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)

Optimal assay conditions are described for 8 hydrolases of Euglena gracilis var. bacillaris, SM-L1 (streptomycin-bleached) strain, 7 of which have an acid pH-optimum. Acid-phosphatase, beta-galactosidase, beta-glucosidase, b-fucosidase, cathepsin D, RNase, DNase, and an esterase are active in cell homogenates. Amylase has very low activity, and beta-glucuronidase, arylsulfatase, beta, N-acetyl-glucosaminidase, alpha-fucosidase, and alpha- and beta-mannosidase are inactive.
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PMID:Hydrolytic enzymes of Euglena gracilis: characterization and activity as a function of culture age and carbon deprivation. 0 4

Cardiac hypertrophy was produced in rats by constriction of the ascending aorta. Removal of the constricting band 10 days after operation resulted in rapid decline in left ventricular (LV) weight and total ventricular RNA. Activities of acid RNase and beta-glucuronidase were elevated 3 days after aortic constriction. Activities of cathepsin D and alkaline RNase were unchanges. Activities of cathepsin D and acid RNase were unchanged 1 and 3 days after removal of constricting band. Ca2+-activated, neutral protease (CAF) isolated from postmitochondrial muscle supernatant was partially purified and characterized. CAF specifically degrades alpha-actinin when incubated with isolated myofibriles in the presence of Ca2+.
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PMID:Lysosomal and neutral hydrolase activity during the regression of cardiac hypertrophy. 0 53

The half-life of cardiac myosin heavy chains (HC) was determined, with leucyl-tRNA as precursor, to be 5.4 days. Myosin HC are labeled more rapidly than actin; myosin light chains (LC1 and LC2) are labeled more slowly than HC. The observed differences are attributable to heterogeneity in the half-lives, e.g., actin, and to the effect of dilution by the existing macromolecular precursor pool (LC1 and LC2). Cardiac and skeletal muscle contain a population of filaments that can be released from myofibrils by ATP-relaxing solution. The easily released filaments (ERF) are devoid of alpha-actinin and M-protein. Labeling of ERF is more rapid than that of residual myofibrils. Cardiac and skeletal muscle contains calcium-activated neutral protease, which selectively removes alpha-actinin when incubated with isolated myofibrils. During development of pressure-induced cardiac hypertrophy, the labeling of LC2 is increased. In regressing cardiac hypertrophy the activities of free and total cathepsin D and of acidic RNase are unaltered.
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PMID:The pathways of protein synthesis and degradation in normal heart and during development and regression of cardiac hypertrophy. 14 38

The kinetic properties of UDP-N-acetylglucosamine:glycoprotein N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) partially purified from the soil amoeba Acanthamoeba castellanii have been studied. The transferase phosphorylated the lysosomal enzymes uteroferrin and cathepsin D 3-90-fold better than nonlysosomal glycoproteins and 16-83-fold better than a Man9GlcNAc oligosaccharide. Deglycosylated uteroferrin was a potent competitive inhibitor of the phosphorylation of intact uteroferrin (Ki of 48 microM) but did not inhibit the phosphorylation of RNase B or the simple sugar alpha-methylmannoside. Deglycosylated RNase (RNase A) did not inhibit the phosphorylation of RNase B or uteroferrin. These results indicate that purified amoeba GlcNAc-phosphotransferase recognizes a protein domain present on lysosomal enzymes but absent in most nonlysosomal glycoproteins. The transferase also exhibited a marked preference for oligosaccharides containing mannose alpha 1,2-mannose sequences, but this cannot account for the high affinity binding to lysosomal enzymes. A. castellanii extracts do not contain detectable levels of N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase, the second enzyme in the biosynthetic pathway for the mannose 6-phosphate recognition marker. We conclude that A. castellanii does not utilize the phosphomannosyl sorting pathway despite expression of very high levels of GlcNAc-phosphotransferase.
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PMID:Characterization of UDP-N-acetylglucosamine:glycoprotein N-acetylglucosamine-1-phosphotransferase from Acanthamoeba castellanii. 131 74

The age-dependent change in activities of seven lysosomal enzymes (cathepsin D, beta-glucuronidase, acid phosphatase, acid/alkaline DNases and acid/alkaline RNases) was studied in four brain regions (cerebrum, hippocampus, pons and cerebellum) of Wistar rats. The activity of cathepsin D was significantly increased with aging in the four regions. The age-dependent change in activities of acid and alkaline DNases showed the characteristic regional difference, and the ratio of acid to alkaline DNases was increased with aging in all regions. Acid RNase showed the lowest activity in 18-month-old rats, and alkaline RNase activity was decreased with aging. The activity of beta-glucuronidase was higher in 2-month-old rats in all of the regions studied. Acid phosphatase showed no significant age-dependent change except in pons. The study demonstrated that all of the lysosomal enzyme activities do not change in parallel with aging, and that the age-dependent change showed the characteristic regional difference.
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PMID:Age-dependent change in activities of lysosomal enzymes in rat brain. 263 Aug 33

The present study was performed to investigate the enzymatic changes in dystrophic chickens compared to those of dystrophic mice. The activities of 14 kinds of aminopeptidases, 5 kinds of endopeptidase, 4 kinds of glycosidases, phosphatase, esterase, and ribonuclease were measured in muscles of control and dystrophic chickens. When the enzyme activities were expressed as specific activity per unit weight of organs, only some of them were found to be significantly elevated in dystrophic chickens; e.g., alanine aminopeptidase (Ala-AP), Gly-AP and cathepsin D. On the contrary, the activities of alpha-D-glycosidase, alpha-D-galactosidase and alpha-D-mannosidase were significantly decreased. Muscular protein contents of dystrophic chickens also tended to be lower than those of controls. These observations offer a striking contrast with the one obtained in the study on dystrophic mice. However, when expressed as specific activity per mg protein, many enzyme activities were found to be significantly elevated suggesting an extensive abnormality of metabolism in dystrophic chickens. Among 14 kinds of aminopeptidase activities, highly significant elevations were seen especially in AP-A, AP-B, Gly-AP, Ala-AP, Ser-AP, Pro-AP, Leu-AP, Met-AP and Trp-AP. Interestingly enough, a statistical approach suggested a significant correlation between the aminopeptidase changes of dystrophic chickens with those of dystrophic mice. In addition to aminopeptidases, there were highly significant increases in the activities of cathepsin D, alpha-D-glucosidase, beta-D-galactosidase, alpha-D-mannosidase, esterase and RNase. These results indicate that the intramuscular metabolic abnormality of dystrophic chickens are generally different from but partly resembled with those of dystrophic mice.
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PMID:Intramuscular enzyme abnormalities of dystrophic chickens compared to those of dystrophic mice. 701 13

Insulin-like growth factor-II (IGF-II) and lysosomal enzymes bearing the mannose 6-phosphate (Man6P) recognition marker, bind to two distinct binding sites of the IGF-II/M6P receptor. The two classes of ligands reciprocally modulate the binding of the other class of ligand to the receptor [Kiess, W., Thomas, C. L., Greenstein, L., Lee, L., Sklar, M. M., Rechler, M. M., Sahagian, G. G. & Nissley, S. P. (1989) J. Biol. Chem. 264, 4710-4714]. We asked whether or not overexpression of pro-IGF-II by cells in culture leads to missorting of lysosomal enzymes. Human embryonal kidney fibroblasts were transfected with the full-length human IGF-II cDNA or a control cDNA. Solution hybridization/RNase protection experiments using a human IGF-II riboprobe showed that two transfectants expressed large quantities of IGF-II mRNA, whereas the non-transfected cells did not. The analysis of conditioned media revealed that these cells secrete approximately 0.15 micrograms and 1.0 micrograms immunoreactive IGF-II/ml and 22 x 10(6) cells and 24 x 10(6) cells within 24 hours. Immunoreactive IGF-II was shown by Western blotting to represent 17-kDa pro-IGF-II. The amount of the lysosomal enzyme, beta-hexosaminidase, was approximately twofold increased in the conditioned media from pro-IGF-II overexpressing cells compared with control media, as shown by Western-blot analysis and immunoprecipitation of media extracts of metabolically labeled cells. The synthesis rate of beta-hexosaminidase was not affected by pro-IGF-II overexpression. In addition, the basal amount of another newly synthesized lysosomal enzyme, the cathepsin D precursor, was also twofold higher in pro-IGF-II overexpressing cells than in control cells. In contrast, the surface binding and cellular uptake rate of a Man6P-containing neoglycoprotein did not differ between the cell lines. The results indicate that the overexpression of pro-IGF-II doubles the secretion and/or reduces the re-uptake of beta-hexosaminidase and cathepsin D to approximately 20% of the total synthesized enzymes in human embryonal kidney fibroblasts compared to control cells. We hypothesize that, in cells synthesizing high amounts of pro-IGF-II, the growth factor may modulate the targeting of a portion of lysosomal enzymes, mainly by partially enhancing the secretion of newly synthesized enzymes and, in addition, possibly by affecting the re-uptake mechanism.
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PMID:Does the overexpression of pro-insulin-like growth factor-II in transfected human embryonic kidney fibroblasts increase the secretion of lysosomal enzymes? 755 47

The 5' flanking sequences, exon 1 and part of intron 1 of the human cathepsin D (CTD)-encoding gene (CTD) have been cloned and sequenced. RNase protection experiments identified two major transcription start points (tsp) located 14 and 63 nucleotides upstream of the start codon. The proximal -14, but not the distal -63 tsp has upstream near-concensus TATAAA and CCAAT sequences. Estrogens increase transcription from the -14 tsp, but not the -63 tsp and CTD is therefore unique among estrogen-regulated genes in having estrogen-regulated and constitutive transcription. Sequencing approximately 800 bp upstream and 600 bp downstream of the tsp failed to identify a consensus 13-bp palindromic estrogen-response element (ERE); however, four half-palindrome GGTCA motifs were located within 340 bp upstream of the -14 bp tsp. Thus, estrogen regulation of CTD may not be mediated by a consensus ERE.
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PMID:The human cathepsin D-encoding gene is transcribed from an estrogen-regulated and a constitutive start point. 826 86

The cathepsin D (cath-D) gene, coding for a ubiquitous lysosomal aspartyl protease, is overexpressed in aggressive human breast cancers, and its transcription is induced by estrogens in hormone-responsive breast cancer cells. We have determined the structure and function of the proximal 5' upstream region of the human cath-D gene from MCF7 cells. We show that the promoter has a compound structure with features of both housekeeping genes (high G+C content and potential transcription factor Sp1 sites) and regulated genes (TATAA sequence). By RNase protection assay, we show that transcription is initiated at five major transcription sites (TSSI to -V) spanning 52 base pairs. In hormone-responsive breast cancer cells, estradiol increased by 6- to 10-fold the level of RNAs initiated at TSSI, which is located about 28 base pairs downstream from the TATA box. The specific regulation by estradiol of transcription starting at site I exclusively was confirmed by primer extension. Moreover, the same estradiol effect was observed in the ZR75-1 cell line and in MDA-MB231 estrogen-resistant breast cancer cells stably transfected with the estrogen receptor. Site-directed mutagenesis indicated that the TATA box is essential for initiation of cath-D gene transcription at TSSI. In breast cancer biopsy samples, high levels of TATA-dependent transcription were correlated with overexpression of cath-D mRNA. We conclude that cath-D behaves, depending on the conditions, as a housekeeping gene with multiple start sites or as a hormone-regulated gene that can be controlled from its TATA box.
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PMID:Cathepsin D gene is controlled by a mixed promoter, and estrogens stimulate only TATA-dependent transcription in breast cancer cells. 841 24

We determined whether recombinant human growth hormone (rhGH) administration might modulate the enzyme degradative capacity of the muscle lysosomal system and influence muscle growth. Muscle cathepsin D, acid RNase and DNase II activities are determined in the gastrocnemius muscle of rhGH-treated post-weaning female BALB/c mice. Linear regressions were used to analyze the relationships of each enzyme with their respective substrate. GH induced a depletion-recovery response of muscle growth through a mechanism which is similar to catch-up growth. In these conditions, cathepsin D activity decreased with age in all animals (GH: 40%; saline: 79%), showing a substantial developmental decline that could reflect changes in the rate of protein breakdown. However, the degradative capacity of cathepsin D was paradoxically unmodified in rhGH-mice compared with saline mice (according to the enzyme vs. substrate linear regression slope), in spite of the increase in enzyme activity elicited by GH. This suggests that the muscle protein breakdown is not increased by GH-treatment in post-weaning mice. The enhancement of muscle protein deposition as indicated by the augmented muscle cell size (protein:DNA ratio) of rhGH-mice (increased 178% from 25 to 50 days) vs. saline, can be attributed to a higher muscle K(RNA). In contrast, acid RNase and DNase II activities directly participate in muscle RNA and DNA degradation. Both nucleases were inhibited by GH treatment (a decrease of 48% and 63%, respectively, vs. saline at 50 days). The decrease in RNase activity suggests an inverse relation between the rate of protein synthesis (high) and acid RNase activity (low), leading to spare muscle RNA for synthesizing protein during catch-up growth. Also, low DNase II activity could contribute to inhibiting of muscle DNA degradation, facilitating muscle growth. Thus, GH seems to act as a direct modulator of the degradative capacity of skeletal muscle nucleases but not of cathepsin D, influencing DNA and RNA degradation during the depletion-recovery response to GH of gastrocnemius muscle in female post-weaning mice.
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PMID:Growth hormone modulates the degradative capacity of muscle nucleases but not of cathepsin D in post-weaning mice. 1749 91


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