Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two unique cathepsin D-type proteases apparently present only in rat thoracic duct lymphocytes and in rat lymphoid tissues are described. One, termed H enzyme, has an apparent molecular weight of similar to95,000; the other, termed L enzyme, has an apparent molecular weight of similar to45,000, in common with that of most cathepsins D from other tissues and species. Both enzymes differ from cathepsin D, however, by a considerably greater sensitivity to inhibition by pepstatin and by a smaller degree of inhibition by an antiserum which inhibits rat liver cathepsin D. H enzyme is converted to L enzyme by treatment with beta-mercaptoethanol; the relationship between the two enzymes remains unknown. H and L enzyme have been detected in rat lymphoid tissues and in mouse spleen, but they are not present in other rat tissues (liver, kidney, adrenals), rabbit tissues, calf thymus, bovine spleen, or human tonsils. As measured on acid-denatured bovine hemoglobin as substrate, both enzymes have pH activity curves identical with that of rat liver cathepsin D, with optimal activity at pH 3.6. Activity on human serum albumin is much less and also shows an optimum at pH 3.6; hence, neither enzyme has the properties of cathepsin E. Thiol-reactive inhibitiors have no effect on the activity of H and L enzyme; thus they do not belong to the B group of cathepsins. Additional information, discussed in this paper, leads us to conclude that partially purified H and L enzymes are cathepsin D-type proteases.
 ...
PMID:Unique cathepsin D-type proteases in rat thoracic duct lymphocytes and in rat lymphoid tissues. 114 Dec 27

The distribution of cathepsins E and D in various rat tissues and blood cells was determined by immunoprecipitation and by immunohistochemistry with discriminative antibodies specific for each enzyme. While cathepsin D was detected in all of the tissues and blood cells tested (except for erythrocytes), cathepsin E had a relatively limited distribution. The cathepsin E content was highest in the stomach and was succeeded in the following order by the urinary bladder, thymus, spleen, cervical lymph node and bone marrow. Significant amounts of cathepsin E were also found in the colon, rectum, jejunum, skin, lung, kidney and submandibular gland. The other tissues tested had little or no detectable cathepsin E content. Of the blood cells tested, lymphocytes and peritoneal neutrophils contained high levels of cathepsin E. Erythrocytes had cathepsin E only as aspartic proteinases. When the subcellular localization of cathepsin E in the neutrophils was investigated by fractionation of the postnuclear supernatants, the enzyme behaved as a soluble cytosolic enzyme. In contrast, cathepsin D was mainly associated with the granular fraction. The immunohistochemical localization of cathepsins E and D was clearly different in the stomach, large intestines, kidney and urinary bladder, but was similar in the lymph node and spleen. The tissue-fixed macrophages, which were notable in the skeletal and cardiac muscle tissues, submucosal layers of the gastrointestinal tracts, salivary gland, lung and trachea, also exhibited similar intense immunoreactivities demonstrative of both cathepsins E and D.
 ...
PMID:Quantitation and immunohistochemical localization of cathepsins E and D in rat tissues and blood cells. 265 14

An examination of the DNA binding domain structure of bovine plasma fibronectin (Fn) was undertaken by a combination of limited proteolytic cleavage and Western blotting. A time course digestion of fibronectin with cathepsin D produced a number of proteolytic fragments possessing DNA binding activity. After two min digestion, two DNA binding fibronectin fragments of Mr approximately 180kd and 120kd were detected. Upon further digestion, a fibronectin fragment of Mr 18kd was detected. Thus it would appear that under physiological ionic strength only a single DNA binding domain exists in the fibronectin molecule. It was also demonstrated that the interaction of fibronectin with DNA is not ionic in nature, as heat denaturation of protein totally abolishes the DNA binding activity. An examination of possible sequence specificity of DNA binding activity of fibronectin was also undertaken by dot blotting the bovine plasma fibronectin and using [32P] labelled lambda FC 40 DNA containing approximately 16 kd of 5' end of the chicken fibronectin gene. Its binding to fibronectin was approximately twice the binding of [32P] labelled wild type lambda, where as binding to control of equimolar concentration of calf thymus histone H 2 A was approximately equal. The use of a smaller subcloned region, a approximately 1.9kb fragment of DNA from the 5' end of chicken fibronectin gene and wild type lambda DNA showed approximately 2 fold increase in histone binding and approximately 7 fold increase in fibronectin binding, indicating preferential fibronectin binding with eukaryotic DNA as compared to prokaryotic DNA. Further investigation of sequence specificity showed that a 0.45kb DNA fragment from the 5' end of chicken fibronectin gene, containing a number of elements characteristic of promoter, demonstrated approximately 2 fold higher level of binding with fibronectin and approximately 3.5 fold less binding activity with equimolar concentration of histone H2A when compared with a 1.4kb fragment of chicken fibronectin gene from the 1st exon. These results suggest fibronectin binding may be preferential to the promoter region of its own gene which could have possibly a regulatory function.
 ...
PMID:The interaction between fibronectin and DNA. 275 Dec 62

Hydrolysis of histones by proteinases from rat liver, skin and other sources was studied by using a rat thymus histone preparation as the substrate and polyacrylamide-gel electrophoresis and densitometric analysis as the methods to detect histone subtypes and their hydrolysis. The rat mast-cell proteinase I effectively hydrolysed histones except type H4. Thrombin hydrolysed effectively histones H1 and H2A, whereas plasmin hydrolysed all types of histones. Cathepsin D hydrolysed especially histone H2A. Cathepsins B and L hydrolysed all histones more slowly, and cathepsin H hydrolysed them extremely slowly. Epidermal aminoendopeptidase did not hydrolyse histones. Trypsin and chymotrypsin were used as reference enzymes, which hydrolysed all types of histones in very low concentrations. This study suggests that a variety of proteinases could play a role in histone hydrolysis. Hydrolysis of a specific subtype of histones, such as histone H2A at pH 6 by cathepsin D, may be directly involved in regulation of epidermal-cell differentiation.
 ...
PMID:Hydrolysis of histones by proteinases. 296 88

The ADP-ribosylation site of histone H1 from calf thymus by purified hen liver nuclear ADP-ribosyltransferase was determined and effects of the ADP-ribose X histone-H1 adduct on cAMP-dependent phosphorylation of the histone H1 were investigated. ADP-ribosylated histone H1 was prepared by incubation of histone H1, 1 mM [adenylate-32P]NAD and the purified ADP-ribosyltransferase. N-Bromosuccinimide-directed bisection of ADP-ribosylated histone H1 showed that the NH2-terminal fragment (Mr = 6000) was modified and contained serine residue 38, the site of phosphorylation by cAMP-dependent protein kinase. Digestion of the NH2-terminal fragment with cathepsin D and trypsin, and purification of this fragment, using high-performance liquid chromatography, yielded a radiolabelled single peptide corresponding to residues 29-34 of histone H1, containing the arginine residue as the ADP-ribosylation site. These results indicate that ADP-ribosylation of histone H1 occurs at the arginine residue 34, sequenced at the NH2-terminal side of the phosphate-accepting serine residue 38. Phosphorylation of histone H1 from calf thymus by cAMP-dependent protein kinase was markedly reduced when histone H1 was ADP-ribosylated. Kinetic studies of phosphorylation revealed that ADP-ribosylated histone H1 was a linear competitive inhibitor of histone H1 and a linear non-competitive inhibitor of ATP.
 ...
PMID:Amino acid sequence of histone H1 at the ADP-ribose-accepting site and ADP-ribose X histone-H1 adduct as an inhibitor of cyclic-AMP-dependent phosphorylation. 299 55

The antiserum raised against the high-molecular-weight acid proteinase from rat gastric mucosa, termed 86-kDa acid proteinase, has been shown to recognize rat cathepsin E, but not cathepsin D (Muto, N. et al. (1987) J. Biochem. 101, 1069-1075). Using this specific antiserum, characteristic distribution of cathepsin E in rats was demonstrated. The enzyme was detected in a limited number of tissues, such as stomach, thymus, spleen, bladder, and erythrocyte membranes. Among them, the highest activity was observed in the stomach. In contrast, cathepsin D immunoreactive with the antiserum specific to rat gastric cathepsin D was demonstrated in all the tissues examined. Cathepsin E-type enzymes partially purified from these five tissues were precipitated in the same manner by the specific antiserum, and they had the same molecular weight, electrophoretic mobility, and resistance against denaturation by 4 M urea. These results indicate that they could be exactly classified as cathepsin E. This type of enzyme was also detectable in mice and guinea pigs, but they showed relatively weak immunoreactivities with the antiserum. Thus, it is concluded that the distribution of cathepsin E is intrinsically different from ordinary cathepsin D, suggesting that it has a different physiological role from cathepsin D.
 ...
PMID:Characteristic distribution of cathepsin E which immunologically cross-reacts with the 86-kDa acid proteinase from rat gastric mucosa. 304 64

To elucidate the metabolic abnormality of musclar dystrophy, 27 kinds of enzyme activity in various organs of control and dystrophic mice were examined. The organs examined included muscle, bone, heart, testis, uterus, spleen, thymus, submaxillary gland, stomach, pancreas, liver, kidney, brain, and lung. The activities of 14 different aminopeptidases, 5 endopeptidases, 4 glycosidases, phosphatase, esterase, and ribonuclease were measured. Most of the enzyme activities were significantly elevated in muscles and bones of dystrophic mice. These organs were similar in their patterns of enzyme abnormality. Among the 14 kinds of aminopeptidase activity studied, the degree of increased activity was greater for the aminopeptidases (AP):Ala-AP, Leu-AP, Met-AP, Phe-AP, Trp-AP, Gly-Pro-Leu-AP. In addition to aminopeptidases, there were significant increases in activities of chymotrypsinlike enzyme, cathepsin C, cathepsin D, several glycosidases and neutral ribonuclease in the muscles of dystrophic mice. Similarly increased enzyme activity was also observed in organs other than muscle and bone. Furthermore, protein content in most organs was higher in dystrophic mice than in those of control mice. These abnormalities were seen in both males and females. The present results suggest that there are extensive abnormalities in the protein metabolism in dystrophic mice. It seems therefore that the therapeutic approach to muscular dystrophy should be studies not only from the well-known abnormality of intramuscular endopeptidases, but from other aspects as well.
 ...
PMID:Various enzyme activities in muscle and other organs of dystrophic mice. 625 14

The immunological properties of acid proteinases from rat spleen, two types of cathepsin D and a cathepsin E-like enzyme, were examined. The rabbit antiserum was prepared against the major form of cathepsin D (cathepsin D-I) from rat spleen. The antiserum quantitatively precipitated the enzyme activity from the purified cathepsin D-I preparation. On immunodiffusion analysis, the antiserum showed an identical reaction with the minor form of cathepsin D (cathepsin D-II) from rat spleen. Immunoelectrophoresis showed that the precipitin line with cathepsin D-II ran somewhat faster to the anode than that with cathepsin D-I. The cathepsin E-like acid proteinaspe was neither precipitated nor inhibited by the antiserum to cathepsin D-I, indicating that the cathepsin E-like enzyme is different from cathepsin D. Immunological gel diffusion with the antiserum indicated that rat spleen cathepsin D was immunologically identical with cathepsin D obtained from rat brain, thymus, lungs, heart, liver, kidneys, and adrenals.
 ...
PMID:Immunochemical difference between cathepsin D and cathepsin E-like enzyme from rat spleen. 676 30

1. Cathepsin D, purified from bovine thymus, has a limited proteolytic effect on types I and III bovine collagens. The alpha 1 (I) chain was cleaved in native or denatured collagen only within the carboxy-terminal extra-helical sequence, the major site being between resides C6 (Leu) and C7 (Ser). The alpha 2 chain was unaffected in native collagen but was slowly cleaved between residues 782 (Phe) and 783 (Leu) in the denatured form. Cleavages, at 45 degrees C, in type III collagen occur within the extra-helical amino-terminal sequence, on the carboxy-terminal side of the lysine residue involved in intermolecular cross-linking. All three sites of action are within sequences of general hydrophobic character. 2. The very restricted cleavage of peptide bonds in denatured collagens can be ascribed to the infrequent occurrence of groupings of more than two hydrophobic residues and to the high content of the conformation-limiting residues proline and hydroxyproline. 3. The previously demonstrated failure of cathepsin D to solubilize a representative proportion of type III collagen from the fibres of bovine skin collagen [P.G. Scott and C.H. Pearson (1978) Biochem, Soc, Trans. 6, 1197-1199] may be explained by lack of ability of the enzyme to act on this collagen at 25 degrees C, in such a manner as to separate molecules joined by intermolecular cross-links involving the amino-terminal extrahelical region of the molecule.
 ...
PMID:Cathepsin D: specificity of peptide-bond cleavage in type-I collagen and effects on type-III collagen and procollagen. 678 4

Activity of acid hydrolases, acid phosphatase, cathepsin D, DNA- and RNAases in lysosomal fractions of liver tissue and peripheric blood lymphocytes as well as concentration of circulating immune complexes in blood serum were studied in thymectomized rats and in thymectomized rats with chronic heliotrinic hepatitis; thymosin and alimentary factors were used for treatment and correction of the impairments observed. The rate of thymus hormones deficiency was found to be responsible for impairments of functional activity of lysosomes in lymphocytes and liver tissue. Activation of the lysosomal enzymes studied was detected within early periods (40 days) after thymectomy, while a decrease in the enzymatic activity was observed within later periods and to the end of the experiment (190 and 370 days). Besides, concentration of circulating immune complexes was increased in liver tissue and the most distinct increase occurred within 370 days after thymectomy. Activity of lysosomal enzymes in liver tissue and lymphocytes and content of circulating immune complexes in blood were normalized in thymectomized animals after treatment with thymosin and alimentary factors.
 ...
PMID:[Change in the state of liver lysosomes and lymphocytes during development of secondary immunodeficiency and in chronic toxic hepatitis]. 837 13


1 2 Next >>