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

---

Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the effect of the angiotensin converting enzyme (ACE) inhibitor, enalaprilat, on mesangial cell (MC) DNA synthesis induced by H2O2, IL-6 and PDGF. MC were incubated with enalaprilat (2.5-100 mumol/l) alone and together with combinations of H2O2 (3 daily pulses of 10(-6) mol/l), IL-6 (5 ng/ml) and PDGF (10 ng/ml). DNA synthesis was assessed after 72 h using [3H]thymidine (3H-TdR) incorporation. Enalaprilat alone had no effect on MC DNA synthesis. Stimulation of MC by H2O2, PDGF and IL-6 alone resulted in increases in 3H-TdR of 4936.6 +/- 1147.5, 5640.5 +/- 1537.6 and 4413.5 +/- 998.4 cpm, respectively (P < 0.05 above control). Only 2.5 mumol/l enalaprilat effected a significant reduction in IL-6 and PDGF-induced DNA synthesis. Incubation of MC with H2O2 + PDGF or H2O2 + IL-6 resulted in increases of 3H-TdR of 6471.9 +/- 1785.1 and 5507.2 +/- 1270 cpm, respectively (P < 0.05 above control). Addition of enalaprilat with either H2O2 + PDGF or H2O2 + IL-6 effected significant reductions in DNA synthesis over the range 2.5-100 mumol/l. These data demonstrate that ACE inhibitors modulate MC DNA synthesis induced by reactive oxygen species.
...
PMID:Modifying influence of enalaprilat on mesangial cell DNA synthesis induced by hydrogen peroxide. 908 1

Redox stress during post-ischemic reperfusion may be the prime signal for processes leading to myocardial remodelling and hypertrophy. Nitric oxide (NO) is antioxidative, antiadhesive for neutrophils (PMN) and antiproliferative. Thus, enhancing endothelial production of NO, e.g. by inhibiting breakdown of endogenous bradykinin via angiotensin converting enzyme (ACE), could be beneficial. The effect of cilazaprilat (CILA, 10 micro M), an ACE inhibitor, on redox status, expression of the adhesion molecule P-selectin, and PMN adhesion under conditions of oxidative stress was investigated in cultured human umbilical vein endothelial cells (HUVECs). Incubation of the cells with H2O2 (0.1 and 1 mm) for 15 min served as oxidative stimulus. The intra- and extracellular concentrations of reduced and oxidized glutathione (GSH and GSSG) were measured by HPLC as indicators of endothelial redox status. Expression of P-selectin was measured by flow cytometry. Furthermore, firm leukocyte adhesion to HUVECs was assessed. In controls, the intracellular ratio GSH/GSSG averaged 47 and dropped to 30 after incubation with 0.1 mm H2O2. The ratio declined to 6.5 with 1 mm H2O2. CILA blocked the effects of 0.1 mm H2O2, but was ineffective against 1 mm peroxide. The extracellular ratio did not discriminate between 0.1 and 1 mm H2O2, falling from 18 to 1 in both situations. P-selectin expression rose from 100% (control) to 146% after 1 mm H2O2 without CILA, but only to 114% in the presence of CILA. PMN adhesion was enhanced from about 1600 PMN per microwell (control) to 4300/well by 1 mm H2O2. CILA had no significant effect on adhesion (3900 PMN/well). Exposure of HUVECs to 0.1 mm H2O2 affected neither P-selectin expression nor PMN adhesion. Consequently, ACE inhibition can mitigate mild (0.1 mm H2O2) but not more severe redox stress in HUVECs. Irrespectively, CILA reduced the upregulation of P-selectin at the higher H2O2 concentration, indicating that this process is regulated independently of the cellular redox status. The firm adhesion of PMN to HUVECs was independent of P-selectin expression.
...
PMID:Effects of ACE-inhibition on redox status and expression of P-selectin of endothelial cells subjected to oxidative stress. 940 70

A new aerobic bacterium was isolated from the sediment of a freshwater pond close to a contaminated site at Amponville (France). It was enriched in a fixed-bed reactor fed with 2,6-dichlorophenol (2,6-DCP)as the sole carbon and energy source at pH 7.5 and room temperature. The degradation of 2,6-DCP followed Monod kinetics at low initial concentrations. At concentrations above 300 microM (50 mg.liter-1), 2,6-DCP increasingly inhibited its own degradation. The base sequence of the 16S ribosomal DNA allowed us to assign the bacterium to the genus Ralstonia (formerly Alcaligenes). The substrate spectrum of the bacterium includes toluene, benzene, chlorobenzene, phenol, and all four ortho- and para-substituted mono- and dichlorophenol isomers. Substituents other than chlorine prevented degradation. The capacity to degrade 2,6-DCP was examined in two fixed-bed reactors. The microbial population grew on and completely mineralized 2,6-DCP at 2,6-DCP concentrations up to 740 microM in continuous reactor culture supplied with H2O2 as an oxygen source. Lack of peroxide completely stopped further degradation of 2,6-DCP. Lowering the acid-neutralizing capacity of the medium to 1/10th the original capacity led to a decrease in the pH of the effluent from 7 to 6 and to a significant reduction in the degradation activity. A second fixed-bed reactor successfully removed low chlorophenol concentrations (20 to 26 microM) with hydraulic residence times of 8 to 30 min.
...
PMID:Aerobic mineralization of 2,6-dichlorophenol by Ralstonia sp. strain RK1. 964 31

The pulmonary endothelium is susceptible to oxidative insults. Catalase conjugated with monoclonal antibodies (MAbs) against endothelial surface antigens, angiotensin-converting enzyme (MAb 9B9) or intercellular adhesion molecule-1 (MAb 1A29), accumulates in the lungs after systemic injection in rats (V. Muzykantov, E. Atochina, H. Ischiropoulos, S. Danilov, and A. Fisher. Proc. Natl. Acad. Sci. USA 93: 5213-5218, 1996). The present study characterizes the augmentation of antioxidant defense by these antibody-catalase conjugates in isolated rat lungs perfused for 1 h with catalase conjugated with either MAb 9B9, MAb 1A29, or control mouse IgG. Approximately 20% of the injected dose of Ab-125I-catalase accumulated in the perfused rat lungs (vs. <5% for IgG-125I-catalase). After elimination of nonbound material, the lungs were perfused further for 1 h with 5 mM hydrogen peroxide (H2O2). H2O2 induced an elevation in tracheal and pulmonary arterial pressures (126 +/- 7 and 132 +/- 5%, respectively, of the control level), lung wet-to-dry weight ratio (7.1 +/- 0.4 vs. 6.0 +/- 0.01 in the control lungs), and ACE release into the perfusate (436 +/- 20 vs. 75 +/- 7 mU in the control perfusates). Both MAb 9B9-catalase and MAb 1A29-catalase significantly attenuated the H2O2-induced elevation in 1) angiotensin-converting enzyme release to the perfusate (215 +/- 14 and 217 +/- 38 mU, respectively), 2) lung wet-to-dry ratio (6.25 +/- 0.1 and 6.3 +/- 0.3, respectively), 3) tracheal pressure (94 +/- 4 and 101 +/- 4%, respectively, of the control level), and 4) pulmonary arterial pressure (103 +/- 3 and 104 +/- 7%, respectively, of the control level). Nonconjugated catalase, nonconjugated antibodies, nonspecific IgG, and IgG-catalase conjugate had no protective effect, thus confirming the specificity of the effect of MAb-catalase. These results support a strategy of catalase immunotargeting for protection against pulmonary oxidative injury.
...
PMID:Immunotargeting of catalase to ACE or ICAM-1 protects perfused rat lungs against oxidative stress. 975 14

Captopril (D-3-mercapto-2-methylpropanoyl-L-proline) is an angiotensin converting enzyme (ACE) inhibitor, used widely in the treatment of hypertension and congestive heart failure. Captopril also inhibits proliferation of a variety of cell types, including several lacking ACE and renin acitvity. We have previously demonstrated that human mammary ductal carcinoma cells are among the cell types whose mitotic activity is inhibited by captopril. In those cells, captopril also reduces estrogen receptor (ER) and increases progesterone receptor (PR) concentrations. The present study evaluated the mechanism of captopril's antiproliferative action in an ER/PR-negative human mammary ductal carcinoma cell line, Hs578T. Cells grown in a 10% serum medium showed negligible changes in the presence of captopril alone. However, in the presence of subphysiologic concentrations of copper salts or copper-loaded ceruloplasmin, captopril caused a dose-dependent reduction in cell number, thymidine incorporation and mitochondrial dehydrogenase activity. In contrast, iron salts and iron-saturated transferrin had no effect on captopril activity. Catalase and horseradish peroxidase nullified the cytotoxic effects of captopril/Cu++, whereas H2O2 mimicked those effects. These data are consistent with the notion of a copper-catalyzed oxidation of captopril, leading to the generation of H2O2 as the cytotoxin to this clinically important cell type.
...
PMID:Mechanism of captopril toxicity to a human mammary ductal carcinoma cell line in the presence of copper. 1051 67

1. Somatic angiotensin I-converting enzyme (ACE) is a protein that contains two similar domains (N- and C-terminal), each possessing an active site. We have examined the effects of a generator of hydroxyl radicals (g*OH: 2,2'-azo-bis(2-amidinopropane)) and hydrogen peroxide (H2O2) on ACE using an in vitro approach. 2. The generator of hydroxyl radicals inactivated ACE in a time (2-6 h)- and concentration (0.3-3 mmol/L)-dependent manner at 37 degrees C. When ACE was coincubated for 4 h with g*OH (3 mmol/L), its activity decreased by 70%. Addition of dimethylthiourea or mannitol + methionine, two *OH scavengers, resulted in a significant protection of ACE activity. Mercaptoethanol and dithiotreitol, two thiol-reducing agents, also efficiently protected ACE activity. 3. The hydrolysis of two natural and domain-specific substrates was explored. The hydrolysis of angiotensin I, preferentially cleaved by the C-domain, was significantly inhibited (57-58%) after 4 h exposure to g*OH (0.3-1 mmol/L). Under the same conditions of exposure, the hydrolysis of N-acetyl-Ser-Asp-Lys-Pro, a specific substrate for the N-domain, was only slightly inhibited by 1 mmol/L g*OH. 4. Hydrogen peroxide, another source of *OH, was used. After exposure to H2O2 (3 mmol/L; 4 h), an 89% decrease in ACE activity was observed. Pretreatment with the iron chelator deferoxamine (1 mmol/L) attenuated H2O2-mediated ACE inactivation, demonstrating that the effect of H2O2 was partly due to its conversion into *OH (Fenton reaction). 5. In summary, our findings demonstrate that g*OH and H2O2 inhibit ACE activity and suggest a preferential action of g*OH on the C-domain of the enzyme.
...
PMID:Inhibitory effect of reactive oxygen species on angiotensin I-converting enzyme (kininase II). 1120 78

The degradation of 2,4-Dichlorophenol (from now on 2,4-DCP) has been carried out on Nafion-Fe (1.78%) in the presence of H2O2 under visible light irradiation. A solution containing 2,4-DCP (TOC 72 mg C/L)) is seen to be mineralized in approximately 1 h in the presence of H2O2 (10 mM) under solar simulated visible light (80 mW cm-2) at pH values between 2.8 and 11. Homogeneous photo-assisted Fenton reactions were capable of mediating 2,4-DCP degradation only up to pH 5.4. The degradation kinetics of 2,4-DCP on Nafion-Fe membranes was more favorable than the one observed during Fenton photo-assisted processes at pH 2.8. The degradation of 2,4-DCP was investigated as a function of the substrate, oxidant concentration and applied light intensity. The Nafion-Fe was seen to be effective over many cycles during the photo-catalytic degradation of 2,4-DCP showing an efficient and stable performance during 2,4-DCP degradation without leaching out Fe(3+)-ions into the solution. Evidence is presented that the degradation at the surface of the Nafion-Fe membrane seems to be controlled by mass transfer and not by chemical reaction of the species in solution. The approach used to degrade 2,4-DCP is shown to be valid for other chloro-carbons like 4-chlorophenol, 2,3-chlorophenol and 2,4,5-trichlorophenol.
...
PMID:Degradation of 2,4-dichlorophenol by immobilized iron catalysts. 1133 46

The reaction mechanism of the oxidation of 2,6-dichlorophenol (2,6-DCP) by horseradish peroxidase (HRP) and H2O2 has been investigated and the reaction products have been characterized by UV-visible and mass spectrometry. Evidence for the dimerization of 2,6-DCP to 3,3',5,5'-tetrachloro-4,4'-dihydroxybiphenyl and the subsequent fast oxidation of this product to the corresponding 3,3',5,5'-tetrachlorodiphenoquinone have been collected. The reaction rate was found to decrease markedly as soon as the pH was raised, with a clear inflection point at pH congruent with 6.6-6.9; it also resulted independent from H2O2 concentration. Since the pK(a) for 2,6-DCP is 6.80, the reaction rate might be influenced by the protonation state of the substrate.
...
PMID:Enzymatic degradation of 2,6-dichlorophenol by horseradish peroxidase: UV-visible and mass spectrometry characterization of the reaction products [corrected]. 1223 Sep 90

Apoptosis is involved in ventricular remodeling after myocardial infarction (MI). We investigated the effects of the vasopeptidase inhibitor (VPI) omapatrilat on cardiomyocyte apoptosis and compared it to the angiotensin converting enzyme inhibitor (ACEI) captopril in the rat post-MI model and in cultured neonatal rat cardiomyocytes. Wistar males rats surviving 4 h post-MI were assigned to omapatrilat (40 or 80 mg/kg/day), captopril (160 mg/kg/day) or no treatment. After 56 days, hemodynamic measurements were performed (n = 96) and rats were sacrificed. One group had assessment of cardiac remodeling and detection of DNA fragments by in situ end labelling method (ISEL), while the other had morphologic measurements and DNA laddering assessed. In addition, cultured neonatal rat cardiomyocytes (n = 6) were treated for 72 h with vehicle, captopril or omapatrilat in the presence or absence of the apoptosis inducing agent H2O2. Omapatrilat and captopril resulted in similar improvements of hemodynamic measurements, ventricular weight and dilatation, cardiac fibrosis and myocardial cell cross-section in large MI rats. Omapatrilat increased scar thickness more than did captopril. All sham-operated groups had little evidence of apoptosis. In the large MI group, there was a significant increase in ISEL-positive cells in the control (0.095 +/- 0.016%) and captopril (0.124 +/- 0.024%) groups in comparison with control sham-operated (0.006 +/- 0.006%), but this increase was limited to the peri-MI area. Omapatrilat (0.012 +/- 0.012% for both doses) prevented the increase in apoptosis in the peri-MI area. Also, omapatrilat but not captopril reduced DNA laddering in large MI. Moreover, in cultured neonatal rat cardiomyocytes, omapatrilat but not captopril reduced apoptosis as assessed by DNA laddering. The VPI omapatrilat, with its combination of NEP and ACE inhibition, suppresses cardiomyocyte apoptosis post-MI and in neonatal cultured rat cardiomyocytes more than the ACEI captopril, but this does not result in significant hemodynamic or morphologic differences between omapatrilat and captopril.
...
PMID:Comparative effects of a vasopeptidase inhibitor vs. an angiotensin converting enzyme inhibitor on cardiomyocyte apoptosis in rats with heart failure. 1467 3

The effect of the photo-Fenton process on biodegradability enhancement of 100 mg x L(-1) aqueous 2,4-dichlorophenol (2,4-DCP) solution has been investigated. An initial concentration of 65 mg x L(-1) H2O2 and 10 mg x L(-1) Fe (II) during 35 minutes of irradiation time was sufficient for total 2,4-DCP removal. At these working conditions, biodegradability, measured as BODS/COD ratio, was increased from 0 for the original solution up to 0.15. Biological oxidation of photo-Fenton pre-treated solutions was performed in a sequencing batch reactor (SBR). After 32 days of start-up, the reactor was fed with different pre-treated solutions and cycle duration was reduced progressively. TOC removal efficiencies in the SBR went from 30 up to 70%.
...
PMID:Combining photo-Fenton process with biological sequencing batch reactor for 2,4-dichlorophenol degradation. 1507 86


<< Previous 1 2 3 4 5 Next >>

---