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)

The present experiments have employed microelectrode techniques (pH and PCO2) and microcalorimetry (total CO2 concentration) to define parameters of acidification in specific structures of the rat testis and epididymis during control conditions and after administration of the carbonic anhydrase inhibitor acetazolamide (20 or 50 mg/kg). Values for in situ pH during control conditions in seminiferous tubules (ST; 6.96 +/- 0.01), proximal caput (PCP; 6.62 +/- 0.01), middle caput (MCP; 6.59 +/- 0.01), middle corpus (MCR; 7.10 +/- 0.02), and proximal cauda epididymidis (PCD; 6.85 +/- 0.01) were significantly more acidic than in testicular artery (TA; 7.36 +/- 0.01) or systemic arterial blood (SAB; 7.40 +/- 0.01) and did not change significantly after acetazolamide. In situ partial pressure of CO2 (PCO2) in TA (52.2 +/- 0.6 mmHg), ST (52.3 +/- 0.4 mmHg), PCP (52.9 +/- 0.4 mmHg), MCP (53.0 +/- 0.7 mmHg), MCR (53.4 +/- 0.4 mmHg), and PCD (52.4 +/- 0.4 mmHg) were indistinguishable from each other, but all values were significantly higher than SAB PCO2 (39.2 +/- 0.5 mmHg). Acetazolamide increased in situ PCO2 significantly in all structures except the MCR. The total CO2 concentration in normal ST fluid (10.7 +/- 0.5 mM) was significantly higher than in "primary" fluid (6.9 +/- 0.3 mM), and both values were well below TA (26.9 +/- 1.3 mM) or SAB (24.6 +/- 0.4 mM) total CO2 concentrations. In the epididymis, total CO2 concentrations were indistinguishable and not different from the value in primary fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Direct evaluation of acidification by rat testis and epididymis: role of carbonic anhydrase. 210 57

The hypoxia-inducible factor 1 complex (HIF-1) is involved in the transcriptional activation of several genes, like erythropoietin and vascular endothelial growth factor, that are responsive to the lack of oxygen. The HIF-1 complex is composed of two b-HLH proteins: HIF-1beta that is constitutively expressed, and HIF-1alpha, that is present only in hypoxic cells. The HIF-1alpha subunit is continuously synthesized and degraded by the ubiquitin-proteasome under oxic conditions. Hypoxia, transition metals, iron chelators, and several antioxidants stabilize the HIF-1alpha protein, allowing the formation of the transcriptionally active HIF-1 complex. The mechanisms of oxygen sensing and the pathways leading to HIF-1alpha stabilization are unclear. Because the involvement of a heme protein oxygen sensor has been postulated, we tested the heme sensor hypothesis by using a luciferase-expressing cell line (B-1), that is highly responsive to hypoxia. Exposure of B-1 cells to carbon monoxide and heme synthesis inhibitors failed to show any effect on the hypoxia responsiveness of these cells, suggesting that heme proteins are not involved in hypoxia sensing. Measurement of iron in recombinantly expressed HIF-1alpha protein revealed that this protein binds iron in vivo. Iron binding was localized to a 129-amino acid peptide between sequences 529 and 658 of the HIF-1alpha protein. Although the exact structure of the iron center has not been yet defined, a 2:1 metal/protein molar ratio suggests a di-iron center, probably similar to the one found in hemerythrin. This finding is compatible with a model where redox reaction may occur directly in the iron center of the HIF-1alpha subunit, affecting its survival in oxic conditions.
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PMID:Hypoxia-inducible factor 1alpha (HIF-1alpha) is a non-heme iron protein. Implications for oxygen sensing. 1037 3

A growing number of physiologically relevant genes are regulated in response to changes in intracellular oxygen tension. It is likely that cells from a wide variety of tissues share a common mechanism of oxygen sensing and signal transduction leading to the activation of the transcription factor hypoxia-inducible factor 1 (HIF-1). Besides hypoxia, transition metals (Co2+, Ni2+ and Mn2+) and iron chelation also promote activation of HIF-1. Induction of HIF-1 by hypoxia is blocked by the heme ligands carbon monoxide and nitric oxide. There is growing, albeit indirect, evidence that the oxygen sensor is a flavoheme protein and that the signal transduction pathway involves changes in the level of intracellular reactive oxygen intermediates. The activation of HIF-1 by hypoxia depends upon signaling-dependent rescue of its alpha-subunit from oxygen-dependent degradation in the proteasome, allowing it to form a heterodimer with HIF-1beta (ARNT), which then translocates to the nucleus and impacts on the transcription of genes whose cis-acting elements contain cognate hypoxia response elements.
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PMID:Oxygen sensing and signaling: impact on the regulation of physiologically important genes. 1038 37

Mature green bananas were treated with the ethylene antagonist 1-methylcyclopropene (1-MCP) at intervals during the 24 h period after initiation of ripening with propylene. Following 1-MCP treatment, the fruits were ripened in either air or propylene while ethylene, carbon dioxide, and volatile production and composition were monitored at regular intervals. The application of 1-MCP significantly delayed and suppressed the onset and magnitude of fruit respiration and volatile production. The 1-MCP treatments also caused a quantitative change in the composition of the aroma volatiles, resulting in a substantial increase in the concentration of alcohols and a decrease in their related esters. The results showed that ethylene has a continuing role in integrating many of the biochemical processes that take place during the ripening of bananas.
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PMID:Relationships between respiration, ethylene, and aroma production in ripening banana. 1056 32

The effect of CO2 on ethylene-induced gummosis (secretion of polysaccharides), weight loss and respiration in tulip bulbs (Tulipa gesneriana L.) was investigated. A pretreatment with 1-MCP prevented these ethylene-induced effects, indicating that ethylene action must have been directed via the ethylene receptor. Treatment with 0.3 Pa ethylene for 2 days caused gummosis on 50% of the total number of bulbs of cultivar Apeldoorn, known to be sensitive for gummosis. Addition of CO2 (10 kPa) reduced the ethylene-induced gummosis to 18%. In a second experiment the influence of ethylene and CO2 on respiration and FW loss of bulbs of the cultivar Leen van der Mark was studied. A range of ethylene partial pressures (0.003-0.3 Pa) was applied continuously for 29 days. Ethylene caused a transient peak in O2 consumption rate during the first days after the start of application. The relation between O2 consumption rate and ethylene partial pressure could be described by Michaelis-Menten kinetics. Respiratory peaks were reduced by CO2. This inhibition by CO2 could not totally be due to competition with ethylene at the receptor binding-site, as was indicated by the use of an O2 consumption model. Pre-treatment of bulbs with 1-MCP and subsequent exposure to CO2 showed that CO2 could influence respiration irrespective of any interaction with ethylene. Ethylene and CO2 both stimulated weight loss. The effect of combined treatments of ethylene and CO2 on weight loss was at least as strong as the sum of the separate effects, which implies that competition between ethylene and CO2 at the receptor binding-site was unlikely.
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PMID:Carbon dioxide and ethylene interactions in tulip bulbs. 1190 80

Ethylene production in pear fruit was studied at 2 degrees C. Several observations showed that the inhibiting effect of CO2 on ethylene production did not operate only via the binding site of the ethylene binding protein. Ethylene production of freshly harvested pears was stimulated by 1-methylcyclopropene (1-MCP), but unaffected or inhibited by CO2 which points to different action sites for both molecules. In climacteric pears, where ethylene production was strongly inhibited by 1-MCP, a range of applied CO2 partial pressures was able to inhibit ethylene production further, to an extent similar to untreated pears. In the case of pears that had been stored for a period of 25 weeks, CO2 only had a clear effect after 1-MCP pretreatment. Respiration measurements showed that the effect of CO2 on ethylene production did not operate via an effect on respiration. Ethylene production models based on measurements of whole pears were used to study CO2 effects. Kinetic parameters derived from the models point to the conversion from ACC to ethylene by ACC oxidase as a possible action site for CO2 inhibition.
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PMID:Carbon dioxide action on ethylene biosynthesis of preclimacteric and climacteric pear fruit. 1273 Feb 72

Fresh raw milks, with low (3.1 x 10(4) cell/ml) and high (1.1 x 10(6) cells/ml) somatic cell count (SCC), were standardized to 3.25% fat, and from each a preserved (with 0.02% potassium dichromate) and an unpreserved portion were prepared. Subsamples of each portion were carbonated to contain 0 (control, pH 6.9) and 1500 (pH 6.2) ppm added CO2, and HCl acidified to pH 6.2 Milk pH was measured at 4 degrees C. For the preserved low- and high-SCC milks, two additional carbonation levels, 500 (pH 6.5) and 1000 (pH 6.3) ppm, were prepared. Milks were stored at 4 degrees C and analyzed on d 0, 7, 14, and 21 for microbial count, proteolysis, and lipolysis. The addition of 1500 ppm CO2, but not HCl, effectively delayed microbial growth at 4 degrees C. In general, in both the low- and high-SCC unpreserved milks, there was more proteolysis and lipolysis in control and HCl acidified milks than in milk with 1500 ppm added CO2. Higher levels of proteolysis and lipolysis in the unpreserved milks without added CO2 were related to higher bacteria counts in those milks. In preserved low- and high-SCC milks, microbial growth was inhibited, and proteolysis and lipolysis were caused by endogenous milk enzymes (e.g., plasmin and lipoprotein lipase). Compared with control, both milk with 1500 ppm added CO2 and milk with HCl acidification had less proteolysis. The effect of carbonation or acidification with HCl on proteolysis in preserved milks was more pronounced in the high SCC milk, probably due to its high endogenous protease activity. Plasmin is an alkaline protease and the reduction in milk pH by added CO2 or HCl explained the reduction in proteolysis. No effect of carbonation or acidification of milk on lipolysis was observed in the preserved low- and high-SCC milks. The CO2 addition to raw milk decreased proteolysis via at least two mechanisms: the reduction of microbial proteases due to a reduced microbial growth and the possible reduction of endogenous protease activity due to a lower milk pH. The effect of CO2 on lipolysis was mostly due to a reduced microbial growth. High-quality raw milk (i.e., low initial bacteria count and low SCC) with 1500 ppm added CO2 can be stored at 4 degrees C for 14 d with minimal proteolysis and lipolysis and with standard plate count < 3 x 10(5) cfu/ml.
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PMID:Effect of CO2 addition to raw milk on proteolysis and lipolysis at 4 degrees C. 1277 72

Genome sequence data of the cold-adapted archaeon, Methanococcoides burtonii, was linked to liquid chromatography-mass spectrometry analysis of the expressed-proteome to define the key biological processes functioning at 4 degrees C. 528 proteins ranging in pI from 3.5 to 13.2, and 3.5-230 kDa, were identified. 133 identities were for hypothetical proteins, and the analysis of these is described separately (Goodchild et al. manuscript in preparation). DNA replication and cell division involves eucaryotic-like histone and MC1-family DNA binding proteins, and 2 bacterial-like FtsZ proteins. Eucaryotic-like, core RNA polymerase machinery, a bacterial-like antiterminator, and numerous bacterial-like regulators enable transcription. Motility involves flagella synthesis regulated by a bacterial-like chemotaxis system. Lsmalpha and Lsmgamma were coexpressed raising the possibility of homo- and hetero-oligomeric complexes functioning in RNA processing. Expression of FKBP-type and cyclophilin-type peptidyl-prolyl cis-trans isomerases highlights the importance of protein folding, and novel characteristics of folding in the cold. Thirteen proteins from a superoperon system encoding proteasome and exosome subunits were expressed, supporting the functional interaction of transcription and translation pathways in archaea. Proteins involved in every step of methylotropic methanogenesis were identified. CO(2) appears to be fixed by a modified Calvin cycle, and by carbon monoxide dehydrogenase. Biosynthesis involves acetyl-CoA conversion to pyruvate by a non-oxidative pentose phosphate pathway, and gluconeogenesis for the conversion of pyruvate to carbohydrates. An incomplete TCA cycle may supply biosynthetic intermediates for amino acid biosynthesis. A novel finding was the expression of Tn11- and Tn12-family transposases, which has implications for genetic diversity and fitness of natural populations. Characteristics of the fundamental cellular processes inferred from the expressed-proteome highlight the evolutionary and functional complexity existing in this domain of life.
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PMID:Biology of the cold adapted archaeon, Methanococcoides burtonii determined by proteomics using liquid chromatography-tandem mass spectrometry. 1559 25

Metabolic acidosis, a common condition in patients with renal failure, may be linked to protein-energy malnutrition (PEM) and inflammation, together also known as malnutrition-inflammation complex syndrome (MICS). Methods of serum bicarbonate measurement may misrepresent the true bicarbonate level, since the total serum carbon dioxide measurement usually overestimates the serum bicarbonate concentration. Moreover, the air transportation of blood samples to distant laboratories may lead to erroneous readings. In patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD), a significant number of endocrine, musculoskeletal, and metabolic abnormalities are believed to result from acidemia. Metabolic acidosis may be related to PEM and MICS due to an increased protein catabolism, decreased protein synthesis, endocrine abnormalities including insulin resistance, decreased serum leptin level, and inflammation among individuals with renal failure. Evidence suggests that the catabolic effects of metabolic acidosis may result from an increased activity of the adenosine triphosphate (ATP)-dependent ubiquitin-proteasome and branched-chain keto acid dehydrogenase. In contrast to the metabolic studies, many epidemiologic studies in maintenance dialysis patients have indicated a paradoxically inverse association between mildly decreased serum bicarbonate and improved markers of protein-energy nutritional state. Hence metabolic acidosis may be considered as yet another element of the reverse epidemiology in ESRD patients. Interventional studies have yielded inconsistent results in CKD and ESRD patients, although in peritoneal dialysis patients, mitigating acidemia appears to more consistently improve nutritional status and reduce hospitalizations. Large-scale, prospective randomized interventional studies are needed to ascertain the potential benefits of correcting acidemia in malnourished and/or inflamed CKD and maintenance hemodialysis patients. Until then, all attempts should be made to adhere to the National Kidney Foundation Kidney Disease and Dialysis Outcome Quality Initiative guidelines to maintain a serum bicarbonate level in ESRD patients of at least 22 mEq/L.
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PMID:Metabolic acidosis and malnutrition-inflammation complex syndrome in chronic renal failure. 1566 May 76

In C4 photosynthesis, phosphoenolpyruvate carboxylase (PEPC) is the enzyme responsible for catalyzing the primary fixation of atmospheric CO2. The activity of PEPC is regulated diurnally by reversible phosphorylation. PEPC kinase (PEPCk), a protein kinase involved in this phosphorylation, is highly specific for PEPC and consists of only the core domain of protein kinase. Owing to its extremely low abundance in cells, analysis of its regulatory mechanism at the protein level has been difficult. Here we employed a transient expression system using maize mesophyll protoplasts. The PEPCk protein with a FLAG tag could be expressed correctly and detected with high sensitivity. Rapid degradation of PEPCk protein was confirmed and shown to be blocked by MG132, a 26S proteasome inhibitor. Furthermore, MG132 enhanced accumulation of PEPCk with increased molecular sizes at about 8 kDa intervals. Using anti-ubiquitin antibody, this increase was shown to be due to ubiquitination. This is the first report to show the involvement of the ubiquitin-proteasome pathway in PEPCk turnover. The occurrence of PEPCks with higher molecular sizes, which was noted previously with cell extracts from various plants, was also suggested to be due to ubiquitination of native PEPCk.
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PMID:The ubiquitin-proteasome pathway is involved in rapid degradation of phosphoenolpyruvate carboxylase kinase for C4 photosynthesis. 1569 55


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