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

---

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

Formalin-fixed paraffin-embedded hippocampal sections of brains with early-onset and late-onset Alzheimer's disease were studied immunohistochemically with antisera against cathepsin D and cathepsin B. In addition to the staining of neuronal perikarya, some of the senile plaques visualized by Bielshowsky silver staining and some of reactive astrocytes were positively stained with the antisera against cathepsin D and cathepsin B in brains with Alzheimer's disease. Abnormal localization of cathepsin D and cathepsin B immunoreactivity in neuronal perikarya was observed in brains with early-onset Alzheimer's disease. These findings demonstrate that the distribution of lysosomal proteases was altered in brains with Alzheimer's disease, suggesting the primary and/or secondary involvement of the lysosomal proteases in the pathological process of Alzheimer's disease.
...
PMID:Abnormal distribution of cathepsins in the brain of patients with Alzheimer's disease. 179 81

The phenomenon of crinophagy in rat pituitary mammotrophs, or lysosomal uptake of prolactin secretory granules, was confirmed by means of double-label immunogold electron microscopy, and shown to be induced in estrogen-stimulated male rats. Rabbit antibodies to rat cathepsin D were used to label lysosomes, and to rat prolactin to label secretory granules. The pituitaries were fixed in 4% formaldehyde and 1% glutaraldehyde, embedded in Lowicryl K4M, and thin sections were exposed successively to primary antibodies, biotin-labelled second antibodies, and streptavidin-gold, with an amplification procedure for cathepsin D. Cathepsin D and prolactin were detected separately on opposite sides of the sections, using 5-nm and 15-nm gold particles. Lysosomal uptake of prolactin secretory granules was not observed in untreated control rats. It was detected in about 26% of lysosome-containing mammotroph cell sections in estrogen-stimulated rats and at 7 h after estrogen withdrawal, but fell to 14% at 24 h and to 2% at 72 h after estrogen withdrawal.
...
PMID:Prolactin crinophagy is induced in the estrogen-stimulated male rat pituitary. 280 96

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.
...
PMID:Role of thiols, pH and cathepsin D in the lysosomal catabolism of serum albumin. 672 34

The amino acid sequences near the glycosylation sites and the oligosaccharide structures have been determined for the lysosomal protease cathepsin D from porcine spleen. Cathepsin D light and heavy chains were separately digested with proteases and the glycopeptides were purified. A single sequence was constructed from the amino acid sequence of the light chain glycopeptides which is: Tyr-Asn-Ser-Gly-Lys-Ser-Ser-Thr-Tyr-Val-Lys-Asn(CH2O)-Gly-Thr-Thr-Phe. A single glycopeptide sequence was also obtained for the heavy chain: Lys-Gly-Ser-Leu-Asp-Tyr-His-Asn(CH2O)-Val-Thr-Arg-Lys-Ala-Tyr. The light chain sequence is homologous with the sequence of porcine pepsin from residues 56 to 71. The heavy chain sequence is homologous with the pepsin sequence from residues 176 to 189. Thus, the 2 oligosaccharide-linked asparagines in cathepsin D correspond to residues 67 and 183 in pepsin and other homologous aspartyl proteases. These positions are located on the surface of the crystal structures of aspartyl proteases. Five oligosaccharides linked to Asn-67 were separated and their structures determined with proton NMR. Four major oligosaccharides are structural variants from the high mannose-type having 3, 5, 6, and 7 mannoses, respectively. A minor structure contained a third GlcNAc. Three oligosaccharide structures were found linked to Asn-183. Two major oligosaccharides are of the high mannose-type each with 5 mannose residues. One of the two contains a fucose linked to a GlcNAc. A third, very minor oligosaccharide contains galactose.
...
PMID:Oligosaccharide units of lysosomal cathepsin D from porcine spleen. Amino acid sequence and carbohydrate structure of the glycopeptides. 682 41

The effects of thiols on the breakdown of 125I-labelled insulin, albumin and formaldehyde-treated albumin by highly purified rat liver cathepsins B, D, H and L at pH 4.0 and 5.5 were studied. At both pH values degradation was strongly activated by the thiols cysteamine, cysteine, dithiothreitol, glutathione and 2-mercaptoethanol, and its rate increased with increasing thiol concentration. Preincubation of the protein substrates with 5 mM-glutathione did not affect concentration. Preincubation of the protein substrates with 5 mM-glutathione did not affect the rate of degradation by cathepsin D or L, and determination of free thiol groups after incubation of the proteins in the presence of glutathione but without cathepsin showed that their disulphide bonds were stable under the incubation conditions. Sephadex G-75 chromatography of the acid-soluble products of insulin digestion by cathepsin D or L suggested that thiols can reduce disulphide bonds in proteins after limited proteolysis. The resultant opening-up of the protein structure would lead to further proteolysis, so that the two processes (proteolysis and reduction) may act synergistically. By using the osmotic protection method it was shown that, at a physiological pH, cysteamine, and its oxidized form cystamine, can cross the lysosome membrane and thus may well be the physiological hydrogen donor for the reduction of disulphides in lysosomes. The results are discussed in relation to the lysosomal storage disease cystinosis.
...
PMID:Role of thiols in degradation of proteins by cathepsins. 705 70

Ligands such as complement fragments (C3, C4), IgG or alpha 2-macroglobulin, which bind antigen (Ag) before their uptake by antigen-presenting cells (APC), are likely to modulate the different steps of Ag processing and presentation. These ligands contribute to internalization and endosomal targeting of Ag; they also influence its processing and, consequently, the binding of resulting peptides to major histocompatibility complex (MHC) class II molecules before presentation to T cells. Complement protein C3 contains, like other members of the alpha 2-macroglobulin family, an intrachain thiolester bond. Conformational alteration or limited proteolysis of C3 into C3b leads to breaking of the thiolester with transient capacity of the revealed carbonyl group to esterify hydroxyl groups of Ag. Ester-linked complexes including tetanus toxin (TT) and C3b were prepared to analyse the influence of bound C3b on TT processing and presentation by APC. Covalent binding of C3b to TT resulted in increased and prolonged stimulation of specific T-cell proliferation. This effect was observed with non-specific B cells, as well as with a TT-specific B-cell clone, as APC. On the other hand, SDS-PAGE analysis of proteolysates of TT or C3b-TT, obtained with endosome/lysosome-enriched subcellular fractions prepared from human Epstein-Barr virus (EBV)-transformed B cells, indicated a delay of TT proteolysis when TT was associated to C3b. Treatment of APC with protease inhibitors, before and during exposure of the cells to Ag, resulted in differences in the inhibition of TT and C3b-TT proteolysis. Using purified cathepsins B and D, we demonstrated that covalent binding of C3b to TT totally abolished TT proteolysis by cathepsin D, while proteolysis by cathepsin B was preserved. This finding and the absence of cathepsin B in endosomes may explain a delay in TT processing when it is associated to C3b. Confirming these data, presentation by formaldehyde-fixed cells of C3b-TT proteolysates showed higher stimulation of specific T-cell clones than formaldehyde-fixed TT proteolysates.
...
PMID:Modulation of antigen processing and presentation by covalently linked complement C3b fragment. 789 Mar 1

The concentration of serum lipoproteins, especially those of low density (LDL) and high density (HDL) lipoprotein, are related to the pathogenesis of arteriosclerosis. However, there is a lack of data concerning lipoprotein distribution in the human arteriosclerotic plaque. To detect these lipoproteins, we performed immunogold labeling on ultrathin sections of fixed and embedded human arteriosclerotic tissue. We used a panel of specific antibodies to different lipoproteins and their apolipoprotein constituents, namely LDL, formaldehyde-fixed LDL, apolipoprotein B-100, HDL, and formaldehyde-fixed apolipoprotein A-I. We also applied antibodies to alpha-actin and cathepsin D to characterize the cells and organelles involved in lipoprotein uptake and metabolism. Semiquantitative evaluation was carried out for a detailed comparison of the results obtained. Electron microscopic examination revealed that the majority of HDL and LDL in the pathological tissue was localized intracellularly in macrophage-derived foam cells and smooth muscle cells, whereas only LDL was found in the extracellular matrix. In some cases, we observed an intracellular accumulation of lipoproteins in electron-dense vesicles, which appeared to be of lysosomal origin, as shown by double labeling with an antibody to cathepsin D. These vesicles were present only in macrophage-derived foam cells, which were localized in the necrotic cores of arteriosclerotic plaques, and could not be found in healthy tissue or in the early stages of arteriosclerotic disease.
...
PMID:In situ immunolocalization of lipoproteins in human arteriosclerotic tissue. 842 36

One hundred fifty-four axillary lymph node-negative invasive ductal carcinomas of the breast were immunohistochemically evaluated for the expression of cathepsin D. Formalin-fixed paraffin sections of each tumor were stained using a polyclonal antibody raised against recombinant procathepsin D. Cathepsin D content of tumor cells and host histiocytes and fibroblasts within or immediately at the invasive border of tumors were assessed separately and correlated with histomorphology, estrogen-receptor content, and patients' survival data. Positive cathepsin D staining of tumor cells was associated with a lower nuclear grade and well-differentiated histology, whereas moderate to strong staining of host cells correlated with larger tumor size, higher nuclear grade, poorly differentiated histomorphology, and lack of estrogen-receptor (ER) protein. No statistically significant correlation was found between cathepsin D in tumor cells and survival. There was, however, a statistically significant correlation between moderate to strong cathepsin D staining of host cells and shorter disease-free and overall survivals. Expression of cathepsin D by host cells, however, did not have an independent influence on survival. The authors conclude that cathepsin D in stromal cells, but not in tumor cells, is associated with aggressive behavior in node-negative invasive ductal carcinomas of breast. Furthermore, determination of cathepsin D in cytosolic extracts of tumors is of no practical value because it may represent cathepsin D content of tumor cells, intratumoral host cells, or both.
...
PMID:Cathepsin D in host stromal cells, but not in tumor cells, is associated with aggressive behavior in node-negative breast cancer. 881 79

To determine the involvement of proteinases with hydrolytic activity towards extracellular matrix and basement membrane, in invasion and metastasis of tumour cells, the expression of cathepsin D, an aspartic proteinase, and cathepsin B, a cysteine proteinase, was studied. Formalin-fixed paraffin-embedded specimens from 13 patients who had squamous cell carcinomas (SCC) with local recurrence, skin and/or lymph node metastasis were examined. Cathepsin D stained intensely as a granular pattern (mature enzyme) in tumour cells of 69% of primary lesions and all the secondary lesions of the patients with SCC. Cathepsin B stained more intensely in SCC cells of all of the primary and secondary lesions than in normal epidermis; staining patterns were almost diffuse (procathepsin B). Granular and diffuse patterns (mature enzyme of cathepsin D and procathepsin B, respectively) appeared in the outer and inner parts of tumour islands, respectively. The presence of the active mature form of cathepsin D and procathepsin B in metastatic skin lesions of SCC was confirmed by Western blotting analysis. The presence and localization of the active mature form of cathepsin D suggests that activated cathepsin D may be involved in the invasion and metastasis of SCC.
...
PMID:Expression of cathepsin D and B in invasion and metastasis of squamous cell carcinoma. 934 30

Methanol oxidation is accompanied by free radicals and formaldehyde formation. It is likely to cause damage of lysosomal membranes. Lysosomal ultrastructure under transmission electron microscope and biochemical localization of cathepsin D were estimated after rats intoxication with methanol. The examination was carried out 6, 12 and 24 h and 2.5 and 7 days after intoxication. Ultrastructural examination showed that methanol causes extension of Golgi apparatus cisterns and an increase in a number of lysosomes. From 12 h to 2 days lysosomes were characterized by damage of structure of membrane enclosing lysosomes. During the first days of intoxication activity of cathepsin D decreased in lysosomes and increased in cytosol. These changes may lead to uncontrolled extralysosomal proteolysis in the liver cells and to the onset of liver tissue destruction.
...
PMID:Ultrastructural evaluation of lysosomes and biochemical changes in cathepsin D distribution in hepatocytes in methanol intoxication. 964 82


1 2 Next >>

---