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)

Acetylcholine stimulates aldosterone secretion in bovine glomerulosa cells in vitro via specific cholinergic receptors. In this study we examined the effect of peripheral muscarinic blockade with atropine on metoclopramide-, angiotensin-II-, and ACTH-stimulated aldosterone secretion in man. Atropine (0.6 mg, iv) administered 10 min before MCP delayed the onset of the plasma aldosterone response and attenuated the mean peak response from 502 +/- 103 (+/- SE) to 322 +/- 72 pmol/L (P less than 0.05) without affecting zero time mean plasma aldosterone levels (144 +/- 28 vs. 136 +/- 36 pmol/L for control and atropine, respectively). This inhibitory effect was not mediated by changes in PRA or plasma potassium or ACTH (as reflected by cortisol) concentrations. Atropine also attenuated the plasma aldosterone response to a low dose angiotensin II infusion (2 ng/kg.min; control, 449 +/- 99 pmol/L; atropine, 297 +/- 78 pmol/L; P less than 0.05). In contrast, atropine had no effect on the plasma aldosterone response to a bolus dose (250 micrograms) of ACTH. Neither atropine (0.6 mg, iv) nor the cholinergic muscarinic agonist bethanechol (5 mg, sc) alone elicited a change in plasma aldosterone. Collectively, these data provide evidence for cholinergic modulation of aldosterone secretion in man. We conclude that cholinergic mechanisms may facilitate the aldosterone responses to angiotensin-II and metoclopramide, but not to ACTH.
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PMID:Evidence for cholinergic modulation of aldosterone secretion in man. 256 95

Protein synthesis and degradation and net uptake and release of amino acids and minerals were examined in the perfused hemicorpus of bilaterally nephrectomized and sham-operated control rats. Animals were studied 30 h after surgery. In comparison with controls, uremic rats had greater urea N appearance (net urea generation) and lower plasma and muscle concentrations of most amino acids. Muscle protein synthesis was not altered, but protein degradation was greater in uremic versus sham rats. There was greater net release of phenylalanine, tyrosine, alanine, total nonessential amino acids, total amino acids, potassium, and phosphorus from the perfused hemicorpus of uremic rats and greater release of citrulline from sham rats. ATP, creatine phosphate, cAMP, and activities of cathepsin B1, cathepsin D, and alkaline protease were not different in muscles of the uremic versus sham rats. Thus, in acutely uremic rats there is increased protein wasting in the hemicorpus due to enhanced protein degradation. The enhanced protein degradation does not appear to be due to increased muscle cathepsin B1, cathepsin D, or alkaline protease activities.
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PMID:Protein and amino acid metabolism in posterior hemicorpus of acutely uremic rats. 630 4

Protein synthesis and degradation and net uptake and release of amino acids and minerals were investigated in the perfused hemicorpus of acutely uremic and control Sprague-Dawley rats. Rats underwent bilateral nephrectomy or sham surgery and were studied 30 hr after surgery. The uremic rats displayed greater urea N appearance (net urea generation), lower plasma and muscle concentrations of most amino acids, and increased muscle protein degradation as compared to control rats. Muscle protein synthesis was slightly but not significantly decreased in the uremic animals. There was greater net release of phenylalanine, tyrosine, alanine, total nonessential amino acids, total amino acids, potassium and phosphorus from the perfused hemicorpus of uremic rats and greater release of citrulline from sham rats. Muscle ATP, creatine phosphate, cyclic-AMP, and activities of cathepsin B1, cathepsin D, and alkaline protease were not different in the uremic and sham rats. These data provide evidence that acutely uremic rats sustain increased muscle protein wasting which is due to enhanced protein degradation. The increased protein degradation does not appear to be due to enhanced activities of muscle cathepsin B1, cathepsin D or alkaline protease.
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PMID:Enhanced muscle protein degradation and amino acid release from the hemicorpus of acutely uremic rats. 636 19

The effect on the electrolyte balance of a dopaminergic agonist (bromocriptine) and an antagonist (metoclopramide) and their effect on renal aldosterone and kallikrein excretion were investigated. Ten normotensive Wistar rats and ten spontaneously hypertensive rats (SHR-Wistar Kioto) were treated with BCR (4 mg/Kg weight b.i.d.) for 4 days; after a week of pharmacological wash-out they received MCP (0,5 mg/Kg weight b.i.d.) for 4 days. Before and after treatment and at the 2nd and 4th day of each treatment diuresis, urinary excretion of aldosterone, kallikrein, sodium, potassium and proteins were measured. During the 24-hour urine collections the rats were kept in separate metabolic cages with free access to food and water. Kallikrein urinary excretion was lower in SHR than in normotensive rats under basal conditions (p 0.05); urinary sodium, potassium, proteins and sodium/potassium rate were also reduced in SHR. After treatment with bromocriptine a further reduction in urinary kallikrein excretion was observed in SHR. After MCP all the parameters were unchanged both in normotensive rats and in SHR, but SHR showed a significant correlation between aldosterone and kallikrein excretion (p less than 0,001); in this condition it seems that in SHR the control exerted by aldosterone on kallikrein excretion is greater than the one exerted by dopamine. It may indicate a defect of the natriuretic and vasodilator dopaminergic system in spontaneously hypertensive rats.
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PMID:[The effect of dopaminergic stimulation and inhibition on the urinary excretion of aldosterone and kallikrein in spontaneously hypertensive rats]. 655 80

Protein synthesis and degradation and net uptake and release of amino acids and minerals were investigated in the perfused hemicorpus of acutely uremic and sham-operated control Sprague-Dawley rats. Rats underwent bilateral nephrectomy or sham surgery and were studied 30 hours after surgery. The uremic rats displayed greater urea nitrogen appearance (net urea generation), lower plasma and muscle intracellular concentrations of most amino acids, and increased protein degradation in the hemicorpus as compared with control animals. Muscle protein synthesis was slightly but not significantly decreased in the uremic animals as compared with controls. There was greater net release of phenylalanine, tyrosine, alanine, total nonessential amino acids, total amino acids, potassium, and phosphorus from the perfused hemicorpus of uremic rats and greater release of citrulline from sham rats. Muscle ATP, creatine phosphate, and cyclic AMP, and muscle cathepsin B1, cathepsin D, and alkaline protease activities were not different in the uremic and control rats. These data provide evidence that acutely uremic rats have increased muscle protein wasting which is due to enhanced protein degradation. The cause of the increased muscle protein degradation is unknown.
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PMID:Effect of acute uremia on protein degradation and amino acid release in the rat hemicorpus. 658 68

It has previously been demonstrated in our laboratory that patients with pseudohypoparathyroidism (PsHP) have impaired PRL responses to TRH and chlorpromazine. We have also observed that these patients have low basal plasma renin activity (PRA) and decreased aldosterone responses to upright posture and isometric handgrip exercise. Since inhibitory dopaminergic modulation of PRL and aldosterone is well established, we have examined whether PsHP is associated with altered dopaminergic inhibition of PRL and aldosterone secretion. To investigate this possibility, we compared the plasma PRL, aldosterone, and PRA responses to the dopamine antagonist metoclopramide (MCP; 10 mg iv) in seven normocalcemic PsHP patients and twelve normal controls. These patients were on no medications except calcium and vitamin D for 2 weeks; they were maintained on a diet containing 50 meq of sodium and 80 meq of potassium for 5 days. Although basal PRL levels were similar in the two groups of subjects, the maximal incremental PRL response in PsHP patients (38.7 +/- 12.6 ng/ml) was less (P less than 0.01) than in normal subjects (61.6 +/- 9.6 ng/ml). Basal supine plasma aldosterone was less (P less than 0.01) in PsHP patients (8.0 +/- 1.1 ng/dl) than in normal subjects (13.4 +/- 2.1 ng/dl). Maximum incremental aldosterone response to MCP (8.7 +/- 1.9 ng/dl) in PsHP patients was also less (P less than 0.01) than in normal subjects (13.4 +/- 2.1 ng/dl). Basal supine PRA was lower (P less than 0.05) in PsHP patients (1.3 +/- 0.3 ng/ml.h) than in normal subjects (2.8 +/- 0.4 ng/ml.h). However, the PRA responses to MCP were similar in both groups. Tonic dopaminergic inhibition of PRL and aldosterone secretion, but not renin secretion, appears to be less pronounced in PsHP patients. This is the first disease state in which reduced aldosterone responses to dopamine antoganism have been observed. Decreased PRL and aldosterone responses to MCP may reflect decreased ambient dopamine levels and/or a reduction in dopamine receptor number or binding affinity.
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PMID:Altered dopaminergic modulation of prolactin and aldosterone secretion in pseudohypoparathyroidism. 701 87

When an effective concentration of doxorubicin (DXR) was added into L1210 of a mouse leukemia cell line, DXR was rapidly distributed much more in the nuclei than in the other organelle within a few minutes. A [14C]DXR-binding fraction was obtained from the cytosol prepared from L1210 cells. The fraction was adsorbed to hydroxylapatite matrix and eluted from the matrix by 50-150 mM potassium phosphate buffer. The fraction showed high DXR-binding and Suc-Leu-Leu-Val-Tyr-MCA-degrading activity. The binding of [14C]DXR was inhibited by unlabeled DXR. Gel chromatography of the fraction with Sephacryl S-300 separated two fractions of high molecular weight (Peak I, approx. 750 kDa) and low molecular weight (Peak II). Peak I showed proteolytic activity. [14C]DXR-binding Peak I had much higher affinity to DNA-cellulose than [14C]DXR-binding Peak II. [14C]DXR-Peak I complex also was retained into the nuclei isolated from L1210 cells, temperature-dependently. These results suggest that a specific carrier to translocate DXR from cytoplasm into nucleus exists in L1210 cell and the carrier is proteasome.
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PMID:Proteasome is a carrier to translocate doxorubicin from cytoplasm into nucleus. 960 Mar 27

1. The effects of mechanical clot removal during early surgery on pharmacological cerebrovascular reactivity after subarachnoid haemorrhage (SAH) were investigated in the monkey. 2. Contractions to potassium chloride, 5-hydroxytryptamine and noradrenaline in rings of proximal parts of middle cerebral arteries (MCP), surrounded with clot, and basilar arteries (BAP), far from the clot, were examined 7 days after SAH, in which an autologous blood clot was bilaterally placed around major cerebral arteries. 3. Compared with the sham-operated group, contractions in the clot removal groups at 48 and 72 h after SAH were reduced in MCP and enhanced in BAP. 4. These results suggest that divergent vascular contractility may occur according to the distance between artery and clot if the clot is removed later than 48 h after SAH.
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PMID:Cerebrovascular contractility after clot removal in monkey subarachnoid haemorrhage. 1038 44

We investigated the potential role of the ubiquitin proteolytic system in the death of cerebellar granule neurons induced by reduction of extracellular potassium. Inhibitors of proteasomal function block apoptosis if administered at onset of this process, but they do not exert such effect when added 2-3 hr later. The same inhibitors also prevent caspase-3 activity and calpain-caspase-3-mediated processing of tau protein, suggesting that proteasomes are involved upstream of the caspase activation. Although the proteasomes seem to play an early primary role in programmed cell death, we found that with progression of apoptosis, during the execution phase, a perturbation in normal ubiquitin-proteasome function occurs, and high levels of ubiquitinated proteins accumulate in the cytoplasm of dying cells. Such accumulation correlates with a progressive decline of proteasome chymotrypsin and trypsin-like activities and, to a lower extent, of postacidic-like activity. Both intracytoplasmic accumulation of ubiquitinated proteins and decline of proteasome function are reversed by the pan-caspase inhibitor Z-VAD-fmk. The decline in proteasome function is accompanied by, and likely attributable to, a marked and progressive decline of deubiquitinating activities. The finding that the proteasomes are early involved in apoptosis and that ubiquitinated proteins accumulate during this process prospect granule neurons as a model system aimed at correlating these events with neurodegenerative diseases.
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PMID:Proteasome involvement and accumulation of ubiquitinated proteins in cerebellar granule neurons undergoing apoptosis. 1063 88

The basic treatment of leishmaniasis consists in the administration of pentavalent antimonials. The mechanisms that contribute to pentavalent antimonial toxicity against the intracellular stage of the parasite (i.e., amastigote) are still unknown. In this study, the combined use of several techniques including DNA fragmentation assay and in situ and cytofluorometry terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling methods and YOPRO-1 staining allowed us to demonstrate that potassium antimonyl tartrate, an Sb(III)-containing drug, was able to induce cell death associated with DNA fragmentation in axenic amastigotes of Leishmania infantum at low concentrations (10 microg/ml). This observation was in close correlation with the toxicity of Sb(III) species against axenic amastigotes (50% inhibitory concentration of 4.75 microg/ml). Despite some similarities to apoptosis, nuclease activation was not a consequence of caspase-1, caspase-3, calpain, cysteine protease, or proteasome activation. Altogether, our results demonstrate that the antileishmanial toxicity of Sb(III) antimonials is associated with parasite oligonucleosomal DNA fragmentation, indicative of the occurrence of late events in the overall process of apoptosis. The elucidation of the biochemical pathways leading to cell death could allow the isolation of new therapeutic targets.
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PMID:Antimonial-mediated DNA fragmentation in Leishmania infantum amastigotes. 1140 24


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