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)

The degradation of cytosol proteins in vitro by purified cathepsin D and cathepsin B1 and by mixtures of lysosomal enzymes, was studied. By means of a double-labelling method, it was shown that the relative rates of degradation of cytosol proteins by the purified enzymes and by mixtures of enzymes under a wide range of conditions in vitro correlated well with their relative rates of turnover in vivo. The complex mixture of cytosol proteins was degraded less rapidly after denaturation than in the native state, both by the purified proteases and by the mixture of lysosomal enzymes. This contrasts with previous results on proteolysis of single purified proteins. The possible role of lysosomal enzymes in turnover in vivo was discussed.
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PMID:Lysosomal enzymes as agents of turnover of soluble cytoplasmic proteins. 24 36

Acute exposures of lungs to nitrous oxide in anesthetic concentration results in an initial lowered free activity of cathepsin D. Chronic exposures with either continuous or interrupted anesthetic exposure increases the free activity of this enzyme.
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PMID:Inhaled nitrous oxide and cathepsin D activity in the lung. 26 58

Because protein degradation in liver and skeletal muscle is increased by thyroid hormones and decreased by thyroidectomy; we investigated the influence of thyroid hormones on the level of lysosomal enzymes. Hypophysectomized rats received daily injections of L-thyroxine or L-triiodothyronine. After 3 days of this regimen, homogenates of liver and skeletal muscle showed a 2- to 3-fold increase in the activities of cathepsin D, cathepsin B, and other lysosomal enzymes including leucine aminopeptidase, acid phosphatase, beta-galactosidase, N-acetylglucosaminidase, and alpha-mannosidase. In liver, this effect reflected increased enzyme activity in the two subcellular fractions that normally contain lysosomes. Titration of cathepsin D with pepstatin indicated that the increase in this activity resulted from an increase in the number of enzyme molecules. These effects occurred with both pharmacologic (thyrotoxic) and physiologic (growth-promoting) doses of thyroid hormones. Liver and skeletal muscle from thyroidectomized rats had approximately 50% of the normal levels of lysosomal enzyme activities. Under these various conditions, heart and kidney, tissues in which protein degradation does not appear to be influenced by thyroid hormones, showed no significant changes in lysosomal hydrolases. Thus, thyroid hormones regulate proteolytic and other lysosomal enzyme activities in those tissues in which these hormones influence protein degradation. Many characteristic features of hyperthyroidism and hypothyroidism may result from changes in levels of lysosomal enzymes.
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PMID:Thyroid hormones control lysosomal enzyme activities in liver and skeletal muscle. 27 25

Muscle tissue levels of lysosomal catheptic enzymes, such as cathepsins D, A, B1, C, and dipeptidyl peptidase II, were measured in control subjects and patients with muscular dystrophies, polymyositis, and certain denervating diseases. The results show that, in general, the activities of these enzymes are increased in muscles of patients with muscular dystrophies and other diseases. The increases in cathepsin D and autolytic activities are not significant until the late stage of the disease process. Cathepsins A, B1, and C are, however, significantly elevated in mildly affected dystrophic and other diseased muscles. Of these catheptic enzymes, cathepsin B1 displays the highest rise at an early stage, suggesting that it may be one of the rate-controlling enzymes of proteolysis. Dipeptidyl peptidase II is increased slightly in dystrophic and other myopathic muscles but is unchanged in denervated muscle. These data clearly implicate the lysosomal group of proteinases as largely responsible for mediating muscle breakdown in the muscular dystrophies and certain other muscle and neuromuscular diseases in man.
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PMID:Muscle breakdown and lysosomal activation (biochemistry). 28 25

Highly purified calf brain cathepsin D (EC 3.4.23.5) selectively splits the Leu77-Phe78 and Ala36-Ala37 peptide bonds of human beta-lipotropin. It is suggested that the formation of human "beta-melanotropin" from gamma-lipotropin, and that of gamma-endorphin from beta-endorphin, is due to the action of cathepsin D during isolation procedures.
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PMID:Action of cathepsin D on human beta-lipotropin: a possible source of human "beta-melanotropin". 29 8

In vitro degradation of insoluble vitreous collagen by the action of collagenolytic cathepsin was studied biochemically. Among bovine ocular tissues, the uvea and the retina showed relatively high collagenolytic activity. The ciliary body revealed the highest specific activities of both cathepsin B and collagenolytic cathepsin. Leupeptin and p-chloromercuribenzoate inhibited both cathepsin B and collagenolytic cathepsin in the ciliary body lysosomes. Pepstatin inhibited cathepsin D, but did not affect cathepsin B and collagenolytic cathepsin. It is suggested that distribution and properties of collagenolytic cathepsin are similar to those of cathepsin B in the bovine eye.
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PMID:The distribution and some properties of collagenolytic cathepsin in the bovine eye. 30 80

The effect of the protease inhibitor, aprotinin, was examined in rats during traumatic shock. In sham-operated control rats, intravenous administration of aprotinin (20,000 or 40,000 KIU/kg) showed no immediate changes in the mean arterial blood pressure and heart rate. In rats subjected to Noble-Collip drum trauma, aprotinin at a dose of 20,000 KIU/kg prolonged survival time to 2.1 +/- 0.3 hr (p less than 0.05) and 40,000 KIU/kg prolonged the survival time of rats to a greater extent (3.1 +/- 0.4 hr, p less than 0.001) compared to rats given only its vehicle (1.1 +/- 0.2 hr, mean +/- SE). The improved survival was accompanied by inhibition of the plasma accumulation of the cardiotoxic peptide, myocardial depressant factor (MDF). However, aprotinin showed no inhibitory effect on the plasma accumulation of the lysosomal enzyme, cathepsin D. Aprotinin has a beneficial effect on traumatic shock in rats possibly by its potent inhibitory action on MDF formation.
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PMID:Protective actions of aprotinin in acute traumatic shock. 31 92

Pepstatin is a low molecular weight, potent inhibitor specific for acid proteases with a Ki value of about 10(-10)M for pepsin. The chemical structure of pepstatin is essentially a hexapeptide which contains two residues of an unusual amino acid, 4-amino-3-hydroxy-6-methylheptanoic acid (statine). The complete structure of pepstatin is isovaleryl-L-valyl-L-valyl-statyl-L-alanyl-statine. To study its mode of inhibition, we prepared several derivatives and measured their kinetics of inhibition. Both N-acetyl-statine and N-acetyl-alanyl-statine are competitive inhibitors for pepsin with Ki values of 1.2 x 10(-4)M and 5.65 x 10(-6)M, respectively. The Ki value for N-acetyl-valyl-statine is 4.8 x 10(-6)M. These statyl derivatives, therefore, are very strong inhibitors. The Ki value for N-acetyl-statine is 600-fold smaller than that of its structural analog N-acetyl-leucine. The derivative which contains two statyl residues in a tetrapeptide exhibits inhibitory properties which approach those of pepstatin itself. Other acid proteases, human pepsin, human gastricsin, renin, cathepsin D, the acid protease from R. chinensis and bovine chymosin, also are inhibited by pepstatin and its derivatives. We suggest that the statyl residue is responsible for the unusual inhibitory capability of pepstatin and that statine is an analog of the previously proposed transition state for catalysis by pepsin and other acid proteases.
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PMID:Pepstatin inhibition mechanism. 33 90

Two types of acid proteinase activity found in rabbit skin homografts were characterized by studying the effect of temperature, pH and polyacrylamide-gel electrophoresis. Their chromatographic behaviour was characterized on DEAE-cellulose, Sephadex G-75, G-100 and G-200, and their molecular weights were estimated by gel filtration. One of the acid proteinases in the homograft resembled cathepsin D (EC 3.4.23.5) of normal skin. The other acid proteinase differed from cathepsin D with respect to heat inactivation, pH optimum and molecular weight; it was not inactivated on heating at 60 degrees C for 60 min, its pH optimum was 2.5 and its molecular weight measured by Sephadex G-100 chromatography was 100 000. In all these respects, the heat-stable proteinase resembles cathepsin E (EC 3.4.23.5) of rabbit polymorphonuclear leucocytes.
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PMID:Characterization of two acid proteinases found in rabbit skin homografts. 34 83

Rat liver cathepsin D (EC 3.4.23.5) was purified using precipitation technique, ion exchange chromatography, molecular sieve chromatography and isoelectric focusing. Rabbit anti-rat cathepsin D IgG was prepared and rat incisor teeth were cross-sectioned in a cryostat. These sections were incubated with FITC-conjugated anti-rat cathepsin D IgG. Marked fluorescence, indicating the localization of cathepsin D, could be seen over the odontoblast and predentin area. No specific fluorescence could be dmonstrated in the pulp connective tissue proper nor in the dentin.
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PMID:Cathepsin D. Purification from rat liver and immunohistochemical demonstration in rat incisor. 35 8


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