Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Renin is stored in synaptosomes of rat brain, separately from cathepsin D and intraneuronal angiotensin II (ANG II) has been demonstrated with the electron-microscope. Although the subcellular localization of other components of the renin-angiotensin system (RAS) have still to be investigated, these data suggest possible intracellular synthesis of ANG II in the brain. Brain ANG II is biochemically identical to the plasma peptide and corresponds to (IIe) 5-ANG II. The peptide level is unchanged after bilateral nephrectomy, and angiotensin I (ANG I) accumulation is observed in nephrectomized animals following brain angiotensin converting enzyme blockade. The significantly greater accumulation of ANG I and reduction of ANG II in stroke prone spontaneously hypertensive Wistar-Kyoto rats (WKY) indicates a higher synthesis and turnover rate of ANG II in SHR. Most converting enzyme inhibitors (CEI) penetrate the brain after chronic oral treatment. Part of their blood pressure lowering action may therefore be explained by an inhibition of the brain RAS.
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PMID:The brain angiotensin system: subcellular localization and interferences with converting enzyme inhibitors. 610 Jun 13

The aim of this study was to develop a method for the measurement of renin activity in small tissue samples obtained from rat brains by the micropunch technique and to investigate the activity of brain renin in spontaneously hypertensive rats. The assay satisfied sensitive and specificity requirements. Angiotensin I was generated at a pH of 6.0; complete recovery of angiotensin I and kinetic studies supported the specificity of the method. Angiotensinase and cathepsin D-like acid protease activity were measured in parallel with renin. Renin was present in all brain regions studied and decreased with the age of the animals. An increased activity of renin was measured in several nuclei of the brain stem and in the neurohypophysis of young hypertensive rats when compared with age-matched normotensive control animals. These differences disappeared in older rats. There was a dissociation between renin and cathepsin D-like acid protease activity. No correlation existed between the distribution of renin and angiotensinase activity. The increased renin activity in brain stem nuclei of spontaneously hypertensive animals is in agreement with previous findings that the brain renin-angiotensin system contributes to the maintenance of high blood pressure in these rats.
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PMID:A micromethod for the measurement of renin in brain nuclei: its application in spontaneously hypertensive rats. 628 32

Renin and cathepsin D were purified by seven-step procedures involving five steps common to both enzymes. These common five steps were extraction of freeze-dried kidney powder in 30% methoxyethanol-water, diethylaminoethyl-cellulose (DEAE-cellulose) batch absorption and elution, pepstatin-aminohexyl-Sepharose chromatography, Sephadex G-100 chromatography, and DEAE-cellulose chromatography. The renin component was purified further by passage through an anti-rat spleen cathepsin D immunoglobulin G-Sepharose (IgG-Sepharose) column followed by carboxymethyl-Sephadex (CM-Sepharose) chromatography which separated two renin components. Cathepsin D activity obtained by the fifth step was purified by passage through an anti-rat kidney renin IgG-Sepharose column followed by DEAE-Sephacel chromatography which separated three cathepsin D components. The homogeneity of renin and cathepsin D preparations was demonstrated by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The two components of renins showed molecular weights of 42 000 and 36 000 by gel filtration and 38 000 and 36 000 by SDS gel electrophoresis, respectively. They showed isoelectric points of 5.35 and 5.65 by electrofocusing in 5% polyacrylamide gels. Their optimum pHs of enzyme activity were 6.5 as determined by using nephrectomized rat plasma as a substrate. Their specific angiotensin I (Ang I) generation activities were 158 and 146 micrograms of Ang I (microgram of protein)-1 h-1, respectively, which correspond to 1100 and 1020 Goldblatt units (mg of protein)-1 h-1. The three cathepsins showed molecular weights of 41 000, 43 000, and 41 000 by gel filtration and 46 000, 45 000, and 46 000 by SDS gel electrophoresis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rat kidney renin and cathepsin D: purification and comparison of properties. 636 Feb 7

We developed new sensitive direct radioimmunoassay for human plasma renin. Renin was purified from Haas' preparation utilizing a pepstatin-C6-Sepharose affinity chromatography. Antiserum, prepared by immunizing rabbits with the purified renin, was used for the direct radioimmunoassay at a final dilution of 1:30,000. The antibody was specific for human renal and plasma renin, but did not cross-react with cathepsin D, trypsin, or renins of mouse, dog, and rat. Radioimmunoassay was performed by the double antibody technique using the delayed tracer addition method. In this method, a standard curve was obtained over a range from 0.2 to 8.0 ng/ml. The values from our assay correlated well with total renin activity measured as the generation rate of angiotensin I after trypsin activation (r = 0.78, p less than 0.01), but correlated weakly with active renin activity. This finding disclosed that both active and inactive renin were detected by this method. In normal participants, plasma renin concentration determined by direct radioimmunoassay was increased by standing and furosemide injection. The plasma renin concentration determined by direct radioimmunoassay of patients with essential hypertension (0.7 to 1.7 ng/ml) was not significantly different from values in normal controls (0.8 to 1.9 ng/ml). The values were higher in patients with renovascular hypertension (1.6 to 2.7 ng/ml), malignant hypertension (2.8 to 3.4 ng/ml) and Bartter's syndrome (1.8 to 2.5 ng/ml), but lower in patients with primary aldosteronism (0.4 to 0.8 ng/ml) than in normal controls. This newly developed radioimmunoassay for human renin was sensitive enough to estimate the levels of renin in plasma of patients with low renin hypertension. It provides a new tool for the understanding of the renin-angiotensin system under various clinical conditions.
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PMID:A new sensitive direct radioimmunoassay for human plasma renin and its clinical application. 638 35

Renin-like activity in the heart and aorta of rats being slightly modified by binephrectomy, its variations in DOCA hypertension and infarcted ventricular muscle were studied. The daily i.p. administration of DOCA 12 mg/kg body weight for 35 days in male adult rats resulted in a significant decrease of renin activity in plasma and tissues of the heart, aorta, hypothalamus and hypophysis. In contrast to renin-like activity, cathepsin D measured in the same animals increased in all organs, except for the plasma. Similar changes of renin-like activity were observed in salt-loaded animals with 1.7% sodium chloride solution ad libitum for 35 days. In the infarcted myocardial ventricular muscle of the rats and rabbits, the tissue isorenin showed a tendency to decrease, associated with a significant increase in cathepsin D activity. Like in aorta, isorenin seems to be a different enzymatic entity of cathepsin D in the myocardial tissue. The measurement of isorenin content of the vascular endothelium and cardiac muscle fibers seems to reveal much higher amounts in the coronary vascular endothelium than in the myocardial fibres. The activation of the enzymatic angiotensin forming mechanisms in the coronary vascular bed could be one of the risk factors in myocardial infarction.
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PMID:A comparative study of the renin-like activity in the heart and vascular system under various experimental conditions. 642 49

In this study we have shown that sodium deprivation of rats increased the number of specific granules and renin activity in atria. Sodium loading and DOCA treatment were found to lower the number of granules and renin activity. Renin activity which is present in both atria and ventricles is not localized in specific granules, as shown by ultracentrifugation and immunocytochemistry. Although this renin activity was partially abolished by preincubation with specific antiserum, the present results do not rule out the possibility that the activity is due to cathepsin D.
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PMID:Relationship of specific granules to renin activity in the myocardium. 676 75

1. A renin-inhibitory material has been partially purified from soluble extracts of the pig kidney cortex by ammonium sulphate precipitation and diethylaminoethylcellulose (DEAE) chromatography and its properties studied. 2. It displayed competitive type kinetics. It did not inhibit cathepsin D, carboxypeptidase A, pancreatic kallikrein or trypsin. 3. Renins from dogs, rabbit and rat were inhibited, but not those from sheep or man, when assayed with pig angiotensinogen. 4. The material was inactivated by treatment with trypsin, N-ethylmaleimide or p-chloromercuribenzoate. 5. Renin-inhibitory activity was not found in plasma from peripheral blood of pigs. 6. It is concluded that the function of the renin inhibitor in the renal cortex of the pig may be restricted to the intrarenal environment.
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PMID:Properties of a renin inhibitor isolated from the pig kidney cortex. 701 9

To clarify the role of Angiotensin II (Ang II) in the sensory system and especially in the trigeminal ganglia, we studied the expression of angiotensinogen (Ang-N)-, renin-, angiotensin converting enzyme (ACE)- and cathepsin D-mRNA, and the presence of Ang II and substance P in the rat and human trigeminal ganglia. The rat trigeminal ganglia expressed substantial amounts of Ang-N- and ACE mRNA as determined by quantitative real time PCR. Renin mRNA was untraceable in rat samples. Cathepsin D was detected in the rat trigeminal ganglia indicating the possibility of existence of pathways alternative to renin for Ang I formation. In situ hybridization in rat trigeminal ganglia revealed expression of Ang-N mRNA in the cytoplasm of numerous neurons. By using immunocytochemistry, a number of neurons and their processes in both the rat and human trigeminal ganglia were stained for Ang II. Post in situ hybridization immunocytochemistry reveals that in the rat trigeminal ganglia some, but not all Ang-N mRNA-positive neurons marked for Ang II. In some neurons Substance P was found colocalized with Ang II. Angiotensins from rat trigeminal ganglia were quantitated by radioimmunoassay with and without prior separation by high performance liquid chromatography. Immunoreactive angiotensin II (ir-Ang II) was consistently present and the sum of true Ang II (1-8) octapeptide and its specifically measured metabolites were found to account for it. Radioimmunological and immunocytochemical evidence of ir-Ang II in neuronal tissue is compatible with Ang II as a neurotransmitter. In conclusion, these results suggest that Ang II could be produced locally in the neurons of rat trigeminal ganglia. The localization and colocalization of neuronal Ang II with Substance P in the trigeminal ganglia neurons may be the basis for a participation and function of Ang II in the regulation of nociception and migraine pathology.
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PMID:Endogenous angiotensinergic system in neurons of rat and human trigeminal ganglia. 1932 83

A paucity of information exists regarding the presence of local renin-angiotensin systems (RASs) in skeletal muscle and associated muscle stem cells. Skeletal muscle and muscle stem cells were isolated from C57BL/6 mice and examined for the presence of a local RAS using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), Western blotting and liquid chromatography-mass spectrometry (LC-MS). Furthermore, the effect of mechanical stimulation on RAS member gene expression was analysed. Whole skeletal muscle, primary myoblasts and C2C12 derived myoblasts and myotubes differentially expressed members of the RAS including angiotensinogen, angiotensin-converting enzyme (ACE), angiotensin II (Ang II) type 1 (AT(1)) and type 2 (AT(2)). Renin transcripts were never detected, however, mRNA for the 'renin-like' enzyme cathepsin D was observed and Ang I and Ang II were identified in cell culture supernatants from proliferating myoblasts. AT(1) appeared to co-localise with polymerised actin filaments in proliferating myoblasts and was primarily found in the nucleus of terminally differentiated myotubes. Furthermore, mechanical stretch of proliferating and differentiating C2C12 cells differentially induced mRNA expression of angiotensinogen, AT(1) and AT(2). Proliferating and differentiated muscle stem cells possess a local stress-responsive RAS in vitro. The precise function of a local RAS in myoblasts remains unknown. However, evidence presented here suggests that Ang II may be a regulator of skeletal muscle myoblasts.
J Renin Angiotensin Aldosterone Syst 2011 Jun
PMID:Skeletal muscle myoblasts possess a stretch-responsive local angiotensin signalling system. 2092 Oct 89


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