Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A thiol protease with properties similar to those of cathepsin B (EC 3.4.22.1) has been isolated and purified from human renal cortex. 2. This enzyme can generate renin activity from renin-suppressed and anephric human plasma at pH 5.5. 3. The renin activity thus generated is inhibited completely by antibody to purified human renal renin. This activation therefore represents the release of inactive renin.
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PMID:Isolation of a renal thiol protease that activates inactive plasma renin. 39 96

We examined by immunocytochemistry the localization of cathepsin B in endocrine cells of rat anterior pituitary lobe, using a monospecific antibody to cathepsin B. By light microscopy, granular immunodeposits for cathepsin B were detected in most endocrine cells of anterior pituitary lobe. Cells immunoreactive for luteinizing hormone (LH) were diffusely immunostained by anti-cathepsin B. By electron microscopy, immunogold particles for cathepsin B were localized in lysosomes of thyrotrophs, somatotrophs, and mammotrophs. In mammotrophs, immunogold particles for cathepsin B were also detected in crinophagic bodies. Double immunostaining co-localized immunogold particles for LH and cathepsin B in secretory granules of gonadotrophs. Immunocytochemistry was also applied to demonstrate localization of renin and prorenin in LH-producing gonadotrophs; immunogold particles for renin were co-localized with those for LH, cathepsin B, or prorenin in their secretory granules. Immunogold particles for prorenin were also co-localized with those for LH or cathepsin B in secretory granules, but prorenin-positive granules appeared less frequently than renin-positive granules. These results suggest that cathepsin B not only plays a role in the protein degradation in lysosomes of anterior pituitary endocrine cells but also participates in the activation of renin in gonadotrophs, as has been demonstrated in secretory granules of juxtaglomerular cells.
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PMID:Immunocytochemical localization of cathepsin B in rat anterior pituitary endocrine cells, with special reference to its co-localization with renin and prorenin in gonadotrophs. 191 37

Human prorenin is the enzymatically inactive biosynthetic precursor of renin. Recent interest has focused on the posttranslational sorting and processing of prorenin to renin since markedly increased levels of circulating prorenin have been associated with both physiological and pathological changes. These observations raise the question of whether prorenin processing may be a regulatory event in renin production in the kidney. In the juxtaglomerular cells of the kidney, prorenin can be sorted to either of two pathways: 1) the regulated pathway, which is mediated by secretory granules, where a thiol protease resembling cathepsin B processes prorenin to renin by cleavage of the amino terminal 43-amino acid prosegment, which allows exposure of the active site of renin, or 2) the constitutive pathway, which is not regulated and does not involve conversion of prorenin to renin. Studies in which segments of prorenin are modified by site-directed mutagenesis suggest that the prosegment and glycosylation are not required for sorting, although they may influence or participate in sorting, or both. Certain areas in the prosegment are important determinants of enzyme activity and ability to cleave the prosegment. Further structural analysis of prorenin will be useful to assess details of its sorting and processing. In addition, a number of extrarenal tissues such as uterine lining, ovarian theca, corpus luteum, pituitary, and adrenal, express the renin gene. These tissues have different capabilities to sort and process prorenin compared with kidney, and some tissues secrete only prorenin. Whether prorenin-to-renin conversion is necessary to activate these local renin-angiotensin systems is a key issue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human prorenin. 201 74

Prorenin, the inactive biosynthetic precursor of renin, is proteolytically cleaved in the renal juxtaglomerular cells to renin. The activity of renin is rate-limiting for generation of angiotensin II in the circulation. We identified a renal thiol protease which activates and accurately cleaves the 43-amino acid prosegment of human recombinant prorenin. In the current studies, 6.5 mg of this protease was purified from human renal cortex using a three-step procedure dependent upon Leu-Leu-arginyl affinity chromatography. This represented an overall 766-fold purification and resulted in three protein bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of molecular weights 30,000, 25,000, and 24,000. All three bands cross-reacted with an anti-human liver cathepsin B antibody upon immunoblot analysis; electrolution of each band and amino-terminal sequence analysis confirmed that the Mr 30,000 protein was mature cathepsin B and the Mr 25,000 and 24,000 bands were cathepsin B subunits. The pH optimum for the hydrolysis of pure human recombinant prorenin by pure renal cathepsin B was 6, and the Michaelis-Menten constant, Km, of the reaction was 1.4 x 10(-9) M. Immunostaining of human kidney using a sheep anti-human cathepsin B antibody demonstrated the presence of cathepsin B in the juxtaglomerular areas of the kidney, as well as in the renal proximal tubules. Electron microscopic immunohistochemistry using the same antibody demonstrated cathepsin B in dense secretory granules of the juxtaglomerular cells. Renin was also shown to be present in these granules. This study provides both biochemical and morphological evidence that renal cathepsin B is a human prorenin-processing enzyme.
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PMID:Identification of renal cathepsin B as a human prorenin-processing enzyme. 206 32

To examine the correlation of localization of prorenin, renin, and cathepsins B, H, and L, immunocytochemistry was applied to rat renal tissue, using a sequence-specific anti-body (anti-prorenin) that recognizes the COOH terminus of the rat renin prosegment. In serial semi-thin sections, immunodeposits for prorenin, renin, and cathepsins B, H, and L were localized in the same juxtaglomerular (JG) cells. Immunodeposits for renin were detected throughout the cytoplasm of the cells, whereas those for prorenin were detected in the perinuclear region. Immunoreactivity for cathepsin B was stronger than that for cathepsins H and L. By electron microscopy, prorenin was localized in small (immature) granules but not in large mature granules, whereas renin was localized mainly in mature granules. In serial thin sections, prorenin, renin, and cathepsin B were colocalized in the same immature granules containing heterogeneously dense material (intermediate granules). By double immunostaining, co-localization of renin with cathepsins B, H, or L was demonstrated in mature granules. The results suggest the possibility that processing of prorenin to renin occurs in immature granules of rat JG cells, and cathepsin B detected in JG cells may be a major candidate for the maturation of renin.
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PMID:Immunocytochemical localization of prorenin, renin, and cathepsins B, H, and L in juxtaglomerular cells of rat kidney. 250 52

Renin, prorenin and cathepsin B were localized in human lactotrophs using immunoelectron microscopic techniques. Renin and prorenin were found in numerous cytoplasmic granules. Cathepsin B, a lysosomal enzyme known to be able to activate prorenin into renin, was also present in cytoplasmic granules of lactotrophs. The co-localization of renin and prolactin in the same secretory granules was demonstrated by double immunolabelling. Renin and cathepsin B were co-localized in some granules by the same technique. These results suggest a local activation of renin in the secretory granules of lactotrophs and support the hypothesis of a possible autocrine action of the renin-angiotensin system on prolactin release.
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PMID:Renin and cathepsin B in human pituitary lactotroph cells. An ultrastructural study. 265 57

Renal cortical high-molecular-weight renin (Mw:60,000) of the dog is a complex of renin (low-molecular-weight renin; Mw:40,000) and a renin binding protein. We detected an enzyme-like substance that catalyzes the conversion from high- into low-molecular-weight renin. When the renal cortical extract was added to the high-molecular-weight renin and the preparation incubated at 37 degrees C for 30 min, the high-molecular-weight renin was converted into the low-molecular-weight form. No such conversion occurred in the case of renal medullary extract. This converting substance was fractionated using concanavalin A Sepharose, 70% ammonium sulfate saturation and DEAE-cellulose chromatography. The converting activity was inhibited by potassium tetrathionate, N-ethylmaleimide and 5,5'-dithiobis-(2-nitrobenzoic acid). These events suggest that this substance is an enzyme possessing sulfhydryl moieties. However, a cathepsin B inhibitor leupeptin did not affect the activity. Accordingly, the high-molecular-weight renin converting enzyme, which is sensitive to sulfhydryl oxidation, may explain the mechanism of interconversion between high- and low-molecular-weight renin involving the oxidation-reduction of tissue sulfhydryl groups.
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PMID:High-molecular-weight renin converting enzyme from dog kidney: detection and fractionation. 388 47

Mature juxtaglomerular epithelioid cell secretory granules of the rat exhibit both renin- and cathepsin B-like immunoreactivity. On the basis of the coexistence with renin at a pH which, according to previous experiments, is probably in the range of that in lysosomes, cathepsin B is suggested to be involved in the activation of renin prior to secretion.
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PMID:Coexistence of renin and cathepsin B in epithelioid cell secretory granules. 390 11

Val-D-Leu-Pro-Phe-Phe-Val-D-Leu, a specific inhibitor of aspartate proteinases of the pepsin type, was synthesized. Its bonding to activated 6-aminohexanoic acid-Sepharose 4B afforded an affinity support suitable for the purification of human, porcine, and chicken pepsin, human gastricsin, and bovine cathepsin D. These enzymes bind to the support over the pH range 2-5 at 0-1.5 M concentration of NaCl. A buffer at pH greater than or equal to 6, low ionic strength, and containing 20% dioxane can serve as a general desorption agent. The proteinases were isolated from the crude extracts by a single-step procedure in a high degree of purity and in yields exceeding 70%; human pepsin, however, was not separated from human gastricsin. The support does not show any binding capacity for rat plasma renin at pH 7.4 and for some cysteine endopeptidases (cathepsin B, H, and L) at pH 3-5. The cathepsin D preparations isolated by affinity chromatography on the new support and on pepstatin-Sepharose were of the same degree of purity as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, N-terminal amino acid sequences, and specific activity.
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PMID:Purification of pepsins and cathepsin D by affinity chromatography on Sepharose 4B with an immobilized synthetic inhibitor. 643 40

Cathepsins B, H, and D, extracted from human kidneys, activate human inactive renin. Inactive renin, obtained from human kidneys, contains two components of Mr 53,000 and 50,000. Upon incubation with 0.5 microM cathepsin B, the Mr of the larger component decreased progressively to 45,000 (similar to the Mr of active renin) without appreciable loss of renin activity. Cathepsin H also activated and decreased the Mr of kidney inactive renin. Plasma inactive renin was activated by the thiol proteases, cathepsins B and H, with less reduction in Mr than that observed in kidney renin.
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PMID:Human kidney cathepsins B and H activate and lower the molecular weight of human inactive renin. 675 87


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