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)

Fifty-three persons occupied in a municipal waste incinerator were examined with respect to their internal exposure to organic substances which may be produced during pyrolysis of organic matter. For this purpose the levels of benzene in blood, polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) in plasma, and mono- (MCPs), di- (DCPs), tri- (TCPs), tetra- (TCEPs) and pentachlorophenol (PCP) and hydroxypyrene in urine were determined. For control purposes, 431 men and women were examined. Significantly higher values for the workers were found for the excretion of hydroxypyrene [median (m): 0.24 vs 0.11 microgram/l; non-smokers], 2,4/2,5-DCP (m: 10.5 vs 3.9 micrograms/l) and 2,4,5-TCP (m: 1.2 vs 0.8 micrograms/l) and for the HCB level in plasma (m: 4.4 vs 2.8 micrograms/l). For the concentrations of 4-MCP and 2,3,4,6/2,3,5,6-TECP, the controls had significantly higher concentrations in urine than did the workers in the incineration plant (m: 4-MCP 1.7 vs 1.2; 2,3,4,6/2,3,5,6-TECP: 1.2 vs 0.3 micrograms/l). No significant differences between workers and controls were detected with respect to benzene in blood (m: 0.20 vs 0.28 microgram/l; non-smokers), 2,4,6-TCP and PCPs in urine (m: 0.85 vs 0.60 and 2.2 vs 2.2 micrograms/l) or the levels of PCB congeners in plasma (m: sigma 138, 153, 180: 5.6 vs 4.1 micrograms/l). The elevated levels of hydroxypyrene, 2,4/2,5-DCP, 2,4,5-TCP and HCB in biological material may be related to the incineration of the waste. These elevations, however, are very small and are of interest more from the environmental than from the occupational point of view.
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PMID:Internal exposure to organic substances in a municipal waste incinerator. 146 96

We have previously described biological model systems for studying tumor suppression in which, by using H-1 parvovirus as a selective agent, cells with a strongly suppressed malignant phenotype (KS or US) were derived from malignant cell lines (K562 or U937). By using cDNA display on the K562/KS cells, 15 cDNAs were now isolated, corresponding to genes differentially regulated in tumor suppression. Of these, TSAP9 corresponds to a TCP-1 chaperonin, TSAP13 to a regulatory proteasome subunit, and TSAP21 to syntaxin 11, a vesicular trafficking molecule. The 15 cDNAs were used as a molecular fingerprint in different tumor-suppression models. We found that a similar pattern of differential regulation is shared by activation of p53, p21(Waf1), and the human homologue of Drosophila seven in absentia, SIAH-1. Because SIAH-1 is differentially expressed in the various models, we characterized it at the protein and functional levels. The 32-kDa, mainly nuclear protein encoded by SIAH-1, can induce apoptosis and promote tumor suppression. These results suggest the existence of a common mechanism of tumor suppression and apoptosis shared by p53, p21(Waf1), and SIAH-1 and involving regulation of the cellular machinery responsible for protein folding, unfolding, and trafficking.
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PMID:SIAH-1 promotes apoptosis and tumor suppression through a network involving the regulation of protein folding, unfolding, and trafficking: identification of common effectors with p53 and p21(Waf1). 1039 49

Bioremediation of consecutive spills of phenol, 2-chlorophenol (2-MCP), 2,4,6-trichlorophenol (2,4,6-TCP) and pentachlororphenol as single pollutants was investigated in eight pilot plant scale sand columns system (100 cm l, 6 cm ID), simulating the conditions, which could be created in the saturated zone of a pristine aquifer following an accidental spill. Bioremediation in this study consisted of re-circulating local groundwater through the polluted site in a controlled manner following a closed-loop configuration. Intrinsic microbial development was enhanced by adding the necessary nutrients. Consecutive accidental spills of 480-mg phenol/kg soil; 140-mg 2-MCP/kg; 14-mg 2,4,6-TCP/kg soil and 17-mg pentachlorophenol (PCP)/kg soil under saturated conditions and a continuous specific discharge of 0.56 cm min(-1) were simulated. Degradation curves demonstrated first-order kinetics. Biodegradation rates (k1) were influenced by consecutive exposures. Calculated rate constants for biodegradation for sole substrate experiments were in the range of 0.06-0.15 day(-1), 0.21-1.20 day(-1), 0.04-2.28 day(-1) and 0.01-0.03 day(-1) for phenol, 2-MCP, 2,4,6-TCP and PCP, respectively. The acclimation of the aquifer to simulated consecutive accidental spills was found to be directly proportional to the cumulative load of each single chlorophenol. A relationship between the octanol water partitioning (Kow) values and the experimental degradation rates (k1) was found.
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PMID:Simulation of bioremediation of chlorophenols in a sandy aquifer. 1246 6

Chlorophenols, mainly used as biocides, are compounds with a wide spectrum of toxic effects, including teratogenic and carcinogenic actions. The aim of this study was to examine possible 4-monochlorophenol (4-MCP) toxicity related to metabolic pathways, which may implicate semiquinones and reactive oxygen species (ROS), in human Hep G2 cells. The effects of 4-MCP were performed through cytotoxicity assays (viability, ATP level), metabolic activities (4-MCP intracellular concentration, NADPH cytochrome P-450 reductase (Cyt P-450 red.) and glutathione-S-transferase activities, CYP 3A7 mRNA expression) and oxidative stress (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities, glutathione status, malondialdehyde concentration, CYP 2E1 mRNA expression). According to the literature, in this work Hep G2 cells were incubated in the continuous presence of 4-MCP at 350 microM over 24 or 48 h. Results showed statistically significant decreases in ATP levels (24 or 48 h, P < 0.05) versus controls. The 4-MCP intracellular concentrations increased as early as 8-24 h and then decreased (P < 0.01). Decreases in Cyt. P-450 red. (24 h, P < 0.05), catalase (24 h, P < 0.05; 48 h, P < 0.01), glutathione peroxidase activities (48 h, P < 0.05) and reduced glutathione concentrations (48 h, P < 0.05) were observed. In addition, exposure to 4-MCP increased mRNA expressions of CYP 3A7 (24 h, P < 0.05; 48 h, P < 0.01) and CYP 2E1 (24 h, P < 0.01) versus controls. Taken together, these results suggest that 4-MCP metabolites could induce oxidative stress conditions in Hep G2 cells.
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PMID:Involvement of oxidative sress in the toxicity of 4-monochlorophenol in Hep G2 cells in culture. 1266 55

The equilibrium and kinetics of chlorophenol (CP) sorption by chitosan, poly D-glucosamine, were studied under simulated groundwater conditions. Lower temperature, from 25 degrees C to 15 degrees C and then 5 degrees C, markedly decreased the adsorption rates by a factor of 30-53% and 7-22%. Comparison between two types of chitosan, flakes and highly swollen beads, demonstrated that the maximum pentachlorophenol (PCP) uptake capacities in Langmuir and Freundlich models depend on the specific surface area of the particle. Low temperature (5 degrees C) significantly increased the PCP uptake capacity in comparison to higher temperatures (15 degrees C and 25 degrees C). PCP uptake capacity was halved at pH levels higher than 6.5, and NaCl concentrations greater than 1% blocked PCP sorption almost completely. Of five kinds of chlorophenols, i.e. 2,4,6-trichlorophenol (2,4,6-TCP), 3,4-dichlorophenol (3,4-DCP), 2,3-dichlorophenol (2,3-DCP), 2,6-dichlorophenol (2,6-DCP), 3-monochlorophenol (3-MCP), TCP had the maximum sorption efficiency on flake-type chitosan, followed by DCPs, and finally MCP (the three kinds of DCP, with the same elemental compositions, achieved similar sorption performances).
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PMID:Removal of chlorophenols from groundwater by chitosan sorption. 1560 85

Previously, we used cDNA microarrays to demonstrate that the phosphatidylinositol and MAP kinase signaling pathways are regulated by nicotine in different rat brain regions. In the present report, we show that, after exposure to nicotine for 14 days, ubiquitin, ubiquitin-conjugating enzymes, 20S and 19S proteasomal subunits, and chaperonin-containing TCP-1 protein (CCT) complex members are upregulated in rat prefrontal cortex (PFC) while being downregulated in the medial basal hypothalamus (MBH). In particular, relative to saline controls, ubiquitins B and C were upregulated by 33% and 47% (P<0.01), respectively, in the PFC. The proteasome beta subunit 1 (PSMB1) and 26S ATPase 3 (PSMC3) genes were upregulated in the PFC by 95% and 119% (P<0.001), respectively. In addition to the protein degradation pathway of the ubiquitin-proteasome complexes, we observed in the PFC an increase in the expression of small, ubiquitin-related modifiers (SUMO) 1 and 2 by 80% and 33%, respectively (P<0.001), and in 3 of 6 CCT subunits by up to 150% (P<0.0001). To a lesser extent, a change in the opposite direction was obtained in the expression of the same gene families in the MBH. Quantitative real-time RT-PCR was used to validate the microarray results obtained with some representative genes involved in these pathways. Taken together, our results suggest that, in response to systemic nicotine administration, the ubiquitin-proteasome, SUMO, and chaperonin complexes provide an intricate control mechanism to maintain cellular homeostasis, possibly by regulating the composition and signaling of target neurons in a region-specific manner.
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PMID:Nicotine coregulates multiple pathways involved in protein modification/degradation in rat brain. 1558 57

Proteome analysis of human umbilical endothelial cells was performed to identify proteins that are modified during vascular endothelial cell growth factor (VEGF)-induced transition from the quiescent into the proliferating-migrative phenotype. Subtractive analysis of two-dimensional gel patterns of human endothelial cells, before and after stimulation with VEGF(165), revealed differences in 85 protein spots. All proteins were identified by peptide sequencing and peptide mass fingerprinting using an electrospray spectrometer. The proteins identified were members of specific families including Ca(2+)-binding proteins, fatty-acid binding proteins, structural proteins, and chaperones. Remarkably, there was a massive activation of cellular machinery for both protein synthesis and protein degradation. Thus, among up-regulated proteins there were members of all groups of heat shock proteins (HSPs; HSP 27, HSP 60, HSP 70p5, HSP 70p8, HSP 90, and HSP 96) and some other proteins showing either chaperone activity or which participate in assembly of multimolecular structures (TCP-1, desmoplakins, junction plakoglobin, GRP 94, thioredoxin related protein, and peptidylprolyl isomerase). The increased expression of HSPs was confirmed at the mRNA level at different stages of treatment with VEGF. Similarly, components of the proteolytic machinery for the degradation of misfolded proteins (ER-60, cathepsin D, proteasome subunits, and protease inhibitor 6) were also up-regulated. On the other hand, changes in the expression of structural proteins (T-plastin, vimentin, alpha tubulin, actin, and myosin) could account, at least in part, for the different morphologies displayed by migrating endothelial cells. In summary, our data show that VEGF levels similar to those during physiological stresses induce a number of genes and multiple endogenous pathways seem to be engaged in restoring cellular homeostasis. To ensure cell survival, the molecular chaperones (the heat shock family of stress proteins) are highly up-regulated providing protein-folding machinery to repair or degrade misfolded proteins.
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PMID:Heat shock proteins and other components of cellular machinery for protein synthesis are up-regulated in vascular endothelial cell growth factor-activated human endothelial cells. 1576 53

Proteasomes are large, multi-subunit particles that act as the proteolytic machinery for most of the regulated intracellular protein degradation in eukaryotic cells. An alteration of proteasome function may be important for the regulation of the meiotic cell cycle. To study the change at the subunit level of the 26S proteasome during meiotic maturation, we purified 26S proteasomes from immature and mature oocytes of goldfish. Two-dimensional polyacrylamide gel electrophoresis was used to separate proteins. For differential analysis, whole spots of the 26S proteasome from goldfish oocytes were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and database analysis. Four spots that were different (only detected in mature oocyte 265 proteasomes and not in immature ones) and four protein spots that were up- or down-regulated were identified unambiguously. The mature-specific spots were not 26S proteasome components but rather their interacting proteins, and were identified as chaperonin-containing TCP-1 subunits and myosin light chain. Minor spots of three subunits of the 20S core particle and one of the 19S regulatory particle showed meiotic cell cycle-dependent changes. These results demonstrate that modifications of proteasomal subunits and cell cycle phase-dependent interactions of proteins with proteasomes occur during oocyte maturation in goldfish.
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PMID:Comparative proteome analysis of changes in the 26S proteasome during oocyte maturation in goldfish. 1679 28

Glutamine behaves as a key nutrient for tumors and rapidly dividing cells. Glutaminase is the main glutamine-utilizing enzyme in these cells, and its activity correlates with glutamine consumption and growth rate. We have carried out the antisense L-type glutaminase inhibition in human MCF7 breast cancer cells, in order to study its effect on the hexosamine pathway and the pattern of protein O-glycosylation. The antisense mRNA glutaminase expressing cells, named ORF19, presented a 50% lower proliferation rate than parental cells, showing a more differentiated phenotype. ORF19 cells had an 80% reduction in glutamine:fructose-6-P amidotransferase activity, which is the rate-limiting step of the hexosamine pathway. Although the overall cellular protein O-glycosylation did not change, the O-glycosylation status of several key proteins was altered. O-glycosylation of O-GlcNAc transferase (OGT), the enzyme that links N-acetylglucosamine to proteins, was fivefold lower in ORF19 than in wild type cells. Inhibition of glutaminase also provoked a 10-fold increase in Sp1 expression, and a significant decrease in the ratio of O-glycosylated to total protein for both Sp1 and the Rpt2 proteasome component. These changes were accompanied by a higher Sp1 transcriptional activity. Proteome analysis of O-glycosylated proteins permitted the detection of two new OGT target proteins: the chaperonin TCP-1 theta and the oncogene Ets-related protein isoform 7. Taken together, our results support the hexosamine pathway and the O-glycosylation of proteins being a sensor mechanism of the nutritional and energetic states of the cell.
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PMID:Antisense glutaminase inhibition modifies the O-GlcNAc pattern and flux through the hexosamine pathway in breast cancer cells. 1761 51

Proteomic profiling of the mouse spermatozoon has generated a unique and valuable inventory of candidates that can be mined for potential contraceptive targets and to further our understanding of the PTMs that regulate the functionality of this highly specialized cell. Here we report the identification of 858 proteins derived from mouse spermatozoa, 23 of which demonstrated testis only expression. The list contained many proteins that are known constituents of murine spermatozoa including Izumo, Spaca 1, 3, and 5, Spam 1, Zonadhesin, Spesp1, Smcp, Spata 6, 18, and 19, Zp3r, Zpbp 1 and 2, Spa17, Spag 6, 16, and 17, CatSper4, Acr, Cylc2, Odf1 and 2, Acrbp, and Acrv1. Certain protein families were highly represented in the proteome. For example, of the 42 gene products classified as proteases, 26 belonged to the 26S-proteasome. Of the many chaperones identified in this proteome, eight proteins with a TCP-1 domain were found, as were seven Rab guanosine triphosphatases. Finally, our list yielded three putative seven-transmembrane proteins, two of which have no known tissue distribution, an extragenomic progesterone receptor and three unique testis-specific kinases all of which may have some potential in the future regulation of male fertility.
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PMID:The mouse sperm proteome characterized via IPG strip prefractionation and LC-MS/MS identification. 1834 Jun 33


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