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:3.4.23.5 (cathepsin D)
4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Impairments of protein metabolism, expressed as predominance of catabolism over anabolism and hypoproteinemia, were observed in one month old rats with experimental burns of the IIIA-IIIB degree, when 20-25% of a body surface was impaired. After administration of steroid drugs (retabolyl at a dose of 1 mg/100 g of body mass or oxymetacyl--4-methyl-5-oxyuracil---at a dose of 5 mg/100 g of body mass) content of protein and urea normalized in blood serum, activity of cathepsin D decreased in tissues, the rate of 35S-methionine incorporation into tissue proteins increased. The pyrimidine derivative oxymetacyl exhibited higher effect on protein metabolism in burns of preadolescent rats as compared with retabolyl.
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PMID:[Effect of retabolyl and oxymetacyl on protein metabolism in experimental burns in immature rats]. 344 45

Cathepsin D in serum of women in labour, retroplacental blood and newborn's blood degradate hemoglobine denatured with urea and the serum protein most intensively in pH 3,5. The denatured protein is more liable to cathepsin D activity than the serum protein. Cathepsin D of the retroplacental blood serum shows the highest activity, the activity in the blood serum of women in labour is lower and it is the lowest in the newborn's blood.
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PMID:[Cathepsin D activity in the blood serum of patients in labor and in the serum of extraplacental and neonatal blood]. 368 72

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

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

Attempts were made to assess the role of thiols and to determine the cathepsins involved in the degradation of serum albumin in mouse liver and kidney lysosomes. Unlike cysteine or beta-mercaptoethanol, reduced glutathione (GSH) did not stimulate the degradation of formaldehyde-treated albumin in liver lysosomes, suggesting that the tripeptide did not penetrate the membrane. However, GSH was a much more effective stimulant of proteolysis in kidney lysosomes than was cysteine at low concentrations, and the effect was saturable at 1-2 mM concentrations. Thiols did not stimulate proteolysis in lysosomes when the disulphide bonds of albumin were reduced and alkylated, suggesting that the stimulatory effects were solely due to disulphide-bond reduction in protein substrates. Results obtained with thiols and iodoacetamide suggested that albumins denatured by disulphide-bond reduction and alkylation, disulphide-bond reduction without alkylation, or by treatment with 8 M-urea, were all degraded primarily by cathepsin D in lysosomes, but formaldehyde-denatured albumin was attacked by thiol proteinases. These findings correlated well with studies on the degradation of these proteins by rat liver lysosome (tritosome) extracts. Studies with the proteinase inhibitors leupeptin and pepstatin and the stimulatory effects of thiols in these extracts suggested that formaldehyde-denatured albumin was degraded primarily by the thiol proteinases, but that native albumin or albumins denatured by disulphide-bond reduction or by treatment with 8 M-urea were attacked by cathepsin D. Denaturation of serum albumin by any of the methods used caused a shift in the pH optimum of albumin catabolism by tritosome extracts or by purified cathepsin D from approx. 3-4 to 5-6. These results were discussed in terms of a possible mechanism for the catabolic aspect of serum albumin turnover.
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PMID:Role of thiols, pH and cathepsin D in the lysosomal catabolism of serum albumin. 672 34

Circular dichroism spectra, thermal transition profiles and proteolytic susceptibility showed that different regions in the multidomain protein fibronectin exhibit different sensitivity against urea denaturation. A 70-kDa fragment obtained by cathepsin D treatment which comprises the N-terminal part of the fibronectin chains, exhibited in 8M urea a spectrum, at 20 degrees C, identical to that of the native fragment and its thermal unfolding was shifted to lower temperatures by only 10 degrees C. The central portions of the fibronectin chains were remarkably unfolded under the same conditions as clearly demonstrated by the spectra and transition profiles of a cathepsin D-raised 125/140-kDa fragment which originates from this region. When fibronectin or its fragments were exposed to 4 or 8M urea at 4 degrees C and the urea subsequently dialysed off, the spectra and transition curves recorded were very similar to those of the native proteins. Nevertheless, this treatment introduced local conformational changes which resulted in the creation of three new cleavage sites for chymotrypsin. The most prominent one was found to be located in the central part of the middle region and no sites were created in the N-terminal 70-kDa region. In the conjunction with sequence information [Petersen et al. (1983) Proc. Natl. Acad. Sci. USA 80, 137-141] it may be concluded that the disulfide rich domains, made up by regions of internal homology of types I and II in the N-terminal portion of fibronectin, exhibit a remarkable conformational stability, whereas the disulfide free middle region which contains type III domains, is much less stable. Some domains in this region are particularly sensitive to urea denaturation and are irreversibly affected already by 4M urea at 4 degrees C. Therefore, the use of high urea concentrations for the elution of fibronectin from affinity columns may lead to an at least partially irreversible unfolding of some domains and a loss of functions associated with these structural elements.
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PMID:Discrimination of different domains in fibronectin on the basis of their stability against urea denaturation. 687 82

We have obtained evidence of thiol endopeptidases in the thyroid which are active in thyroglobulin degradation in vitro. Four pepstatin-insensitive endopeptidase fractions were distinguished in extracts of rabbit thyroids by gel filtration on Bio-Gel A-0.5m. An enzyme from one fraction was obtained in highly purified form and was found to be identical to cathepsin B described in other tissues. Endopeptidases in the three remaining fractions were designated as cathepsins 180K, 110K, and 45K, respectively, on the basis of their estimated molecular size. These were partially purified by either organomercurial affinity chromatography or DEAE-cellulose chromatography. They are identified as thiol endopeptidases on the basis of their sensitivity to inhibition by both leupeptin and the thiol-blocking agent iodoacetic acid and by their activation with the reducing agent glutathione. Each is distinguished from cathepsin B on the basis of molecular size and limited ability to hydrolyze benzoylarginine-2-naphthylamide. The action of the thiol endopeptidases on [125I]thyroglobulin was analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate or in sodium dodecyl sulfate and urea. In each instance, the initial peptide fragments were approximately 40-45K and 30K, with iodothyronine contents similar to or less than that of intact thyroglobulin. Later products of digestion than that of intact thyroglobulin. Later products of digestion included first, 20K peptides, which showed a low iodothyronine content, and finally, peptides of approximately 10K, which showed a 1.5-fold enrichment of T4 and T3 over that of intact thyroglobulin. Each of the thiol endopeptidases had a synergistic effect when incubated with cathepsin D and [125I]thyroglobulin. Among the products of such incubations were small iodopeptides, which were iodothyronine-enriched, and free T4, itself. The results show that thiol endopeptidases are present in the thyroid gland and are collectively as important as cathepsin D in the hydrolysis of thyroglobulin in vitro. The action of these enzymes must be considered along with that of cathepsin D in understanding thyroglobulin hydrolysis in vivo.
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PMID:Thyroglobulin degradation by thyroidal proteases: action of thiol endopeptidases in vitro. 704 63

Two methods have been developed to discriminate simultaneously between the main part of cysteine proteinase activity (cathepsin L) and all aspartic proteinase activity (mainly cathepsin D) in rat organs, using Z-Phe-Phe-CHN2 which at 5 mumol/l completely inhibits cathepsin L from rat liver and, on the other hand, pepstatin which at 0.5 mumol/l completely inhibits cathepsin D. Substrates are double-labeled cytosol proteins from rat liver at pH 3.0 or azocasein in 3 mol/l urea at pH 5.0. Several organs from rat, pigeon, frog and carp have been investigated using these methods. Especially kidneys from rat, frog and carp contain a high Z-Phe-Phe-CHN2 inhibited activity. Investigating the different liver cell types we could confirm earlier findings that Kupffer cells and endothelial cells contain more pepstatin inhibited activity than parenchymal cells.
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PMID:Inhibition of cysteine proteinase activity by Z-Phe-Phe-diazomethane and of aspartic proteinase activity by pepstatin in different organs from some animals and isolated cells from rat liver. 705 5

Cathepsin D was purified by two-step affinity chromatography on concanavalin A-- and pepstatin--Sepharose. The main purification was achieved by washing the enzyme bound to the pepstatin--Sepharose column with buffered 6 M-urea. This step separated cathepsin D from all low- and high-molecular-weight impurities. Although the 1700-fold purified acid proteinase was homogeneous on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, it still showed microheterogeneity.
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PMID:Two-step affinity-chromatographic purification of cathepsin D from pig myometrium with high yield. 732 70


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