intrapancreatic levels of conjugated dienes compared with controls. The intrapancreatic and systemic release of MCP- 1 and IL-6 was also decreased in the prophylactic group 3 and 6 hours after AP induction. In addition, NAC pretreatment also reduced hepatic IL-6 production at 3 and 6 hours after starting cerulein challenge. In CDE-induced AP, the severity of lung injury (hypoxemia, MPO content) was decreased, and survival was improved by NAC. NAC administered in a prophylactic protocol limits the severity of experimental acute pancreatitis in mice, as well as its systemic complications and related mortality.
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PMID:N-acetylcysteine decreases severity of acute pancreatitis in mice. 1070 32


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