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 distribution and biochemical properties of the renin activity present in the dog brain were compared with those of the lysosomal enzyme cathepsin D. Renin and cathepsin activity were present in all brain regions studied, in association with high angiotensinase activity. Brain renin activity was partially purified by ammonium sulfate fractionation and Sephadex gel filtration, resulting in the removal of angiotensinase activity. The specific brain renin activity increased approximately one hundred times during this procedure; cathepsin D activity accompanied the brain renin activity throughout the purification and showed a similar increase in specific activity. The renin and cathepsin activity in the partially purified preparation behaved identically during isoelectric focusing. The partially purified renin and cathepsin activity exhibited saturation kinetics with their respective substrates and were without activity above pH 6.0. Both enzyme activities were irreversibly inhibited by the pepsin inhibitor pepstatin, in nanomolar concentrations. These data, in conjunction with the literature concerning brain cathepsin, suggest that the renin activity in brain is due to cathepsin D, and that this renin activity exhibited by cathepsin D may be of limited significance under physiological conditions.
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PMID:Renin activity in dog brain: enzymological similarity to cathepsin D. 18 Dec 41

1. Renin was purified 30 000-fold from rat kidneys by chromatography on DEAE-cellulose and SP-Sephadex, and by affinity chromatography on pepstatinyl-Sepharose. 2. The enzymatic properties of isorenin from rat brain, pseudorenin from hog spleen, cathepsin D from bovine spleen, and renin from rat kidneys were compared: Isorenin, pseudorenin and cathepsin D generate angiotensin from tetradecapeptide renin substrate with pH optima around 4.9, renin at 6.0. With sheep angiotensinogen as substrate, isorenin, pseudorenin and cathepsin D have similar pH profiles (pH optima at 3.9 and 5.5), in contrast to renin (pH optimum at 6.8). 3. The angiotensin-formation from tetradecapeptide by isorenin, pseudorenin and cathepsin D was inhibited by albumin, alpha-and beta-globulins. These 3 enzymes have acid protease activity at pH 3.2 with hemoglobin as the substrate. Renin is not inhibited by proteins and has no acid protease activity. 4. Renin generates angiotensin I from various angiotensinogens at least 100 000 times faster than isorenin, pseudorenin or cathepsin D, and 3000 000 times faster than isorenin when compared at pH 7.2 with rat angiotensinogen as substrate. 5. The 3 'non-renin' enzymes exhibit a high sensitivity to inhibition by pepstatin (Ki less than 5.10(-10) M), in contrast to renin (Ki approximately 6-10(-7) M), at pH 5.5. 6. It is concluded from the data that isorenin from rat brain and pseudorenin from hog spleen are closely related to, or identical with cathepsin D.
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PMID:Isorenin, pseudorenin, cathepsin D and renin. A comparative enzymatic study of angiotensin-forming enzymes. 62 74

Human renal renin (EC 3.4.99.19) and pseudorenin were easily separated in a single step by affinity chromatography on hemoglobin-Sepharose-2B. Renin and pseudorenin were monitored by their actions on crude and partially purified hog protein renin substrates at neutral and acidic pH and on synthetic labelled polymeric renin substrate. Under the conditions employed (0.1 M sodium acetate (pH 3.5)/1 M sodium chloride at 4 degrees C) renin does not bind to the affinity adsorbent while pseudorenin is effectively bound and can be eluted only after raising the pH to 6.5. Pseudorenin-free renin prepared by this method is devoid of proteolytic activity toward hemoglobin. The chromatographic behaviour of renal pseudorenin on hemoglobin-Sepharose-2B is similar to that of cathepsin D.
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PMID:Separation of human renal renin and pseudorenin by affinity chromatography on hemoglobin-Sepharose-2B. 65 43

Controversy exists whether vascular smooth muscle cells in vivo synthesize renin, thereby providing a critical component of the hypothesized vascular renin-angiotensin system. To examine this question, we enzymatically isolated and pooled the medial layer of thoracic aortas from Sprague-Dawley rats that were either untreated or enalapril treated for 3 days, isolated messenger RNA (mRNA), and performed Northern blot analysis with rat complementary DNA (cDNA) probes for renin, cathepsin D, and cathepsin E. Renin mRNA was detected in kidney but was not detected in aortic smooth muscle from the untreated or enalapril-treated groups. Cathepsin E mRNA was detected in enalapril-treated aorta and kidney, and cathepsin D mRNA was detected in all tissues examined. cDNA was synthesized and subjected to polymerase chain reaction analysis by using primers corresponding in sequence to regions conserved throughout the aspartic proteinases. Cathepsins D and E were amplified from kidney and aortic cDNA. Renin was less consistently amplified from the aortic cDNA and was much less abundant than cathepsin E or cathepsin D. These results suggest that 1) renin mRNA is present in aortic smooth muscle cells in vivo in quantities detectable only after multiple rounds of polymerase chain reaction amplification, 2) renin mRNA is not upregulated in aortic smooth muscle after converting enzyme inhibition, and 3) cathepsins D and E are the predominant aspartic proteinases in aortic smooth muscle.
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PMID:Polymerase chain reaction analysis of renin in rat aortic smooth muscle. 159 70

Renin is an aspartyl protease which is highly homologous to the lysosomal aspartyl protease cathepsin D. During its biosynthesis, cathepsin D acquires phosphomannosyl residues that enable it to bind to the mannose 6-phosphate (Man-6-P) receptor and to be targeted to lysosomes. The phosphorylation of lysosomal enzymes by UDP-GlcNAc:lysosomal enzyme N-acetylglucosaminylphosphotransferase (phosphotransferase) occurs by recognition of a protein domain that is thought to be present only on lysosomal enzymes. In order to determine whether renin, being structurally similar to cathepsin D, also acquires phosphomannosyl residues, human renin was expressed from cloned DNA in Xenopus oocytes and a mouse L cell line and its biosynthesis and posttranslational modifications were characterized. In Xenopus oocytes, the majority of the renin remained intracellular and underwent a proteolytic cleavage which removed the propiece. Most of the renin synthesized by oocytes was able to bind to a Man-6-P receptor affinity column (53%, 57%, and 90%, in different experiments), indicating the presence of phosphomannosyl residues. In the L cells, the majority of the renin was secreted but 5-6% of the renin molecules contained phosphomannosyl residues as demonstrated by binding of [35S]methionine-labeled renin to the Man-6-P receptor as well as direct analysis of [2-3H]mannose-labeled oligosaccharides. Although the level of renin phosphorylation differed greatly between the two cell types examined, these results demonstrate that renin is recognized by the phosphotransferase and suggest that renin contains at least part of the lysosomal protein recognition domain.
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PMID:Renin, a secretory glycoprotein, acquires phosphomannosyl residues. 296 Jun 82

Synaptosomes and lysosomes of rat brain were separated by differential centrifugation and a two-step gradient centrifugation with colloidal silica-gel (Percoll). The organelles were identified by the measurement of established marker-enzymes and by electronmicroscopy. Renin activity, measured by radioimmunoassay for angiotensin I (ANG I), was localized in the synaptosomes and cathepsin D-activity was found in the lysosomal fraction. Converting-enzyme activity was present in the renin-containing synaptosomes. Part of the brain renin activity could be activated by pre-incubation with trypsin. Affinity chromatography of an organelle-enriched brain fraction was carried out using a caseinyl-sepharose column and resulted in the separation of renin from cathepsin D activity; the renin peak was inhibited by antibodies raised against rat kidney renin. We conclude, that the formation of ANG I and its activation to angiotensin II (ANG II) by converting enzyme is possible in synaptosomes. This adds further evidence to an intraneuronal synthesis of ANG I and ANG II in the brain and is in support of previous results demonstrating an intraneuronal localization of the components of the brain renin-angiotensin system.
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PMID:Localization of renin (EC 3.4.23) and converting enzyme (EC 3.4.15.1) in nerve endings of rat brain. 298 84

Renin and Cathepsin D activities were measured in different cerebral structures in foetuses, during the first month of life and in the adult rats. There are differences in the renin activity and cathepsin D activity both in the cerebral structures and during the ontogenetic development. While the cathepsin D was much increased in newly born animals as compared to foetuses and remained fairly constant during the rest of life, the cerebral renin activity was constantly decreasing toward adulthood. It was found that during the first two weeks after birth there is a renin activity increase in the cerebral cortex and hypothalamus, followed by a decrease and, at the end of the first month of life after birth, the values were equal to those found in adult animals. The same variations were found in the epiphysis between the 45th and 50th day after birth.
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PMID:The ontogenetic evolution of cerebral renin and cathepsin D in the rat. 311 63

There is increasing evidence which suggests that the adrenal gland contains the renin-angiotensin cycle. The localization of renin has been reported to be mainly in the zona glomerulosa rather than the fasciculata medullary portion. In the present study we have investigated extracts from aldosteronomas (n = 3), which are believed to derive from the zona glomerulosa cells. In addition, we have attempted to characterize the biochemical properties of the adrenal renin. Sizable quantities of renin-like activity (32.0 +/- 7.7 ng of angiotensin I generated h-1 mg-1 of protein, mean +/- SEM) were detected in the extracts. This renin-like activity was inhibited by anti-renin antibody raised against pure renin (mean, 95% of the total renin-like activity), indicating that it was not due to the non-specific action of proteases such as cathepsin D. The optimum pH of the tissue renin-like enzyme was 6.0 for rat plasma substrate. Differences were found, however, in the molecular mass (36,000, 37,000, 44,000 and 48,000), binding to concanavalin A and isoelectric points (4.40, 4.68 and 5.00). These results confirm the existence of specific renin in aldosteronoma. Renin microheterogeneity could be evidence for local production of the enzyme.
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PMID:Multiple forms of immunoreactive renin in human adrenocortical tumour tissue from patients with primary aldosteronism. 329 70

Immunocytochemical and biochemical techniques have been utilized in the present study to characterize renin in brain cell cultures. With the use of renin-specific antibody, positive renin staining was seen in neuronal and in astrocytic glial cells using the peroxidase-antiperoxidase method. Renin concentration was pH-dependent with highest concentrations at 5.5, decreasing from pH 6.0 to 6.5. At pH 7.4 no renin was detectable in either glial or neuronal cells. The contribution of cathepsin D to the measured renin was about 10% at pH 5.5; 7% at pH 6.0 and 3% at pH 6.5. Comparison of glial with neuronal cells from WKY rats revealed significantly elevated renin at pH 5.5 in glial cells. No difference was seen between glial and neuronal renin levels in WKY rats at pH 6.0 and 6.5. At pH 5.5 and 6.0 renin was significantly increased in neuronal cells of SHR compared to WKY, whereas at pH 6.5 no difference was observed. The renin concentration in cells kept for 2 days in serum-free medium did not differ from those measured in cells kept in serum-containing medium. The generated peptide was identified as [Ile5]Angiotensin I on reversed-phase HPLC.
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PMID:Presence of renin in primary neuronal and glial cells from rat brain. 332 28

Mature secretory granules of epithelioid cells--the so-called renin granules--exhibit certain properties, which in this particular combination are expressed only by lysosomes: Renin granules have autophagic capabilities; they react to the application of lipidosis-inducing, lysosomotropic substances by the gradual accumulation of polar lipids; all secretory granules of epithelioid cells contain acid phosphatase until maturity; and exogenous tracers reach renin granules without labeling the Golgi complex. Several functional implications can therefore be considered. Hydrolytic enzymes, constitutive elements of the granule matrix, might either cleave inactive prorenin to yield active renin within the granules or, by unspecific hydrolysis of renin, participate in the regulation of the overall quantity of secretory product. Autophagic phenomena, the involvement of renin granules in the traffic of exogenous tracers, and the build-up of polar lipids following experimental interference with lipid catabolism indicate a large turnover of membrane material in renin granules. They also suggest that cytoplasmic and extracellular fluid gains access to the granule content and may thus be involved there in the regulation of biochemical reactions by changing the intragranular milieu or via signal molecules. In addition to the lysosome-like properties of epithelioid cell secretory granules, the secretory product, renin, as a carboxyl protease, is structurally related to other acidic proteases. In the case of cathepsin D, even functional similarities exist.
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PMID:Are the renin-containing granules of juxtaglomerular epithelioid cells modified lysosomes? 388 48


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