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)

We have compared the digestion of bradykinin, lysyl bradykinin, and kinin degradation products by carboxypeptidases N, B and A (CPN, CPB and CPA). Carboxypeptidase N removed the C-terminal arginine from bradykinin or lysyl bradykinin to leave the des-Arg derivative of each, and no further degradation occurred regardless of enzyme concentration or time of incubation. However, both CPB and CPA degraded the des-Arg derivatives to remove the C-terminal phenylalanine. The inhibitory effect of phosphate ions upon this activity of CPB (but not CPA) suggests that CPA may be responsible for the formation of free phenylalanine seen upon degradation of kinins in plasma or serum. However, angiotensin converting enzyme degraded des-Arg9-bradykinin in plasma or serum prior to such Phe removal to yield the pentapeptide Arg-Pro-Pro-Gly-Phe and the tripeptide Ser-Pro-Phe. We demonstrated that CPB degraded Arg-Pro-Pro-Gly-Phe but not Ser-Pro-Phe; this reaction was also inhibited by phosphate ions. Carboxypeptidase A, on the other hand, liberated Phe from both peptides in phosphate-buffered saline and accounted, at least in part, for the free phenylalanine detected. Carboxypeptidase N did not digest the aforementioned pentapeptide or tripeptide. It is clear that carboxypeptidase B and carboxypeptidase A had overlapping activities, depending upon the substrate tested, and were distinguished by the effects of different ionic environments. We further suggest a role for carboxypeptidases other than CPN in the degradation of kinins in human plasma or serum.
...
PMID:Studies of the digestion of bradykinin, lysyl bradykinin, and kinin-degradation products by carboxypeptidases A, B, and N. 371 39

Granulomatous inflammatory lesions in murine schistosomiasis mansoni undergo a spontaneous diminution at the chronic phase of the disease concurrent with an increase in angiotensin I-converting enzyme (ACE) activity. The objective of this investigation was to determine whether T cells influence ACE activity within the granulomas. Cyclophosphamide and cimetidine treatments of mice, which augment delayed-type hypersensitivity reactions, enhanced liver granuloma size and decreased granuloma ACE activity. The suppression of liver granuloma by the adoptive transfer of spleen cells from chronically infected, immunomodulated mice into recipients with acute infection increased ACE activity of granulomas and granuloma macrophages. The increased ACE activity was dependent upon the transfer of Thy 1.2+ splenic lymphocytes. The level of the ACE activity was proportionate to the number of administered spleen cells. Thus, the level of ACE activity within the egg-induced granuloma is dependent upon T lymphocytes present in the spleen and granulomas of infected animals.
...
PMID:Alteration of granuloma angiotensin I-converting enzyme activity by regulatory T lymphocytes in murine schistosomiasis. 627 3

Cyclophosphamide causes lung injury in rats through its ability to generate free radicals with subsequent endothelial and epithelial cell damage. In order to observe the protective effects of a potent anti-inflammatory antioxidant, curcumin (diferuloyl methane) on cyclophosphamide-induced early lung injury, healthy, pathogen free male Wistar rats were exposed to 20 mg/100 g body weight of cyclophosphamide, intraperitoneally as a single injection. Prior to cyclophosphamide intoxication oral administration of curcumin was performed daily for 7 days. At various time intervals (2, 3, 5 and 7 days post insult) serum and lung samples were analyzed for angiotensin converting enzyme, lipid peroxidation, reduced glutathione and ascorbic acid. Bronchoalveolar lavage fluid was analyzed for biochemical constituents. The lavage cells were examined for lipid peroxidation and glutathione content. Excised lungs were analyzed for antioxidant enzyme levels. Biochemical analyses revealed time course increases in lavage fluid total protein, albumin, angiotensin converting enzyme (ACE), lactate dehydrogenase, N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, acid phosphatase, lipid peroxide levels and decreased levels of glutathione (GSH) and ascorbic acid 2, 3, 5 and 7 days after cyclophosphamide intoxication. Increased levels of lipid peroxidation and decreased levels of glutathione and ascorbic acid were seen in serum, lung tissue and lavage cells of cyclophosphamide groups. Serum angiotensin converting enzyme activity increased which coincided with the decrease in lung tissue levels. Activities of antioxidant enzymes were reduced with time in the lungs of cyclophosphamide groups.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Modulation of cyclophosphamide-induced early lung injury by curcumin, an anti-inflammatory antioxidant. 775 45

Focal segmental glomerulosclerosis (FSGS) is the most common glomerulopathy leading to end-stage renal disease in children and transplantation is complicated by recurrent disease in a significant percentage of children. Treatment of recurrent FSGS has included high-dose steroids, high-dose cyclosporine (CSA), plasmapheresis, and ACE inhibitors with mixed results. We have had a consistent approach using oral cyclophosphamide (CTX) to treat recurrent FSGS since 1982. Three patients with ESRD secondary to nephrotic syndrome had recurrent disease. Biopsies in all 3 were consistent with recurrent FSGS. Patients were begun on a 8-12 week course of 1-2 mg/kg/day of CTX and dosage was adjusted for WBC count. Azathioprine was with held during CTX. Patients' dosage at the end of 12 weeks ranged from 0.89-1.75 mg/kg/day. All patients tolerated CTX well. After 8-12 weeks of treatment, 2 patients with nephrotic syndrome normalized their serum albumin and had negative to trace protein on urinary dipstick. One patient with proteinuria decreased his protein excretion from 770 to 340 mg/m2/day. At follow-up at 8, 38, and 125 months post-transplant, these 3 patients have stable graft function and negative to trace protein on urinalysis. The patient followed for 125 months has had 2 additional relapses at 51 and 82 months post-transplant that were treated successfully with pulse intravenous steroids. Three pediatric patients with recurrent focal segmental glomerulosclerosis post-renal transplant were treated with oral CTX and had significant improvement in proteinuria and preservation of graft function. This suggests that oral CTX is a potentially effective and well-tolerated treatment for recurrent FSGS in children.
...
PMID:Recurrent focal segmental glomerulosclerosis in pediatric renal transplant recipients: successful treatment with oral cyclophosphamide. 786 17

The antiinflammatory, antioxidant activity of taurine and niacin against cyclophosphamide-induced early lung injury in rats was investigated. A single intraperitoneal injection of cyclophosphamide markedly altered the levels of several biomarkers in bronchoalveolar lavage fluid: total protein, albumin, angiotensin converting enzyme, lactate dehydrogenase, lactate, N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, acid phosphatase and lipid peroxidation product were significantly elevated. In contrast, decreased levels of total reduced glutathione (GSH) and ascorbic acid were observed. Cyclophosphamide significantly increased malondialdehyde levels in serum and lung. Significant increases in lung content of lipid hydroperoxides were seen that paralleled the decreased levels of total reduced glutathione and total sulfhydryl groups. Pretreatment of rats with daily intraperitoneal injection of taurine plus niacin 7 days prior to and 2 days after cyclophosphamide insult significantly inhibited the development of lung injury, prevented the alterations in lavage fluid biomarkers associated with inflammatory reactions, with less lipid peroxidation and restoration of antioxidants. In conclusion, our results suggest that taurine and niacin in combination is efficient in blunting cyclophosphamide-induced pulmonary damage.
...
PMID:In vivo administration of taurine and niacin modulate cyclophosphamide-induced lung injury. 786 92

1. The aim of this study was a pharmacological characterization of the multiple NANC inhibitory transmission systems producing relaxation of the circular muscle of guinea-pig proximal colon. In the presence of atropine (1 microM), guanethidine (3 microM) and of the tachykinin NK1 and NK2 receptor antagonists, SR 140333 (0.3 microM) and MEN 10627 (1 microM), respectively, electrical field stimulation (EFS) produced a frequency-dependent (0.1-3 Hz) relaxation. During a cumulative frequency-response curve, the maximal relaxant effect was produced at 3 Hz and approached the maximal relaxation to 1 microM isoprenaline. In the presence of both apamin (0.3 microM) and L-nitroarginine (L-NOARG, 100 microM), EFS failed to evoke relaxation up to 1 Hz; at 1-10 Hz, a slowly developing relaxation ensured which approached 50% of the Emax to isoprenaline. The EFS-evoked NANC relaxation, either in the presence or absence of apamin and L-NOARG, was unaffected by in vitro capsaicin pretreatment (10 microM for 15 min). 2. Three protocols of EFS were developed for further pharmacological analysis: (a) EFS at 1 Hz for 5 s in the presence of L-NOARG, producing a transient fast apamin-sensitive relaxation; (b) EFS at 1 Hz for 5 s in the presence of apamin, producing a transient fast L-NOARG-sensitive relaxation; and (c) EFS at 10 Hz for 5 s in the presence of both apamin and L-NOARG, producing a transient but slowly developing and more sustained relaxation. 3. The neutral endopeptidase inhibitor, thiorphan (1-10 microM), enhanced and prolonged the apamin- and L-NOARG-resistant NANC relaxation produced by EFS at 10 Hz, without affecting that evoked at 1 Hz in the presence of apamin or L-NOARG. The angiotensin converting enzyme inhibitor, captopril (1-10 microM) was without effect. 4. The cAMP analogue inhibitor of protein kinase A, Rp-cAMPs (100-300 microM) significantly reduced and shortened the NANC relaxation produced by 10 Hz EFS in the presence of L-NOARG without affecting that produced by 1 Hz EFS in the presence of apamin or L-NOARG. 5. The inhibitor of sarcoplasmic reticulum Ca-ATPase, cyclopiazonic acid (CPA, 3-10 microM for 60 min) abolished the 1 Hz EFS-induced relaxation in the presence of L-NOARG, and greatly inhibited that produced by 10 Hz EFS in the presence of both apamin and L-NOARG. The relaxation produced by 1 Hz EFS in the presence of apamin was inhibited by about 32% at 10 microM only. 6. Nifedipine (1 microM) did not affect the EFS-induced NANC relaxations. In the presence of nifedipine, tetraethylammonium (TEA, 1 mM) enhanced the 1 Hz EFS-induced relaxation in the presence of L-NOARG (158% of control) and that produced by 10 Hz EFS in the presence of apamin and L-NOARG (215% of control) while that evoked by 1 Hz EFS in the presence of apamin was slightly affected (109% of control). 7. In the presence of atropine, guanethidine, SR 140333 and MEN 10627, bath application of human vasoactive intestinal polypeptide (VIP, 0.1 nM-10 nM) produced a concentration-dependent, slowly developing relaxation of colonic strips. The relaxation to VIP was unaffected by apamin (0.3 microM), L-NOARG (100 microM), nifedipine (1 microM) or nifedipine plus TEA (1 mM); it was inhibited by CPA (10 microM) and Rp-cAMPs (100 microM) and was potentiated by thiorphan (10 microM). 8. The putative VIP receptor antagonist, VIP(10-28) (10 microM) did not affect the VIP-induced relaxation nor the NANC relaxation to 10 Hz EFS in the presence of apamin and L-NOARG. 9. The present findings provide evidence that three distinct NANC inhibitory mechanisms mediate relaxation of the circular muscle of the guinea-pig proximal colon. The first system provides a fast relaxation in response to low frequency of stimulation and may involve the action of a transmitter(s) (possibly ATP) which mobilizes intracellular Ca2+ from sarcoplasmic reticulum leading to the activation of apamin-sensitive K+ channels. The second system likewise provides a fast relaxation of the colon in
...
PMID:Characterization of the apamin- and L-nitroarginine-resistant NANC inhibitory transmission to the circular muscle of guinea-pig colon. 888 60

For the treatment of different forms of systemic sclerosis (SSc), drugs play a predominant role. Depending on disease activity as well as type and severity of cutaneous, vascular and internal organ manifestations, different systemic (antiinflammatory, immunosuppressive, antifibrotic) or organ-specific therapies are used. The scientific basis of most treatment modalities is insufficient and incomplete. There is sufficient evidence for an antiinflammatory and antiproliferative efficacy of glucocorticosteroids, methotrexate, cyclophosphamide and cyclosporine A in the treatment of diffuse cutaneous systemic sclerosis. Vasoactive therapies play an important role in treating Raynaud's phenomenon (nifedipine or other dihydropyridines, prostaglandin analogs, losartan, prazosine), and arterial (ACE blockers, AT-1 antagonists) or pulmonary (epoprostenol) hypertension. Cyclophosphamide is effective in fibrosing alveolitis, prokinetic substances (metoclopramid, domperidone) in gastroesophageal dysmotility or octreotide in intestinal pseudoobstruction. Physical therapies (e.g., massage) are poorly studied. In particular cases, surgical measures (e.g., removal of calcifications) are necessary.
...
PMID:[Evidence-based therapy of systemic sclerosis]. 1182 42

Systemic sclerosis (SSc) is a multi-system disease characterized by skin fibrosis and visceral disease. Therapy is organ and pathogenesis targeted. In this review, we describe novel strategies in the treatment of SSc. Utilizing the MEDLINE and the COCHRANE REGISTRY, we identified open trials, controlled trials, for treatment of SSc from 1999 to April 2005. We used the terms scleroderma, systemic sclerosis, Raynaud's phenomenon, pulmonary hypertension, methotrexate, cyclosporin, tacrolimus, relaxin, low-dose penicillamine, IVIg, calcium channel blockers, losartan, prazocin, iloprost, N-acetylcysteine, bosentan, cyclophosphamide, lung transplantation, ACE inhibitors, anti-thymocyte globulin, and stem cell transplantation. Anecdotal reports were omitted. Methotrexate, cyclosporin, tacrolimus, relaxin, low-dose penicillamine, and IVIg may be beneficial in improving the skin tightness in SSc. Calcium channel blockers, the angiotensin II receptor type 1 antagonist losartan, prazocin, the prostacyclin analogue iloprost, N-acetylcysteine and the dual endothelin-receptor antagonist bosentan may be beneficial for Raynaud's phenomenon. Epoprostenol and bosentan are approved for therapy of pulmonary hypertension (PAH). Other options under investigation include intravenous or aerolized iloprost. Cyclophosphamide (CYC) pulse therapy is effective in suppressing active alveolitis. Stem cell and lung transplantation is a viable option for carefully selected patients. Renal crisis can be effectively managed when hypertension is aggressively controlled with angiotensin converting enzyme (ACE) inhibitors. Patients should continue taking ACE inhibitors even after beginning dialysis in hope of discontinuing dialysis. Antithymocyte globulin and mycophenolate mofetil appear safe in SSc. The improvement in skin score and the apparent stability of systemic disease during the treatment period suggest that controlled studies of these agents are justified. Stem cell transplantation is under investigation for severe disease. Novel therapies are currently being tested in the treatment of SSc and have the potential of modifying the disease process and overall clinical outcome. The evaluation of these studies is still a difficult process.
...
PMID:New therapeutic strategies for systemic sclerosis--a critical analysis of the literature. 1629 21

Systemic sclerosis (scleroderma) is considered as the most severe connective tissue disease. It is characterized by an abnormal immune activation, a vasculopathy and a fibrosis of the skin and of multiple internal organs. Numerous progress in the understanding of the pathogenesis with identification of key molecules have permit to introduce novel treatments that improve the management of some aspects of the disease. ACE inhibitors are effective in resolving renal crisis. Cyclophosphamide is useful for treatment of fibrosing alveolitis. Prostaglandins, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors permit to improve the treatment of the vascular complications (digital ulcerations, pulmonary arterial hypertension) of scleroderma.
...
PMID:[Pathogenic mechanisms in systemic sclerosis and their therapeutical consequences. Part 2: treatment]. 1671 Nov 51

Progressive, irreversible fibrosis is one of the most clinically significant consequences of ionizing radiation on normal tissue. When applied to lungs, it leads to a complication described as idiopathic pneumonia syndrome (IPS) and eventually to organ fibrosis. For its high mortality, the condition precludes treatment with high doses of radiation. There is widespread interest to understand the pathogenetic mechanisms of IPS and to find drugs effective in the prevention of its development. This report summarizes our experience with the protective effects of L 158,809, an angiotensin II (ANG II) receptor blocker, and two angiotensin converting enzyme (ACE) inhibitors in the development of IPS and the role of transforming growth factor beta (TGF-beta) and of alpha-actomyosin (alpha SMA) in pathogenesis of radiation induced pulmonary fibrosis in an experimental model of bone marrow transplant (BMT). Male WAG/Riji/MCV rats received total body irradiation and a regimen of cyclophosphamide (CTX) in preparation for bone marrow transplant. While one group of animals remained untreated, the remainders were subdivided into three groups, each of them receiving either the ANG II receptor blocker or one of the two ACE inhibitors (Captopril or Enalapril). Each of the three drugs was administered orally from 11 days before the transplant up to 56 days post transplant. At sacrifice time the irradiated rats receiving only CTX showed a chronic pneumonitis with septal fibrosis and vasculitis affecting, in particular, small caliber pulmonary arteries and arterioles. Their lung content of hydroxyproline was also markedly elevated in association with the lung concentrations of thromboxane (TXA2) and prostaglandin (PGI(2)), (two markers of pulmonary endothelial damage). A significant increase of alpha actomyosin staining was observed in vessels, septa and macrophages of the same animals which also overexpressed TGF-beta. When L 158,809, Captopril and Enalapril were added to the radiation and cytoxan treatment, a significant amelioration of the histological damage as well as the overexpression of alpha SMA was observed. Lung concentrations of hydroxyproline, PGI(2), TXA2 and TGF-beta were also observed in these animals so that the values of these compounds were closer to those measured in untreated control rats than to their irradiated and cytoxan treated counterparts. Angiotensin II plays an important role in the regulation of TGF-beta and alpha SMA, two proteins involved in the pathogenesis of pulmonary fibrosis. The finding that ACE inhibitors or ANG II receptor blockers protect the lungs from radiation induced pneumonitis and fibrosis reaffirms the role that ANG II plays in this inflammatory process and suggests an additional indication of treatment of this condition, thus opening a new potential pharmacologic use of these drugs.
...
PMID:Effect of an angiotensin II receptor blocker and two angiotensin converting enzyme inhibitors on transforming growth factor-beta (TGF-beta) and alpha-actomyosin (alpha SMA), important mediators of radiation-induced pneumopathy and lung fibrosis. 1750 16


1 2 Next >>

---