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

The presence of acetone-soluble renin inhibitors in normal plasma has been proposed to explain the variation of plasma reactivity (PRR) in samples from normotensive and hypertensive subjects. In our experience, acetone extraction decreased PRR in relation to unextracted control values, an observation which is not consistent with the circulating lipid-renin inhibitor hypothesis. Exposure to acetone at -40 degrees C for 1 minute invariably denatured some endogenous angiotensinogen. The PRR in extracted and unextracted plasma was positively correlated with the concentration of available angiotensinogen, r = 0.955 (p < 0.05), and r = 0.964 (p < 0.01), respectively, but the addition of exogenous substrate did not uniformly increase PRR in acetone-treated plasma above control values. These data argue against the use of acetone extraction to demonstrate the existence of circulating lipid-renin inhibitors. Acetone removed 14% to 25% of the normal plasma lipids and although the extract contained most of the major lipid classes, neutral lipids were the most abundant (73% by weight). The presence of acetone-soluble phospholipids appeared to increase angiotensin I formation in the partially purified renin-angiotensinogen system, but phospholipids interfered with the radioimmunoassay and resulted in an overestimation of angiotensin I. Plasma neutral lipids decreased in vitro renin activity by 13% (p < 0.025) but this degree of inhibition suggests that lipid-renin interactions may have minimal in vivo physiological significance. In contrast to previous reports, we found the correlation between PRR and endogenous angiotensinogen in normotensive and hypertensive plasmas to be statistically significant (r = 0.643, p < 0.01). Inactivated human angiotensinogen was also shown to be an inhibitor of renin in vitro. This effect could have possibly influenced PRR values that were determined by others in the presence of inactivated angiotensinogen.
 ...
PMID:Evidence against acetone-soluble renin inhibitors in normal human plasma. 39 42

The circulating RA (renin-angiotensin) system is essential for the regulation of blood pressure and electrolyte balance. Recently, plasma prorenin has been reported to significantly increase its level in diabetes and to be possibly non-proteolytically activated by binding to the PRR [(pro)renin receptor] on the cell membrane reported in several tissues during circulation. Although many pathological aspects have been researched, there is a lack of sufficient information on the biochemical structure and biological function of this hPRR (human PRR) because of the difficulty in increasing hPRR expression. In the present study, GFP(uv)-hPRR (hPRR fused with green fluorescence protein when excited with long-wave UV light) was successfully expressed by using BmMNPV (Bombyx mori multiple nucleopolyhedrovirus) bacmid DNA in silkworm (Bombyx mori) larvae. Some of the hPRR was expressed in the haemolymph of silkworm larvae and some of the hPRR was located in the fat body of silkworm larvae. The binding ability of hPRR expressed in the haemolymph and fat body with renin or prorenin was analysed by ELISA and surface plasmon resonance using a biosensor respectively. These binding assays suggest that the expressed hPRR has a functional bioactivity. hPRR preparation in silkworm larvae would, therefore, be useful for biochemical and biomedical researches related to PRR.
 ...
PMID:Expression of functional human (pro)renin receptor in silkworm (Bombyx mori) larvae using BmMNPV bacmid. 1770 88

The renin-angiotensin (RA) system is important for the regulation of blood pressure and electrolyte balance, and renin is the rate-limiting enzyme in this system. The recent discovery of (pro)renin receptor (PRR) has reinforced the functional role of the RA system. PRR non-proteolytically activates prorenin and its role has attracted the attention of researchers towards the RA system. However, there is insufficient information on the biochemical structure and biological functioning of PRR due to the difficulty of measuring PRR expression. In this work, human PRR (hPRR) with intact transmembrane and C-terminal domain (hPRR-wTM) and PRR without this domain (hPRR-w/oTM) were expressed in insect cells using baculovirus expression system (BES). Both hPRR-wTM and hPRR-w/oTM were fused with FLAG peptide by its N-terminus. Most of the hPRR-wTM was expressed in cell fraction and hPRR-w/oTM was secreted into the culture medium. hPRR-wTM was solubilized from the membrane fraction of recombinant baculovirus-infected cells by various detergents, suggesting that hPRR-wTM might be a transmembrane protein. hPRR-wTM was purified from the solubilized fraction using anti-FLAG M2 antibody agarose. Binding of purified hPRR-wTM to renin immobilized onto sensor chips was directly proportional to the hPRR-wTM concentration. Approximately 225 microg of functional hPRR-wTM was purified from 80 ml of baculovirus-infected cell culture. Scale-up of this system will lead to mass production and crystallization of hPRR-wTM and determination of its biochemical structure and biological function.
 ...
PMID:Expression and purification of human (pro)renin receptor in insect cells using baculovirus expression system. 1817 23

(Pro)renin receptor (PRR), the newest member of the renin-angiotensin system (RAS), is turning out to be an important player in the regulation of the cardiovascular system. It plays a pivotal role in activation of the local RAS and stimulates signalling pathways involved in proliferative and hypertrophic mechanisms. However, the role of PRR in the brain remains unknown. Thus, our objective in this study was to determine whether a functional PRR is present in neurons within the brain. Neuronal co-cultures from the hypothalamus and brainstem areas of neonatal rat brain express PRR mRNA. Immunoreactivity for PRR was primarily localized on the neuronal cell soma and in discrete areas in the neurites. Treatment of neurons with renin, in the presence of 2 microm losartan, caused a time- and dose-dependent stimulation of phosphorylation of extracellular signal related kinase ERK1 (p44) and ERK2 (p42) isoforms of mitogen-activated protein kinase. Optimal stimulation of fourfold was observed within 2 min with 20 nm renin. Electrophysiological recordings showed that treatment of the neurons with renin, in the presence of 2 microm losartan, resulted in a steady and stable decrease in action potential frequency. A 46% decrease in action potential frequency was observed within 5 min of treatment and was attenuated by co-incubation with a PRR blocking peptide. These observations demonstrate that the PRR is present in neurons within the brain and that its activation by renin initiates the MAP kinase signalling pathway and inhibition of neuronal activity.
 ...
PMID:Characterization of a functional (pro)renin receptor in rat brain neurons. 1832 51

The (pro)renin receptor (PRR) is believed to potentiate the renin-angiotensin system (RAS), conferring to prorenin, a likely pathological role at tissue level. The PRR has been identified in the microvascular endothelial cells of the retina, in which it seems to be involved in pathological neovascularization processes. In the present study, we sought to explore PRR expression and prorenin action in human retinal pigment epithelium (RPE) cells, as well as its potential implication in extracellular matrix (ECM) turnover. Isolated RPE cells from donor human eyes as well as freshly isolated human retinas demonstrated expression of PRR at mRNA and protein levels. Moreover, we demonstrate that PRR expressed in the RPE cells is functional, as shown by prorenin-induced increases in Erk1/2 phosphorylation. PRR expression was also shown to be regulated by its main physiological agonist prorenin. We found evidence that the PRR may be involved in ECM-remodeling processes through a prorenin-induced upregulation of type I collagen. Immunostaining analysis of human retinas revealed higher PRR and type I collagen expression in the RPE of eye donors with dry age-related macular degeneration (AMD) and hypertension, supporting the in vitro findings using human-isolated RPE cells. Taken together, the present study demonstrates for the first time that the PRR is expressed in human RPE and suggests a molecular mechanism by which hypertension may exacerbate the pathology of dry AMD.
 ...
PMID:(Pro)renin receptor is expressed in human retinal pigment epithelium and participates in extracellular matrix remodeling. 1958 Aug 9

The renin-angiotensin system (RAS) plays a central role in the brain to regulate blood pressure (BP). This role includes the modulation of sympathetic nerve activity (SNA) that regulates vascular tone; the regulation of secretion of neurohormones that have a critical role in electrolyte as well as fluid homeostasis; and by influencing behavioral processes to increase salt and water intake. Based on decades of research it is clear that angiotensin II (Ang II), the major bioactive product of the RAS, mediates these actions largely via its Ang II type 1 receptor (AT1R), located within hypothalamic and brainstem control centers. However, the mechanisms of brain RAS function have been questioned, due in large part to low expression levels of the rate limiting enzyme renin within the central nervous system. Tissue localized RAS has been observed in heart, kidney tubules and vascular cells. Studies have also given rise to the hypothesis for localized RAS function within the brain, so that Ang II can act in a paracrine manner to influence neuronal activity. The recently discovered (pro)renin receptor (PRR) may be key in this mechanism as it serves to sequester renin and prorenin for localized RAS activity. Thus, the PRR can potentially mitigate the low levels of renin expression in the brain to propagate Ang II action. In this review we examine the regulation, expression and functional properties of the various RAS components in the brain with particular focus on the different roles that PRR may have in BP regulation and hypertension.
 ...
PMID:A current view of brain renin-angiotensin system: Is the (pro)renin receptor the missing link? 1972 38

An important role of the decoy peptide sequence has recently been suggested in vitro for the binding of prorenin to the (pro)renin receptor [PRR]. In this study, other prospective crucial regions in renin and prorenin responsible for their interaction with PRR were investigated using various kinds of peptides, e.g., the "hinge" S149QGVLKEDVF158 designed from the structure of renin also common to prorenin, L1PPTDTTTF8P, L1PPTDTTTFKRIFLKR15P and the decoy (R10PIFLKRMPSI19P) designed from the predicted structure of prorenin. For the kinetic analysis, the recombinant hPRR was immobilized on the biosensor surface through a specific anti-PRR antibody. In case of the equilibrium state analysis, the PRR was directly adsorbed on plastic wells for observing the bindings of renin/prorenin. The dissociation constants (KD) for the bindings of renin and prorenin to the pre-adsorbed receptors were 4.5 and 1.0 nM, respectively, similar to those stated in the kinetic study by BIAcore assay. The "hinge" region peptide bound to PRR in a dose-dependent manner with a KD estimated 17.0 nM which was five times higher than that of the decoy. The KD values for L1PPTDTTTF8P and L1PPTDTTTFKRIFLKR15P were 52 and 7.6 nM, respectively. The "hinge" peptide, as the decoy, inhibited the bindings of renin and prorenin to PRR. The inhibition constant (Ki) for the binding of renin and prorenin by the decoy and "hinge" were 16.7 and 15.1, and 37.1 and 30.7 nM, respectively. These in vitro studies suggest that renin has a single and prorenin has at least two high affinity binding sites for the PRR.
 ...
PMID:Prorenin has high affinity multiple binding sites for (pro)renin receptor. 1973 64

1. (Pro)renin receptor (PRR) binding to renin or prorenin mediates angiotensin (Ang) II-dependent and -independent effects. Expression of the PRR is increased in kidneys of diabetic rats, but its role in diabetic nephropathy is unknown. In the present study, we investigated the contribution of the PRR to the development of diabetic nephropathy through enhancement of renal production of tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta. 2. Normoglycaemic control and streptozotocin-diabetic Sprague-Dawley rats were used in the study. The urine albumin : creatinine ratio (UACR), renal interstitial fluid (RIF) levels of AngII, TNF-alpha and IL-1beta and renal expression of TNF-alpha and IL-1beta were evaluated in control, untreated diabetic and diabetic rats treated with either a PRR blocker (PRRB; 0.2 mg/kg per day NH3-RILLKKMPSV-COOH), the AT(1) receptor antagonist valsartan (2 mg/kg per day) or combined therapy, administered directly into the renal cortical interstitium for 14 days via osmotic minipumps. 3. Compared with values in normoglycaemic control rats, UACR and RIF AngII, TNF-alpha and IL-1beta were significantly higher in untreated diabetic rats. Treatment of diabetic rats with the PRRB or valsartan alone and in combination significantly reduced UACR and RIF TNF-alpha and IL-1beta levels. Renal expression of TNF-alpha and IL-1beta was higher in untreated diabetic rats than in control rats, but was reduced significantly following treatment with PRRB or valsartan alone and in combination. Renal PRR expression was increased in untreated and PRRB-treated diabetic rats and reduced in rats receiving valsartan alone or combination therapy. The PRRB had no effect on RIF AngII levels, whereas valsartan alone and in combination with the PRRB significantly increased AngII levels. 4. In conclusion, the PRR is involved in the development and progression of kidney disease in diabetes by enhancing renal production of the inflammatory cytokines TNF-alpha and IL-1beta, independent of renal AngII effects.
 ...
PMID:(Pro)renin receptor contributes to diabetic nephropathy by enhancing renal inflammation. 1993 Apr 21

(Pro)renin receptor (PRR) is present in renal glomeruli, and its expression is up-regulated in diabetes. Similarly, renal inflammation is increased in the presence of hyperglycemia. The linkage between PRR and renal inflammation is not well established. We hypothesized that glucose-induced up-regulation of PRR leads to increased production of the proinflammatory factors IL-1beta and cyclooxygenase-2 (COX-2). Studies were conducted in rat mesangial cells (RMCs) exposed to 30 mm D-glucose for 2 wk followed by PRR small interfering RNA knockdown, IL-1 receptor blockade with IL-1 receptor antagonist or angiotensin II type 1 receptor blockade with valsartan. The results showed that D-glucose treatment up-regulates prorenin, renin, angiotensin II, PRR, IL-1beta, and COX-2 mRNA and protein expression and increases phosphorylation of ERK1/2, c-Jun N-terminal kinase, c-Jun, and nuclear factor-kappaB (NF-kappaB) p65 (serine 276,468 and 536), respectively. PRR small interfering RNA attenuated PRR, IL-1beta, and COX-2 mRNA and protein expressions and significantly decreased angiotensin II production and phosphorylation of ERK1/2 and NF-kappaB p65 associated with high glucose exposure. Similarly, IL-1 receptor antagonist significantly reduced COX-2 mRNA and protein expression induced by high glucose. COX-2 inhibition reduced high-glucose-induced PRR expression. We conclude that glucose induces the up-regulation of PRR and its ligands prorenin and renin, leading to increased IL-1beta and COX-2 production via the angiotensin II-dependent pathway. It is also possible that PRR could enhance the production of these inflammatory cytokines through direct stimulation of ERK1/2-NF-kappaB signaling cascade.
 ...
PMID:Glucose promotes the production of interleukine-1beta and cyclooxygenase-2 in mesangial cells via enhanced (Pro)renin receptor expression. 1986 3

The (pro)renin receptor (PRR) binds renin and prorenin, its proenzyme inactive form. Receptor-bound prorenin becomes enzymatically active and binding then activates the MAP kinases ERK1/2 and p38 pathways, leading to upregulation of profibrotic and cyclooxygenase-2 genes independent of angiotensin II generation. These characteristics explain the interest in the potential role of PRR in organ damage in diseases associated with activation of the renin-angiotensin system (RAS), in particular hypertension and diabetes. Although identification of PRR has improved our understanding of the physiology of the tissue RAS, its role in pathology is far from clear. Transgenic animals overexpressing PRR ubiquitously or selectively in smooth-muscle cells develop high BP or glomerulosclerosis, and increased expression of PRR is reported in models of hypertension or kidney damage. However, definitive proof is still lacking for a role for PRR in disease, or by showing improvement of disease by tissue-specific ablation of PRR or by administration of a specific PRR antagonist. Furthermore, the early embryonic lethality seen in PRR-null mice suggests PRR has additional essential cellular functions we do not understand.
 ...
PMID:The biology of the (pro)renin receptor. 1991 80


1 2 3 4 5 6 7 8 Next >>