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. Mouse kidney was homogenized in a mixture of serine-metallo- and thiol-enzyme inhibitors. The homogenate proteins were separated with respect to size and charge by gel filtration, agarose electrophoresis and polyacrylamide-gel electrophoresis. 2. Renin was localized by its enzymatic activity by using the antibody trapping radio-immunoassay for angiotensin I, before and after acid treatment and limited proteolysis. Renin was also localized by its antigenic properties by using antirenin antibodies elicited against pure mouse submaxillary renin. The antibody cross-reacted fully with mouse kidney renin and with high-molecular-weight renin forms in mouse plasma. 3. In the kidney only fully enzymically active 40 000 renin could be detected enzymically and antigenically. No high-molecular-weight renin or inactive renin was demonstrable. 4. Two electrophoretically different renin forms were seen in accordance with renin being a glycoprotein. They were both fully enzymically active with identical specific enzymatic activities. 5. The mouse kidney renin had a specific enzymatic activity identical with that of pure mouse submaxillary renin, being 0.4 Goldblatt unit/microgram.
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PMID:Renin in the mouse kidney has a molecular weight of 40 000. 701

Sections of juxtaglomerular cells from sodium-deficient rats were subjected to radioautography after a single intravenous injection of L-tyrosine-3,5 3H or of L-fucose 3H to identify the sites of synthesis and to follow the migration of newly-formed proteins and glycoproteins. As early as 2 min after injection of L-tyrosine 3H, the label was highest in the rough endoplasmic reticulum (RER), suggesting that cisternal ribosomes are sites of protein synthesis. By 60 min, much of the label had migrated from the RER to the Golgi complex. Some radioactivity was already present over specific granules by 2 min but a peak was reached at 4 h. The label over myofilaments was evident at all time intervals, indicating a certain incorporation of tyrosine into their contractile and/or structural proteins. The label over the cell surface peaked at 4 h. After injection of L-fucose 3H, there was an early and important relative specific radioactivity in the Golgi complex at 5 min with a peak at 20 min and a decrease thereafter. The label increased slightly but steadily in secretory granules and cell surface to reach maxima at 4 h. A low level of radioactivity was recorded in mitochondria at all time intervals. After injection of both fucose 3H and tyrosine 3H, the label was detected at relatively low levels in the cytosol. These results suggest that renin, as the major secretory glycoprotein of juxtaglomerular cells, is synthetized in the RER, packaged in the Golgi complex and found relatively rapidly in newly-formed secretory granules. Part of the fucose and tyrosine labels is also associated with the thick cell coat of these cells.
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PMID:Synthesis and migration of proteins and glycoproteins in juxtaglomerular cells of sodium-deficient rats. An ultrastructural radioautographic study. 706 98

1. A human urinary thermostable glycoprotein (ABG-TsU) believed to be a homologue of the plasma aldosterone-binding globulin (ABG) was isolated and purified by differential ultrafiltration, ion-exchange chromatography and gel filtration to electrophoretic homogeneity; it showed a charge heterogeneity in electrofocussing. 2. ABG-TsU was administered intraperitoneally to male rats in small daily doses (7 microgram/day per rat). Sustained hypertension developed in 5--8 days. 3. The treated rats showed no changes in plasma electrolytes, aldosterone or plasma renin activity; however, a significant increase in heart weight was observed. 4. This hypertension appears to be adrenal dependent since it is prevented by bilateral adrenalectomy or administration of an aldosterone antagonist, but not by adrenalectomy when aldosterone is given concomitantly with ABG-TsU.
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PMID:Experimental essential hypertension in the rat? 731 37

Human renin substrate (angiotensinogen) was purified from outdated bank plasma. Purification procedures included ammonium sulfate precipitation, DEAE-cellulose column chromatography, concanavalin A-Sepharose column chromatography, Hydroxylapatite column chromatography preparative isoelectric focusing and Ultrogel AcA 44 gel filtration. The final recovery was 10% and the specific angiotensin I content of 10.5 micrograms/mg of protein was obtained. Polyacrylamide gel and SDS-polyacrylamide gel electrophoresis and analytical ultracentrifugal analyses showed the homogeneity of the purified renin substrate. The molecular weight of 60900 was determined by sedimentation equilibrium studies. Human renin substrate was a glycoprotein containing 13% carbohydrate. Cystine could not be detected on amino acid analysis. The purified renin substrate showed the isoelectric point heterogeneity (pI, 4.6 and 4.9).
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PMID:Isolation and characterization of human renin substrate. 737 24

Renal insufficiency due to congenital obstructive nephropathy is a consequence of arrested or abnormal renal growth. A number of experimental studies have shown that the younger the age at the time of unilateral ureteral obstruction (UUO), the more severe the growth impairment of the ipsilateral kidney, and the greater the compensatory growth of the opposite kidney ("counterbalance"). Urinary obstruction in early fetal life results in renal dysplasia and a decrease in the number of functioning nephrons. The renin-angiotensin system is highly activated in early development, and UUO further increases this activity, resulting in vasoconstriction and glomerular contraction. Long-term UUO also causes progressive interstitial fibrosis, which presumably contributes to arrested growth of the kidney. This may result from excessive deposition of extracellular matrix stimulated by increased expression of transforming growth factor-beta 1. Neonatal UUO delays the expression of epidermal growth factor, and prolongs the expression of peritubular alpha smooth muscle actin, suggesting that renal maturation is delayed by UUO. Renal apoptosis is increased by UUO, which may contribute to the reduced DNA content of the neonatal obstructed kidney. Renal expression of clusterin, a glycoprotein associated with cell adhesion and protection from apoptosis, is increased by ipsilateral UUO, and also presumably modulates renal growth. Thus, renal growth and development are impaired by UUO through complex interactions between regulators of cell proliferation, cell destruction, and extracellular matrix.
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PMID:Effects of ureteral obstruction on renal growth. 756 14

Angiotensinogen is a glycoprotein synthesized mainly in hepatocytes and secreted into the circulation. Angiotensinogen is cleaved by the enzyme renin to produce angiotensin I, which is further converted into a vasoconstricting peptide, angiotensin II, the biologically active peptide of the renin angiotensin system. The concentration of angiotensinogen is rate-limiting in the production of angiotensin I and therefore plays an important role in the regulation of angiotensin II production. The development of recombinant DNA technology has introduced new directions for the study of the angiotensinogen molecule. The human, rat and mouse angiotensinogen gene contains five exons interrupted by four intervening sequences and spans 12 kb approximately. In its 5' flanking region multiple regulating elements, as well as the major control elements, are present. The cloning and sequencing of the angiotensinogen cDNA demonstrates the similarity of angiotensinogen to various serine protease inhibitors produced by the liver and was the beginning of studies looking for new physiological roles of angiotensinogen, in addition to the substrate for renin. The circulating levels of angiotensinogen are altered in many different physiological and pathological states. High levels of this protein are seen in hypercorticism, inflammation, pregnancy, and contraceptive therapy, and low levels are associated with adrenal insufficiency and converting enzyme inhibition. These variations are mostly due to modifications of the hepatic biosynthesis under the control of hormonal factors such as glucocorticoid, estrogen, thyroid hormone, insulin and angiotensin II. In addition, it has been found that these changes in the hepatic biosynthesis are due mainly to changes in the angiotensinogen gene expression.
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PMID:[Structure and regulation of the expression of the angiotensinogen gene]. 823 38

Renin is a glycoprotein that is heterogeneous with respect to carbohydrate content and net charge. In an attempt to clarify the role of renin isoelectric heterogeneity in renal renin storage and secretion, the isoelectric profile of renal renin, secreted renin, and circulating renin were directly assessed and compared under basal and stimulated conditions by the use of an in vivo blood perfused rabbit kidney preparation. Under basal conditions, the kidney preferentially stored and secreted the relatively basic isoelectric forms of renin. Acute stimulation of renin secretion (reduced renal perfusion pressure and angiotensin-converting enzyme inhibition) significantly increased the secretion of the relatively basic isoelectric forms but had very little effect on the secretion of the relatively acidic renin forms. Circulating renin was composed primarily of relatively basic forms, which increased disproportionately after stimulation of renin secretion. These findings suggest that the isoelectric heterogeneity of renin is important in the cellular processing of renin and can be explained by a two-pool model in which the relatively acidic isoelectric forms of renin are constitutively secreted (and not stored) and the relatively basic isoelectric forms represent a regulated pathway in which they are stored and rapidly released in response to acute secretory stimuli. Preferential hepatic extraction of the more basic isoelectric forms has previously been described. Data from this study suggest that the disproportionate increase in circulating basic forms of renin observed after acute stimulation reflects the net effect of preferential renal the more basic renin isoelectric forms. The disproportionate increase in relatively basic circulating renin forms after acute secretory stimulation results in an overall circulating renin activity with a shorter half-life.
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PMID:Role of renin isoelectric heterogeneity in renal storage and secretion of renin. 828 14

The peptide vasoconstrictors angiotensin II and endothelin-1, originally described as being derived exclusively from the plasma renin-angiotensin system and vascular endothelium, respectively, have been demonstrated to be produced independently of these sources. Local tissue angiotensin-generating systems are well documented and endothelin production has been demonstrated for a variety of nonendothelial cells, including vascular smooth muscle cells. There is increasing evidence that these locally produced vasoconstrictor peptides may contribute to blood vessel homeostasis, as well as the development of vascular pathologic conditions. Results obtained from pharmaceutical intervention in humans and animals of these systems strongly support this hypothesis. In addition to their vasoconstrictor properties, angiotensin II and endothelin-1 act as potent biologic effectors. In vitro, both vasoconstrictor peptides appear to modulate the activity of autocrine feedback loops in vascular smooth muscle cells. The activity of these feedback loops in vivo may represent a central mechanism for regulation and phenotypic differentiation of this cell type. The most well-established autocrine feedback loops of vascular smooth muscle cells are constituted by platelet-derived growth factor and transforming growth factor-beta, both of which are influenced by the action of angiotensin II and endothelin-1. The effects of the peptide vasoconstrictors on the (auto-) regulated feedback loops are of long-term structural importance, since both vasoconstrictors (via autocrine growth modulators) may influence the composition of the extracellular matrix of vascular smooth muscle cells. This includes effects on the synthesis and secretion of thrombospondin, fibronectin, tenascin, etc. The secretion of extracellular matrix glycoproteins themselves and incorporation into extracellular matrix in vitro appear to be linked to the activity of the autocrine feedback loops: e.g., stimulation of thrombospondin mRNA results in secretion of the glycoprotein only in the concomitant presence of exogenous platelet-derived growth factor, whereas the expression of fibronectin and tenascin may be directed by transforming growth factor-beta. The influence of angiotensin II and endothelin-1 on vascular smooth muscle cell surface receptor expression may represent a secondary mode of action of these vasoconstrictor peptides. Endothelin-1, for instance, can rapidly down-regulate platelet-derived growth factor-alpha receptor mRNA and both angiotensin II and endothelin-1, via induction of transforming growth factor-beta, may interrupt the platelet-derived growth factor based autocrine feedback loop. In vivo, the highly complex interactions between local and systemic vasoconstrictor production, autoregulated feedback loops, and extracellular matrix (which also serves as a reservoir for growth and differentiation modulators) are central to vessel homeostasis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of peptide vasoconstrictors on vessel structure. 848 51

Renal insufficiency as a result of congenital obstructive nephropathy is a consequence of impaired renal growth: chronic unilateral ureteral obstruction (UUO) results in greater injury to the immature kidney than to the adult kidney. The neonatal kidney responds to UUO by marked activation of the renin-angiotensin system, which contributes to severe vasoconstriction and progressive interstitial fibrosis of the obstructed kidney. The latter results in part because of activation of transforming growth factor-beta 1 by angiotensin II. Chronic UUO in the neonatal rat delays maturation of the obstructed kidney, possibly in part through suppressed expression of epidermal growth factor. In addition to affecting growth factors, UUO stimulates apoptosis in the obstructed kidney, which is quantitatively greater in the neonate than in the adult. In contrast, expression of clusterin, a glycoprotein that may play a protective role in the response to UUO, is greater in the adult than in the neonatal obstructed kidney. The response of the developing kidney to UUO is similar in a number of respects to cystic kidney disease. This includes a reduction in epidermal growth factor, and increased apoptosis that may result from suppression of bcl-2, an oncoprotein that inhibits apoptosis. Improved knowledge of the cellular and molecular basis for cystic renal disorders should lead to specific intervention in fetuses and infants with congenital obstructive nephropathy, thereby improving renal growth and development.
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PMID:Growth factors and apoptosis in neonatal ureteral obstruction. 886

Obtaining high quality protein crystals remains a rate-limiting step in the determination of three-dimensional X-ray structures. A frequently encountered problem in this respect is the high or heterogeneous carbohydrate content of many eukaryotic proteins. A number of reports have demonstrated the use of enzymatic deglycosylation in the crystallization of certain glycoproteins. Although this is an attractive tool, there are some problems that hinder the more widespread use of glycosidases in crystallization. First, commercially available glycosidases are relatively expensive, which virtually prohibits their use on a large scale. Second, the glycosidase must be removed from the glycoprotein of interest following deglycosylation, which is not always straightforward. To circumvent these problems we have cloned the two most generally useful glycosidases, peptide-N-glycosidase F and endoglycosidase F1 from Flavobacterium meningosepticum, as fusion proteins with glutathione S-transferase. The fusion not only allows rapid purification of these enzymes from Escherichia coli cell extracts, but also permits rapid removal from target proteins following deglycosylation. We have used these enzymes to obtain crystals of phytase from Aspergillus ficuum and acid phosphatase from Aspergillus niger and to obtain a new crystal form of recombinant human renin.
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PMID:Deglycosylation of proteins for crystallization using recombinant fusion protein glycosidases. 897 70


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