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

A comparative study has been performed on populations of Unionidae from the Lake Suszek and Brda river situated in the centre of Tucholski Landscape Park, around which there are no factories and the Pilica river--affected by the influence of the nearby town agglomeration. Mussels collected from Suszek were also treated (72 h) with various concentrations of dichlorophenol (DCP; 0.1, 0.15, 0.2 ppm) and paraquat (PQ; 1, 5, 10 ppm) in laboratory conditions (aquarium). The activities of glutathione S-transferase (GST) and cytochrome P450 monooxygenase system (NAD(P)H ferricyanide reductase, NAD(P)H cytochrome c reductase), cytochrome P450 content and b(5) in microsomal and cytosolic fractions of digestive gland were investigated. The differences in enzyme activities between groups of mussels, which were exposed to various concentrations of chemical pollutants, as well as the dependence on geographical distribution in Poland, were observed. In experiments with DCP the dose-dependent increase in GST activity was found, but no changes after PQ treatment were observed. Results, in experiments with DCP and PQ, have varied from no change to increase or decrease in the measured monooxygenase activities and cytochrome P450 content. Increases have been recorded in two cases (NADPH ferricyanide reductase and cytochrome P450) after exposure to DCP and in the case of NADH ferricyanide reductase following the exposure to PQ. NAD(P)H cytochrome c reductase activity and content of P450 decreased considerably in 5 and 10 ppm PQ-treated mussels. Thus, the treatment with DCP and PQ in water changed the properties of the mussels digestive gland cytochrome P450 monooxygenase system. These changes may be used as a bioindicator, at the molecular level, of exposure to those xenobiotics not only in controlled experiments (aquaria) but also in the natural environment.
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PMID:Comparative study of the xenobiotic metabolising system in the digestive gland of the bivalve molluscs in different aquatic ecosystems and in aquaria experiments. 1229 71

This study investigated the effect of reduced free fatty acid (FFA) availability on pyruvate dehydrogenase activation (PDHa) and carbohydrate metabolism during moderate aerobic exercise. Eight active male subjects cycled for 40 min at 55% Vo(2 peak) on two occasions. During one trial, subjects ingested 20 mg/kg body mass of the antilipolytic drug nicotinic acid (NA) during the hour before exercise to reduce FFA. Nothing was ingested in the control trial (CON). Blood and expired gas measurements were obtained throughout the trials, and muscle biopsy samples were obtained immediately before exercise and at 5, 20, and 40 min of exercise. Plasma FFA were lower in the NA trial (0.13 +/- 0.01 vs. 0.48 +/- 0.03 mM, P < 0.05), and the respiratory exchange ratio (RER) was increased with NA (0.93 +/- 0.01 vs. 0.89 +/- 0.01, P < 0.05), resulting in a 14.5 +/- 1.8% increase in carbohydrate oxidation compared with CON. PDHa increased rapidly in both trials at exercise onset but was approximately 15% higher (P < 0.05) throughout exercise in the NA trial (2.44 +/- 0.19 and 2.07 +/- 0.12 mmol x kg wet muscle(-1) x min(-1) for NA and CON at 40 min). Muscle glycogenolysis was 15.3 +/- 9.6% greater in the NA trial vs. the CON trial but did not reach statistical significance. Glucose 6-phosphate contents were elevated (P < 0.05) in the NA trial at 30 and 40 min of exercise, but pyruvate and lactate contents were unaffected. These data demonstrate that the reduction of exogenous FFA availability increased the activation of PDH and carbohydrate oxidation during moderate aerobic exercise in men. The increased activation of PDH was not explained by changes in muscle pyruvate or the ATP/ADP ratio but may be related to a decrease in the NADH/NAD(+) ratio or an epinephrine-induced increase in calcium concentration.
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PMID:Effects of reduced free fatty acid availability on skeletal muscle PDH activation during aerobic exercise. Pyruvate dehydrogenase. 1255 53

Evidence implicates hyperglycemia-derived oxygen free radicals as mediators of diabetic complications. However, intervention studies with classic antioxidants, such as vitamin E, failed to demonstrate any beneficial effect. Recent studies demonstrate that a single hyperglycemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain seems to be the first and key event in the activation of all other pathways involved in the pathogenesis of diabetic complications. These include increased polyol pathway flux, increased advanced glycosylation end product formation, activation of protein kinase C, and increased hexosamine pathway flux. Superoxide overproduction is accompanied by increased nitric oxide generation, due to an endothelial NOS and inducible NOS uncoupled state, a phenomenon favoring the formation of the strong oxidant peroxynitrite, which in turn damages DNA. DNA damage is an obligatory stimulus for the activation of the nuclear enzyme poly(ADP-ribose) polymerase. Poly(ADP-ribose) polymerase activation in turn depletes the intracellular concentration of its substrate NAD(+), slowing the rate of glycolysis, electron transport, and ATP formation, and produces an ADP-ribosylation of the GAPDH. These processes result in acute endothelial dysfunction in diabetic blood vessels that, convincingly, also contributes to the development of diabetic complications. These new findings may explain why classic antioxidants, such as vitamin E, which work by scavenging already-formed toxic oxidation products, have failed to show beneficial effects on diabetic complications and may suggest new and attractive "causal" antioxidant therapy. New low-molecular mass compounds that act as SOD or catalase mimetics or L-propionyl-carnitine and lipoic acid, which work as intracellular superoxide scavengers, improving mitochondrial function and reducing DNA damage, may be good candidates for such a strategy, and preliminary studies support this hypothesis. This "causal" therapy would also be associated with other promising tools such as LY 333531, PJ34, and FP15, which block the protein kinase beta isoform, poly(ADP-ribose) polymerase, and peroxynitrite, respectively. While waiting for these focused tools, we may have other options: thiazolinediones, statins, ACE inhibitors, and angiotensin 1 inhibitors can reduce intracellular oxidative stress generation, and it has been suggested that many of their beneficial effects, even in diabetic patients, are due to this property.
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PMID:New insights on oxidative stress and diabetic complications may lead to a "causal" antioxidant therapy. 1271 23

Excessive production of reactive oxygen species (ROS) occurs in many diseases and oxidation may be a common disease mechanism generally. The original "oxidation hypothesis" concerning the pathogenesis of atherosclerosis was posited in the context of the putative central role of oxidized LDL in the process. Atherosclerosis has three major characteristic features: inflammation with accumulation of T-cells and, in particular, monocytes, which become lipid rich foam cells; remodeling of the arterial wall; and the non-random localization of lesions to areas of disturbed flow or of low shear stress. The evidence is reviewed that each of these characteristics can be attributed to excessive ROS, which are derived from cellular oxidases, especially, the NAD(P)H oxidases. This expanded concept of the central role of oxidation in the pathogenesis of atherosclerosis has led to a renewed and intense interest in the potential role of antioxidants in therapy. The vascular protective effects of existing drugs such as statins and ACE inhibitors that are not related to serum lipid alterations are attributed to their indirect but effective roles as antioxidants. These data as well as evidence that newly developed antioxidant drugs show promise, not only in experimental animals but also clinically, are reviewed.
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PMID:The Jeremiah Metzger Lecture. Pathogenesis of atherosclerosis: redox as a unifying mechanism. 1281 26

Genetic polymorphisms have the potential to predict disease susceptibility. This may be especially useful among individuals with a high-risk lifestyle, so that the genotyping could be adopted for disease prevention through modifications toward a lower-risk lifestyle. We started a program of free genotype announcements in a polymorphism study among health checkup examinees at the Nagoya University Hospital on June 9, 2003. Since such announcements remain controversial for fear of unexpected harmful effects and counseling system, the accumulated evidence on the association between disease risk and genotypes announcements in our study was reviewed in this article. The genotypes used were those of alcohol dehydrogenase 2 (ADH2) Arg47His, aldelhyde dehydlrogenase 2 (ALDH2) Glu487Lys, NAD(P)H: quinone oxidoreductase (NQO1) C609T, glutathlione S transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), interleukin-1B (IL-1B) C-31T, and tumor necrosis factor A (TNF-A) T-1031C, angiotensin converting enzyme (ACE) Ins/Del. Since showed a potential for widespread use in health checkups, the information on the above polymorphisms seems worth documenting. Although there have been no complaints from the participants to date, careful treatments are requested.
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PMID:Associations between disease risk and eight polymorphisms adopted for genotype announcements at Nagoya University Hospital. 1527 68

In diabetes oxidative stress plays a key role in the pathogenesis of vascular complications, and an early step of such damage is considered the development of an endothelial dysfunction. Hyperglycemia directly promotes an endothelial dysfunction inducing process of overproduction of superoxide and consequently peroxynitrite that damages DNA and activates the nuclear enzyme poly(ADP-ribose) polymerase. This process, depleting NAD+, slowing glycolysis, ATP formation and electron transport, results in acute endothelial dysfunction in diabetic blood vessels and contributes to the development of diabetic complications. Classic antioxidants, like vitamin E, failed to show beneficial effects on diabetic complications probably due to their only "symptomatic" action. It is now evident that, statins, ACE inhibitors, AT-1 blockers, calcium channel blockers and thiazolinediones have a strong intracellular antioxidant activity, and it has been suggested that many of their beneficial ancillary effects are due to this property. Statins increase NO bioavailability and decrease superoxide production, probably interfering with NAD(P)H activity and modulating eNOS expression. ACE inhibitors and AT-1 blockers prevent hyperglycemia-derived oxidative stress modulating angiotensin action and production. This effect is of particular interest because hyperglycemia is able to directly modulate cellular angiotensin generation. Calcium channel blockers inhibit the peroxidation of cell membrane lipids and their subsequent intracellular translocation. Thiazolinediones bind and activate the nuclear peroxisome proliferator-activated receptor gamma, a nuclear receptor of ligand-dependent transcription factors. The inhibition of this receptors lead to inhibition of the inducible nitric oxide synthase and consequently reduction of peroxynitrite generation. This preventive activity against oxidative stress generation can justify a large utilization and association of this compound for preventing complications in diabetic patients, where antioxidant defences have been shown to be defective.
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PMID:Antioxidant therapy in diabetic complications: what is new? 1532 Aug 13

R-2-hydroxy-4-phenylbutyric acid (R-HPBA) is an important intermediate in the manufacture of angiotensin converting enzyme inhibitors. In this work, a recombinant D-lactate dehydrogenase (LDH) was used to transform 2-oxo-4-phenylbutyric acid (OPBA) to R-HPBA, with concomitant oxidation of beta-nicotinamide adenine dinucleotide (NADH) to NAD(+). The cofactor NADH was regenerated by formate dehydrogenase (FDH) present in whole cells of Candida boidinii, which were pre-treated with toluene to make them permeable. The whole cells used in the process were more stable and easier to prepare as compared with the isolated FDH from the cells. Kinetic study showed that the reaction rate was dependent on the concentration of cofactor, NAD(+), and that both R-HPBA and OPBA inhibited the reaction. A novel method for co-immobilization of whole cells and LDH enzyme on cotton cloth was developed using polyethyleneimine (PEI), which induced the formation of PEI-enzyme-cell aggregates and their adsorption onto cotton cloth, leading to multilayer co-immobilization of cells and enzyme with high loading (0.5 g cell and 8 mg LDH per gram of cotton cloth) and activity yield ( > 95%). A fibrous bed bioreactor with co-immobilized cells and enzyme on the cotton cloth was then evaluated for R-HPBA production in fed-batch and repeated batch modes, which gave relatively stable reactor productivity of 9 g/L . h and product yield of 0.95 mol/mol OPBA when the concentrations of OPBA and R-HPBA were less than 10 g/L.
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PMID:Biotransformation of R-2-hydroxy-4-phenylbutyric acid by D-lactate dehydrogenase and Candida boidinii cells containing formate dehydrogenase coimmobilized in a fibrous bed bioreactor. 1603 87

There is growing evidence indicating that oxidative stress is a key contributor to the pathogenesis and progression of Parkinson's disease. The brain, and particularly the basal ganglia, possesses a local rennin-angiotensin system. Angiotensin activates NAD(P)H-dependent oxidases, which are a major intracellular source of superoxide, and angiotensin converting enzyme inhibitors (ACEIs) have shown antioxidant properties. We treated mice with MPTP and the ACEI captopril to study the possible neuroprotective and antioxidant effects of the latter on the dopaminergic system. Pre-treatment with captopril induced a significant reduction in the MPTP-induced loss of dopaminergic neurons in the substantia nigra and a significant reduction in the loss of dopaminergic terminals in the striatum. Furthermore, captopril reduced the MPTP-induced increase in the levels of major oxidative stress indicators (i.e. lipid peroxidation and protein oxidation) in the ventral midbrain and the striatum. Captopril did not reduce striatal MPP(+) levels, MAO-B activity or dopamine transporter activity, which may reduce MPTP neurotoxicity. Our results suggest that angiotensin-converting enzyme inhibitors may be useful for treatment of Parkinson's disease, and that further investigation should focus on the neuroprotective capacity of these compounds.
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PMID:Reduction of dopaminergic degeneration and oxidative stress by inhibition of angiotensin converting enzyme in a MPTP model of parkinsonism. 1667 18

Currently, aldosterone is believed to be involved in the development of cardiovascular injury as a potential cardiovascular risk hormone. However, its exact cellular mechanisms remain obscure. This study was undertaken to examine the effect of aldosterone on superoxide production in cultured rat aortic endothelial cells with possible involvement of the small GTP-binding (G) protein Rac1. The aldosterone levels showed a time-dependent (6-24 h) and dose-dependent (10(-8) to 10(-6) m) increase in superoxide generation, whose effect was abolished by mineralocorticoid receptor antagonist (eplerenone), Src inhibitor (PP2), and reduced nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase inhibitor (apocynin). Aldosterone activated NADP(H) oxidase and Rac1, whose effects were abolished by eplerenone. The aldosterone-induced superoxide generation was abolished either by nonselective small G protein inhibitor (Clostridium difficile toxin A) or dominant-negative Rac1. Dominant-negative Rac1 also inhibited aldosterone-induced ACE gene expression. Thus, the present study is the first to demonstrate that aldosterone induces superoxide generation via mineralocorticoid receptor-mediated activation of NAD(P)H-oxidase and Rac1 in endothelial cells, thereby contributing to the development of aldosterone-induced vascular injury.
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PMID:Aldosterone induces superoxide generation via Rac1 activation in endothelial cells. 1807 8

A newly synthesized substrate, 3-hydroxybutyrylglycyl-glycyl-glycine (3HB-GGG), was applied to the assay of ACE-inhibiting activity to overcome the smaller selectivity and sensitivity of the conventional method. In this study, an ACE-inhibiting assay was improved by the use of a water-soluble tetrazolium salt, 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate sodium salt (WST-1), for the detection of 3-hydroxybutyrate, derived from 3HB-GGG. The optimized conditions were as follows: 0.333 mM NAD(+), 0.333 mM WST-1, 0.1 mM EDTA, 0.633 U ml(-1) diaphorase, and 0.700 U ml(-1) 3-hydroxybutyrate dehydrogenase. The developed assay was efficiently applicable to evaluate the ACE-inhibiting activity of practical ACE inhibitors.
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PMID:Assay of angiotensin I-converting enzyme-inhibiting activity based on the detection of 3-hydroxybutyrate with water-soluble tetrazolium salt. 1868 50


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