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)

Short-term vasectomy was studied in adult male rats in order to ascertain whether cytosolic or lysosomal hydrolases were differently affected 100 days after vas ligation. The secretory form of alpha-1,4-glucosidase remained unchanged while the lysosomal form of the enzyme and also cathepsin D increased in the cytosol of both caput and cauda epididymis. This set of data demonstrates for the first time that a triggering mechanism which stimulates lysosomal activity is present all along the rat epididymis. Disposal of the continuous influx of spermatozoa from the testis could therefore require both an active and a passive process.
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PMID:Fate of alpha-1,4-glucosidases and cathepsin D in the rat epididymis after vasectomy. 210 99

With the aim of gaining knowledge about the lysosomal apparatus of the rat epididymis, four acid hydrolases were analysed in homogenates of the whole organ and, in other experiments, in separated segments: proximal and distal caput, corpus and cauda. The activities were similar to those in the liver, and they were 50% recovered in a cytosol of 43 000 g x 60 min. Ten days after castration all segments showed similar changes, the activities of beta-glucuronidase and cathepsin D increased above normal levels while those of DNAase and acid phosphatase were found slightly decreased. After vasectomy region I (caput and corpus) showed decreased beta-glucuronidase activity and increased acid phosphatase activity. The activity of cathepsin D increased in both regions. In cryptorchid rats (90 days) the epididymis greatly decreased in weight, the activities of acid phosphatase and DNAase slightly decreased in region II (cauda) and in region I, respectively. In the abdominal epididymis (90 days) only region II decreased in weight. DNAase activity decreased in region I while cathepsin D did so in both regions. The results showed that a) the enzymes behave quite independently from each other, suggesting the existence of a specific regulation for each of them b) there were characteristic changes in enzymatic activity for each experimental condition.
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PMID:Acid hydrolases in the epididymis of normal, castrated, vasectomized, cryptorchid and cryptepididymal rats. 611 43

Cathepsins are specific proteases in lysosomes that participate in the degradation of proteins, some of which are derived from endocytosis. In this study we examined the immunocytochemical localization of cathepsin B and D antibodies in cells of rat testis and epididymis, using light and electron microscopic immunocytochemistry. In testis, cathepsin D was immunolocalized over lysosomes of Sertoli cells and Leydig cells and on the acrosome of spermatids. Cathepsin B was found over lysosomes of macrophages. Non-ciliated cells of the efferent ducts revealed intense immunogold labeling over lysosomes with both anti-cathepsin B and D antibodies. In epididymis, cathepsins B and D showed marked variations in expression over the different epithelial cells and regional differences for a given cell type. Anti-cathepsin D antibodies showed intense labeling over lysosomes of principal cells in the corpus and proximal cauda. In contrast, anti-cathepsin B antibodies revealed intensely labeled lysosomes of principal cells of the distal initial segment, intermediate zone, and caput epididymidis, with weaker labeling in other regions. Clear cells of the proximal caput epididymidis revealed intensely labeled lysosomes for anti-cathepsin D antibodies. In the distal caput, clear cells showed a variable reaction pattern from intensely labeled to unreactive. Basal cells of teh intermediate zone and proximal caput region were intensely reactive for anti-cathepsin D antibodies. There was no staining over clear or basal cells with anti-cathepsin B antibodies. Taken together, these results demonstrate cell-specific and regional differences in the distribution of cathepsins B and D in cells of the male reproductive system. Such results suggest substrate specificity with regard to protein turnover within lysosomes of cells of testis and epididymis.
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PMID:Differential expression of cathepsins B and D in testis and epididymis of adult rats. 773 May 93

The way in which the human epididymis modifies spermatozoa during their sojourn in this structure might be clarified by knowledge of the nature of its secretions. We have examined the presence of several lysosomal hydrolases in human epididymal tissue and fluids, and their synthesis and secretion by monolayer cultures. Tissues were obtained from men undergoing orchidectomy for prostatic carcinoma. The enzymes cathepsin D and acid alpha-glucosidase were localised in the lysosomes of epithelial cells from the corpus epididymidis, by an immunocytochemical technique. Cathepsin D was also found in epithelial cells of the efferent ducts within lysosomes, apical vesicles and multivesicular bodies. No immunolocalisation of acid glucosidase in the efferent ducts or on the microvilli of the corpus was demonstrable. Cathepsin D, beta-hexosaminidase (N-acetylglucosaminidase) and alpha-glucosidase were measurable in the luminal fluid from the human corpus epididymidis; beta-hexosaminidase was secreted into the culture medium by confluent monolayers of epididymal and efferent duct cells. Immunoprecipitation of cell extracts and culture medium of these cultures incubated with 35S-methionine revealed that the precursors of cathepsin D and beta-hexosaminidase were synthesized and secreted by such monolayers. Thus, active lytic enzymes are secreted by the human epididymis and could modify sperm membranes.
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PMID:Immunocytochemical localisation of some lysosomal hydrolases, their presence in luminal fluid and their directional secretion by human epididymal cells in culture. 778 Oct 38

Apical and narrow cells of the initial segment and intermediate zone of the adult rat epididymis were glutaraldehyde fixed and Epon embedded for routine light (LM) and electron (EM) microscopic analysis and Bouin fixed and paraffin embedded for LM immunocytochemical analysis in order to examine their structural features, distribution, and functions. The goblet-shaped apical cells comprised 10.7 +/- 1.0% of the total epithelial population in the proximal initial segment but only 1.3 +/- 0.5% in the intermediate zone. In the EM, these cells presented numerous mitochondria, few C-shaped vesicles, and a pale round or oblong nucleus located in the upper half of their cytoplasm. The slender elongated narrow cells increased from 2.8 +/- 0.3% in the proximal initial segment to 6.3 +/- 0.4% in the intermediate zone. In an EM analysis, these cells presented numerous C-shaped vesicles and mitochondria and a small flattened nucleus located in the upper half of their cytoplasm. The structural features of both these cell types differed not only from each other but also from the neighboring principal and basal cells of each region. Of the various antibodies examined to lysosomal proteins, narrow and apical cells expressed high levels of cathepsin D, while beta-hexosaminidase A was expressed at high levels in narrow cells but only moderately in apical cells. Apical cells were intensely reactive for the Yf subunit of glutathione S-transferase (GST)-P, whereas no reaction was seen in narrow cells; the Yo subunit of GST was localized within both cell types but only in the proximal initial segment. Narrow cells exclusively expressed carbonic anhydrase II. Selective differences in the immunolocalization of these various proteins were also noted between these two cell types and principal and basal cells. The localization of cathepsin D and beta-hexosaminidase A within narrow and apical cells suggests these cells may be involved in the degradation of specific proteins within their lysosomes, whereas the presence of GSTs may aid in protecting spermatozoa from a changing environment of harmful electrophiles. Localization of carbonic anhydrase II exclusively within narrow cells suggests that these cells may modify the pH of the lumen resulting in the quiescence of sperm motility in the proximal end of the epididymis. Together, the data indicate that apical and narrow cells differ not only from each other but also from principal and basal cells in their structure and relative distribution. They also express different proteins within the distinct epididymal regions, indicating that they perform different functions.
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PMID:Apical and narrow cells are distinct cell types differing in their structure, distribution, and functions in the adult rat epididymis. 879 11

Beta-hexosaminidase (Hex) is a lysosomal enzyme that exists as two major isoenzymes: Hex A (subunit structure, alphabeta) and Hex B (betabeta). The presence of Hex in the testis and epididymis suggests important roles for the enzyme and its substrates in male fertility and reproductive functions. Disruption of the Hexb gene encoding the beta-subunit of Hex has led to the generation of a mouse model of human Sandhoff disease that survives to adulthood, enabling us to analyze the effects of Hex A and Hex B deficiency on epithelial cellular morphology of the male reproductive tract. At 1 and 3 months of age, the testes, efferent ducts, and epididymides of Hex-deficient (Hexb -/-) and wild-type (Hexb +/+) mice were perfuse fixed and analyzed by routine light and electron microscopy (LM and EM, respectively) as well as with immunocytochemistry employing antibodies to lysosomal proteins. In the testis, the morphological appearance and topographical arrangement of the cell types of the seminiferous epithelium of Hexb -/- mice were similar to those of wild-type animals at both ages. Both Sertoli and germ cells appeared to be unaffected. However, at both ages, myoid cells and macrophages showed an increased number of lysosomes in their cytoplasm as compared with the number seen in controls. The epithelial cells of the efferent ducts also showed an accumulation of lysosomes that increased with age as compared with controls. Principal cells of the entire epididymis revealed an increase in the size and number of lysosomes at 1 month of age as compared with those of controls, and by 3 months, these lysosomes often filled the supranuclear and basal regions of the cells. Narrow cells of the distal initial segment and intermediate zone, normally slender cells showing several lysosomes, became greatly enlarged and entirely filled with lysosomes in Hexb -/- mice. Clear cells of the caput, corpus, and cauda regions also showed a progressive increase in the size and number of lysosomes with age as compared with controls; the clear cells of the mutant mice were often enlarged and at times bulged into the lumen. Some basal cells of each epididymal region in Hexb -/- mice were similar to controls at 1 and 3 months, showing few lysosomes, while others showed an accumulation of lysosomes. Lysosomes of all affected epithelial cells were of varying sizes, but many large ones were present, apparently resulting from lysosomal fusion. Although pale stained, their identification as lysosomes was confirmed by EM immunocytochemistry with anti-cathepsin D and anti-Hex A antibodies. Predominantly in the proximal initial segment, large, pale cellular aggregates were noted in the LM analysis at the base of the epithelium, which by EM analysis were identified as belonging to two different cell types, narrow cells and halo cells. Taken together, these data reveal an increase in the size and number of lysosomes in all epithelial cell types lining the efferent ducts and entire epididymis as well as in myoid cells and macrophages of the testis. In the light of data showing epididymal defects restricted predominantly to the initial segment in Hexa -/- (Hex A-deficient) mice, our data on the Hexb -/- mice demonstrate a major role for Hex that can be fulfilled by either Hex A or Hex B in the epididymis.
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PMID:I. Abnormalities in cells of the testis, efferent ducts, and epididymis in juvenile and adult mice with beta-hexosaminidase A and B deficiency. 1059 18

Beta-hexosaminidase (Hex) is a lysosomal enzyme that exists as two isoenzymes: Hex A (subunit structure alphabeta) and Hex B (betabeta). Its presence in the testis and epididymis suggests important roles for Hex and its substrates in male fertility and reproductive functions. Disruption of the Hexa gene encoding the alpha-subunit of Hex has led to the generation of a mildly affected mouse model of human Tay-Sachs disease, allowing us the opportunity to analyze the effects of isolated Hex A deficiency on epithelial cellular morphology of the male reproductive tract. At 5 weeks and at 3, 5, and 12 months, the testes, efferent ducts and epididymides of Hex A-deficient (Hexa -/-) and wild-type (Hexa +/+) mice were perfuse fixed and analyzed by routine light and electron microscopy as well as with immunocytochemistry employing antibodies to lysosomal enzymes. In the testis, the seminiferous epithelium of Hexa -/- mice appeared comparable to that of wild-type mice in appearance and topographical arrangement of its cell types at all ages examined. Also, no differences were noted for the efferent ducts. In contrast, there were striking abnormalities in the epididymides of the mutant mice; however, the abnormalities were mainly restricted to the initial segment and intermediate zone. Principal cells of these regions at 5 weeks showed a dramatic increase in the number of lysosomes as compared with those from wild-type animals, and this progressed with increasing age. Furthermore, unlike the few small lysosomes present in wild-type mice, those of Hexa -/- mice were at times enlarged and often filled the supranuclear and basal regions of these cells. In the light microscope, large, dense cellular aggregates were noted at the base of the epithelium in the proximal initial segment that corresponded in the electron microscope to two different cell types, both of which increased in size with age. One aggregate was considered to belong to narrow cells on the basis of the presence of numerous cup-shaped vesicles characteristic of these cells; they appeared to be dislocated from the upper half of the epithelium. In the distal initial segment and intermediate zone, narrow cells were readily identified, but rather than being slender as in the control animals, they were greatly enlarged and filled with pale lysosomes in mutant mice. The second type of cellular aggregate noted in the proximal initial segment corresponded to halo cells. They contained numerous small and large lysosomes and small, Golgi-related, dense, core granules characteristic of halo cells. On the basis of the large size of these cells, they appeared to be actively internalizing substances from the intercellular space. In contrast, principal and clear cells of the caput, corpus, and cauda regions did not appear to show a significant increase in number or size of lysosomes as compared with those of wild-type animals. All structures identified as lysosomes in the various cell types were immunoreactive for cathepsin D. The present data thus reveal that isolated Hex A deficiency results in region- and cell-specific abnormalities in the epididymis but in no apparent abnormalities in the testis or efferent ducts. Specific roles for Hex A that cannot be compensated for by other isozymes of Hex appear to exist within lysosomes of epithelial cells predominantly of the initial segment and intermediate zone. Taken together, the results also suggest that the inability to degrade endocytosed substrates normally acted upon by Hex A in lysosomes of principal and narrow cells leads to their accumulation, eventual fusion, and increased size.
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PMID:II. Characterization and development of the regional- and cellular-specific abnormalities in the epididymis of mice with beta-hexosaminidase A deficiency. 1059 19

The proteins that are neosynthesized and secreted in the different regions of the human epididymis were determined by in vitro biosynthesis of epididymal tubules, and the luminal proteins were collected by microperfusion of each tubule. The preparations were analyzed by two-dimensional gel electrophoresis and the proteins were identified by mass spectrometry. Some of the major proteins identified corresponded to serum compounds such as albumin, transferrin and alpha-1-antitrypsin. The other proteins identified included lactotransferrin, clusterin, PEBP, NCP2/CTP/HE1, HE3, Crisp, actin, calmodulin, E12, PGDS, l-lactate dehydrogenase, malate dehydrogenase, carbonic anhydrase, triose phosphate isomerase, glutamyltransferase, glutathione S-transferase P, thioredoxin peroxidase, superoxide dismutase, cathepsin D and cystatin. Epididymal activity is highly regionalized in most species. However, in this study in humans, there were only minor changes in the major proteins secreted. It is suggested that this specificity might be related to the difference between species in the location of the epididymis where sperm become fertile.
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PMID:Human epididymal secretome and proteome. 1643 Oct 15

We evaluated the relationships between proteins in cauda epididymis fluid (CEF) and fertility scores of dairy bulls. Fertility was expressed as the percentage point deviation (PD) of bull nonreturn rate from the average fertility of all bulls at an artificial insemination center. The number of services for each bull ranged from 1074 to 52 820, and PD values ranged from +7.7% to -6.6%. CEF from 20 bulls was obtained from vasa deferentia cannulae and was separated from sperm by centrifugation immediately after collection. Samples were evaluated by 2-dimensional (2-D) sodium dodecyl sulfate polyacrylamide gel electrophoresis gels stained with Coomassie blue, and polypeptide maps were analyzed by PDQuest software. Protein quantities, defined as the total integrated optical density of the spots, were compared between groups of high-fertility sires (n = 12; PD >or= 0) and low-fertility sires (n = 8; PD < 0) and were also used as independent variables in regression analysis. Proteins were identified by capillary liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry. An average of 118 spots was detected in 2-D maps of the CEF, but we were unable to distinguish any protein that was expressed only in high-fertility or in low-fertility bulls. However, the amount of alpha-L-fucosidase 2 and cathepsin D was 2.3- and 2.4-fold greater (P < .05) in high-fertility than in low-fertility bulls, respectively. Conversely, the intensities of 3 isoforms (24-27 kd; pl 6.3-5.8) of prostaglandin D-synthase (PGDS) were from 3.2- to 2.2-fold greater in low-fertility sires (P < .05). An empirical regression model established that a significant proportion (R(2) = 0.72; P < .0001) of the variation in fertility scores (PD values) was explained by the intensities of cathepsin D and 1 isoform of PGDS (24 kd; pl 6.3). Thus, multiple proteins present in the CEF are potential biomarkers of fertility in high-use, mature Holstein bulls.
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PMID:Proteins of the cauda epididymal fluid associated with fertility of mature dairy bulls. 1658 9

Cathepsin D is a cysteine endopeptidase that belongs to the lysosomal enzyme family. The aim of the study was to evaluate the enzyme immunoexpression and activity in selected male genital organs in mature Wistar rats. The activity of cathepsin D was measured spectrophotometrically in homogenates of the testis, epididymis, seminal vesicle and prostate. Immunohistochemical staining was also performed in the ductus deferens. Enzyme activity was found in the following sequence: testis>epididymis>dorsal prostatic lobe>seminal vesicle>lateral prostatic lobe>ventral prostatic lobe. Although there were differences in enzyme activity between various organs of the male reproductive system, cathepsin D immunoreactivity was seen exclusively in the Sertoli and Leydig cells in the testis.
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PMID:The activity and immunoexpression of cathepsin D in rat male reproductive organs. 1677 97


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