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)

Kidney protein was converted to a form of active renin by kidney cathepsin B isozymes. The three isozymes showed similar catalytic behavior for prorenin. The optimal pH for the activation was in the range of 4.0-5.0 and the reaction was completely inhibited by leupeptin. The molecular weight and the isoelectric point of the activated prorenin were 40,000 and pH 4.9. As a minor product, an activated prorenin having an isoelectric point of 5.2 was also produced.
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PMID:Activation of kidney prorenin by kidney cathepsin B isozymes. 704 Mar 62

Cysteine-proteinase activity was observed in homogenates of human-cadaver renal cortex. This activity co-purified with renin enzymic activity until separation by aminohexyl-Sepharose--pepstatin affinity chromatography. The cysteine proteinase was purified 1780-fold after the following successive chromatographic procedures: Sephadex G-75, DEAE-cellulose DE-52, and an organomercurial affinity resin. The proteinase activity was dependent upon activation by thiol-containing compounds such as dithiothreitol, as well as by EDTA, and was inhibited by the thiol-group-specific alkylating reagents iodoacetic acid and N-ethylmaleimide. DE-52 cellulose chromatography resolved the cysteine proteinase into two components. On the basis of molecular size (26 000 daltons), activity as a function of pH, stability as a function of pH, substrate specificity and thermal lability, the major component (95%) has been identified as cathepsin B. The DE-52 cellulose elution pattern of the minor component (5%) is suggestive of cathepsin H [Schwartz & Barrett (1980) Biochem. J. 191, 487-497] Enzymic activity was determined with synthetic substrates, in particular alpha-N-benzoyl-DL-arginine 2-naphthylamide (Bz-Arg-NNap), thus precluding the detection of cathepsin L [Kirschke, Langner, Wiederanders, Ansorge, Bohley & Broghammer (1976) Acta Biol. Med. Germ. 35, 285-299]. Inhibition by dimethyl sulphoxide was observed in the determination of Km = 7.0 +/- 0.4 mM for the substrate Bz-Arg-NNap, and care must therefore be taken in the preparation of substrate solutions.
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PMID:Cathepsin B from human renal cortex. 713 3

Renin is synthesized from an inactive precursor, prorenin, through cleavage at a pair of basic amino acids catalyzed by prorenin processing enzyme (PPE). A lysosomal protease, cathepsin B, has been suggested to be a strong candidate for PPE. However, there still remains a possibility that other protease(s) can also catalyze prorenin processing. We studied the subcellular distribution of PPE in human renal cortex using pure recombinant prorenin as a PPE assay substrate. PPE and renin activities, and cathepsin B activity and protein were colocalized in the lysosomal fraction. The PPE activity was completely inhibited by a cathepsin B specific inhibitor, CA074. Taken together with the immunohistochemical data showing that cathepsin B and PPE are colocalized in dense secretory granules of juxtaglomerular cells of kidney, we conclude that cathepsin B is the authentic PPE in human kidney.
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PMID:Role of cathepsin B as prorenin processing enzyme in human kidney. 758 19

The pathogenesis of cardiac hypertrophy in chronic uremia is poorly understood. In the present study, the long-term effects of chronic uremia on cardiac morphology and various cysteine proteinases of the heart were investigated in rats with and without antihypertensive therapy by the angiotensin converting enzyme inhibitor enalapril or by the calcium channel blocker verapamil. 16 weeks after subtotal nephrectomy considerable uremia had developed associated with arterial hypertension, rise in heart weight and heart weight/body weight ratio. Morphologically myocardial cells developed marked hypertrophy. Determination of various cysteine proteinases by fluorometry revealed a significant decline of cathepsin B activity while the activities of cathepsin H and L were unchanged. Antihypertensive treatment with enalapril and verapamil normalized the blood pressure and improved renal function significantly. Myocardial cell hypertrophy and the enhanced heart weight/body weight ratio were normalized under treatment with enalapril but not with verapamil. Simultaneously, the impaired cathepsin B activity returned to the normal range after enalapril treatment. It is concluded that the cardiac hypertrophy in uremia is at least partly caused by an activation of the circulating and/or cardiac renin-angiotensin system. Impaired proteinase activity in the uremic state may be involved in the development of cardiac hypertrophy.
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PMID:Prevention of cardiac hypertrophy in experimental chronic renal failure by long-term ACE inhibitor administration: potential role of lysosomal proteinases. 773 49

Both renin and cathepsin B were co-localized in identical granules of adreno-cortical cells. At day 16 of gestation, many renin-containing granules were observed and gold particles showed homogeneous intragranular distribution; whereas, those for cathepsin B was distributed heterogeneously. At day 18 of gestation, renin immunoreactivity was decreased or undetectable, whereas cathepsin B was still demonstrated at the same level as on day 16 of gestation.
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PMID:Adrenal renin is localized in lysosomal granules. 812 67

Cathepsin B, a representative lysosomal cysteine proteinase, has been demonstrated to coexist with renin in secretary granules of rat pituitary LH/FSH cells and renal juxtaglomerular cells. We investigated immunocytochemically the localization of cathepsins B, H, and L in the submandibular gland of male mice, in which active renin is also produced. By light microscopy, granular immunodeposits for cathepsin B were detected in epithelial cells of the gland, particularly in granular duct cells and interstitial cells. Immunoreactivity for cathepsins H and L was mainly found in interstitial cells, although that for cathepsin H was weakly seen in acinar cells. By electron microscopy, immunogold particles indicating cathepsin B intensely labeled small granules near the Golgi complex of granular duct cells and weakly labeled large secretory granules, whereas those showing renin labeled both granules. Double immunostaining co-localized immunogold particles showing renin and cathepsin B in small perinuclear granules near the Golgi complex. Some immunopositive granules seemed to be closely associated with the Golgi elements. These results indicate that the co-localization of renin and cathepsin B is also seen in secretory granules of granular duct cells in the mouse submandibular gland, as seen in rat juxtaglomerular and LH/FSH cells. This suggests that cathepsin B is one of the possible candidates for the renin-processing enzyme.
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PMID:Coexistence of renin and cathepsin B in secretory granules of granular duct cells in male mouse submandibular gland. 842 6

Conversion of prorenin to renin results from proteolytic cleavage of a 43-amino-acid prorenin prosegment in renal juxtaglomerular cells. The enzyme that performs this processing is not known. Of several enzymes proposed, cathepsin B is a candidate because it colocalizes with renin in juxtaglomerular cell secretory granules and accurately cleaves the prosegment of human prorenin in vitro. It is not known whether cathepsin B can perform this function in the cell. We examined this using secretory granule-containing rat GH4C1 cells transfected with a human preprorenin expression vector. When treated with secretagogue (KCl 50 mmol/L + forskolin 10 micromol/L), these cells secrete 95% prorenin and 5% active renin into the medium, indicating little prorenin processing activity. In contrast, when the cells are cotransfected with a vector that expresses human preprocathepsin B or mouse prohormone convertase 1, secretagogue-induced secretion of active renin increased to 12% and 16.5%, respectively. With antisera that recognize the prosegment and renin, prorenin and renin were identified as proteins of 47 and 43 kD, respectively, and an antibody specific to the prosegment precipitated only the 47-kD species. These results do not address whether cathepsin B is the authentic renal prorenin processing enzyme. However, the results do demonstrate that cathepsin B can localize to the appropriate subcellular compartment and process prorenin to renin in GH4C1 cells and are consistent with a role for this enzyme in prorenin processing.
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PMID:Cathepsin B is a prorenin processing enzyme. 861 95

A 3-fold increase in active renin was found after a kidney cortex extract was incubated with plasma from either normal or nephrectomized rats (0.34 +/- 0.04 to 1.34 +/- 0.08 and 1.60 +/- 0.06 micrograms Angiotensin I/mg tissue/hr, respectively). A plasma protein that activates renal renin was purified 900-fold. Purification of the protein was achieved by a combination of ammonium sulfate fractionation, molecular filtration on Sephacryl S-200 HR and ion-exchange chromatography on Mono Q HR 5/5 associated to an fast performance liquid chromatography (FPLC) system. The protein shows a molecular weight of approximately 54,000 Da. Renin activation was not inhibited by serine protease inhibitors, such as phenylmethyl sulfonylfluoride, aprotinin, soybean trypsin inhibitor and N-tosyl-L-phenylalanine chloromethyl ketone or by the cystein protease inhibitors N-ethylmaleimide and leupeptin. By using enzyme inhibitors, it was found that the activation process is not mediated by kallikrein, plasmin, tonin, cathepsin B or trypsin-like enzymes. From these results, we conclude that there is in circulating plasma a previously unidentified enzyme capable of activating inactive kidney renin. However, the possibility that this protein acts by activating the renin-substrate reaction cannot be dismissed.
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PMID:Activation of renal renin by a protein plasma fraction: a novel enzymatic mechanism. 865 95

Renin, which catalyzes the initial proteolytic cleavage reaction in the production of angiotensins, is first synthesized as a zymogen, prorenin, and requires the proteolytic removal of an amino-terminal prosegment for activation in vivo. The lysosomal hydrolase cathepsin B has been proposed as a prorenin processing enzyme based on reports of its co-localization with renin in the secretory granules of certain tissues and its ability to activate prorenin in vitro. In the current study, scanning mutagenesis was used to identify the amino acids which determine the site selectivity of prorenin cleavage by human cathepsin B in vitro. Co-expression assays in AtT-20 cells were also used to test for the ability of cathepsin B to cleave human prorenin within cells. Our results suggest that a basic lysine residue at the -2 position from the cleavage site is required for cathepsin B cleavage of prorenin in vitro and that the structure of prorenin itself may account for the selection of the proper cleavage site. In addition, although cathepsin B appears to be correctly sorted to lysosomes, the enzyme exhibits prorenin processing activity in transfected AtT-20 cells, raising the question of the cellular localization in which the processing event occurs.
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PMID:Prorenin processing by cathepsin B in vitro and in transfected cells. 992 50

The localization of cathepsin B, a potential promoter of prolactin (PRL) release via extra renal renin-angiotensin system in the adenohypophysis, and its inhibitor cystatin C in the human adenohypophysis and in pituitary adenomas were examined using single and dual immunohistochemical staining. In the adenohypophysis, cathepsin B was expressed in about 50% of the ACTH-producing cells, and in 5% or less of the GH- and PRL-producing cells. In contrast, cystatin C was expressed in about 70% of the GH- and PRL-producing cells, but in only 5% or less of the ACTH-producing cells. PRL-producing adenomas strongly expressed cathepsin B, but only weakly expressed cystatin C, a pattern of staining contrary to the expression in normal PRL-producing cells. The above results suggest that cathepsin B may play a role in promoting PRL release especially in PRL-producing adenomas.
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PMID:Expression of cathepsin B and cystatin C in the human adenohypophysis and in pituitary adenomas. 1060 86


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