Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Met-enkephalin is degraded by peptidases present in the hemolymph fluid and hemocyte membrane suspension of Mytilus edulis. Degradation of Met-enkephalin is rapid in the fluid and slower in the membrane. 2. Aminopeptidase activity is bestatin sensitive in hemocyte membrane and highest in the fluid of the hemolymph, which appears to have a component which is insensitive to inhibitor. 3. ACE activity is found only in the fluid of the hemolymph. 4. Carboxypeptidase and NEP (CD10: "enkephalinase") are membrane bound and the former appears to predominate. Phosphoramidon inhibits not only NEP, as expected, but the invertebrate carboxypeptidase as well.
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PMID:Degradation of Met-enkephalin by hemolymph peptidases in Mytilus edulis. 133 5

Cardiovascular disease in all its clinical manifestations progresses significantly as age advances and takes its heaviest toll in the elderly. Hypertension becomes the dominant risk factor for cardiovascular disease in this age group because of its high incidence. Traditionally, diastolic rather than systolic blood pressure has been regarded as the main risk factor for cardiovascular complications in hypertension, although it is becoming clearer that the risk of cardiovascular complications is likely to be associated mainly with systolic pressure in the elderly. Various intervention drug trials in elderly patients seem to indicate that hypotensive drug treatment can decrease cardiovascular mortality, mainly by decreasing cerebrovascular mortality. The EWPHE used a diuretic combination with methyldopa, and the HEP study used atenolol with a thiazide diuretic. The multicenter Systolic Hypertension in the Elderly Program (SHEPS) currently underway in the United States is likely to also provide some answers. The place of newer agents such as ACE inhibitors or calcium antagonists is still undetermined. Calcium antagonist drugs have been reported to be effective, and possibly more so in the elderly than in a younger population, although this assumption is not proven and may not be valid. Pharmacokinetic studies in the elderly are very few, although the studies reported indicate a reduced clearance. Studies also indicate that Nifedipine Retard tablets are effective, with a low incidence of adverse effects. There are no trials, however, looking at the long-term benefit of treating elderly hypertensive patients with either nifedipine tablets or other calcium-channel blockers.
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PMID:Hypertension in the elderly. 207 5

We evaluated the usefulness of serum ACE, BALF lymphocyte%, CD4+/CD8+ ratio when diagnosing pulmonary parenchymal lesion in patients with sarcoidosis. The results showed the substantial usefulness but lesser specificity. Furthermore, we evaluated the values of the above three parameters in terms of the judgment of the disease activity and the reliability for foreseeing the prognosis in BHL sarcoidosis. Elevated serum ACH had a good relationship with the disease activity in both nonsmoker and smoker cases. BALF lymphocyte % also had in smoker cases. But none of three parameters showed a significant relationship with the prognosis in BHL sarcoidosis.
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PMID:[Diagnosis and parameters for the evaluation of disease activity and prognosis in patients with pulmonary sarcoidosis]. 216 36

Small cell lung cancer requires aggressive combination chemotherapy. The three active agents, doxorubicin (A) 45 mg/m2 i.v. day 1, cyclophosphamide (C) 1.0 mg/m2 i.v. day 1 and VP16-213 (E) 50 mg/m2/day i.v. days 1-5 were given together. The combination (ACE) was given every 21 days without chest irradiation. One hundred and seventy-four patients have been stratified for extent of disease and randomized on three sequential studies testing ACE vs ACE + MER immunotherapy (38 patients), or ACE vs ACE alternating with CCNU, methotrexate, vincristine and procarbazine (109 patients), or ACE vs ACE II (ACE with continuous VP16-213 - 100 mg/m2/day X 5 days - 27 patients - ongoing). The immunotherapy and the alternating non-cross resistant combination have not proven beneficial with respect to response or survival. The ACE combination, regardless of additional treatments, has produced greater than 90% response overall. In limited disease the complete response (CR) frequency is 65%. The median survival for limited disease overall is 14 months and 18 months for patients achieving CR. In extensive disease the CR frequency is 40% with a median survival of 9 months overall and 13 months for patients achieving CR. Response frequency and survival are identical in the first two studies and 20-30% of patients with limited disease are long-term survivors with one late relapse (greater than 3 years). Patients who achieved CR had a significantly longer survival regardless of other factors such as performance status or extent of disease. Prophylactic cranial irradiation was demonstrated to be useful in prevention or delaying CNS metastases in patients who achieved CR. The third generation study of high-dose VP16-213 infusion seeks to increase the CR frequency. ACE chemotherapy without chest irradiation is a highly effective treatment for all patients with small cell lung cancer and compares favorably with all other studies with or without adjuvant radiotherapy.
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PMID:Doxorubicin, Cyclophosphamide and VP16-213 (ACE) in the treatment of small cell lung cancer. 628 82

Type II integral membrane proteins are anchored by a signal-peptide/membrane-anchor domain (SA domain) located near their N-terminus, whereas type I membrane proteins are anchored by stop-transfer sequences usually located near the C-terminus. In this study we have attempted to transform neutral endopeptidase-24.11 (EC 3.4.24.11; NEP), a type II membrane protein, into a type I membrane protein. Three type I mutant proteins were constructed by fusion of topogenic sequences to the C-terminus of SecNEP, a soluble form of NEP. The first two type I mutants, SecNEP-TMC and SecNEP-TMIC, were constructed by fusing in frame the cytosolic and SA domains of NEP to the C-terminus of SecNEP. These two fusion proteins differ only in the orientation of the cytosolic tail. The third type I mutant, SecNEP-ACE, was constructed by fusing in frame the stop-transfer and cytosolic domains of angiotensin I-converting enzyme (EC 3.4.15.1; ACE) to the C-terminus of SecNEP. Our results suggest that: (1) the NEP ectodomain can be anchored with a type I topology in the endoplasmic reticulum (ER) membrane by both NEP and ACE topogenic sequences; (2) SecNEP-TMC and SecNEP-TMIC were transport-incompetent and needed proteolytic cleavage in the C-terminal region to leave the ER, whereas SecNEP-ACE was transported out of the ER as a type I membrane protein. Therefore we concluded that the nature of topogenic sequences determines the transport-competence of topological mutants of neutral endopeptidase-24.11.
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PMID:The nature of topogenic sequences determines the transport competence of topological mutants of neutral endopeptidase-24.11. 749 41

Analysis of SP and NKA metabolism by human vascular endothelium, relative to that in human plasma, identified integrative, multiple pathways for the processing of circulating SP (but not NKA) by angiotensin-converting enzyme (ACE; EC 3.4.15.1), dipeptidyl(amino)peptidase IV (DAP IV; EC 3.4.14.5), and aminopeptidase M (AmM; EC 3.4.11.2). In contrast, SP and NKA, which may diffuse into or be neurally released within the vessel wall, were both metabolized by smooth muscle neutral endopeptidase-24.11 (NEP-24.11; EC 3.4.24.11). Collectively, these studies indicate peptide-specific and site-specific differential processing of SP and NKA by human plasma and vasculature.
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PMID:Metabolism of substance P and neurokinin A by human vascular endothelium and smooth muscle. 752 48

The degradation of bradykinin in semen and on washed sperm cells of various species (human, pig, cattle, sheep) is mainly controlled by two peptidases, the angiotensin-converting enzyme (ACE/kininase II; E.C. 3.4.15.1) and neutral metalloendopeptidase (NEP; E.C. 3.4.24.11). In addition, minor activities of kininase I (carboxypeptidase N/CPN; E.C. 3.4.17.3) were measured exclusively in human samples. Samples of the investigated species varied considerably in their ratios of the activities of bradykinin degrading peptidases. This should be considered in any approach aimed at maintaining the promoting effect of bradykinin on sperm motility by use of enzyme inhibitors.
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PMID:The enzymatic degradation of bradykinin in semen of various species. 782 45

Neutral endopeptidase (NEP, EC 3.4.24.11), angiotensin-converting enzyme (ACE, EC 3.4.15.1) and carboxypeptidase N (CPN, EC 3.4.17.3) are potentially important enzymes which regulate the degradation of neuropeptides, such as bradykinin (BK) and substance P (SP), in the respiratory mucosa. Some neuropeptides are also degraded by these enzymes in vitro and in vivo. We investigated the localization of these enzymes in the human nasal mucosa by an indirect immunohistochemical technique (immunogold silver staining). NEP-immunoreactive areas were present in the epithelium, the serous cells of the submucosal glands, and the endothelial cells of small vessels. The epithelium and the serous cells were the predominant areas of NEP immunoreactivity in the nasal mucosa. ACE-immunoreactive areas were seen in the outer layer of the epithelium, the endothelial cells of vessels, and widely distributed in the superficial lamina propria. The endothelial cells of the vessels showed maximum positive intensity to ACE. CPN-immunoreactive areas were observed in the epithelium, the endothelium of vessels and the superficial lamina propria, except for the gland cells. The superficial lamina propria exhibited maximum immunoreactivity for CPN. We observed that the enzymes were widely distributed in the nasal mucosa. The epithelium, including the epithelial cells and glycocalyx, contains all three enzymes. These enzymes play an important role in the mucosal immunity of the respiratory mucosa by degrading active neuropeptides. These results show that NEP secretion is regulated by a glandular, cholinergic control. On the other hand, ACE and CPN secretion are regulated by vascular permeability.
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PMID:Immunological localization of neuropeptide-degrading enzymes in the nasal mucosa. 783 83

The efficacy of alcohol screening questionnaires, the TWEAK, T-ACE, NET, MAST, and CAGE, in detecting periconceptional risk-drinking, > or = 1 oz absolute alcohol/day, was investigated in 4743 African-American women attending an inner-city prenatal clinic who had reported ever drinking. Sensitivity, specificity, positive predictive value, efficiency, follow-up rates, and receiver operating characteristics of the questionnaires were examined to compare the overall effectiveness of the questionnaires and their performance at cut-points defining positive scores ranging from 1 to 3. Relatively little difference between TWEAK, T-ACE, and MAST was seen in the receiver operating characteristic accuracy indices; NET and CAGE lagged behind. Sensitivity/specificity scores for the two questionnaires most sensitive at cut-point 1 were TWEAK (87/72) and T-ACE (83/75). At cut-point 2, sensitivity was optimized with respect to specificity; TWEAK (79/83) was significantly more sensitive than T-ACE (70/85; p = 0.002). At cut-point 3, the two most sensitive tests were MAST (61/92) and TWEAK (59/94). In general, measures of merit were not greatly affected by the time between conception and the administration of the screens. Screening was most sensitive for women interviewed during the first 15 weeks of pregnancy; risk-drinkers tended to delay entry into prenatal care, increasing positive predictive values associated with screening later in pregnancy. This study confirms the utility, when screening for risk-drinking during pregnancy, of brief questionnaires that assess alcohol intake indirectly by asking women about their tolerance to alcohol's effects, psychological consequences of drinking, and significant others' concern about their drinking. It validates T-ACE and provides preliminary data indicating that TWEAK may outperform T-ACE.
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PMID:Screening for pregnancy risk-drinking. 784 99

Neutral endopeptidase inhibition (NEP-I) and angiotensin converting enzyme inhibition (ACE-I) act synergistically to produce acute beneficial hemodynamic effects in models of heart failure. Blockade of the formation of angiotensin II (Ang II) acting together with potentiation of the natriuretic peptides, bradykinin and other vasoactive peptides may mediate the interaction of dual enzyme inhibition. In this study, the potential roles of Ang II repression and bradykinin potentiation were evaluated in conscious cardiomyopathic hamsters with compensated heart failure. The Ang II AT1 receptor antagonist, SR 47436 (BMS-186295), was administered at 30 mumol/kg, i.v. followed by i.v. infusion at 1 mumol/kg/min in combination with NEP-I (SQ-28603 at 30 mumol/kg i.v.). Cardiac preload (left ventricular end diastolic pressure) and afterload (left ventricular systolic pressure) decreased significantly more after the combination of Ang II blockade and NEP-I than after either treatment alone. This indicated that repression of Ang II contributes importantly to the NEP-I/ACE-I interaction. Bradykinin B2 receptor antagonism by Hoe 140 at 100 micrograms/kg, i.v. significantly blunted the decrease in left ventricular end diastolic pressure but not the decrease in left ventricular systolic pressure after dual NEP-I/ACE-I (SQ-28603 and enalaprilat each at 30 mumol/kg, i.v.). This suggests that bradykinin potentiation contributes to the preload-reducing, but not the afterload-reducing, acute effects of NEP-I/ACE-I. Hence, both Ang II repression and bradykinin potentiation are factors contributing to the synergistic hemodynamic effects of combined NEP-I and ACE-I in hamsters with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Repression of angiotensin II and potentiation of bradykinin contribute to the synergistic effects of dual metalloprotease inhibition in heart failure. 785 75


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