Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative damage, through increased production of free radicals, is believed to be involved in UV-induced cataractogenesis (eye lens opacification). The possibility of UVB radiation causing damage to important lenticular enzymes was assessed by irradiating 3 months old rat lenses (in RPMI-1640 medium) at 300 nm (100 microWcm(-2)) for 24 h, in the absence and presence of ascorbic acid, alpha-tocopherol acetate and beta-carotene. UVB irradiation resulted in decreased activities of hexokinase, glucose-6-phosphate dehydrogenase, aldose reductase, and Na, K- ATPase by 42, 40, 44 and 57% respectively. While endopeptidase activity (229%) and lipid peroxidation (156%) were increased, isocitrate dehydrogenase activity was not altered on irradiation. In the presence of externally added ascorbic acid, tocopherol and beta-carotene (separately) to the medium, the changes in enzyme activities (except endopeptidase) and increased lipid peroxidation, due to UVB exposure, were prevented. These results suggest that UVB radiation exerts oxidative damage on lens enzymes and antioxidants were protective against this damage.
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PMID:Protection against UVB inactivation (in vitro) of rat lens enzymes by natural antioxidants. 1039 Nov 22

Ammonia stimulates cortical collecting duct (CCD) net bicarbonate reabsorption by activating an apical H(+)-K(+)-ATPase through mechanisms that are independent of ammonia's known effects on intracellular pH and active sodium transport. The present studies examined whether this stimulation occurs through soluble N-ethylmaleimide-sensitive fusion attachment receptor (SNARE) protein-mediated vesicle fusion. Rabbit CCD segments were studied using in vitro microperfusion, and transepithelial bicarbonate transport was measured using microcalorimetry. Ammonia's stimulation of bicarbonate reabsorption was blocked by either chelating intracellular calcium with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester or by inhibiting microtubule polymerization with colchicine compared with parallel studies performed in the absence of these inhibitors. An inactive structural analog of colchicine, lumicolchicine, did not alter ammonia's stimulation of bicarbonate reabsorption. Tetanus toxin, a zinc endopeptidase specific for vesicle-associated SNARE (v-SNARE) proteins, prevented ammonia from stimulating net bicarbonate reabsorption. Consistent with the functional evidence for v-SNARE involvement, antibodies directed against a conserved region of isoforms 1-3 of the tetanus toxin-sensitive, vesicle-associated membrane protein (VAMP) members of v-SNARE proteins labeled the apical and subapical region of collecting duct intercalated cells. Similarly, antibodies to NSF protein, a protein involved in activation of SNARE proteins for subsequent vesicle fusion, localized to the apical and subapical region of collecting duct intercalated cells. These results indicate that ammonia stimulates CCD bicarbonate reabsorption through an intracellular calcium-dependent, microtubule-dependent, and v-SNARE-dependent mechanism that appears to involve insertion of cytoplasmic vesicles into the apical plasma membrane of CCD intercalated cells.
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PMID:Mechanisms through which ammonia regulates cortical collecting duct net proton secretion. 1199 29

1. Cirrhosis is associated with cardiovascular and renal dysfunction including sodium retention. Many vasoactive peptides such as atrial natriuretic peptide (ANP) and endothelin-1 (ET-1) are degraded by neutral endopeptidase 24.11 (NEP). We investigated the hemodynamic and renal effects of thiorphan, a NEP inhibitor, in a rat cirrhosis model. 2. Cirrhosis was induced by chronic bile duct ligation, and controls had sham operation. Systemic and renal hemodynamics in conscious, restrained animals were determined using radiolabeled microspheres, and glomerular filtration rate (GFR) was measured by (3)H-inulin clearance. Plasma ANP and ET-1, and renal cGMP and Na(+) - K(+) ATPase activity were assayed. These variables were measured at baseline and after intravenous infusion of thiorphan (0.5 mg kg(-1) loading dose followed by 0.1 mg kg(-1) min(-1) x 30 min). 3. Thiorphan significantly decreased cardiac output, and increased systemic vascular resistance in controls, whereas in cirrhotic rats these variables were unchanged. 4. Compared to the controls, cirrhotic rats showed a decreased baseline GFR and urine sodium excretion, and the latter was significantly increased by thiorphan. 5. Thiorphan increased plasma ET-1 levels in controls, but not cirrhotic rats. ANP levels were not significantly increased in either group by thiorphan. 6. Thiorphan significantly increased cGMP concentrations and decreased Na(+) - K(+) ATPase activity of renal medulla but not cortex in cirrhotic rats; no effect was observed in the control rats. 7. We conclude that thiorphan induces natriuresis in cirrhotic rats by a direct renal medullary mechanism via cGMP and Na(+) - K(+) ATPase, without affecting systemic hemodynamics. This may potentially be useful in patients with ascites.
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PMID:Effects of the neutral endopeptidase inhibitor thiorphan on cardiovascular and renal function in cirrhotic rats. 1274 26

Porphyromonas gingivalis, one of the causative agents of adult periodontitis, can invade and survive within host epithelial cells. The molecular mechanisms by which P. gingivalis induces uptake and adapts to an intracellular environment are not fully understood. In this study, we have investigated the genetic responses of P. gingivalis internalized within human gingival epithelial cells (GECs) in order to identify factors involved in invasion and survival. We compared the differential display of arbitrarily PCR-amplified gene transcripts in P. gingivalis recovered from GECs with the display of transcripts in P. gingivalis control cultures. Over 20 potential differentially expressed transcripts were identified. Among these, pepO, encoding an endopeptidase, and genes encoding an ATP-binding cassette (ABC) transporter and a cation-transporting ATPase were upregulated in GECs. To investigate the functionality of these gene products, mutants were generated by insertional inactivation. Compared to the parental strain, mutants of each gene showed a significant reduction in their invasion capabilities. In addition, GEC cytoskeletal responses to the mutants were distinct from those induced by the parent. In contrast, adhesion of the mutant strains to GECs was not affected by lack of expression of the gene products. These results suggest that PepO, a cation-transporting ATPase, and an ABC transporter are required for the intracellular lifestyle of P. gingivalis.
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PMID:Identification of Porphyromonas gingivalis genes specifically expressed in human gingival epithelial cells by using differential display reverse transcription-PCR. 1521 15

FtsH is a cytoplasmic membrane protein that has N-terminally located transmembrane segments and a main cytosolic region consisting of AAA-ATPase and Zn2+-metalloprotease domains. It forms a homo-hexamer, which is further complexed with an oligomer of the membrane-bound modulating factor HflKC. FtsH degrades a set of short-lived proteins, enabling cellular regulation at the level of protein stability. FtsH also degrades some misassembled membrane proteins, contributing to their quality maintenance. It is an energy-utilizing and processive endopeptidase with a special ability to dislocate membrane protein substrates out of the membrane, for which its own membrane-embedded nature is essential. We discuss structure-function relationships of this intriguing enzyme, including the way it recognizes the soluble and membrane-integrated substrates differentially, on the basis of the solved structure of the ATPase domain as well as extensive biochemical and genetic information accumulated in the past decade on this enzyme.
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PMID:Cellular functions, mechanism of action, and regulation of FtsH protease. 1591 Feb 74

We used temperature-responsive culture dishes onto which the temperature-responsive polymer, poly(Nisopropylacrylamide), was covalently grafted for tissue engineering. Confluent cells harvested as intact sheets from these surfaces by simple temperature reduction can be transferred to various surfaces including additional culture dishes, other cell sheets, and tissues. In order to examine the maintenance of cell polarity, Madin-Darby canine kidney cells and human primary renal proximal tubule epithelial cells which had developed apical-basal cell polarity in culture, were subjected to cell sheet transfer. This functional and structural cell polarity, which is susceptible to treatment with trypsin, was examined by immunohistochemistry and transmission electron microscopy. Using our cell-sheet method, the noninvasive transfer of these cell sheets retaining typical distributions of Na+/K+-ATPase, GLUT-1, SGLT-1, aquaporin-1, neutral endopeptidase and dipeptidylendopeptidase IV, could be achieved. The transferred cell sheets also developed numerous microvilli and tight junctions at the apical and lateral membranes, respectively. For biochemical analysis, immunoblotting of occludin, a transmembrane protein that composes tight junctions, was conducted and results confirmed that occludin remained intact after cell sheet transfer. This two-dimensional cell sheet manipulation method promises to be useful for tissue engineering as well as in the investigation of epithelial cell polarity.
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PMID:A noninvasive transfer system for polarized renal tubule epithelial cell sheets using temperature-responsive culture dishes. 1608 52

Previous genome-wide screens identified over 100 host genes whose deletion/down-regulation affected tombusvirus replication and 32 host genes that affected tombusvirus RNA recombination in yeast, a model host for replication of Tomato bushy stunt virus (TBSV). Down-regulation of several of the identified host genes affected the accumulation levels of p33 and p92(pol) replication proteins, raising the possibility that these host factors could be involved in the regulation of the amount of viral replication proteins and, thus, they are indirectly involved in TBSV replication and recombination. To test this model, we developed a tightly regulated expression system for recombinant p33 and p92(pol) replication proteins in yeast. We demonstrate that high accumulation level of p33 facilitated efficient viral RNA replication, while the effect of p33 level on RNA recombination was less pronounced. On the other hand, high level of p92(pol) accumulation promoted TBSV RNA recombination more efficiently than RNA replication. As predicted, Rpb11p, which is part of the polII complex, affected the accumulation levels of p33 and p92(pol) as well as altered RNA replication and recombination. An in vitro assay with the tombusvirus replicase further supported that Rpb11p affects TBSV replication and recombination only indirectly, via regulating p33 and p92(pol) levels. In contrast, the mechanism by which Rpt4p endopeptidase/ATPase and Mps1p threonine/tyrosine kinase affect TBSV recombination is different from that proposed for Rpb11p. We propose a model that the concentration (molecular crowding) of replication proteins within the viral replicase is a factor affecting viral replication and recombination.
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PMID:Host transcription factor Rpb11p affects tombusvirus replication and recombination via regulating the accumulation of viral replication proteins. 1768 83

Although deoxycorticosterone acetate (DOCA)-salt hypertension is a volume dependent model of hypertension, it shows polyuria and natriuresis. It is expected that dysregulation of aquaporin water channels (AQPs) and sodium transporters associated with natriuretic peptide (NP) system may play an escape role in sodium retaining state. One week after left unilateral nephrectomy, rats were subcutaneously implanted with silastic DOCA (200 mg/kg) strips. Physiologic saline was supplied as a drinking water to all animals. 4 weeks after operation, the protein expression of AQPs, sodium transporters, and endopeptidase (NEP) was determined in the kidneys by semiquantitative immunoblotting and immunohistochemistry. The mRNA expression of NP system was determined by real-time polymerase chain reaction. The amount of urinary ANP excretion was measured by radioimmunoassay. In DOCA-salt rats, urine osmolality was decreased while urinary excretion of sodium was increased. The expression of AQP1-3 as well as that of alpha-1 subunit of Na,K-ATPase, NHE3, NKCC2 and NCC was decreased in the kidney. The mRNA expression of ANP, brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP) was increased in the kidney. The expression of NEP was decreased, and urinary ANP excretion was increased. Downregulation of AQPs and sodium transporters may contribute to mineralocorticoid escape in DOCA-salt hypertension. Increased expression of natriuretic peptides associated with downregulation of NEP may play a role in natriuresis.
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PMID:Altered regulation of renal sodium transporters and natriuretic peptide system in DOCA-salt hypertensive rats. 1942 59

GCPs (glycoproteases) are members of the HSP70 (heat-shock protein 70)/actin ATPase superfamily that are highly conserved in taxonomically diverse species from bacteria to man, suggesting an essential physiological role. Although originally identified and annotated as putative endopeptidases, a proteolytic activity could not be confirmed for these proteins. Our survey of genome databases revealed that all eukaryotic organisms contain two GCP genes [called GCP1 and GCP2/Kae1 (kinase-associated endopeptidase 1)], whereas prokaryotes have only one, either of the GCP1- (Bacteria) or the GCP2/Kae1- (Archaea) type. GCP2/Kae1 is essential for telomere elongation and transcription of essential genes, although little is known about the localization, expression and physiological role of GCP1. In the present study on GCP1-type proteins from eukaryotic organisms we demonstrated that GCP1 is a mitochondrial protein in Homo sapiens [called here GCP1/OSGEPL1 (O-sialoglycoprotein endopeptidase)] and Arabidopsis thaliana, which is located/anchored to the mitochondrial inner membrane. Analysis of mRNA and protein levels revealed that the expression of GCP1/OSGEPL1 in A. thaliana and H. sapiens is tissue- and organ-specific and depends on the developmental stage, suggesting a more specialized function for this protein. We showed that homozygous A. thaliana GCP1 T-DNA (transferred DNA) insertion lines were embryonic lethal. Embryos in homozygous seeds were arrested at the globular stage and failed to undergo the transition into the heart stage. On the basis of these data we propose that the mitochondrial GCP1 is essential for embryonic development in plants.
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PMID:Eukaryotic GCP1 is a conserved mitochondrial protein required for progression of embryo development beyond the globular stage in Arabidopsis thaliana. 1969 17

In a previous paper we demonstrated that Ang-(3-4) counteracts inhibition of the Ca(2+)-ATPase by Ang II in the basolateral membranes of kidney proximal tubules cells (BLM). We have now investigated the enzymatic routs by which Ang II is converted to Ang-(3-4). Membrane-bound angiotensin converting enzyme, aminopeptidases and neprilysin were identified using fluorescent substrates. HPLC showed that Plummer's inhibitor but not Z-pro-prolinal blocks Ang II metabolism, suggesting that carboxypeptidase N catalyzes the conversion Ang II--> Ang-(1-7). Different combinations of bestatin, thiorphan, Plummer's inhibitor, Ang II and Ang-(1-5), and use of short proteolysis times, indicate that Ang-(1-7)--> Ang-(1-5)--> Ang-(1-4)--> Ang-(3-4) is a major route. When Ang III was combined with the same inhibitors, the following pathway was demonstrated: Ang III--> Ang IV--> Ang-(3-4). Ca(2+)-ATPase assays with different Ang II concentrations and different peptidase inhibitors confirm the existence of these pathways in BLM and show that a prolyl-carboxypeptidase may be an alternative catalyst for converting Ang II to Ang-(1-7). Overall, we demonstrated that BLM have all the peptidase machinery required to produce Ang-(3-4) in the vicinity of the Ca(2+)-ATPase, enabling a local RAS axis to effect rapid modulation of active Ca(2+) fluxes.
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PMID:A scrutiny of the biochemical pathways from Ang II to Ang-(3-4) in renal basolateral membranes. 1970 99


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